A Phase 2/3 Study to Evaluate the Safety and Efficacy of Long-Acting Capsid Inhibitor GS-6207 in Combination with an Optimized Background Regimen in Heavily Treatment Experienced People Living with HIV-1 Infection with Multidrug Resistance

Phase 1

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

Registration Number: EUCTR2019-003814-16-ES

Lead Sponsor: Gilead Sciences, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 100

Inclusion Criteria

1) Willing and able to provide written informed consent
2) Adult aged = 18 years (at all sites) or adolescent aged = 12 and weighing = 35 kg (at sites in North America and Dominican Republic)
3) Are receiving a stable failing ARV regimen for > 8 weeks before Screening and willing to continue the regimen until Day 1. Participants in Cohort 1 must also be willing to continue the failing regimen until completing the Functional Monotherapy Period (Day 1 to Day 14)
4) Have HIV 1 RNA = 400 copies/mL at Screening
5) Have screening or available historical HIV resistance reports showing resistance to = 2 antiretroviral medications from each of = 3 of the 4 main classes of antiretroviral medications (NRTI, NNRTI, PI, INSTI). Resistance to FTC or 3TC associated with the presence of the M184V/I RT mutation cannot be used for the purpose of determining this eligibility criterion
6) Have = 2 fully active ARV remaining from the 4 main classes that can be effectively combined to form a viable regimen in the opinion of the investigator based on resistance, tolerability, contraindication, safety, drug access, or acceptability to the participant
7) Able and willing to receive an optimized background regimen together with GS 6207. Participants with an OBR without a fully active agent may be enrolled if the investigator considers that there is a favorable risk-benefit ratio for the participant. With prior approval from Gilead Sciences, components of the OBR may be investigational (ie not yet approved)
8) A negative serum pregnancy test is required for all women at Screening
9) Men and women of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
10) Lactating women must agree to discontinue nursing before administration of GS-6207
Are the trial subjects under 18? yes
Number of subjects for this age range: 15
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion Criteria

1) An opportunistic illness requiring acute therapy within the 30 days prior to screening
2) Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days before screening
3) Active tuberculosis infection
4) Acute hepatitis within 30 days prior to Screening visit
5) Untreated or newly treated (< 3 months prior to screening) Hepatitis B Virus (HBV) infection. Hepatitis B infection is defined as screening results showing either or both of:
a. Positive HBV surface antigen
b. Positive HBV core antibody and negative HBV surface antibody
6) Hepatitis C virus (HCV) antibody positive and HCV RNA > LLOQ
7) A history of or current clinical decompensated liver cirrhosis (eg ascites, encephalopathy, or variceal bleeding)
8) Treatment with immunosuppressant therapies or chemotherapeutic agents < 3 months before screening, or expected to receive these agents or systemic steroids during the study (eg, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies)
9) A history (< 5 years) of or ongoing malignancy (including untreated carcinoma in-situ) other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non invasive cutaneous squamous carcinoma. Participants with biopsy-confirmed cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Day 1 and are not anticipated to require systemic therapy during the study
10) Current alcohol or substance use judged by the Investigator to potentially interfere with the participant’s study compliance
11) Clinically significant abnormal ECG at the Screening visit
12) Any of the following laboratory values at screening:
a. Estimated GFR = 60 mL/min using Cockcroft-Gault formula for participants = 18 years of age {Cockcroft 1976} and Schwartz Formula for participants < 18 years of age for creatinine clearance
b. ALT > 5 x upper limit of normal (ULN)
c. Direct bilirubin > 1.5 x ULN
d. Platelets < 50,000/mm3
e. Hemoglobin < 8.0 g/dL
13) Participation or planned participation in any other clinical trial (including observational trials) without prior approval from the sponsor throughout the study
14) Prior use of, or exposure to, GS-6207
15) Known hypersensitivity to the IMP, the metabolites, or formulation excipient
16) Use or planned use of exclusionary medications, refer to Section 5.4
17) 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 dosing requirements

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the antiviral activity of GS-6207 administered as an add-on to a failing regimen (functional monotherapy) for people living with HIV (PLWH) with multidrug resistance (MDR) as determined by the proportion of participants achieving at least 0.5 log10 reduction from baseline in HIV 1 RNA at the end of Functional Monotherapy Period;Secondary Objective: To evaluate the safety and efficacy of GS-6207 in combination with an optimized background regimen at Weeks 26 and 52;Primary end point(s): The proportion of participants in Cohort 1 achieving = 0.5 log10 copies/ml reduction from baseline in HIV 1 RNA at the end of the Functional Monotherapy Period;Timepoint(s) of evaluation of this end point: End of functional monotherapy period

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): The proportion of participants in Cohort 1 with plasma HIV 1 RNA < 50 copies/mL and < 200 copies/mL at Weeks 26 and 52 visits based on the US FDA defined snapshot algorithm;Timepoint(s) of evaluation of this end point: Weeks 26 and 52 of treatment

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