Study to Compare an Oral Weekly Islatravir/Lenacapavir Regimen With Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed People With HIV-1 (ISLEND-1)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gilead Sciences Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

16 Jan 2025 → ongoing

Decision date (initial)

2024-12-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Gilead Sciences Inc

External identifiers

EU CT number

2024-514046-37-00

ClinicalTrials.gov

NCT06630286

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety, Therapy

To evaluate the efficacy of switching to oral weekly islatravir (ISL; MK-8591)/lenacapavir (LEN; GS-6207) tablet regimen versus continuing B/F/TAF in virologically suppressed people with HIV (PWH) at Week 48

Secondary objectives 2

1. To evaluate the efficacy of switching to oral weekly ISL/LEN versus continuing B/F/TAF in virologically suppressed people with HIV at Weeks 48 and 96
2. To evaluate the safety and tolerability of oral weekly ISL/LEN

Conditions and MedDRA coding

HIV-1 Infection

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Participants 18 years of age or older at screening and able to understand and give written informed consent.
2. 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.
3. Plasma HIV-1 RNA levels < 50 copies/mL at screening.
4. Participants are receiving B/F/TAF for ≥ 6 months prior to screening and willing to continue until Day 1.
5. 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.
6. Note: Other protocol defined Inclusion criteria may apply.

Exclusion criteria 14

1. 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.
2. 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.
3. History of or current clinical decompensated liver cirrhosis (eg, ascites, encephalopathy, or variceal bleeding).
4. 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.
5. Active malignancy requiring acute systemic therapy.
6. Abnormal electrocardiogram (ECG) at the screening visit that is clinically significant as determined by the investigator.
7. 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.
8. Participation or planned participation in any other clinical study (including observational studies) without prior approval from the sponsor.
9. Known hypersensitivity to any of the study drugs, their metabolites, or formulation excipients.
10. 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.
11. 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.
12. Participants who plan to continue breastfeeding during the study.
13. 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.
14. Note: Other protocol defined Exclusion criteria may apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 [Time Frame: Week 48]

Secondary endpoints 4

1. Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Determined by the US FDA-Defined Snapshot Algorithm
2. Proportion of Participants with HIV-1 RNA < 50 Copies/mL at Weeks 48 and 96 as Determined by the US FDA-Defined Snapshot Algorithm
3. The change from baseline in CD4+ T-cell count at Weeks 48 and 96
4. Proportion of Participants Discontinuing ISL/LEN due to Treatment-Emergent Adverse Events (AEs)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 1

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gilead Sciences Inc.

Sponsor organisation

Gilead Sciences Inc.

Address

333 Lakeside Drive

City

Foster City

Postcode

94404-1147

Country

United States

Scientific contact point

Organisation

Gilead Sciences Inc.

Contact name

EU CT Support

Public contact point

Organisation

Gilead Sciences Inc.

Contact name

EU CT Support

Third parties 5

Locations

3 EU/EEA countries · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 23 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications