Ph 3b, BIC/FTC/TAF to DTG/3TC FDC, 96 Week switch, efficacy, safety, and tolerability study in ART-experienced older adults living with HIV with virologic suppression

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Viiv Healthcare UK Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

29 Nov 2023 → 10 Feb 2026

Decision date (initial)

2023-11-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

ViiV Healthcare UK Limited

External identifiers

EU CT number

2022-503137-66-00

ClinicalTrials.gov

NCT05911360

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the maintenance of virologic suppression of DTG/3TC at Week 48 post-switch from BIC/FTC/TAF

Secondary objectives 1

1. To evaluate the antiviral activity, immunologic effects, and incidence of disease progression (HIV-associated conditions, AIDS and death) of DTG/3TC over time To assess viral resistance in participants experiencing protocol-defined virologic failure over time To evaluate the safety and tolerability of DTG/3TC over time

Conditions and MedDRA coding

Human immunodeficiency virus (HIV)

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Age at least 50 years at the time of obtaining informed consent. Eligible participants must sign a written Informed Consent Form before any protocol-specified assessments are conducted. Enrolment 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.
2. Male or female. Female participant is eligible to participate if she is not pregnant (as confirmed by a negative serum hCG test at Screening and a negative urine hCG test at Enrolment) and not lactating.
3. Adults Living with HIV-1 with documented plasma HIV-1 RNA <50 c/mL within 3 months prior to Screening.
4. Must have been on uninterrupted ART for ≥1 year (except for brief periods [less than 30 days] where all ART was stopped due to tolerability and/or safety concerns)
5. Must be on uninterrupted BIC/FTC/TAF for at least 6 months prior to Screening
6. Plasma HIV-1 RNA <50 c/mL at Screening
7. No known prior regimen switches due to documented virologic failure (defined as a confirmed plasma HIV 1 RNA ≥200 c/mL)
8. Participants with unknown full treatment/clinical history beyond 5 years prior to Screening may be eligible upon discussion and agreement with the medical monitor.
9. Participant is capable of giving written informed consent
10. Participants enrolled in France must be affiliated to, or a beneficiary of, a social security category.

Exclusion criteria 23

1. Pregnant or breastfeeding women or those planning to become pregnant or breastfeed during the study
2. Active CDC Stage 3 disease is excluded, except for cutaneous Kaposi's sarcoma not needing systemic therapy. CD4 cell counts below 200 cells/mm3 (historical or current) are not exclusionary
3. Participants showing signs and symptoms suggestive of active SARS-CoV-2 infection within 14 days before enrolment
4. Participants with severe hepatic impairment (Class C) as per Child-Pugh classification.
5. Evidence of hepatitis B virus (HBV) infection based on the results of testing at Screening: • Participants positive for hepatitis B surface antigen (HBsAg) are excluded • Participants negative for hepatitis B surface antibody (anti-HBs) but positive for hepatitis B core antibody (anti-HBc), regardless of their HBsAg status or HBV DNA results, are excluded • Participants who test positive for anti-HBc (negative HBsAg status) and positive for anti-HBs (indicating past and/or current evidence of immunity to HBV) are immune to HBV and are not excluded.
6. Participants with HCV co-infection are eligible if: liver enzymes meet entry criteria; there is no anticipated requirement for concomitant HCV treatment with potential adverse drug interactions, and HCV disease has undergone appropriate work-up and is not advanced or associated with cirrhosis. Additional information e.g., imaging, biopsy results or prior treatment, should be considered by investigators as per protocol to confirm eligibility.
7. Participants with unstable liver disease or known biliary abnormalities (except for Gilbert's syndrome, asymptomatic gallstones or otherwise stable chronic liver disease).
8. History of liver cirrhosis with or without hepatitis viral co-infection.
9. Untreated syphilis infection (positive rapid plasma reagin at Screening). Participants at least 7 days post completed treatment are eligible.
10. History or presence of allergy or intolerance to the study treatment, its components, drugs of their class, or other allergies that contraindicate participation.
11. Ongoing malignancy other than cutaneous Kaposi’s sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia.
12. Participants with significant suicidality risk, based on investigator judgment or history of suicidal behavior or ideation.
13. Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of screening.
14. Treatment with radiation therapy, cytotoxic chemotherapeutic agents, or systemic immune suppressants within 28 days of screening.
15. Participants exposed to experimental drugs or vaccines within either 28 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 the first dose of investigational product).
16. Anwendung eines Behandlungsschemas, das aus einer einzelnen oder einer dualen ART besteht, die in den Behandlungsleitlinien nicht empfohlen wird.
17. Any known history of regimen switches due to virologic failure (confirmed plasma HIV 1 RNA ≥200 c/mL)
18. Participants receiving protocol-defined prohibited medications who are unwilling or unable to switch to an alternate medication
19. Any evidence of any major 3TC resistance associated mutations (M184V/I and/or K65R and/or MDR) or presence of any major INSTI resistance associated mutation in any available prior resistance genotype assay test result.
20. Participants with verified Grade 4 laboratory abnormalities, except for Grade 4 lipid abnormalities.
21. Alanine aminotransferase (ALT) levels ≥5 times the upper limit of normal (ULN) or ALT ≥3xULN with bilirubin ≥1.5xULN (with >35% direct bilirubin)
22. Participants with estimated creatine clearance <30mL/min per 1.73 m2 using the refitted, race-neutral Chronic Kidney Disease Epidemiology Collaboration method
23. Participants currently or expected to participate in another interventional study after randomization, unless previously approved by the study medical monitor

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Participants with plasma HIV-1 RNA ≥ 50 copies/mL (Snapshot algorithm) at Week 48

Secondary endpoints 3

1. Participants with plasma HIV-1 RNA ≥ 50 copies/mL (Snapshot algorithm) at 24 and 96 weeks Participants with plasma HIV-1 RNA <50 copies/mL (Snapshot algorithm) at 24, 48 and 96 weeks Absolute values and changes from baseline in CD4+ cells count and CD4:CD8 ratio at 24, 48 and 96 weeks Occurrence of disease progression (HIV associated conditions, AIDS, and death) through Weeks 24, 48 and 96.
2. Occurrence of viral resistance in participants meeting confirmed virologic withdrawal criterion over time
3. Occurrence of DTG/3TC-non-Serious Adverse drug-related reactions, all SAEs and proportion of participants who discontinue treatment due to AEs

Investigational products

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

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Viiv Healthcare UK Limited

Sponsor organisation

Viiv Healthcare UK Limited

Address

980 Great West Road

City

Brentford

Postcode

TW8 9GS

Country

United Kingdom

Scientific contact point

Organisation

Viiv Healthcare UK Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Viiv Healthcare UK Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 13

Locations

8 EU/EEA countries · 24 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 247 files

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

Application history

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