Ignite Creation Date:
2025-12-25 @ 5:06 AM
Ignite Modification Date:
2026-04-14 @ 5:22 PM
Study NCT ID:
NCT02968927
Status:
UNKNOWN
Last Update Posted:
2019-01-10
First Post:
2016-09-08
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
TB Host Directed Therapy
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D014376', 'term': 'Tuberculosis'}], 'ancestors': [{'id': 'D009164', 'term': 'Mycobacterium Infections'}, {'id': 'D000193', 'term': 'Actinomycetales Infections'}, {'id': 'D016908', 'term': 'Gram-Positive Bacterial Infections'}, {'id': 'D001424', 'term': 'Bacterial Infections'}, {'id': 'D001423', 'term': 'Bacterial Infections and Mycoses'}, {'id': 'D007239', 'term': 'Infections'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000068338', 'term': 'Everolimus'}, {'id': 'D001310', 'term': 'Auranofin'}, {'id': 'D002762', 'term': 'Cholecalciferol'}, {'id': 'C000718973', 'term': 'CC-11050'}], 'ancestors': [{'id': 'D020123', 'term': 'Sirolimus'}, {'id': 'D018942', 'term': 'Macrolides'}, {'id': 'D007783', 'term': 'Lactones'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D006051', 'term': 'Aurothioglucose'}, {'id': 'D050607', 'term': 'Organogold Compounds'}, {'id': 'D009942', 'term': 'Organometallic Compounds'}, {'id': 'D002782', 'term': 'Cholestenes'}, {'id': 'D002776', 'term': 'Cholestanes'}, {'id': 'D013256', 'term': 'Steroids'}, {'id': 'D000072473', 'term': 'Fused-Ring Compounds'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}, {'id': 'D013261', 'term': 'Sterols'}, {'id': 'D014807', 'term': 'Vitamin D'}, {'id': 'D012632', 'term': 'Secosteroids'}, {'id': 'D008563', 'term': 'Membrane Lipids'}, {'id': 'D008055', 'term': 'Lipids'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 200}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2016-11', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-01', 'completionDateStruct': {'date': '2020-12', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2019-01-09', 'studyFirstSubmitDate': '2016-09-08', 'studyFirstSubmitQcDate': '2016-11-17', 'lastUpdatePostDateStruct': {'date': '2019-01-10', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2016-11-21', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2018-09', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Change in FEV1 from baseline to 2 and 6 months', 'timeFrame': 'days 56 and 180', 'description': 'FEV1 (% of expected value)'}, {'measure': '18F-FDG PET/CT imaging (change from baseline to 2 months):', 'timeFrame': 'day 56', 'description': 'Maximum and mean standardized uptake values (SUV)'}, {'measure': 'Serum neopterin', 'timeFrame': 'day 56', 'description': 'change from baseline b. CRP'}, {'measure': 'Quantiferon gold in tube', 'timeFrame': 'day 56', 'description': 'change from baseline'}, {'measure': 'Gene expression profiles (exploratory)', 'timeFrame': 'days 56 and 180', 'description': 'Change from baseline to 2 and 6 months in gene expression profiles'}, {'measure': 'PD-1 expression (exploratory)', 'timeFrame': 'days 56 and 180', 'description': 'PD-1 expression on CD4 and CD8 lymphocytes'}], 'primaryOutcomes': [{'measure': 'SAEs and SUSARs', 'timeFrame': 'through day 180', 'description': 'For auranofin, everolimus, and vitamin D: the proportions of patients experiencing suspected unexpected serious adverse reactions (SUSARs).\n\nFor CC-11050: the proportion of patients experiencing treatment emergent serious adverse events (SAEs).'}], 'secondaryOutcomes': [{'measure': 'TEAEs other than SAEs and SUSARs', 'timeFrame': 'through day 180', 'description': 'TEAEs other than SAEs, categorized according to severity, drug relatedness, and leading to early withdrawal.'}, {'measure': 'Sputum culture status on day 56', 'timeFrame': 'day 56', 'description': 'Proportion of patients with positive sputum cultures on solid culture medium after 8 weeks of treatment'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'conditions': ['Tuberculosis']}, 'referencesModule': {'references': [{'pmid': '33740465', 'type': 'DERIVED', 'citation': 'Wallis RS, Ginindza S, Beattie T, Arjun N, Likoti M, Edward VA, Rassool M, Ahmed K, Fielding K, Ahidjo BA, Vangu MDT, Churchyard G. Adjunctive host-directed therapies for pulmonary tuberculosis: a prospective, open-label, phase 2, randomised controlled trial. Lancet Respir Med. 2021 Aug;9(8):897-908. doi: 10.1016/S2213-2600(20)30448-3. Epub 2021 Mar 16.'}]}, 'descriptionModule': {'briefSummary': 'To examine the safety and preliminary efficacy of multiple adjunctive host directed TB therapies (TB HDT), to assess their potential to shorten TB treatment and/or prevent permanent lung damage.', 'detailedDescription': 'OBJECTIVES:\n\nTo determine the safety and preliminary efficacy of 4 TB HDT candidates:\n\n1. Safety (treatment emergent serious adverse events and SUSARs)\n2. Microbiologic effects in sputum (culture conversion, change in MGIT TTP) and blood (WBA)\n3. PET/CT imaging\n4. Serum markers of inflammation\n5. Effects on Mtb-specific and general immune function\n6. Pulmonary effects (spirometry, 6MWT, O2 saturation, and St. George Respiratory Symptom Questionnaire) In each case, TB HDT effects will be determined by comparison to patients treated with standard TB therapy alone with regard to a common set of primary and secondary endpoints.\n\nPRIMARY ENDPOINTS\n\n1. For auranofin, everolimus, and vitamin D: the proportions of patients experiencing suspected unexpected serious adverse reactions (SUSARs).\n2. For CC-11050: the proportion of patients experiencing treatment emergent serious adverse events (SAEs).'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Willing and able to provide signed written consent or witnessed oral consent in the case of illiteracy, prior to undertaking any trial-related procedures.\n2. Aged 18 to 65 years, male, or if female, either not of reproductive potential (post-menopause, or status-post surgical sterilization) or with an intrauterine contraceptive device in place.\n3. Body weight (in light clothing without shoes) between 40 and 90 kg.\n4. First episode of pulmonary tuberculosis diagnosed by positive sputum AFB smear with subsequent culture confirmation OR positive Xpert TB/RIF with Ct \\<20 \\[4\\].\n5. RIF susceptibility diagnosed by Xpert TB/RIF OR Hain test\n6. Chest radiograph meeting criteria for moderate or far advanced pulmonary tuberculosis \\[5\\]\n7. HIV-1 seronegative\n8. HBsAg negative\n\nExclusion Criteria:\n\n1. Any condition for which participation in the trial, as judged by the investigator, could compromise the well-being of the subject or prevent, limit or confound protocol specified assessments\n2. Current or imminent treatment for malaria.\n3. Is critically ill, and in the judgment of the investigator has a diagnosis likely to result in death during the trial or the follow-up period.\n4. TB meningitis or other forms of severe tuberculosis with high risk of a poor outcome as judged by the investigator.\n5. History of allergy or hypersensitivity to any of the trial therapies or related substances, including known allergy or suspected hypersensitivity to rifampin or rifabutin.\n6. Having participated in other clinical trials with investigational agents within 8 weeks prior to trial start or currently enrolled in an investigational trial.\n7. Subjects with any of the following at screening:\n\n 1. Cardiac arrhythmia requiring medication;\n 2. Prolongation of QT/QTc interval with QTcF (Fridericia correction) \\>450 ms;\n 3. History of additional risk factors for Torsade de Pointes, (e.g., heart failure, hypokalemia, family history of Long QT Syndrome);\n 4. Any clinically significant ECG abnormality, in the opinion of the investigator.\n 5. Patients requiring concomitant medications that prolong the QT inter-val.\n8. Random blood glucose \\>140 mg/dL, or history of unstable Diabetes Mellitus which required hospitalization for hyper- or hypoglycaemia within the past year prior to start of screening.\n9. Use of systemic corticosteroids within the past 28 days.\n10. Subjects with any of the following abnormal laboratory values:\n\n 1. creatinine \\>2 mg/dL\n 2. haemoglobin \\<8 g/dL\n 3. platelets \\<100x109 cells/L\n 4. serum potassium \\<3.5\n 5. aspartate aminotransferase (AST) ≥2.0 x ULN\n 6. alkaline phosphatase (AP) \\>5.0 x ULN\n 7. total bilirubin \\>1.5 mg/dL'}, 'identificationModule': {'nctId': 'NCT02968927', 'acronym': 'TBHDT', 'briefTitle': 'TB Host Directed Therapy', 'organization': {'class': 'OTHER', 'fullName': 'The Aurum Institute NPC'}, 'officialTitle': 'A Ph2 Randomized Trial to Evaluate the Safety Preliminary Efficacy and Biomarker Response of Host Directed Therapies Added to Rifabutin-modified Standard Therapy in Adults With Drug-Sensitive Smear-Positive Pulmonary TB', 'orgStudyIdInfo': {'id': 'TBHDT-AUR1-8-178'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': '2HRbEZ/4HRb', 'description': '2HRbZE', 'interventionNames': ['Drug: 2HRbZE/4HRb']}, {'type': 'EXPERIMENTAL', 'label': 'Everolimus', 'description': 'Everolimus 0.5 MG', 'interventionNames': ['Drug: Everolimus 0.5 MG', 'Drug: 2HRbZE/4HRb']}, {'type': 'EXPERIMENTAL', 'label': 'Auranofin', 'description': 'Auranofin 6 MG', 'interventionNames': ['Drug: Auranofin 6 MG', 'Drug: 2HRbZE/4HRb']}, {'type': 'EXPERIMENTAL', 'label': 'Vitamin D', 'description': 'Vitamin D3', 'interventionNames': ['Drug: Vitamin D3', 'Drug: 2HRbZE/4HRb']}, {'type': 'EXPERIMENTAL', 'label': 'CC-11050', 'description': 'CC-11050', 'interventionNames': ['Drug: CC-11050', 'Drug: 2HRbZE/4HRb']}], 'interventions': [{'name': 'Everolimus 0.5 MG', 'type': 'DRUG', 'armGroupLabels': ['Everolimus']}, {'name': 'Auranofin 6 MG', 'type': 'DRUG', 'armGroupLabels': ['Auranofin']}, {'name': 'Vitamin D3', 'type': 'DRUG', 'armGroupLabels': ['Vitamin D']}, {'name': 'CC-11050', 'type': 'DRUG', 'armGroupLabels': ['CC-11050']}, {'name': '2HRbZE/4HRb', 'type': 'DRUG', 'otherNames': ['rifabutin-modified TB therapy'], 'armGroupLabels': ['2HRbEZ/4HRb', 'Auranofin', 'CC-11050', 'Everolimus', 'Vitamin D']}]}, 'contactsLocationsModule': {'locations': [{'zip': '1736', 'city': 'Tembisa', 'state': 'Gauteng', 'country': 'South Africa', 'facility': 'The Aurum Institute: Tembisa Clinical Research Centre', 'geoPoint': {'lat': -26.00979, 'lon': 28.22762}}], 'overallOfficials': [{'name': 'Robert S Wallis, MD,FIDSA', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'The Aurum Institute NPC'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'The Aurum Institute NPC', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}