INSTI's For The Management of HIV-associated TB

HIV/AIDS Clinical Trial

— INSIGHT  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04734652
• Other study ID #: CAPRISA 093
• Secondary ID: 1R01AI152142-01
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 18, 2022
• Est. completion date: August 31, 2024

Study information

• Verified date: April 2024
• Source: Centre for the AIDS Programme of Research in South Africa
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is being conducted to assess the antiretroviral activity of a fixed-drug, single tablet, combination of Bictegravir 50mg/ Emtricitabine 200mg/ Tenofovir alafenamide 25mg (Biktarvy®) dosed twice daily in HIV-1 infected, ART-naïve patients with TB co-infection receiving a rifampicin-based tuberculosis (TB) treatment regimen. This study will assess the activity of Bictegravir and dolutegravir-containing ART regimens in patients with drug-susceptible TB through 48 weeks

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 122
• Est. completion date: August 31, 2024
• Est. primary completion date: January 19, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 105 Years

Eligibility

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)

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• HIV/AIDS
• Tuberculosis
• Tuberculosis, Pulmonary

Intervention

Combination Product:
• Biktarvy®
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.
• TLD- fixed-drug combination single tablet
Standard of care Dolutegravir-based regimen

Locations

Country	Name	City	State
South Africa	CAPRISA Springfield Clinical Research Site	Durban	KwaZulu-Natal

Sponsors (5)

Lead Sponsor	Collaborator
Centre for the AIDS Programme of Research in South Africa	Johns Hopkins University, Medical Research Council, South Africa, National Institute of Allergy and Infectious Diseases (NIAID), University of Cape Town

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Viral suppression rate	Viral suppression rate (HIV-1 RNA <50 copies/mL) at week 24 in the BIC arm (using the FDA snapshot algorithm)	Week 24
Secondary	Viral suppression rates	Viral suppression rates (HIV-1 RNA <50 copies/mL) in the DTG arm and at 12 and 48 weeks in the BIC arm	At weeks 12, 24 and 48
Secondary	BIC Drug concentrations ("Area under the plasma concentration versus time curve (AUC)"	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	Week 4, 8 12, 24, 32 and 40
Secondary	BIC Drug concentrations [Peak Plasma Concentration (Cmax)]	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	Week 4, 8 12, 24, 32 and 40
Secondary	BIC Drug concentrations [Trough/Minimum Plasma Concentration Ctrough)	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	Week 4, 8 12, 24, 32 and 40
Secondary	The incidence of TB associated IRIS	To assess the incidence of TB associated IRIS in each arm	Through week 24
Secondary	The tolerability of treatment in each arm	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
Secondary	Frequency of ART drug resistance mutations	To assess frequency of ART drug resistance mutations in participants with detectable viral load	study visit weeks 24 and 48.