Ignite Creation Date:
2025-12-24 @ 7:49 PM
Ignite Modification Date:
2025-12-29 @ 7:02 PM
Study NCT ID:
NCT01119703
Status:
COMPLETED
Last Update Posted:
2015-12-29
First Post:
2010-05-05
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Vaccine Hyporesponse in Healthy Elderly Participants (MK-0000-131 AM2)
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'removedCountries': ['Canada', 'United States']}, 'interventionBrowseModule': {'meshes': [{'id': 'D013745', 'term': 'Tetanus Toxoid'}, {'id': 'D017325', 'term': 'Hepatitis B Vaccines'}, {'id': 'D014612', 'term': 'Vaccines'}], 'ancestors': [{'id': 'D014121', 'term': 'Toxoids'}, {'id': 'D001688', 'term': 'Biological Products'}, {'id': 'D045424', 'term': 'Complex Mixtures'}, {'id': 'D014761', 'term': 'Viral Hepatitis Vaccines'}, {'id': 'D014765', 'term': 'Viral Vaccines'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'ClinicalTrialsDisclosure@merck.com', 'phone': '1-800-672-6372', 'title': 'Vice President, Late Stage Development Group Leader', 'organization': 'Merck Sharp & Dohme Corp'}, 'certainAgreement': {'otherDetails': 'The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission.', 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'eventGroups': [{'id': 'EG000', 'title': 'All Participants', 'description': 'Participants who received at least one dose of each vaccine', 'otherNumAtRisk': 174, 'otherNumAffected': 14, 'seriousNumAtRisk': 174, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Injection Site Pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 174, 'numAffected': 14}], 'organSystem': 'General disorders', 'sourceVocabulary': 'MedDRA 15.0'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Antibody Titer Responses to Hepatitis B Virus Surface Antigen (HBV sAg) Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '143', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Elderly Participants', 'description': 'Healthy participants 65 years of age and older.'}], 'classes': [{'title': 'Predicted Titer', 'categories': [{'measurements': [{'value': '2.27', 'spread': '1.24', 'groupId': 'OG000'}]}]}, {'title': 'Measured Titer', 'categories': [{'measurements': [{'value': '2.12', 'spread': '1.91', 'groupId': 'OG000'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': 'Coefficient of Determination %', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-9.1', 'ciLowerLimit': '-13.8', 'ciUpperLimit': '-0.7', 'estimateComment': 'Crossvalidated; negative values mean that the fitted model performs worse than chance on the test set.', 'groupDescription': 'Null hypothesis for Predicted versus Measured Titers states that Coefficient of Determination % (CD%) \\<= 20%; whereas the alternative hypothesis is \\> 20%. CD% was obtained by fitting a random forest model to the measured titers, which included all baseline biomarkers as predictors.', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and 1 month after final vaccination', 'description': 'Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to HBV sAg were then measured 1 month after final vaccination, based on enzyme linked immunosorbent assay (ELISA), and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected prior to vaccination at baseline, to measure a wide variety of biomarkers by messenger RNA (mRNA) profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln).', 'unitOfMeasure': 'ln International Units', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.'}, {'type': 'PRIMARY', 'title': 'Antibody Titer Responses to Tetanus Booster Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '143', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Elderly Participants', 'description': 'Healthy participants 65 years of age and older'}], 'classes': [{'title': 'Predicted Titer', 'categories': [{'measurements': [{'value': '1.40', 'spread': '1.24', 'groupId': 'OG000'}]}]}, {'title': 'Measured Titer', 'categories': [{'measurements': [{'value': '1.32', 'spread': '1.84', 'groupId': 'OG000'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': 'Coefficient of Determination %', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '17.6', 'ciLowerLimit': '10.6', 'ciUpperLimit': '20.9', 'estimateComment': 'Crossvalidated; negative values mean that the fitted model performs worse than chance on the test set.', 'groupDescription': 'Null hypothesis for Predicted versus Measured Titers states that Coefficient of Determination % (CD%) \\<= 20%; whereas the alternative hypothesis is \\> 20%. CD% was obtained by fitting a random forest model to the measured titers, which included all baseline biomarkers as predictors.', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and 1 month after final vaccination', 'description': 'Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to tetanus were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected prior to vaccination at baseline, to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln).', 'unitOfMeasure': 'ln International Units', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.'}, {'type': 'PRIMARY', 'title': 'Antibody Titer Responses to Reduced Diphtheria Toxin Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '143', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Elderly Participants', 'description': 'Healthy participants 65 years of age and older'}], 'classes': [{'title': 'Predicted Titer', 'categories': [{'measurements': [{'value': '-0.43', 'spread': '1.25', 'groupId': 'OG000'}]}]}, {'title': 'Measured Titer', 'categories': [{'measurements': [{'value': '-0.46', 'spread': '1.77', 'groupId': 'OG000'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': 'Coefficient of Determination %', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '27.8', 'ciLowerLimit': '19.6', 'ciUpperLimit': '32.4', 'estimateComment': 'Crossvalidated; negative values mean that the fitted model performs worse than chance on the test set.', 'groupDescription': 'Null hypothesis for Predicted versus Measured Titers states that Coefficient of Determination % (CD%) \\<= 20%; whereas the alternative hypothesis is \\> 20%. CD% was obtained by fitting a random forest model to the measured titers, which included all baseline biomarkers as predictors.', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and 1 month after final vaccination', 'description': 'Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to diphtheria were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected prior to vaccination at baseline, to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln).', 'unitOfMeasure': 'ln International Units', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.'}, {'type': 'PRIMARY', 'title': 'Antibody Titer Responses to Oral Cholera Vaccine (WC/rBS), Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '143', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Elderly Participants', 'description': 'Healthy participants 65 years of age and older'}], 'classes': [{'title': 'Predicted Titer', 'categories': [{'measurements': [{'value': '5.24', 'spread': '0.99', 'groupId': 'OG000'}]}]}, {'title': 'Measured Titer', 'categories': [{'measurements': [{'value': '5.20', 'spread': '1.55', 'groupId': 'OG000'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': 'Coefficient of Determination %', 'ciPctValue': '95', 'paramValue': '3.3', 'ciLowerLimit': '-2.8', 'ciUpperLimit': '8.5', 'estimateComment': 'Crossvalidated; negative values mean that the fitted model performs worse than chance on the test set.', 'groupDescription': 'Null hypothesis for Predicted versus Measured Titers states that Coefficient of Determination % (CD%) \\<= 20%; whereas the alternative hypothesis is \\> 20%. CD% was obtained by fitting a random forest model to the measured titers, which included all baseline biomarkers as predictors.', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and 3 weeks after final vaccination', 'description': 'Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to cholera were then measured 3 weeks after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected prior to vaccination at baseline, to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln).', 'unitOfMeasure': 'ln International Units', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.'}, {'type': 'PRIMARY', 'title': 'Post-vaccination Antibody Titer Responses to Different Vaccines in Healthy, Elderly, Participants.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '143', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Elderly Participants', 'description': 'Healthy participants 65 years of age and older'}], 'classes': [{'title': 'Hepatitis B', 'categories': [{'measurements': [{'value': '2.12', 'spread': '1.91', 'groupId': 'OG000'}]}]}, {'title': 'Tetanus', 'categories': [{'measurements': [{'value': '1.32', 'spread': '1.84', 'groupId': 'OG000'}]}]}, {'title': 'Diphtheria', 'categories': [{'measurements': [{'value': '-0.46', 'spread': '1.77', 'groupId': 'OG000'}]}]}, {'title': 'Cholera', 'categories': [{'measurements': [{'value': '5.20', 'spread': '1.55', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.66', 'groupIds': ['OG000'], 'paramType': "Spearman's Correlation Coefficient", 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.04', 'ciLowerLimit': '-0.2', 'ciUpperLimit': '0.13', 'estimateComment': 'Within-participant rank correlation', 'groupDescription': 'Diphtheria versus Hepatitis B', 'statisticalMethod': "Fisher's Z-transformation", 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '0.26', 'groupIds': ['OG000'], 'paramType': "Spearman's Correlation Coefficient", 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.10', 'ciLowerLimit': '-0.07', 'ciUpperLimit': '0.25', 'estimateComment': 'Within-participant rank correlation', 'groupDescription': 'Diphtheria versus Cholera', 'statisticalMethod': "Fisher's Z-transformation", 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '<0.001', 'groupIds': ['OG000'], 'paramType': "Spearman's Correlation Coefficient", 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.40', 'ciLowerLimit': '0.26', 'ciUpperLimit': '0.53', 'estimateComment': 'Within-participant rank correlation', 'groupDescription': 'Diphtheria versus Tetanus', 'statisticalMethod': "Fisher's Z-transformation", 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '0.04', 'groupIds': ['OG000'], 'paramType': "Spearman's Correlation Coefficient", 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.17', 'ciLowerLimit': '-0.32', 'ciUpperLimit': '-0.01', 'estimateComment': 'Within-participant rank correlation', 'groupDescription': 'Hepatitis B versus Cholera', 'statisticalMethod': "Fisher's Z-transformation", 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '0.30', 'groupIds': ['OG000'], 'paramType': "Spearman's Correlation Coefficient", 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.09', 'ciLowerLimit': '-0.25', 'ciUpperLimit': '0.08', 'estimateComment': 'Within-participant rank correlation', 'groupDescription': 'Hepatitis B versus Tetanus', 'statisticalMethod': "Fisher's Z-transformation", 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '0.36', 'groupIds': ['OG000'], 'paramType': "Spearman's Correlation Coefficient", 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.08', 'ciLowerLimit': '-0.09', 'ciUpperLimit': '0.24', 'estimateComment': 'Within-participant rank correlation', 'groupDescription': 'Cholera versus Tetanus', 'statisticalMethod': "Fisher's Z-transformation", 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': '3 weeks or 1 month after each final vaccination', 'description': 'Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to each of these four antigens were then measured 1 month after each final vaccination (3 weeks for cholera toxin), based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln).', 'unitOfMeasure': 'ln International Units', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.'}, {'type': 'SECONDARY', 'title': 'Antibody Titer Responses to Hepatitis B Virus Surface Antigen (HBV sAg) Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '143', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Elderly Participants', 'description': 'Healthy participants 65 years of age and older'}], 'classes': [{'title': 'Predicted Titer', 'categories': [{'measurements': [{'value': '2.25', 'spread': '1.24', 'groupId': 'OG000'}]}]}, {'title': 'Measured Titer', 'categories': [{'measurements': [{'value': '2.12', 'spread': '1.91', 'groupId': 'OG000'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': 'Coefficient of Determination %', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-9.5', 'ciLowerLimit': '-16.6', 'ciUpperLimit': '-2.7', 'estimateComment': 'Crossvalidated; negative values mean that the fitted model performs worse than chance on the test set.', 'groupDescription': 'Null hypothesis for Predicted versus Measured Titers states that Coefficient of Determination % (CD%) \\<= 20%; whereas the alternative hypothesis is \\> 20%. CD% was obtained by fitting a random forest model to the measured titers, which included all Day 7 biomarkers as predictors.', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'Day 7 and 1 month after final vaccination', 'description': 'Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to HBV sAg were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected at 7 days post-baseline vaccination to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln).', 'unitOfMeasure': 'ln International Units', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.'}, {'type': 'SECONDARY', 'title': 'Antibody Titer Responses to Tetanus Booster Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '143', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Elderly Participants', 'description': 'Healthy participants 65 years of age and older'}], 'classes': [{'title': 'Predicted Titer', 'categories': [{'measurements': [{'value': '1.43', 'spread': '1.27', 'groupId': 'OG000'}]}]}, {'title': 'Measured Titer', 'categories': [{'measurements': [{'value': '1.32', 'spread': '1.84', 'groupId': 'OG000'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': 'Coefficient of Determination %', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '23.7', 'ciLowerLimit': '14.0', 'ciUpperLimit': '29.7', 'estimateComment': 'Crossvalidated; negative values mean that the fitted model performs worse than chance on the test set.', 'groupDescription': 'Null hypothesis for Predicted versus Measured Titers states that Coefficient of Determination % (CD%) \\<= 20%; whereas the alternative hypothesis is \\> 20%. CD% was obtained by fitting a random forest model to the measured titers, which included all Day 7 biomarkers as predictors.', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'Day 7 and 1 month after each final vaccination', 'description': 'Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to tetanus were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected 7 days post-baseline vaccination to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log(ln).', 'unitOfMeasure': 'ln International Units', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.'}, {'type': 'SECONDARY', 'title': 'Antibody Titer Responses to Reduced Diphtheria Toxin Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '143', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Elderly Participants', 'description': 'Healthy participants 65 years of age and older'}], 'classes': [{'title': 'Predicted Titer', 'categories': [{'measurements': [{'value': '-0.37', 'spread': '1.36', 'groupId': 'OG000'}]}]}, {'title': 'Measured Titer', 'categories': [{'measurements': [{'value': '-0.46', 'spread': '1.77', 'groupId': 'OG000'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': 'Coefficient of Determination %', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '36.7', 'ciLowerLimit': '28.7', 'ciUpperLimit': '41.5', 'estimateComment': 'Crossvalidated;negative values mean that the fitted model performs worse than chance on the test set.', 'groupDescription': 'Null hypothesis for Predicted versus Measured Titers states that Coefficient of Determination % (CD%) \\<= 20%; whereas the alternative hypothesis is \\> 20%. CD% was obtained by fitting a random forest model to the measured titers, which included all Day 7 biomarkers as predictors.', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'Day 7 and 1 month after final vaccination', 'description': 'Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to diphtheria were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected 7 days post-baseline vaccination to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log(ln).', 'unitOfMeasure': 'ln International Units', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.'}, {'type': 'SECONDARY', 'title': 'Antibody Titer Responses to Oral Cholera Vaccine (WC/rBS), Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '143', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Elderly Participants', 'description': 'Healthy participants 65 years of age and older'}], 'classes': [{'title': 'Predicted Titer', 'categories': [{'measurements': [{'value': '5.24', 'spread': '0.96', 'groupId': 'OG000'}]}]}, {'title': 'Measured Titer', 'categories': [{'measurements': [{'value': '5.20', 'spread': '1.55', 'groupId': 'OG000'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': 'Coefficient of Determination %', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-2.2', 'ciLowerLimit': '-7.8', 'ciUpperLimit': '4.4', 'estimateComment': 'Crossvalidated; negative values mean that the fitted model performs worse than chance on the test set.', 'groupDescription': 'Null hypothesis for Predicted versus Measured Titers states that Coefficient of Determination % (CD%) \\<= 20%; whereas the alternative hypothesis is \\> 20%. CD% was obtained by fitting a random forest model to the measured titers, which included all Day 7 biomarkers as predictors.', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'Day 7 and 3 weeks after final vaccination', 'description': 'Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to cholera were then measured 3 weeks after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected 7 days post-baseline vaccination to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log(ln).', 'unitOfMeasure': 'ln International Units', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Younger Participants', 'description': 'Participants 25 to 40 years of age.'}, {'id': 'FG001', 'title': 'Elderly Participants', 'description': 'Participants 65 years old and older.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '30'}, {'groupId': 'FG001', 'numSubjects': '144'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '30'}, {'groupId': 'FG001', 'numSubjects': '143'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '30', 'groupId': 'BG000'}, {'value': '144', 'groupId': 'BG001'}, {'value': '174', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Younger Participants', 'description': 'Aged 25 to 40 years old'}, {'id': 'BG001', 'title': 'Elderly Participants', 'description': 'Aged 65 years and older'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '33.9', 'spread': '3.6', 'groupId': 'BG000'}, {'value': '70.2', 'spread': '4.1', 'groupId': 'BG001'}, {'value': '63.9', 'spread': '14.3', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'Years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '18', 'groupId': 'BG000'}, {'value': '77', 'groupId': 'BG001'}, {'value': '95', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '12', 'groupId': 'BG000'}, {'value': '67', 'groupId': 'BG001'}, {'value': '79', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Cryopreserved peripheral blood mononuclear cells (PBMCs) obtained from whole blood samples.'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 174}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2010-07'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2015-11', 'completionDateStruct': {'date': '2011-11', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2015-11-30', 'studyFirstSubmitDate': '2010-05-05', 'resultsFirstSubmitDate': '2012-10-16', 'studyFirstSubmitQcDate': '2010-05-06', 'lastUpdatePostDateStruct': {'date': '2015-12-29', 'type': 'ESTIMATED'}, 'resultsFirstSubmitQcDate': '2012-10-16', 'studyFirstPostDateStruct': {'date': '2010-05-07', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2012-11-22', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2011-11', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Antibody Titer Responses to Hepatitis B Virus Surface Antigen (HBV sAg) Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants.', 'timeFrame': 'Baseline and 1 month after final vaccination', 'description': 'Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to HBV sAg were then measured 1 month after final vaccination, based on enzyme linked immunosorbent assay (ELISA), and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected prior to vaccination at baseline, to measure a wide variety of biomarkers by messenger RNA (mRNA) profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln).'}, {'measure': 'Antibody Titer Responses to Tetanus Booster Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants.', 'timeFrame': 'Baseline and 1 month after final vaccination', 'description': 'Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to tetanus were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected prior to vaccination at baseline, to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln).'}, {'measure': 'Antibody Titer Responses to Reduced Diphtheria Toxin Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants.', 'timeFrame': 'Baseline and 1 month after final vaccination', 'description': 'Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to diphtheria were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected prior to vaccination at baseline, to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln).'}, {'measure': 'Antibody Titer Responses to Oral Cholera Vaccine (WC/rBS), Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants.', 'timeFrame': 'Baseline and 3 weeks after final vaccination', 'description': 'Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to cholera were then measured 3 weeks after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected prior to vaccination at baseline, to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln).'}, {'measure': 'Post-vaccination Antibody Titer Responses to Different Vaccines in Healthy, Elderly, Participants.', 'timeFrame': '3 weeks or 1 month after each final vaccination', 'description': 'Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to each of these four antigens were then measured 1 month after each final vaccination (3 weeks for cholera toxin), based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln).'}], 'secondaryOutcomes': [{'measure': 'Antibody Titer Responses to Hepatitis B Virus Surface Antigen (HBV sAg) Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants.', 'timeFrame': 'Day 7 and 1 month after final vaccination', 'description': 'Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to HBV sAg were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected at 7 days post-baseline vaccination to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln).'}, {'measure': 'Antibody Titer Responses to Tetanus Booster Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants.', 'timeFrame': 'Day 7 and 1 month after each final vaccination', 'description': 'Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to tetanus were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected 7 days post-baseline vaccination to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log(ln).'}, {'measure': 'Antibody Titer Responses to Reduced Diphtheria Toxin Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants.', 'timeFrame': 'Day 7 and 1 month after final vaccination', 'description': 'Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to diphtheria were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected 7 days post-baseline vaccination to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log(ln).'}, {'measure': 'Antibody Titer Responses to Oral Cholera Vaccine (WC/rBS), Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants.', 'timeFrame': 'Day 7 and 3 weeks after final vaccination', 'description': 'Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to cholera were then measured 3 weeks after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected 7 days post-baseline vaccination to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log(ln).'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Vaccine Hyporesponse'], 'conditions': ['Vaccine Response Impaired']}, 'descriptionModule': {'briefSummary': 'This study evaluated whether it is possible in healthy elderly participants to generate baseline biomarker-based prediction rules (PdR) for vaccine response (post baseline absolute serum antibody titer) using each of the protocol selected vaccines separately; and examined the rank correlation coefficients of pairs of post vaccination antibody titers within the same elderly individuals.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '25 Years', 'samplingMethod': 'PROBABILITY_SAMPLE', 'studyPopulation': 'Adults 25 to 40 years old or 65 years and older', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Male or female aged 25 to 40 years old or 65 years of age or older at the prestudy (screening) visit\n* Has no fever on day of screening\n* Lacks Hepatitis B surface antigen seroreactivity\n* If female 25 to 40 years of age, is not pregnant nor breastfeeding, and agrees to use effective contraception\n\nExclusion Criteria:\n\n* Has a prior history of Hepatitis B Virus infection\n* Has BMI (Body Mass Index) \\>35\n* If female 25 to 40 years of age, is pregnant, or expecting to conceive, donate eggs or breastfeed\n* Has received immune globulin and/or blood products within 3 months prior to first dose received\n* Has a history of immunosuppression resulting from disease (e.g., malignancy; human immunodeficiency virus \\[HIV\\] infection), or is currently taking corticosteroids or other immunosuppressive/cytotoxic therapy (cancer chemotherapy or organ transplantation)\n* Has an active neoplastic disease\n* Has had any infection including upper respiratory viral syndrome in the 6 weeks prior to planned collection of baseline laboratory samples\n* Has received a live virus vaccine or an inactivated vaccine or is scheduled to receive a live virus vaccine or an inactivated vaccine in the period from 6 weeks prior to receipt of the first vaccine through the completion of all study visits'}, 'identificationModule': {'nctId': 'NCT01119703', 'briefTitle': 'Vaccine Hyporesponse in Healthy Elderly Participants (MK-0000-131 AM2)', 'organization': {'class': 'INDUSTRY', 'fullName': 'Merck Sharp & Dohme LLC'}, 'officialTitle': 'A Phase I, Open-Label Observational Study to Develop a Prospective Predictor of Vaccine Hyporesponse in Healthy Elderly Subjects', 'orgStudyIdInfo': {'id': '0000-131'}, 'secondaryIdInfos': [{'id': 'MK-0000-131', 'type': 'OTHER', 'domain': 'Merck'}]}, 'armsInterventionsModule': {'armGroups': [{'label': 'Arm 1: Healthy, elderly participants', 'description': 'Healthy participants 65 years old and older.', 'interventionNames': ['Biological: Tetanus & Diphtheria booster vaccine (Td)', 'Biological: TwinrixTM [Hepatitis A Inactivated & Hepatitis B (Recombinant) Vaccine]', "Biological: Dukoral® Traveler's Diarrhea Vaccine (WC/rBS)"]}, {'label': 'Arm 2: Healthy, young, participants', 'description': 'Healthy participants 25 to 40 years old.', 'interventionNames': ['Biological: Tetanus & Diphtheria booster vaccine (Td)', 'Biological: TwinrixTM [Hepatitis A Inactivated & Hepatitis B (Recombinant) Vaccine]', "Biological: Dukoral® Traveler's Diarrhea Vaccine (WC/rBS)"]}], 'interventions': [{'name': 'Tetanus & Diphtheria booster vaccine (Td)', 'type': 'BIOLOGICAL', 'description': 'Tetanus \\& Diphtheria booster vaccine (Td), single intramuscular dose', 'armGroupLabels': ['Arm 1: Healthy, elderly participants', 'Arm 2: Healthy, young, participants']}, {'name': 'TwinrixTM [Hepatitis A Inactivated & Hepatitis B (Recombinant) Vaccine]', 'type': 'BIOLOGICAL', 'description': 'TwinrixTM \\[Hepatitis A Inactivated \\& Hepatitis B (Recombinant) Vaccine\\], intramuscular, two doses of standard three dose regimen (opposite arms)', 'armGroupLabels': ['Arm 1: Healthy, elderly participants', 'Arm 2: Healthy, young, participants']}, {'name': "Dukoral® Traveler's Diarrhea Vaccine (WC/rBS)", 'type': 'BIOLOGICAL', 'description': "Dukoral® Traveler's Diarrhea Vaccine, recombinant Cholera toxin B subunit (WC/rBS), standard two oral doses per treatment regimen", 'armGroupLabels': ['Arm 1: Healthy, elderly participants', 'Arm 2: Healthy, young, participants']}]}, 'contactsLocationsModule': {'overallOfficials': [{'name': 'Francois St-Maurice, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Anapharm'}, {'name': 'Denis Audet, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Anapharm'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Merck Sharp & Dohme LLC', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}