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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 112
- 试验地点
- 7
- 主要终点
- Serum PK Parameters MAD: Dose 1 and Dose 5: Cmax of GS-0145
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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 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/Exclusion criteria may apply.
研究组 & 干预措施
Group A Single Ascending Dose (SAD): GS-0415
Participants will receive single escalating doses of GS-0415 via subcutaneous (SC) or intravenously (IV) on Day 1.
干预措施: GS-0415 (Drug)
Group A SAD: Placebo
Participants will receive placebo to match the single escalating doses of GS-0415 via SC or IV on Day 1.
干预措施: GS-0415 Placebo (Drug)
Group B SAD: GS-0415
Participants will receive single escalating doses of GS-0415 via SC or IV on Day 1.
干预措施: GS-0415 (Drug)
Group B SAD: Placebo
Participants will receive placebo to match the single escalating doses of GS-0415 via SC or IV on Day 1.
干预措施: GS-0415 Placebo (Drug)
Group C Multiple Ascending Dose (MAD): GS-0415
Participants will receive escalating doses of GS-0415 via SC or IV at five different timepoints up to Date 57.
干预措施: GS-0415 (Drug)
Group C MAD: Placebo
Participants will receive placebo to match escalating doses of GS-0415 via SC or IV at five different timepoints up to Day 57.
干预措施: GS-0415 Placebo (Drug)
结局指标
主要结局
Serum PK Parameters MAD: Dose 1 and Dose 5: Cmax of GS-0145
时间窗: Up to 99 days
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs)
时间窗: First dose date up to 99 days
Percentage of Participants Experiencing Clinical Laboratory Abnormalities
时间窗: First dose date up to 99 days
Serum Pharmacokinetic (PK) Parameter (After Single Ascending Dose (SAD)): AUCinf of GS-0145
时间窗: 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
时间窗: 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
时间窗: Up to 99 days
AUCtau is defined as the area under the concentration versus time curve over the dosing interval.
次要结局
- 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)