LENACAPAVIR, ISLATRAVIR for HIV-1 infection

Inclusion criteria

• {"criterion_text":"- Participants 18 years of age or older at screening and able to understand and give written informed consent.\n- HIV-1 RNA < 50 copies/mL for ≥ 6 months before screening, as documented by: a) One HIV-1 RNA < 50 copies/mL immediately preceding the 24 week period prior to screening. b) Within 24 weeks prior to screening, if HIV-1 RNA results are available, all levels must be < 50 copies/mL. c) 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.\n- Plasma HIV-1 RNA levels < 50 copies/mL at screening.\n- Are receiving guideline-recommended standard of care treatment such as International Antiviral Society (IAS), Department of Health and Human Services (DHHS), European AIDS Clinical Society (EACS) consisting of 2 or 3 ARVs for ≥ 6 months prior to screening and willing to continue until Day 1. Participants in Treatment Group 2 must also be willing to continue their standard of care through at least Week 96. a) INSTI combined with 1 or 2 NRTIs (B/F/TAF, DTG/ABC/3TC, DTG+TXF/FTC, DTG/TDF/3TC, DTG/3TC, RAL+TXF/FTC, RAL+TDF/3TC, EVG/c/TXF/FTC), or b) Boosted PI combined with 2 NRTIs (D/C/F/TAF, boosted DRV+TXF/FTC, boosted DRV+TDF/3TC), or c) NNRTI combined with 2 NRTIs (DOR/TDF/3TC, DOR+TXF/FTC, DOR+TDF/3TC, RPV/TXF/FTC, RPV+TXF/FTC, RPV+TDF/3TC). Notes: RAL can be taken either once or twice daily; all other agents are to be taken once daily, including and single tablet regimen. TXF = TAF or TDF. Boosted PI taken once daily with cobicistat or ritonavir.\n- 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."}

Exclusion criteria

• {"criterion_text":"- Prior virologic failure.\n- 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\n- Active hepatitis C virus (HCV) coinfection, defined as detectable HCV RNA. Note: particpants with prior/inactive HCV infection (defined as undetectable HCV RNA) may be enrolled.\n- Any of the following laboratory values at screening: 1. Creatinine clearance (CLcr) ≤ 30 mL/min according to the Cockcroft-Gault formula 2. Alanine aminotransferase (ALT) > 5 x upper limit of normal (ULN) 3. Direct bilirubin > 1.5 x ULN 4. Platelets < 50,000/μL 5. Hemoglobin < 8.0 g/dL\n- Participation or planned participation in any other clinical study (including observational studies) without prior approval from the sponsor.\n- Known hypersensitivity to any of the study drugs, their metabolites, or formulation excipients.\n- 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.\n- 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.\n- Participants who plan to continue breastfeeding during the study.\n- 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.\n- History of or current clinical decompensated liver cirrhosis (eg, ascites, encephalopathy, or variceal bleeding).\n- Active malignancy requiring acute systemic therapy.\n- Abnormal electrocardiogram (ECG) at the screening visit that is clinically significant as determined by the investigator.\n- 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. (See Appendix 11.8.2 for United Kingdom [UK]-specific requirements for this criterion).\n- Prior use of, or exposure to, ISL or LEN.\n- Active, serious infections requiring parenteral therapy within 30 days before randomization.\n- Active tuberculosis infection.\n- Acute hepatitis within 30 days before randomization."}

Primary endpoints

• {"endpoint_text":"- The proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 as determined by the United States (US) Food and Drug Administration (FDA)-defined snapshot algorithm","definition_or_measurement_approach":"Determined by the US FDA-defined snapshot algorithm (proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 using the FDA snapshot approach)."}

Secondary endpoints

• {"endpoint_text":"- Proportion of Participants with HIV-1 RNA ≥ 50 copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm","definition_or_measurement_approach":"Determined by the US FDA-defined snapshot algorithm (proportion with HIV-1 RNA ≥ 50 copies/mL at Week 96)."}
• {"endpoint_text":"- Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 48 and 96 as Determined by the US FDA-defined Snapshot Algorithm","definition_or_measurement_approach":"Determined by the US FDA-defined snapshot algorithm (proportion with HIV-1 RNA < 50 copies/mL at Weeks 48 and 96)."}
• {"endpoint_text":"- The change from baseline in CD4+ T-cell count at Weeks 48 and 96","definition_or_measurement_approach":"Change from baseline in absolute CD4+ T-cell count measured at Weeks 48 and 96."}
• {"endpoint_text":"- The proportion of participants discontinuing ISL/LEN due to treatment-emergent adverse events (AEs)","definition_or_measurement_approach":"Proportion of participants who discontinue ISL/LEN due to treatment-emergent adverse events (AEs) recorded during the study."}

Methods

• Country-specific recruitment arrangements documents and public study flyers were submitted (files present for Poland, Germany, Netherlands, Spain). Channels indicated by document types: study flyers and recruitment arrangements (public) — documents: K1_GS-US-563-5926_Recruitment-Arrangments_PL_Polish_Public; K1_GS-US-563-5926_Recruitment-Arrangements_DE_Public and Addendum_to_Recruitment-Arrangements_DE_Public; K1_GS-US-563-5926_Recruitment-Arrangements_NL_Public; K1_GS-US-563-5926_Recruitment-Arrangements_ES_Public. (No further recruitment channel details provided in the JSON.)

Poland

Earliest CTIS Part Ii Submission Date

22-11-2024

Latest Decision Or Authorization Date

02-03-2026

Processing Time Days

465

Number Of Sites

2

Number Of Participants

9

Germany

Earliest CTIS Part Ii Submission Date

26-11-2024

Latest Decision Or Authorization Date

03-03-2026

Processing Time Days

462

Number Of Sites

4

Number Of Participants

22

Netherlands

Earliest CTIS Part Ii Submission Date

26-11-2024

Latest Decision Or Authorization Date

27-02-2026

Processing Time Days

458

Number Of Sites

2

Number Of Participants

7

Spain

Earliest CTIS Part Ii Submission Date

21-11-2024

Latest Decision Or Authorization Date

09-03-2026

Processing Time Days

473

Number Of Sites

4

Number Of Participants

38

Primary sponsor

Full Name

Gilead Sciences Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

PPD Development LP

Responsibilities

Clinical Monitoring, Medical Monitoring, Pharmacovigilance, Site Intelligence and Activation

Third parties

• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"Clinical Monitoring, Medical Monitoring, Pharmacovigilance, Site Intelligence and Activation","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"Central Lab","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Signant Health LLC","duties_or_roles":"Electronic data capture / eConsent / eCOA vendor (role code 3)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"eCOA Services, Medication Adherence","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Investigator Meetings","organisation_type":"Hospital/Clinic/Other health care facility"}