A Phase Ib, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Multiple-Ascending Doses of RO7303509 in Participants With Systemic Sclerosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 25
- 主要终点
- Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of RO7303509 treatment in participants with systemic sclerosis (SSc) during a multiple-ascending-dose (MAD) portion of the trial. In the MAD phase, increasing doses of study drug will be tested sequentially. For each dose tested, the MAD stage will consist of a treatment period of 12 weeks followed by either a safety follow-up period of 13 weeks or continued treatment in an optional open-label safety extension (OSE) stage of 52 weeks to assess the long-term safety. All patients in the OSE stage will receive RO7303509 and no patient will receive placebo.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Inclusion Criteria for the MAD Stage:
- •Weight of 45-150 kg at screening
- •Diagnosis of SSc, as defined by 2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria and ≤ 10 years disease duration from first non-Raynaud's symptom
- •Agreement to remain abstinent or use an effective contraceptive method among males and females with childbearing potential for 4 months after last dose of study drug
- •Inclusion Criteria for the OSE Stage:
- •No clinically significant change in eligibility status
- •Completion of the MAD and ability to roll over into the OSE within 5 days
排除标准
- •Active rheumatic autoimmune disease other than SSc requiring treatment with disease-modifying therapy
- •Pulmonary disease with forced vital capacity (FVC) ≤ 50% of predicted
- •History or clinical manifestations of significant metabolic, hepatic, renal, pulmonary, cardiovascular, hematologic, gastrointestinal, urologic, neurologic, or psychiatric disorders
- •History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
- •Pregnant or breastfeeding, or intending to become pregnant during the study or within 4 months after the final dose of study drug
- •Major surgery within 8 weeks prior to screening, or major planned surgery during the study or within 3 months after the final dose
- •Positive hepatitis C virus (HCV) antibody, hepatitis B surface antigen (HBsAg), or human immunodeficiency virus (HIV) antibody test at screening
- •Any serious medical condition or abnormality in clinical laboratory tests
研究组 & 干预措施
MAD Stage
Participants will be randomized in a ratio of 4:1 to receive RO7303509 or placebo, as subcutaneous (SC) injection, one time per month for 3 months. You have a 20% chance of getting placebo.
干预措施: RO7303509 (Drug)
MAD Stage
Participants will be randomized in a ratio of 4:1 to receive RO7303509 or placebo, as subcutaneous (SC) injection, one time per month for 3 months. You have a 20% chance of getting placebo.
干预措施: Placebo (Drug)
OSE Stage
Every participant in the OSE stage will receive study drug and no participant will receive placebo. Participants will receive RO7303509 as SC injection at the same dose as that administered during the MAD stage, one time per month for up to a year.
干预措施: RO7303509 (Drug)
结局指标
主要结局
Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters
时间窗: Up to approximately 17 months
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
时间窗: Up to approximately 17 months
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
时间窗: Up to approximately 17 months
Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Test Results
时间窗: Up to approximately 17 months
次要结局
- MAD Stage: Maximum Serum Concentration (Cmax) of RO7303509(Predose on Day 1 and at multiple timepoints up to Day 113 or early termination (ET) visit)
- MAD Stage: Area Under the Concentration vs Time Curve (AUC) of RO7303509(Predose on Day 1 and at multiple timepoints up to Day 113 or ET visit)
- MAD Stage: Time to Maximum Concentration (Tmax) of RO7303509(Predose on Day 1 and at multiple timepoints up to Day 113 or ET visit)
- MAD Stage: Total Clearance (CL) of RO7303509(Predose on Day 1 and at multiple timepoints up to Day 113 or ET visit)
- MAD Stage: Half-Life (t1/2) of RO7303509(Predose on Day 1 and at multiple timepoints up to Day 113 or ET visit)
- MAD and OSE Stage: Percentage of Participants With Anti-Drug Antibodies (ADAs) Against RO7303509(MAD Stage: Predose on Day 1 and at multiple timepoints up to Day 113 (Week 16) or ET visit; OSE Stage: Predose and multiple timepoints up to Week 52; (up to approximately 1.3 years))
- MAD Stage: Volume of Distribution (V) of RO7303509(Predose on Day 1 and at multiple timepoints up to Day 113 or ET visit)