HIV -1 Infection
Conditions
Brief summary
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
DRUGGS-0415
Administered SC or IV
DRUGGS-0415 Placebo
Administered SC or IV
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Intervention model description
Participants in SAD cohorts will receive a single dose and participants in the MAD cohorts will receive multiple doses at different time points.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key 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 for ≥ 12 months before and 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 Key
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: 1. Positive HBV surface antigen, regardless of HBV core antibody status, at the Screening visit 2. 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 as assessed by the investigator 3.) Significant drug sensitivity or drug allergy ('but not limited to anaphylaxis or drug-induced liver injury) as assessed by the investigator 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) | First dose date up to 99 days | — |
| Percentage of Participants Experiencing Clinical Laboratory Abnormalities | First dose date up to 99 days | — |
| Serum Pharmacokinetic (PK) Parameter (After Single Ascending Dose (SAD)): AUCinf of GS-0145 | Up to 43 days | AUCinf is defined as the area under the concentration versus time curve extrapolated to infinite time, calculated as AUClast + (Clast/λz). |
| Serum PK Parameters (SAD): Cmax of GS-0145 | Up to 43 days | Cmax is defined as the maximum observed concentration of drug. |
| Serum PK Parameters Multiple Ascending Dose (MAD): Dose 1 and Dose 5: AUCtau of GS-0145 | Up to 99 days | AUCtau is defined as the area under the concentration versus time curve over the dosing interval. |
| Serum PK Parameters MAD: Dose 1 and Dose 5: Cmax of GS-0145 | Up to 99 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Percentages of participants With of Treatment-Emergent Anti-GS-0415 Antibodies | Up to 99 days |
| Percentages of participants With Virological Rebound (Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) ≥ 50 copies/mL) | Up to 99 days |
Countries
United States
Contacts
CONTACTGilead Clinical Study Information Center
STUDY_DIRECTORGilead Study Director
Gilead Sciences
Outcome results
None listed