Ignite Creation Date:
2025-12-25 @ 5:04 AM
Ignite Modification Date:
2026-03-08 @ 5:56 AM
Study NCT ID:
NCT01370018
Status:
COMPLETED
Last Update Posted:
2021-09-28
First Post:
2011-06-06
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Therapy to Elevate CD4 Counts in HIV-1 Disease
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000163', 'term': 'Acquired Immunodeficiency Syndrome'}], 'ancestors': [{'id': 'D015658', 'term': 'HIV Infections'}, {'id': 'D000086982', 'term': 'Blood-Borne Infections'}, {'id': 'D003141', 'term': 'Communicable Diseases'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D015229', 'term': 'Sexually Transmitted Diseases, Viral'}, {'id': 'D012749', 'term': 'Sexually Transmitted Diseases'}, {'id': 'D016180', 'term': 'Lentivirus Infections'}, {'id': 'D012192', 'term': 'Retroviridae Infections'}, {'id': 'D012327', 'term': 'RNA Virus Infections'}, {'id': 'D014777', 'term': 'Virus Diseases'}, {'id': 'D012897', 'term': 'Slow Virus Diseases'}, {'id': 'D000091662', 'term': 'Genital Diseases'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D007153', 'term': 'Immunologic Deficiency Syndromes'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000515', 'term': 'alpha 1-Antitrypsin'}], 'ancestors': [{'id': 'D006023', 'term': 'Glycoproteins'}, {'id': 'D006001', 'term': 'Glycoconjugates'}, {'id': 'D002241', 'term': 'Carbohydrates'}, {'id': 'D015843', 'term': 'Serpins'}, {'id': 'D010455', 'term': 'Peptides'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D000209', 'term': 'Acute-Phase Proteins'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D000510', 'term': 'Alpha-Globulins'}, {'id': 'D012712', 'term': 'Serum Globulins'}, {'id': 'D005916', 'term': 'Globulins'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'cynthia.bristow@alpha1biologics.com', 'phone': '6314446238', 'title': 'Cynthia L. Bristow, MS, PhD', 'organization': 'Institute for Human Genetics and Biochemistry'}, 'certainAgreement': {'piSponsorEmployee': True, 'restrictiveAgreement': False}, 'limitationsAndCaveats': {'description': 'One HIV infected patient enrolled, but entered the study with elevated inflammatory markers which were were not within the eligibility criteria.'}}, 'adverseEventsModule': {'timeFrame': '9 weeks to 1 year post therapy', 'eventGroups': [{'id': 'EG000', 'title': 'Alpha-1-Proteinase Inhibitor', 'description': 'This pilot study was performed to show that Zemaira® treatment can be used in HIV-1 patients to elevate alpha-1-Proteinase Inhibitor and has the added benefit of elevating CD4 cells.', 'otherNumAtRisk': 4, 'deathsNumAtRisk': 4, 'otherNumAffected': 0, 'seriousNumAtRisk': 4, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'CD4/CD8 Ratio', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Alpha-1-Proteinase Inhibitor in HIV', 'description': 'This pilot study was performed to show that Zemaira® treatment can be used in HIV-1 patients to elevate alpha-1-Proteinase Inhibitor and has the added benefit of elevating CD4 cells.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.44', 'spread': '0.30', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': '9 weeks after initiation of treatment', 'unitOfMeasure': 'Ratio', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Alpha-1-Proteinase Inhibitor/HIV', 'description': 'This pilot study was performed to examine the efficacy of alpha-1 proteinase inhibitor augmentation in HIV-1 infected patients undergoing research treatment to elevate alpha-1-proteinase inhibitor and thereby, CD4 helper immune cells.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '4'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '3'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'Did not meet criteria for analysis', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Alpha-1-Proteinase Inhibitor in HIV', 'description': 'This pilot study was performed to examine the efficacy of alpha-1 proteinase inhibitor augmentation in 4 HIV-1 infected patients undergoing research treatment to elevate alpha-1-proteinase inhibitor and thereby, CD4 helper immune cells.Study subjects were evaluated at Baseline and weekly for at least 8 weeks.'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '3', 'groupId': 'BG000'}]}, {'title': '>=65 years', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Sex/Gender, Customized', 'classes': [{'title': 'Male', 'categories': [{'measurements': [{'value': '4', 'groupId': 'BG000'}]}]}, {'title': 'Female', 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '4', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'CD4 counts', 'classes': [{'categories': [{'measurements': [{'value': '294', 'spread': '125', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'cells/uL', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'CD8', 'classes': [{'categories': [{'measurements': [{'value': '829', 'spread': '281', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'cells/uL', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'CD4/CD8 Ratio', 'classes': [{'categories': [{'measurements': [{'value': '0.40', 'spread': '0.19', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'Ratio', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'active alpha-1 proteinase inhibitor', 'classes': [{'categories': [{'measurements': [{'value': '8', 'spread': '3', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'μM', 'dispersionType': 'STANDARD_DEVIATION'}], 'populationDescription': 'HIV patients were receiving antiretroviral medication with adequate suppression of virus. No patients had previously received alpha-1 proteinase inhibitor treatment.'}}, 'protocolSection': {'designModule': {'phases': ['PHASE2', 'PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 4}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2006-12'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-08', 'completionDateStruct': {'date': '2007-02', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2021-08-31', 'studyFirstSubmitDate': '2011-06-06', 'resultsFirstSubmitDate': '2014-01-06', 'studyFirstSubmitQcDate': '2011-06-08', 'lastUpdatePostDateStruct': {'date': '2021-09-28', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2021-08-31', 'studyFirstPostDateStruct': {'date': '2011-06-09', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2021-09-28', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2007-02', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'CD4/CD8 Ratio', 'timeFrame': '9 weeks after initiation of treatment'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['CD4 counts', 'cholesterol'], 'conditions': ['HIV Disease']}, 'referencesModule': {'references': [{'type': 'RESULT', 'citation': 'Bristow, C.L., Cortes, J., Mukhtarzad R., Trucy, M., Franklin, A., Romberg, V., Winston, R. 2010. α1Antitrypsin therapy increases CD4+ lymphocytes to normal values in HIV-1 patients. In Soluble Factors Mediating Innate Immune Responses to HIV Infection, (ed. M. Alfano). Bentham Science Publishers, http://www.alpha1biologics.com/BristowChapter.pdf'}, {'pmid': '24229737', 'type': 'RESULT', 'citation': 'Bristow CL, Modarresi R, Babayeva MA, LaBrunda M, Mukhtarzad R, Trucy M, Franklin A, Reeves RE, Long A, Mullen MP, Cortes J, Winston R. A feedback regulatory pathway between LDL and alpha-1 proteinase inhibitor in chronic inflammation and infection. Discov Med. 2013 Nov;16(89):201-18.'}, {'pmid': '31824943', 'type': 'RESULT', 'citation': 'Bristow CL, Ferrando-Martinez S, Ruiz-Mateos E, Leal M, Winston R. Development of Immature CD4+CD8+T Cells Into Mature CD4+ T Cells Requires Alpha-1 Antitrypsin as Observed by Treatment in HIV-1 Infected and Uninfected Controls. Front Cell Dev Biol. 2019 Nov 21;7:278. doi: 10.3389/fcell.2019.00278. eCollection 2019.'}]}, 'descriptionModule': {'briefSummary': 'For more than 20 years, alpha-1-proteinase inhibitor therapy has been the standard treatment for patients who have inherited alpha-1-proteinase inhibitor deficiency. Adult patients with this condition eventually develop emphysema. Most HIV-1 patients who have low viral load also have alpha-1-proteinase inhibitor deficiency. The number of CD4 cells in blood increases when alpha-1-proteinase inhibitor increases. Patients will be asked to participate in a pilot study to see whether the use of Zemaira® (alpha-1-proteinase inhibitor) can increase blood levels of alpha-1-proteinase inhibitor and consequently increase CD4 counts.', 'detailedDescription': 'HIV-1 patients will be asked to participate in a pilot study to see whether the use of Zemaira increases blood levels of alpha-1-proteinase inhibitor and consequently increase CD4 counts.\n\nHIV-1 patients will receive weekly treatment with Zemaira for 8 weeks by intravenous infusion. Blood will be collected immediately prior to each infusion. Blood will be collected at each visit. Exploratory assessments and not pre-specified outcome measurements will include complete blood count, lymphocyte phenotype, HIV-1 viral load, lipid levels, blood chemistry, and markers of inflammation from patient medical records. Exploratory and not pre-specified outcome measures will include extended lymphocyte phenotype and lymphocyte function using residual blood collected.'}, 'eligibilityModule': {'sex': 'MALE', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '70 Years', 'minimumAge': '30 Years', 'genderBased': True, 'genderDescription': 'Female subjects were not included in this pilot study to avoid pregnancy-related issues.', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. HIV-1 patients must have confirmed HIV-1 disease, diagnosed using the standard criteria and be on antiretroviral therapy. Patients with inherited alpha-1 proteinase inhibitor deficiency (PIzz) must not have previously received alpha-1 proteinase inhibitor therapy. Uninfected volunteers will be age and gender matched.\n2. HIV-1 patients must have measurable disease, defined as HIV-1 infected patients on antiretroviral therapy with undetectable HIV RNA (\\<500 HIV-1 RNA copies/ml) and CD4 counts more than 200 and less than 400 cells/uL.\n3. Age at least 18 years and under 65 years.\n4. HIV-1 patients must have active alpha-1 proteinase inhibitor below 11uM (normal is 18-53 uM).\n5. HIV-1 patients must have one year history (prior to the study) with CD4 counts greater than 200 and less than 400 cells/uL.\n6. Volunteers must have no evidence of malignancy.\n\nExclusion Criteria:\n\n1. Recent illness that will prevent the patient from participating in required study activities.\n2. Patients receiving other investigational agents.\n3. Patients with known malignancies.\n4. Patients with more than 500 HIV RNA copies/mL.\n5. Patients with more than 400 CD4 cells/uL.\n6. Uncontrolled illness including, but not limited to, ongoing or active infection, myeloid dysplastic syndrome, anemia, bone marrow failure, DiGeorge Syndrome, thymic disorders, or psychiatric illness/social situations that would limit compliance with study requirements.'}, 'identificationModule': {'nctId': 'NCT01370018', 'briefTitle': 'Therapy to Elevate CD4 Counts in HIV-1 Disease', 'organization': {'class': 'OTHER', 'fullName': 'Institute for Human Genetics and Biochemistry'}, 'officialTitle': 'Zemaira (Alpha-1-Proteinase Inhibitor) Therapy in HIV-1 Disease', 'orgStudyIdInfo': {'id': 'R06-005'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'alpha-1 proteinase inhibitor in HIV', 'description': 'HIV-1 infected individuals treated with Alpha-1 proteinase inhibitor', 'interventionNames': ['Biological: alpha-1-Proteinase Inhibitor']}], 'interventions': [{'name': 'alpha-1-Proteinase Inhibitor', 'type': 'BIOLOGICAL', 'otherNames': ['Zemaira', 'Prolastin'], 'description': 'Alpha-1-Proteinase Inhibitor was delivered I.V. A patient weighing 150 pounds was infused with approximately ½ cup containing 8.4 grams of alpha-1-Proteinase Inhibitor. Patients were admitted to hospital for infusion. The I.V. infusion was approximately 1 teaspoon/minute. Patients received weekly infusions of alpha-1-Proteinase Inhibitor for 8-12 weeks. At the time of infusion, 40ml (3 Tablespoons) of blood was collected (IRB approval #R04-003). The blood sample was used to monitor viral load, CD4 cell numbers, and alpha-1-Proteinase Inhibitor.', 'armGroupLabels': ['alpha-1 proteinase inhibitor in HIV']}]}, 'contactsLocationsModule': {'locations': [{'zip': '10003', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'Cabrini Medical Center', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}], 'overallOfficials': [{'name': 'Cynthia L Bristow, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Icahn School of Medicine at Mount Sinai'}, {'name': 'Jose Cortes, MD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Beth Israel Medical Center'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Institute for Human Genetics and Biochemistry', 'class': 'OTHER'}, 'collaborators': [{'name': 'CSL Behring', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Assistant Professor, Mount Sinai School of Medicine', 'investigatorFullName': 'Cynthia L Bristow, PhD', 'investigatorAffiliation': 'Institute for Human Genetics and Biochemistry'}}}}