Evaluation of a Weekly Oral Islatravir/Lenacapavir Regimen Versus Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed HIV-1 Patients
- Trial ID
- 2024-514046-37-00
- Protocol
- GS-US-563-5925
- Sponsor
- Gilead Sciences Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase 3, randomized, double-blind, active-controlled study is to evaluate the **efficacy** of switching to an oral weekly Islatravir/Lenacapavir (ISL/LEN) tablet regimen compared to continuing Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) in virologically suppressed individuals with **HIV-1 infection** at Week 48. This evaluation is clinically relevant as it may offer an alternative treatment regimen that could improve adherence and quality of life for patients by reducing the frequency of medication intake.
Secondary objectives include: - Evaluating the efficacy of switching to oral weekly ISL/LEN versus continuing B/F/TAF in virologically suppressed individuals with HIV at Weeks 48 and 96. - Assessing the safety and tolerability of the oral weekly ISL/LEN regimen. These objectives are crucial for determining the long-term viability and patient acceptability of the ISL/LEN regimen as a potential treatment option.
Participants
The clinical trial involves a total of **504 participants** diagnosed with **HIV-1 Infection**. The study population includes both male and female subjects, aged 18 years and older, who are virologically suppressed. Participants were selected based on their ability to provide informed consent and their HIV-1 RNA levels being consistently below 50 copies/mL for at least six months prior to screening. The trial includes individuals who have been receiving the B/F/TAF regimen for a minimum of six months before the study and are willing to continue this regimen until the start of the trial. The study population also includes individuals assigned female at birth who are of childbearing potential and engage in heterosexual intercourse, with a requirement to adhere to specified contraceptive methods. The trial considers a vulnerable population, ensuring comprehensive ethical oversight. Lifestyle factors such as diet and physical activity are not specified in the available data.
Plans and Procedures
The clinical trial is a **Phase 3**, randomized, double-blind, active-controlled study designed to evaluate the efficacy of switching to an oral weekly regimen of **islatravir/lenacapavir** in individuals with **HIV-1 infection** who are virologically suppressed on a regimen of **bictegravir/emtricitabine/tenofovir alafenamide**. The primary objective is to assess the proportion of participants with **HIV-1 RNA** levels ≥ 50 copies/mL at Week 48, as determined by the US FDA-defined snapshot algorithm. The trial is expected to conclude by August 2030, with recruitment starting in January 2025.
Participants will be involved in the study for a maximum treatment period of one year. The trial includes several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor **HIV-1 RNA** levels and other health parameters, and an end-of-study visit to assess the final outcomes. The inclusion criteria require participants to be 18 years or older, with documented **HIV-1 RNA** levels < 50 copies/mL for at least six months prior to screening. Exclusion criteria are not specified in the provided data.
Participants may be withdrawn from the study if they experience treatment-emergent adverse events or if they no longer meet the inclusion criteria. The study will utilize a double-blind methodology to ensure unbiased results, with participants randomly assigned to either the experimental or control group. The trial will also evaluate secondary endpoints, including the proportion of participants with **HIV-1 RNA** < 50 copies/mL at Weeks 48 and 96, and changes in CD4 T-cell counts at these time points.
Treatment
The clinical trial involves the evaluation of an oral weekly regimen of **Islatravir/Lenacapavir** in participants with HIV-1 who are virologically suppressed. The experimental medication, Islatravir/Lenacapavir, is administered in tablet form. Two formulations are used: a 2 mg/300 mg fixed-dose combination (FDC) tablet and a 0.5 mg/300 mg FDC tablet. Both formulations are manufactured by Gilead Sciences Inc. and are intended for oral use. The dosing schedule involves weekly administration, with the specific dosage determined by the formulation used. The active substances, **Lenacapavir** and **Islatravir**, are of chemical origin. Islatravir is also known by its synonyms, 4'-Ethynyl-2-Fluoro-2'-Deoxyadenosine, 2'-Deoxy-4'-C-Ethynyl-2-Fluoroadenosine, and MK-8591.
The comparator treatment in this study is **Biktarvy**, a film-coated tablet containing 50 mg of **Bictegravir**, 200 mg of **Emtricitabine**, and 25 mg of **Tenofovir Alafenamide**. This medication is also manufactured by Gilead Sciences Ireland Unlimited Company and is administered orally. Participants in the comparator group will continue their current regimen of Biktarvy, which is taken daily. The active substances in Biktarvy are of chemical origin, and Bictegravir is also known by the synonym GS-9883.
In addition to the experimental and comparator treatments, the study includes placebo treatments labeled as PTM Biktarvy and PTM ISL/LEN. These are not associated with any active substances and are used to maintain the double-blind nature of the trial. The placebo treatments do not have a specified pharmaceutical form or route of administration.
Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment regimen. The trial aims to assess the efficacy of the Islatravir/Lenacapavir regimen compared to the standard Biktarvy treatment over a 48-week period.
Efficacy
The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints related to **HIV-1** RNA levels in participants. The primary endpoint is the proportion of participants with **HIV-1** RNA levels ≥ 50 copies/mL at Week 48, as determined by the United States Food and Drug Administration (FDA)-defined snapshot algorithm. This measurement will be conducted at Week 48 to determine the efficacy of switching to an oral weekly Islatravir/Lenacapavir regimen compared to continuing Bictegravir/Emtricitabine/Tenofovir (B/F/TAF) in virologically suppressed individuals with **HIV-1**.
Secondary endpoints include the proportion of participants with **HIV-1** RNA levels ≥ 50 copies/mL and < 50 copies/mL at Weeks 48 and 96, also determined by the FDA-defined snapshot algorithm. Additionally, changes from baseline in Cluster of Differentiation 4 (CD4) T-cell count at Weeks 48 and 96 will be assessed. The proportion of participants discontinuing Islatravir/Lenacapavir due to treatment-emergent adverse events will also be evaluated from Day 1 up to Week 48. These endpoints will provide comprehensive data on the efficacy and safety of the treatment regimen over the specified time frames.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participants 18 years of age or older at screening and able to understand and give written informed consent.
- HIV-1 RNA < 50 copies/mL for ≥ 6 months before screening, as documented by: • One HIV-1 RNA < 50 copies/mL immediately preceding the 24 week period prior to screening. • Within 24 weeks prior to screening, if HIV-1 RNA results are available, all levels must be < 50 copies/mL. • During the 6 to 12 months period prior to screening, transient detectable viremia ≥ 50 copies/mL is acceptable (“blip”), as long as it is not confirmed on 2 consecutive visits.
- Plasma HIV-1 RNA levels < 50 copies/mL at screening.
- Participants are receiving B/F/TAF for ≥ 6 months prior to screening and willing to continue until Day 1.
- Participants assigned female at birth and of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified methods of contraception as described in Appendix 11.5.
- Note: Other protocol defined Inclusion criteria may apply.
Exclusion Criteria
- Participants who meet any of the following exclusion criteria are not eligible to be enrolled in this study: 1) Prior virologic failure. 2) Prior use of, or exposure to, ISL or LEN. 3) Active, serious infections requiring parenteral therapy within 30 days before randomization. 4) Active tuberculosis infection. 5) Acute hepatitis within 30 days before randomization. 6) HBV infection, as determined below at the screening visit: a) Positive HBV surface antigen. OR b) Positive HBV core antibody and negative HBV surface antibody. Note: participants found to be susceptible to HBV infection (eg, negative hepatitis B surface antibody at the screening visit, regardless of prior HBV vaccination history) should be recommended to receive HBV vaccination.
- Active hepatitis C virus (HCV) coinfection, defined as detectable HCV RNA. Note: participants with prior/inactive HCV infection (defined as undetectable HCV RNA) may be enrolled.
- History of or current clinical decompensated liver cirrhosis (eg, ascites, encephalopathy, or variceal bleeding).
- Treatment < 3 months prior to screening or anticipated treatment during the study period with immunosuppressant therapies, hydroxyurea, foscarnet, radiation, or cytotoxic chemotherapeutic agents without approval from sponsor prior to randomization. Agents disallowed in Section 5.3 may not be considered for sponsor approval.
- Active malignancy requiring acute systemic therapy.
- Abnormal electrocardiogram (ECG) at the screening visit that is clinically significant as determined by the investigator.
- Any of the following laboratory values at screening: a) CLcr ≤ 30 mL/min according to the Cockcroft-Gault formula. {Cockcroft 1976} b) Alanine aminotransferase > 5 upper limit of normal (ULN). c) Direct bilirubin > 1.5 ULN. d) Platelets < 50,000/μL. e) Hemoglobin < 8.0 g/dL.
- Participation or planned participation in any other clinical study (including observational studies) without prior approval from the sponsor.
- Known hypersensitivity to any of the study drugs, their metabolites, or formulation excipients.
- Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the participant unsuitable for the study or unable to comply with dosing requirements.
- Participants of childbearing potential (as defined in Appendix 11.5) who have a positive serum pregnancy test at screening or positive urine and serum pregnancy tests at Day 1 prior to study drug administration.
- Participants who plan to continue breastfeeding during the study.
- Requirement for ongoing therapy or use of any prohibited medications listed in Section 5.3 within 30 days prior to screening through the last dose of study drug.
- Note: Other protocol defined Exclusion criteria may apply.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Recruiting | 31 Jan 2025 | 25 |
 Germany | Not Recruiting | 31 Jan 2025 | 30 |
 Spain | Not Recruiting | 31 Jan 2025 | 32 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Biktarvy 50 mg/200 mg/25 mg film-coated tablets | Comparator | FILM-COATED TABLETS | ORAL USE | 00 | 1 | PRD6357588 |
PTM ISL/LEN | Placebo | N/A | — | — | — | N/A |
ISLATRAVIR/LENACAPAVIR | Test | TABLET | ORAL USE | 00 | 1 | PRD11488101 |
ISLATRAVIR/LENACAPAVIR | Test | TABLET | ORAL USE | 00 | 1 | PRD11488102 |
PTM Biktarvy | Placebo | N/A | — | — | — | N/A |