A Phase IIb Clinical Trial of GSK3640254 + Dolutegravir (DTG) in HIV-1 Infected Treatment-Naive Adults

Phase 1

• Conditions: Human Immunodeficiency Virus Type-1 (HIV-1); MedDRA version: 20.1Level: LLTClassification code 10068341Term: HIV-1 infectionSystem Organ Class: 100000004862; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2021-000016-28-PT
• Lead Sponsor: ViiV Healthcare UK Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-06-21
• Study Completion: 2023-05-11
• Last Update Posted: 5 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 85

Inclusion Criteria

Age:
1. Participants must be 18 years of age inclusive, at the time of signing the informed consent.
Type of Participant and Disease Characteristics:
2. Treatment-naïve, defined as no ARVs (in combination or monotherapy) received after a known diagnosis of HIV-1 infection;
NOTE: Use of PrEP (prior to known HIV-1 infection) is allowed and still meets inclusion. PrEP is used by individuals who are not infected with HIV-1 but who are at high risk for acquiring the virus. PrEP alone is not sufficient to treat HIV and the use of PrEP is stopped if/when a diagnosis of HIV is made.
3. Documented HIV infection and Screening plasma HIV-1 RNA =1000 c/mL;
4. Screening CD4+ T-cell count =250 cells/mm3;
Weight:
5. Body weight =50.0 kg (110 lbs.) for men and =45.0 kg (99 lbs) for women and body mass index (BMI) > 18.5 kg/m2. Calculations will utilize sex assigned at birth;
Sex:
Sex and Contraceptive/Barrier Requirements:
6. Male and female
a. Participants who are male at birth: There are no contraceptive requirements for participants who are male at birth
b. Participants who are female at birth:
Contraceptive use by participants who are female at birth should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• A participant who is female at birth is eligible to participate if they are not pregnant or breastfeeding, and one of the following conditions applies:
o Is not a participant of childbearing potential (PONCBP) as defined in Section 10.4.
OR
o Is a POCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, as described in Section 10.4 during the study intervention period and until after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention.
o If a hormonal method is selected, the participant is required to be clinically stable on it for at least one month prior to starting treatment in the study.
• A POCBP must have a negative highly sensitive serum pregnancy test at Screening and a negative urine pregnancy test at Day 1 before starting study intervention .
o If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
• Additional requirements for pregnancy testing during and after study intervention are located in Section 8.2.5 Pregnancy Testing.
• The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a participant with an early undetected pregnancy Informed Consent:
7. Capable of giving signed informed consent as described in Section 10.1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Other:
8. For participants enrolled in France: a participant will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 72
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

Exclusion Criteria

1. Any evidence of an active Centers for Disease Control and Prevention (CDC) Stage 3 disease [CDC, 2014], except cutaneous Kaposi’s sarcoma not requiring systemic therapy;
2. 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;
3. Presence of primary HIV infection, evidenced by acute retroviral syndrome (e.g., fever, malaise, fatigue, etc) and/or evidence of recent (within 3 months) documented viremia without antibody production and/or evidence of recent (within 3 months) documented seroconversion;
4. Known history of liver cirrhosis with or without viral hepatitis co-infection;
5. 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), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment)
6. History of ongoing or clinically relevant hepatitis within the previous 6 months;
7. History of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation;
8. Any history of significant underlying psychiatric disorder, in the opinion of the Investigator or Medical Monitor, including but not limited to schizophrenia, bipolar disorder with or without psychotic symptoms, other psychotic disorders, or schizotypal (personality) disorder; or a clinical assessment of suicidality based on the responses on the eC-SSRS.
9. Any history of major depressive disorder with or without suicidal features, or anxiety disorders, that required medical intervention (pharmacologic or not) such as hospitalization or other inpatient treatment and/or chronic (>6 months) outpatient treatment;
10. Any pre-existing physical or other psychiatric condition (including alcohol or drug abuse), which, in the opinion of the Investigator or Medical Monitor (with or without psychiatric evaluation), could interfere with the participant’s ability to comply with the dosing schedule and protocol evaluations or which might compromise the safety of the participant;
11. A pre-existing condition, in the opinion of the Investigator or Medical Monitor, that could interfere with normal gastrointestinal anatomy or motility (e.g., gastroesophageal reflux disease [GERD], gastric ulcers, gastritis, inflammatory bowel disease), hepatic and/or renal function, or with the absorption, metabolism, and/or excretion of the study interventions or render the participant unable to take oral study treatment;
12. Myocardial infarction, acute coronary syndrome, unstable angina, stroke, transient ischemic attack, or intermittent claudication in the past 3 months;
13. Familial or personal history of long QT syndrome or sudden cardiac death;
14. Medical history, current or historical, of significant cardiac arrhythmias or ECG findings which, in the opinion of the Investigator or Medical Monitor, will interfere with the safety of the participant;
15. Active treatment for a viral infection other than HIV-1, such as Hepatitis B, with an agent that is active against HIV-1 (were known to be infected with HIV-1 after treatment for Hepatitis B was completed);
16. Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening;
17. Treatment with any

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate antiviral efficacy of GSK3640254 + DTG, relative to DTG + 3TC at Week 24 in HIV-1 infected, ART-naïve participants ;Secondary Objective: • To evaluate the antiviral activity of GSK3640254 + DTG relative to DTG + 3TC at Week 48;<br>• To evaluate safety and tolerability of GSK3640254 when given in combination with DTG, relative to DTG + 3TC;<br>• To assess the development of viral resistance to GSK3640254 and other on-study ART in participants experiencing virologic failure through Week 48;<br>• To assess the steady-state exposure of GSK3640254 when given in combination with DTG.;Primary end point(s): Proportion of participants with plasma HIV-1 RNA <50 c/mL at Week 24 using the FDA snapshot algorithm;Timepoint(s) of evaluation of this end point: Week 24

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • Proportion of participants with plasma HIV-1 RNA <50 c/mL at Week 48 using the FDA snapshot algorithm;<br>• Absolute values and changes from baseline in HIV-1 RNA through Weeks 24 and 48;<br>• Absolute values and changes from baseline in CD4+ T-cell counts through Weeks 24 and 48;<br>• Frequency of SAEs, Deaths and AEs leading to Discontinuation through Weeks 24 and 48;<br>• AEs of special interest (AESIs) through Weeks 24 and 48;<br>• Changes in genotypic and/or phenotypic profiles of virus compared to baseline;<br>• The steady-state plasma PK parameters of GSK3640254 will be assessed based on Sparse PK sampling through Week 48 <br><br>;Timepoint(s) of evaluation of this end point: Please refer to the time period specified in E.5.2 Secondary end point section.