A study to evaluate the efficacy, safety, and tolerability of using an oral once-daily 2 drug regimen compared to an oral once-daily 3 drug regimen for the treatment of HIV-1 in adults who have not previously taken antiretroviral therapy

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

14 Feb 2024 → ongoing

Decision date (initial)

2024-01-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

ViiV Healthcare UK Limited

External identifiers

EU CT number

2023-504993-40-00

ClinicalTrials.gov

NCT05979311

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To demonstrate the non-inferior antiviral activity of DTG/3TC compared to BIC/FTC/TAF in antiretroviral-naïve PWH.

Secondary objectives 4

1. To demonstrate the antiviral, immunologic effects and incidence of disease progression (HIV-associated conditions, AIDS and death) with the use of DTG/3TC compared to BIC/FTC/TAF
2. To evaluate the time to virologic suppression with DTG/3TC compared to BIC/FTC/TAF in antiretroviral-naïve PHW.
3. To assess the development of viral resistance in participants experiencing confirmed virologic failure
4. To evaluate renal (in urine and blood) and bone (in blood) biomarkers in participants treated with DTG/3TC compared to BIC/FTC/TAF

Conditions and MedDRA coding

Human immunodeficiency virus (HIV)

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. All participants eligible for enrolment in the study must meet all of the following criteria: - Age ≥18 years (or older, if required by local regulations) at the time of obtaining informed consent. - Male or female. Female participant is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotropin (hCG) test at Screening and a negative urine hCG test at Enrolment) and not lactating. - Antiretroviral-naïve (no prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection) PWH. - Participant (or participant’s Legally Acceptable Representative) is capable of giving written informed consent. - Participants enrolled in France must be affiliated to, or a beneficiary of, a social security category.

Exclusion criteria 6

1. A participant will not be eligible for inclusion in this study if any of the following criteria apply: 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, and CD4 cell counts below 200 cells/mm3. 3. Previous or current allergy or intolerance to the study treatment, its components, drugs of their class, or other allergies that contraindicate participation. 4. Ongoing or clinically relevant pancreatitis. 5. Ongoing malignancy, except for specific cases agreed upon by the Investigator and Medical Monitor
2. 6. Severe hepatic impairment (Class C) as per Child-Pugh classification. 7. Unstable liver disease or known biliary abnormalities (excluding Gilbert's syndrome, asymptomatic gallstones or stable chronic liver disease). 8. History of liver cirrhosis with or without hepatitis viral co-infection. 9. Alanine aminotransferase (ALT) levels ≥5 times the upper limit of normal (ULN) or ALT ≥3xULN with bilirubin ≥1.5xULN (with >35% direct bilirubin) 10. Significant suicidality risk, based on investigator judgment or history of suicidal behavior or ideation.
3. 11. Signs and symptoms suggestive of active SARS-CoV-2 infection within 14 days before enrolment. 12. Evidence of hepatitis B virus (HBV) infection based on the results of testing at Screening, unless immune. 13. 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. 14. Untreated syphilis infection (positive RPR at Screening). Participants ≥7 days post completed treatment are eligible. 15. Major resistance-associated mutations to specified drugs based on resistance guidelines.
4. 16. Recent exposure to experimental drugs or vaccines, meeting protocol-defined conditions, before first dose of study drug. 17. Treatment with radiation therapy, cytotoxic chemotherapeutic agents, or systemic immune suppressants within 28 days of screening. 18. Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of screening. 19. Treatment with agents active against HIV-1, except recognized antiretroviral therapy (ART), within 28days of first study dose. 20. Participants receiving protocol-defined prohibited medications who are unwilling or unable to switch to alternate medication
5. 21. Grade 4 laboratory abnormalities, excluding lipid abnormalities. 22. Acute laboratory abnormalities at Screening that, per investigator judgement, preclude participation in a clinical trial. 23. Estimated creatine clearance below 30 mL/min per 1.73 m2 using the refitted, race-neutral CKD-EPIcr_R method 24. Known or suspected acquisition of HIV-1 during either pre-exposure prophylaxis or post-exposure prophylaxis use, requiring consultation with Medical Monitor before enrolment. 25. Conditions affecting drug absorption, distribution, metabolism, or excretion.
6. 26. Pre-existing conditions that may interfere with dosing, protocol compliance, or participant safety. 27. Current or expected participation in another interventional study after randomization, unless pre- approved by the medical monitor

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Participant with plasma HIV-RNA <50 copies/mL as per Snapshot algorithm at Week 48

Secondary endpoints 4

1. Participant with plasma HIV-1 RNA <50 c/mL (c/mL) at Weeks 96 as per the Snapshot algorithm
2. - Participant with HIV-RNA >/= 50 c/mL as per Snapshot algorithm at Week 48, and Week 96
3. - Change from Baseline in HIV-1 RNA (log10 c/mL) and CD4+ cell count and CD4/CD8 ratio over time through Week 48 and Week 96.
4. - Occurrence of disease progression (HIVassociated conditionsAIDS and death) through Week 48 and Week 96.

Investigational products

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

Test 2

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 11

Locations

11 EU/EEA countries · 46 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 287 files

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

Application history

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