A Multicenter, Randomized, Placebo-Controlled Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Pharmacodynamics of Multiple Ascending Doses of GS-0272 in Adult Participants With Rheumatoid Arthritis
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 55
- 试验地点
- 45
- 主要终点
- Pharmacokinetics (PK) of GS-0272: AUCtau
研究概览
简要总结
The goals of this clinical study are to learn more about the study drug, GS-0272, and its safety and tolerability following multiple doses in participants with rheumatoid arthritis (RA).
The primary objectives of this study are to assess the safety and tolerability of multiple ascending doses of GS-0272 and to characterize the pharmacokinetics of GS-0272 following multiple doses of GS-0272, in participants with RA.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age limit for the Republic of Korea for male or nonpregnant female is between 19 and 75 years of age.
- •Part A (Rheumatoid Arthritis (RA) Cohorts)-Specific Inclusion Criteria:
- •Diagnosis of RA at least 3 months prior to screening fulfilling the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria.
- •Ongoing treatment with 1 or 2 conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for at least 12 weeks prior to the first dose of study drug, with a stable dose for at least 4 weeks prior to the first dose of study drug, as follows:
- •Individuals must not be on a biologic disease-modifying antirheumatic drugs (bDMARD)/targeted synthetic disease-modifying antirheumatic drug (tsDMARD) at Day 1 or during the study and must discontinue b/tsDMARD use for at least 4 weeks (with the exception of rituximab, which must be discontinued for at least 16 weeks) prior to the first dose of study drug.
- •Part B (Active RA Cohort)-Specific Inclusion Criteria:
- •Participant is seropositive as demonstrated by a positive anti-cyclic citrullinated peptide (anti-CCP) antibody and/or positive rheumatoid factor at screening.
- •Participant has an elevated high-sensitivity C-reactive protein (hsCRP) greater than upper limit of normal (ULN).
- •Participant has 6 or more swollen and 6 or more tender joints as assessed on the SJC66/TJC
- •Distal interphalangeal joints will not be counted towards the 6 joint eligibility.
- •Participant has had inadequate response or intolerance to at least 1 but not more than 3 bDMARD/tsDMARD therapeutics with no more than 2 MOAs. A lack of response is defined as documented continued or recurrent disease activity after at least 12 weeks of treatment of RA.
排除标准
- •Meet any of the protocol-specified infection criteria (hepatitis C, Hepatitis B, HIV, tuberculosis, others).
- •Inadequate response or intolerance to more than 3 bDMARDs/tsDMARDs with more than 2 MOAs.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Part B: Active RA Cohort: GS-0272 or Placebo
Part B will include participants with moderate-to-severe RA. Part B will have only 1 cohort (Cohort 4). Participants in Cohort 4 will be randomized in a 2:1 ratio to receive either GS-0272 or placebo for 12 weeks.
干预措施: Placebo (Drug)
Part B: Active RA Cohort: GS-0272 or Placebo
Part B will include participants with moderate-to-severe RA. Part B will have only 1 cohort (Cohort 4). Participants in Cohort 4 will be randomized in a 2:1 ratio to receive either GS-0272 or placebo for 12 weeks.
干预措施: GS-0272 (Drug)
Part A: Rheumatoid Arthritis (RA) Cohorts: GS-0272 or Placebo
Part A will include participants with RA. Part A will have 3 cohorts. Each cohort in Part A will be randomized in a 3:1 ratio to receive either ascending doses of GS-0272 or placebo for 12 weeks.
Dosing will begin in Cohort 1. Cohorts 2 and 3 will be initiated upon review of blinded safety data from the preceding cohort.
干预措施: Placebo (Drug)
Part A: Rheumatoid Arthritis (RA) Cohorts: GS-0272 or Placebo
Part A will include participants with RA. Part A will have 3 cohorts. Each cohort in Part A will be randomized in a 3:1 ratio to receive either ascending doses of GS-0272 or placebo for 12 weeks.
Dosing will begin in Cohort 1. Cohorts 2 and 3 will be initiated upon review of blinded safety data from the preceding cohort.
干预措施: GS-0272 (Drug)
结局指标
主要结局
Pharmacokinetics (PK) of GS-0272: AUCtau
时间窗: Day 1 predose through Day 197
AUCtau is defined as the area under the concentration versus time curve over the dosing interval.
Percentage of Participants Experiencing Adverse Events (AEs)
时间窗: First dose up to Week 12 plus 70 days
PK of GS-0272: Cmax
时间窗: Day 1 predose through Day 197
Cmax is defined the maximum observed plasma drug concentration.
Percentage of Participants Experiencing Serious Adverse Events (SAEs)
时间窗: First dose up to Week 12 plus 70 days
Percentage of Participants With Laboratory Abnormalities
时间窗: First dose up to Week 12 plus 70 days
PK of GS-0272: Tmax
时间窗: Day 1 predose through Day 197
Tmax is defined as the time to maximum observed concentration.
次要结局
- Prevalence of Antidrug Antibodies (ADAs) for GS-0272(Baseline (Day 1) through Day 197)
- Incidence of ADAs for GS-0272(Baseline (Day 1) through Day 197)
- Part B: Change from Baseline in Disease Activity Score 28 (DAS28) C-Reactive Protein (CRP) in Participants with Moderate-to-Severe RA(Baseline, Week 12)