- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04734652
INSTI's For The Management of HIV-associated TB (INSIGHT)
A Phase 2b Study to Evaluate the Efficacy, Safety and PK of a Combination of Bictegravir, Emtricitabine, and Tenofovir Alafenamide Fumarate for Treatment of HIV-1 Infection in Patients With DS-TB on a Rifampicin-based Regimen
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Primary objective: To characterize viral suppression rates (proportion of patients with suppressed viral load) at week 24 in the BIC arm
Secondary objectives:
To characterize viral suppression rates at weeks 12, 24 and 48 in the standard of care treatment (SOC) arm (currently, TDF 300mg/3TC 300mg/DTG 50mg) and at weeks 12 and 48 in the BIC/FTC/TAF arm.
To compare the pharmacokinetics (PK) of BIC when given twice daily and co-administered with Rifampicin during tuberculosis treatment vs when given alone after discontinuation of Rifampicin
To assess the incidence of TB associated IRIS in each arm, through week 24.
To characterize the tolerability of treatment in each arm by assessing frequency of clinician-initiated treatment interruptions or switches through week 48.
To assess frequency of ART drug resistance mutations in participants with detectable viral load at study visit weeks 24 and 48.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Smita Maharaj
- Phone Number: 0510 +27316550510
- Email: Smita.Maharaj@caprisa.org
Study Contact Backup
- Name: Resha Boodhram, MSc
- Phone Number: 0669 +27316550669
- Email: resha.boodhram@caprisa.org
Study Locations
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KwaZulu-Natal
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Durban, KwaZulu-Natal, South Africa, 4001
- CAPRISA Springfield Clinical Research Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Adults ≥ 18 years of age with Karnofsky score ≥ 70
- Confirmed rifampicin-susceptible tuberculosis and/or
- On first-line rifampicin-based tuberculosis treatment (not > 8 weeks at the time of enrolment)
- Documented HIV-1 infection, ART-naïve OR ART non-naïve (patients to have no exposure to ART medication at least ≥ 3 months at the time of enrollment)
- Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2
- Alanine aminotransferase (ALT) ≤3 times the upper limit of normal (ULN)
- Total bilirubin ≤2.5 times ULN
- Creatinine ≤2 times ULN
- Hemoglobin ≥ 7.0 g/dL (6.5 g/dL for females)
- Platelet count ≥ 50,000/mm3
- Absolute Neutrophil Count (ANC) ≥650/mm3
- Able and willing to provide written informed consent
- Female patients agree to use both a barrier and a non-barrier form of contraception during the study, starting at least 14 days prior to enrolment
Exclusion Criteria:
- Pregnancy or breastfeeding (or planned pregnancy within 12 months of study entry)
- Prior use of antiretroviral drugs for pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP) < 3 months at the time of enrolment
- Hepatitis B surface antigen positive OR Hepatitis B virus (HBV) infection OR active systemic infections (other than HIV-1 infection) requiring systemic antibiotic or antifungal therapy current or within 30 days prior to baseline that could, in the opinion of the investigator, interfere with study procedures or assessment of study outcomes
- Participants with a CD4+ cell count of < 50 cells/ μl
- Any verified Grade 4 laboratory abnormality, with the exception of, Grade 4 triglycerides. A single repeat test is allowed during the Screening period to verify a result
- Patients on metformin (> 500mg, 12hourly)
- Patients with an uncontrolled psychiatric co-morbidity. Patients who, in the investigator's judgment, pose a significant suicidality risk. Recent history of suicidal behavior and/or suicidal ideation may be considered as evidence of serious suicide risk
- Other condition or circumstance deemed by clinician/investigators to be detrimental to patient safety or study conduct
- Unwilling to be part of the main pharmacokinetic (PK) study and have PK blood draws done (NB there is a semi-intensive PK substudy which is optional)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: BIC arm
The Intervention Arm ART regimen is a fixed-drug combination of a single tablet co-formulated regimen containing Bictegravir 50mg Emtricitabine 200mg and tenofovir alafenamide 25mg (BIC/FTC/TAF; Biktarvy®) that will be taken twice a day during rifampicin-containing TB treatment and 2 weeks after stopping TB treatment, thereafter the BIC/FTC/TAF single tablet co-formulation will be taken once daily.
|
Biktarvy® is a fixed dose combination, single tablet containing bictegravir (BIC), emtricitabine (FTC), and tenofovir alafenamide (TAF) for oral administration. BIC is an integrase strand transfer inhibitor (INSTI). FTC, a synthetic nucleoside analog of cytidine, is an HIV nucleoside analog reverse transcriptase inhibitor (HIV NRTI). TAF, an HIV NRTI, is converted in vivo to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5'-monophosphate. Each tablet contains 50 mg of BIC (equivalent to 52.5 mg of bictegravir sodium), 200 mg of FTC, and 25 mg of TAF (equivalent to 28 mg of tenofovir alafenamide fumarate) and the following inactive ingredients: croscarmellose sodium, magnesium stearate, and microcrystalline cellulose. |
Active Comparator: DTG Arm
Dolutegravir 50mg /Lamivudine 300mg/ Tenofovir 300mg (TLD- fixed-drug combination single tablet) plus Dolutegravir 50mg evening dose during TB treatment and for two weeks after completion of TB treatment, then TLD once daily thereafter- as per Standard of Care (SOC)
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Standard of care Dolutegravir-based regimen
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Viral suppression rate
Time Frame: Week 24
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Viral suppression rate (HIV-1 RNA <50 copies/mL) at week 24 in the BIC arm (using the FDA snapshot algorithm)
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Week 24
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Viral suppression rates
Time Frame: At weeks 12, 24 and 48
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Viral suppression rates (HIV-1 RNA <50 copies/mL) in the DTG arm and at 12 and 48 weeks in the BIC arm
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At weeks 12, 24 and 48
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BIC Drug concentrations ("Area under the plasma concentration versus time curve (AUC)"
Time Frame: Week 4, 8 12, 24, 32 and 40
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BIC drug levels (AUC) when given twice daily and co-administered with Rifampicin vs. during TB treatment vs when given alone after TB treatment completion
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Week 4, 8 12, 24, 32 and 40
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BIC Drug concentrations [Peak Plasma Concentration (Cmax)]
Time Frame: Week 4, 8 12, 24, 32 and 40
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BIC drug levels (Cmax) when given twice daily and co-administered with Rifampicin vs. during TB treatment vs when given alone after TB treatment completion
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Week 4, 8 12, 24, 32 and 40
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BIC Drug concentrations [Trough/Minimum Plasma Concentration Ctrough)
Time Frame: Week 4, 8 12, 24, 32 and 40
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BIC drug levels ( Ctrough) when given twice daily and co-administered with Rifampicin vs. during TB treatment vs when given alone after TB treatment completion
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Week 4, 8 12, 24, 32 and 40
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The incidence of TB associated IRIS
Time Frame: Through week 24
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To assess the incidence of TB associated IRIS in each arm
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Through week 24
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The tolerability of treatment in each arm
Time Frame: Through week 48
|
To characterize the tolerability of treatment in each arm by assessing frequency of clinician-initiated treatment interruptions or switches through week 48
|
Through week 48
|
Frequency of ART drug resistance mutations
Time Frame: study visit weeks 24 and 48.
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To assess frequency of ART drug resistance mutations in participants with detectable viral load
|
study visit weeks 24 and 48.
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Anushka Naidoo, PhD, Centre for the AIDS Programme of Research in South Africa (CAPRISA)
- Study Director: Kogieleum Naidoo, PhD, Centre for the AIDS Programme of Research in South Africa
- Principal Investigator: Kelly Dooley, MD, Vanderbilt University Medical Center
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Infections
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Lung Diseases
- Bacterial Infections
- Bacterial Infections and Mycoses
- Gram-Positive Bacterial Infections
- Actinomycetales Infections
- Mycobacterium Infections
- Slow Virus Diseases
- Urogenital Diseases
- Genital Diseases
- HIV Infections
- Tuberculosis
- Acquired Immunodeficiency Syndrome
- Tuberculosis, Pulmonary
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Reverse Transcriptase Inhibitors
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- HIV Integrase Inhibitors
- Integrase Inhibitors
- Tenofovir
- Lamivudine
- Dolutegravir
Other Study ID Numbers
- CAPRISA 093
- 1R01AI152142-01 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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