A study to evaluate the efficacy, safety, participant choice and preference of an oral once-daily regimen or a long-acting injectable regimen every two months for 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

6 Dec 2023 → 20 Apr 2026

Decision date (initial)

2023-11-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

ViiV Healthcare UK Limited

External identifiers

EU CT number

2023-503893-19-00

ClinicalTrials.gov

NCT05917509

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

"• To evaluate the length of time required to suppress the HIV virus in the blood with DTG/3TC in antiretroviral-naive adult participants living with HIV.
• To demonstrate the maintenance of virologic suppression over 1 year following choice of CAB + RPV LA every 2 months in adult participants with HIV after initial suppression with DTG/3TC."

Secondary objectives 9

1. • To evaluate the antiviral activity, immunologic effects, and incidence of disease progression (HIV-associated conditions, AIDS and death) with the use of CAB + RPV LA and DTG/3TC over time.
2. • To assess the development of viral resistance in participants experiencing confirmed virologic failure.
3. • To evaluate the safety and tolerability of CAB + RPV LA every 2 months and DTG/3TC administered once daily.
4. • To assess patient-reported treatment satisfaction.
5. • To assess bother from HIV-related symptoms.
6. • To assess health-related quality of life.
7. • To assess anxiety and depression.
8. • To assess HIV-related stigma, feelings about diagnosis and treatment choice, change in mood due to therapy.
9. • To explore the association between treatment modality/frequency and fear of disclosure, daily reminder of HIV status, and adherence anxiety.

Conditions and MedDRA coding

HIV-1 infection

Study design 5 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. • Age ≥18 years (or older, if required by local regulations) at the time of obtaining informed consent.
2. • Male or female. A 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.
3. • Plasma HIV-1 RNA ≥1,000 c/mL at Screening.
4. • Antiretroviral-naïve (defined as no prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection) prior to enrolment.
5. • Participant is capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form and in this protocol. Eligible participants must sign a written ICF 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.
6. • Participants enrolled in France must be affiliated to, or a beneficiary of, a social security category.

Exclusion criteria 14

1. • Women who are pregnant or breastfeeding or plan to become pregnant or breastfeed during the study.
2. • History or presence of allergy or intolerance to the study drugs or their components or drugs of their class, or a history of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates study participation.
3. • Ongoing or clinically relevant pancreatitis.
4. • Clinically significant cardiovascular disease, as defined by recent history (within the last 6 months) or current evidence of congestive heart failure, symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PTCA) or any clinically significant cardiac disease.
5. • Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial neoplasia; other localized malignancies require agreement between the Investigator and the Medical Monitor for inclusion of the participant prior to enrolment.
6. • Hereditary coagulation and platelet disorders (e.g. haemophilia or von Willebrand Disease); or current or anticipated need for chronic anti-coagulation, with the exception of the use of low-dose acetylsalicylic acid (≤325 mg).
7. • Participants with severe hepatic impairment (Class C) as determined by Child-Pugh classification.
8. • Unstable liver disease as defined by any of the following: presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice or cirrhosis, or decompensated cirrhosis (e.g. ascites, encephalopathy, or variceal bleeding), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per Investigator assessment).
9. • History of liver cirrhosis with or without hepatitis viral co-infection.
10. • Participants determined by the Investigator to have a high risk of seizures, including participants with an unstable or poorly controlled seizure disorder. A participant with a prior history of seizure may be considered for enrolment if the Investigator believes the risk of seizure recurrence is low. All cases of prior seizure history should be discussed with the Medical Monitor prior to enrolment.
11. • Participants who, in the Investigator's judgment, pose a significant suicide risk. Participant’s recent history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk.
12. • Signs and symptoms which, in the opinion of the Investigator, are suggestive of active SARS-CoV-2 infection within 14 days prior to enrolment.
13. • Untreated syphilis infection (positive rapid plasma reagin [RPR] at Screening without clear documentation of treatment) are excluded. Participants with a false positive RPR (with negative treponemal test) or serofast RPR result (persistence of a reactive nontreponemal syphilis test despite history of adequate therapy and no evidence of re-exposure) may enroll after consultation with the Medical Monitor. Participants who completed treatment at least 7 days prior to Screening are eligible.
14. • Exposure to an experimental drug or experimental vaccine within either 30 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 first dose of study treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. •Time to virologic suppression (HIV viral load less than 50 copies per milliliter [c/mL]) from Day 1 (DTG/3TC).
2. • Participant with HIV viral load less than 50 c/mL as per the Snapshot algorithm after 1 year on treatment (CAB + RPV LA).

Secondary endpoints 15

1. • Participant with plasma HIV-1 RNA <50 c/mL as per Snapshot algorithm at Month 12 (DTG/3TC).
2. • Participant with plasma HIV-1 RNA greater than or equal to 50 c/mL as per Snapshot algorithm at Month 12 (DTG/3TC) / Month 11 (CAB + RPV LA).
3. • Participant with plasma HIV-1 RNA <50 c/mL and <200 c/mL over time, from Baseline (Day 1) through Day of Choice (all participants) and through Month 12 (DTG/3TC) / Month 11 (CAB + RPV LA).
4. • Absolute values and change from Baseline (Day 1) in plasma HIV-1 RNA (log10 c/mL) through Day of Choice (all participants) and Month 12 (DTG/3TC).
5. • Absolute values and changes from Baseline (Day 1) in CD4+ cell count over time including through Day of Choice (all participants) and Month 12 (DTG/3TC) / Month 11 (CAB + RPV LA).
6. • Participant meeting confirmed virologic failure (CVF) criteria over time.
7. • Occurrence of disease progression (HIV-associated conditions, acquired immunodeficiency syndrome [AIDS] and death) through Day of Choice (all participants) and through Month 12 (DTG/3TC) / Month 11 (CAB + RPV LA).
8. • Occurrence of viral resistance to CAB, RPV, DTG and 3TC through Day of Choice (all participants) and through Month 12 (DTG/3TC) / Month 11 (CAB + RPV LA).
9. • Occurrence of serious AEs; drug-related AEs (excluding injection site reactions [ISRs]); and AEs leading to discontinuation of study intervention, over time including through Day of Choice (all participants) and through Month 12 (DTG/3TC) / Month 11 (CAB + RPV LA).
10. • Change from Baseline (Week 4) in total “treatment satisfaction” score, and individual item scores of the HIV Treatment Satisfaction Status Questionnaire (HIVTSQs) at Day of Choice, Month 6 (DTG/3TC) / Month 5 (CAB + RPV LA) and Month 12 (DTG/3TC) / Month 11 (CAB + RPV LA) or Withdrawal.
11. • Change in total score and individual bothersome symptoms from Baseline (Day 1) to Day of Choice; and Day of Choice to Month 6 and Month 12 (DTG/3TC) using the Symptom Distress Module (SDM).
12. • Change in health-related quality of life across six domains from Baseline (Day 1) to Day of Choice; and Day of Choice to Month 5 and 11 for participants receiving CAB + RPV LA; Baseline (Day 1) to Day of Choice, Month 6 and Month 12 for participants receiving DTG/3TC using the WHOQoL-HIV-BREF.
13. • Change in anxiety and depression score from Baseline (Day 1) to Day of Choice; and Day of Choice to Months 5/6 and 11/12 for participants receiving DTG/3TC and CAB + RPV LA using the Patient Health Questionnaire 9 (PHQ-9) and General Anxiety Disorder 7 (GAD-7).
14. • Change in response to single item questions from Baseline (Day 1 or Week 4) to Day of Choice; and Day of Choice to Months 5/6 and 11/12 for participants receiving CAB + RPV LA and DTG/3TC using bespoke questions.
15. • Change in response to assessments from Day of Choice to Month 5 and to Month 11 for participants on CAB + RPV LA using ViiV Healthcare-developed single-item questions.

Investigational products

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

Test 5

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 10

Locations

4 EU/EEA countries · 20 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 102 files

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

Application history

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