Study of GS-0415 and How It Works in People With HIV

Official title

A First-in-Human Phase 1b, Single-Blind, Placebo-controlled Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) Study to Evaluate Safety and Pharmacokinetics of GS-0415 in People With HIV-1 Who Are Virologically Suppressed on Antiretroviral Treatment

Overview

The goals of this clinical study are to learn more about the study drug GS-0415, safety, tolerability, and pharmacokinetics (PK) of single ascending doses (SAD) and multiple ascending doses (MAD) of subcutaneous (SC) and intravenous (IV) GS-0415 in people with HIV-1 (PWH) on antiretroviral treatment. The primary objectives of this study are to evaluate the safety and tolerability of escalating, single and multiple subcutaneous (SC) and intravenous (IV) doses of GS-0415, administered in PWH who are virologically suppressed on antiretroviral therapy (ART) and to evaluate the pharmacokinetics (PK) of GS-0415.

Interventions

• Drug GS-0415
  Administered SC or IV
• Drug GS-0415 Placebo
  Administered SC or IV

Primary outcome measures

• Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) [Time frame: First dose date up to 99 days]
• Percentage of Participants Experiencing Clinical Laboratory Abnormalities [Time frame: First dose date up to 99 days]
• Serum Pharmacokinetic (PK) Parameter (After Single Ascending Dose (SAD)): AUCinf of GS-0145 [Time frame: Up to 43 days]
• Serum PK Parameters (SAD): Cmax of GS-0145 [Time frame: Up to 43 days]
• Serum PK Parameters Multiple Ascending Dose (MAD): Dose 1 and Dose 5: AUCtau of GS-0145 [Time frame: Up to 99 days]
• Serum PK Parameters MAD: Dose 1 and Dose 5: Cmax of GS-0145 [Time frame: Up to 99 days]

Secondary outcome measures (2)

• Percentages of participants With of Treatment-Emergent Anti-GS-0415 Antibodies [Time frame: Up to 99 days]
• Percentages of participants With Virological Rebound (Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) ≥ 50 copies/mL) [Time frame: Up to 99 days]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years and age ≤ 65 years at screening
• On stable antiretroviral (ARV) treatment for ≥ 12 consecutive months prior to screening, throughout the duration of study treatment and follow-up
• The following ARV agents are not allowed as part of the current ART regimen: entry inhibitors (maraviroc, enfuvirtide, ibalizumab, or fostemsavir)
• Plasma HIV-1 RNA < 50 copies/mL at screening with at least 2 documented HIV-1 RNA <50 copies/mL within the last 12 months.
• Clusters of differentiation 4 (CD4) count ≥ 350 cells/μL
• Weight ≥ 50 kg and ≤ 110 kg at screening and Day 1
• Body mass index (BMI) ≥ 18.5 kg/m2 and ≤ 35 kg/m2 at screening and Day 1

Exclusion criteria

• Documented history of pre-ART CD4 nadir < 100 cells/μL. Unknown pre-ART CD4 nadir is acceptable
• Known to have initiated ART within 6 months of HIV infection. Unknown time between infection and ART initiation is acceptable
• Females who are pregnant or breastfeeding or who may wish to become pregnant during the study or within 42 days after last study drug administration
• Have chronic hepatitis B virus (HBV) as determined by either:

• Positive HBV surface antigen, regardless of HBV core antibody status, at the Screening visit
• Positive HBV core antibody and negative HBV surface antibody, regardless of HBV surface antigen status, at the Screening visit
• Have active hepatitis C virus (HCV) infection:

1.) Positive anti-HCV antibody and negative HCV polymerase chain reaction (PCR) results are acceptable

• Have a history of any of the following:

2.) Significant serious skin disease, such as but not limited to rash, food allergy, eczema, psoriasis, or urticaria

3.) Significant drug sensitivity or drug allergy ('but not limited to anaphylaxis or drug-induced liver injury)

4.) Known hypersensitivity to the study drugs, their metabolites, or to formulation excipients

5.) Previous or current history of bleeding disorder, platelet disorder including unexplained acute or chronic thrombocytopenia

6.) Autoimmune diseases including Type 1 diabetes mellitus

7.) Serious or active medical or psychiatric illness that would interfere with participant treatment, assessment, or compliance with the protocol.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07719491 · GS-US-531-7345

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗