Study of B/F/TAF in Participants Switching from CAB + RPV to B/F/TAF for HIV-1 Infection.

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

7 Mar 2024 → 23 Apr 2025

Decision date (initial)

2024-02-07

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Gilead Sciences, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy

To assess the safety of switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in virologically suppressed participants unable/unwilling to continue on cabotegravir and rilpivirine (CAB+RPV) IM injections or wishing to switch to oral therapy through Week 12

Secondary objectives 4

1. To assess the pharmacokinetics of bictegravir (BIC), CAB and RPV after switching to B/F/TAF from CAB+RPV
2. To assess the efficacy and persistence of B/F/TAF after switching from CAB+RPV
3. To assess the safety of B/F/TAF after switching from CAB+RPV through Week 24
4. To evaluate treatment satisfaction of switching to B/F/TAF from CAB+RPV

Conditions and MedDRA coding

HIV-1 infection

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Participants 18 years of age or older and able to understand and give written informed consent.
2. PWH or provider decision to switch off CAB+RPV IM injections due to intolerance, inconvenience, AEs, or willing to switch to (and intention to remain on) daily B/F/TAF.
3. Currently virologically suppressed (HIV-1 RNA < 50 copies/mL) on CAB+RPV IM injections (Q2M).
4. Currently on CAB+RPV IM injections (Q2M) and received at least one dose of CAB+RPV IM injection; no missed CAB+RPV injections
5. Ability to receive B/F/TAF up to 7 days prior to the next scheduled dose of CAB+RPV.
6. Documented plasma HIV-1 RNA < 50 copies/mL during treatment for ≥ 6 months preceding the screening visit. a) Unconfirmed HIV-1 RNA ≥ 50 copies/mL (transient detectable viremia, or “blip”) prior to screening are acceptable. b) If the lower limit of detection of the local HIV-1 RNA assay is < 50 copies/mL (eg, < 20 copies/mL), the HIV-1 RNA level cannot exceed 50 copies/mL on 2 consecutive visits.
7. Adequate renal function Estimated GFR ≥ 30 mL/min according to the Cockcroft-Gault formula {Cockcroft 1976} based on serum creatinine and actual body weight as measured at screening and upon admission, eg, a) Male: (140 – 𝐴𝑔𝑒 [𝑦𝑒𝑎𝑟𝑠]) ´ (𝑊𝑒𝑖𝑔ℎ𝑡 [𝑘𝑔]) 72 ´ (𝑆𝑒𝑟𝑢𝑚 𝐶𝑟𝑒𝑎𝑡𝑖𝑛𝑖𝑛𝑒 [𝑚𝑔/𝑑𝐿]) = 𝐶𝐿𝑐𝑟 (𝑚𝐿/𝑚𝑖𝑛) b) Female: (140 – 𝐴𝑔𝑒 [𝑦𝑒𝑎𝑟𝑠]) ´ (𝑊𝑒𝑖𝑔ℎ𝑡 [𝑘𝑔]) 72 ´ (𝑆𝑒𝑟𝑢𝑚 𝐶𝑟𝑒𝑎𝑡𝑖𝑛𝑖𝑛𝑒 [𝑚𝑔/𝑑𝐿]) × 0.85 = 𝐶𝐿𝑐𝑟 (𝑚𝐿/𝑚𝑖𝑛)
8. Participants assigned female at birth of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception as described in Appendix 11.5.
9. Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN)
10. Total bilirubin ≤ 1.5 mg/dL (≤ 26 μmol/L), or normal direct bilirubin.
11. No documented or suspected resistance to BIC, FTC, or tenofovir (TFV).
12. Must be willing and able to comply with all study requirements.

Exclusion criteria 12

1. Positive serum pregnancy test (Appendix 11.5) or pregnant
2. Known hypersensitivity to the study drug, its metabolites, or any formulation excipient
3. History of B/F/TAF intolerance
4. History of previous INSTI virologic failure including CAB+RPV
5. Requirement for ongoing therapy with any prohibited medications listed in local prescribing information for B/F/TAF starting within 30 days prior to screening until 30 days following the last dose of study drug.
6. Have been treated within 3 months of study screening or expected to receive during the study immunosuppressant therapies or chemotherapeutic agents (eg, chronic [at least 4 weeks] systemic steroids, immunoglobulins, and other immune- or cytokine-based therapies).
7. Participation in any other clinical study, including observational studies, without prior approval from the sponsor is prohibited while participating in this study
8. Need for oral ART bridge or use of other ARV agents prior to starting B/F/TAF on Day 1
9. Chronic hepatitis B virus (HBV) infection
10. Current alcohol or substance use judged by the investigator to potentially interfere with participant study compliance.
11. Serious illness requiring hospitalizations within 30 days prior to screening and during the screening period.
12. 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 the dosing requirements.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Proportion of participants experiencing treatment-emergent Grade 3 or 4 study drug-related adverse events (AEs) through Week 12
2. Proportion of participants experiencing treatment-emergent Grade 3 or 4 laboratory abnormalities through Week 12

Secondary endpoints 5

1. Plasma concentrations of BIC, CAB and RPV at Day 1, Week 4, 12, and 24, as appropriate
2. Proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Weeks 12 and 24 (missing = excluded and discontinuation = failure)
3. Number and proportion of participants with B/F/TAF discontinuation by Weeks 12 and 24
4. Proportion of participants experiencing treatment-emergent grade 3 or 4 laboratory abnormalities through Week 24
5. Change in HIV treatment satisfaction (HIVTSQc) score at Week 4

Investigational products

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

Test 1

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 11

Locations

1 EU/EEA country · 3 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 6 files

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

Application history

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