A Study to Evaluate the Efficacy, Safety, and Tolerability of Using an Oral Once-daily 2 Drug Regimen Compared to an Oral Once-daily 3 Drug Regimen for the Treatment of Human Immunodeficiency Virus (HIV)-1 in Adults Who Have Not Previously Taken Antiretroviral Therapy

JRCT ID: jRCT2051230132

Registered date:19/11/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: HIV infections
• Date of first enrollment: 15/12/2023
• Target sample size: 412
• Countries of recruitment: Germany,Japan,Spain,Japan,UK,Japan,France,Japan,Italy,Japan,Belgium,Japan,Denmark,Japan,Greece,Japan,Portugal,Japan,Poland,Japan,Sweden,Japan,Switzerland,Japan,Ireland,Japan,Israel,Japan,Argentina,Japan,Mexico,Japan
• Study type: Interventional

Intervention(s)

One tablet of the fixed-dose combination of Dolutegravir (50 mg) and Lamivudine (300 mg) is administered orally once daily
Or
One tablet of the 3-drug fixed dose combination of Bictegravir (50 mg), Emtricitabine (200 mg), and Tenofovir Alafenamide (25 mg) is administered orally once daily

Outcome(s)

• Primary Outcome: Percentage of participants with plasma HIV- Ribonucleic acid (RNA) less than (<)50 copies per milliliter (c/mL) as per snapshot algorithm at Week 48

Secondary Outcome

-Percentage of participants with plasma HIV-1 RNA <50 c/mL as per snapshot algorithm at Weeks 24 and 96
-Percenage of participants with HIV-RNA greater than or equal to (>=)50 c/mL as per snapshot algorithm at Weeks 24, 48, and 96
-Change from Baseline in HIV-1 RNA (log10 c/mL) and CD4+ cell count and CD4/CD8 ratio over time through Week 24, Week 48 and Week 96.
-Occurrence of disease progression (HIVassociated conditions, AIDS and death) through Week 24, Week 48 and Week 96.
-Time to virologic suppression (HIV-1 RNA <50 c/mL) from Baseline (Day 1).
-Participant meeting CVW over time.
-Occurrence of treatment emergent resistance to DTG, 3TC, BIC, FTC and TAF in participants meeting CVW criteria
-Changes and percent changes from Baseline in estimated glomerular filtration rate (using the refitted, CKD-EPIcr_R method) and urinary protein/creatinine at Weeks 48 and 96
-Change and percent change from Baseline in renal and bone biomarkers at Week 48 and Week 96
-Change from Baseline (Week 4) in HIVTSQs total treatment satisfaction score, domains and individual responses at Weeks 12, 24, 48 and 96.
-Change from Baseline in bothersome symptoms using the Symptom Distress Module at Weeks 4, 12, 24, 48 and 96.
-Absolute waist and hip circumference, waist to hip ratio, waist to height ratio, weight, blood pressure (BP) and BMI change and participant with weight change >5% from Baseline at Weeks 48, 24 and 96.
-Change in total and regional (trunk and extremities) fat by Dual-energy X-ray absorptiometry (DXA) at Week 48 and Week 96
-Change in total and regional (trunk and extremities) fat-free mass by DXA at Week 48 and Week 96
-Change and percent change from Baseline in lumbar and hip bone mineral density (BMD) and trabecular bone score (TBS) by DXA at Weeks 48 and 96
-Occurrence of metabolic syndrome at Weeks 48 and 96
-Change plasma lipids (total, HDL-, and LDLcholesterol, triglycerides) from Baseline at Week 48 and Week 96
-Change in fasting glucose, insulin, HOMA-IR, HbA1c from Baseline at Week 48 and Week 96
-Change in QDiabetes score and FIB-4 score from Baseline at Week 48 and Week 96
-Change from Baseline in Framingham and DAD(Data collection on Adverse events of anti-HIV Drugs) cardiovascular risk scores at Weeks 48 and 96
-Change from Baseline in systolic and diastolic blood pressure at Week 24, 48 and 96

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

-Participants with age >=18 years (or older, if required by local regulations) at the time of obtaining informed consent.
-An individual participant is eligible to participate if they are not pregnant (as confirmed by a negative serum human chorionic gonadotropin (hCG) test at Screening and a negative urine hCG test at Enrollment) and not lactating.
-Antiretroviral-naive (no prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection) person living with HIV.
-Participant (or participant's legally acceptable representative [LAR]) is capable of giving written informed consent.
-Eligible participants or their LAR must sign a written Informed Consent Form before any protocol-specified assessments are conducted. Enrollment of participants who are unable to provide direct informed consent is optional and will be based on local legal/regulatory requirements and site feasibility to conduct protocol procedures.

Exclude criteria

1. Individuals who are pregnant or breastfeeding or plan to become pregnant or breastfeed during the study.
2. Any evidence of a current Centers for Disease Control and Prevention (CDC) Stage 3 disease; with the exception of cutaneous Kaposi's sarcoma not requiring systemic therapy, and CD4+ count <200 cells/mm3 (neither is exclusionary).
3. History or presence of allergy or intolerance to the study drugs or their components or drugs of their class, or a history of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates study participation.
4. Ongoing or clinically relevant pancreatitis.
5. Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial neoplasia; other localized malignancies require agreement between the Investigator and the Medical Monitor for inclusion of the participant prior to enrolment.
6. Participants with severe hepatic impairment (Class C) as determined by Child-Pugh classification.
7. Unstable liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice or cirrhosis), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment).
8. History of liver cirrhosis with or without hepatitis viral co-infection.
9. Alanine aminotransferase (ALT) -5 times the upper limit of normal (ULN) or ALT -3xULN and bilirubin -1.5xULN (with >35% direct bilirubin).
10. Participants determined by the Investigator to have a high risk of seizures, including participants with an unstable or poorly controlled seizure disorder. A participant with a prior history of seizure may be considered for enrolment if the Investigator believes the risk of seizure recurrence is low. All cases of prior seizure history should be discussed with the Medical Monitor prior to enrolment.
11. Participants who, in the investigator's judgment, pose a significant suicide risk. Participant's recent history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk.
12. Signs and symptoms which, in the opinion of the Investigator, are suggestive of active COVID-19 (e.g., fever, cough) infection within 14 days prior to enrollment.
13. Evidence of Hepatitis B virus (HBV) infection based on the results of central lab testing at Screening for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HBcAb), Hepatitis B surface antibody (HBsAb) and HBV Deoxyribonucleic Acid (DNA) as follows:
-Participants positive for HBsAg are excluded;
-Participants negative for HBsAb and negative for HBsAg but positive for HBcAb may be excluded based on the following consideration:
i. Exclude if HBV DNA is detected [either < Lower Limit of Quantification (LLoQ), > Upper Limit of Quantification (ULoQ) OR numerical value (ie, between LLoQ and ULoQ)]
ii. Not excluded if HBV DNA is negative, not detected
14. Participants with HCV co-infection at Screening are eligible only if:
i. liver enzymes meet entry criteria; and
ii. HCV disease is not anticipated to require on-study treatment with any agent(s) that have potential adverse DDIs with the study interventions; and
iii. HCV disease has undergone appropriate work-up and is not advanced and will not require treatment prior to the primary endpoint or later visit. Additional information (where available) on participants with HCV coinfection at screening should include results from any liver biopsy, Fibroscan, ultrasound, or other fibrosis evaluation, history of cirrhosis or other decompensated liver disease, prior treatment, and timing/plan for HCV treatment.
iv. In the event that recent biopsy or imaging data is not available or inconclusive, the Fib-4 score will be used to verify eligibility
a. Fib-4 score >3.25 is exclusionary;
b. Fib-4 scores 1.45 - 3.25 requires Medical Monitor consultation.
Fibrosis 4 Score Formula:
a. (Age x AST) / (Platelets x ( sqr [ ALT ])
15. Untreated syphilis infection (positive RPR at Screening without clear documentation of treatment) are excluded. Participants with a false positive RPR (with negative treponemal test) or serofast RPR result (persistence of a reactive nontreponemal syphilis test despite history of adequate therapy and no evidence of re-exposure) may enroll after consultation with the Medical Monitor. Participants who completed treatment at least 7 days prior to Screening are eligible.
16. Presence of any major resistance-associated mutations as defined by the International Antiviral Society-United States of America (IAS-USA) resistance guidelines to DTG, 3TC, BIC, FTC or TAF in the Screening result.
17. Exposure to an experimental drug or experimental vaccine within either 30 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent (whichever is longer), prior to first dose of study treatment.
18. Treatment with any of the following agents within 28 days of Screening:
-radiation therapy;
-cytotoxic chemotherapeutic agents;
-tuberculosis therapy with the exception of isoniazid (isonicotinylhydrazid,INH);
-immunomodulators that alter immune responses such as chronic systemic corticosteroids, interleukins, or interferons.
19. Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.
20. Treatment with any agent with documented activity against HIV-1 in vitro within 28 days of first dose of study treatment. Treatment with acyclovir/valacyclovir is permitted.
21. Participants receiving any protocol-defined prohibited medication3and who are unwilling or unable to switch to an alternate medication.
22. Any verified Grade 4 laboratory abnormality, with the exception of Grade 4 lipid abnormalities.
23. Any acute laboratory abnormality at Screening, which, in the opinion of the investigator, would preclude the participant's participation in an interventional clinical trial.
24. Participant has estimated creatine clearance <30 mL/min per 1.73 m2 using the refitted, race-neutral Chronic Kidney Disease Epidemiology Collaboration (CKD-EPIcr_R) method.
25. Participants known or suspected to have acquired HIV-1 concurrent with use of PrEP or PEP must be discussed with the Medical Monitor prior to enrolment.
26. Any condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the study drugs or render the participant unable to receive study medication.
27. Any pre-existing physical or mental condition (including substance use disorder) which, in the opinion of the Investigator, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant.
28. Participant is currently participating in, or anticipates being selected for, any other interventional study.

Related Information

• Primary Sponsor: Kajiwara Makoto