A Phase 1/2, Randomized, Double-Blinded, Placebo-Controlled, Combined Single and Multiple Ascending Dose Study Evaluating the Safety, Tolerability, and Biological Activity of MRT5005 Administered by Nebulization to Adult Subjects With Cystic Fibrosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 42
- 试验地点
- 16
- 主要终点
- Parts A, B and D: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events
研究概览
简要总结
This Phase 1/2, first-in-human study evaluated the safety and tolerability of single and multiple escalating doses of MRT5005 administered by nebulization to the respiratory tract of adult subjects with cystic fibrosis (CF).
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of CF as defined by both of the following:
- •Two CF disease-causing cystic fibrosis transmembrane conductance regulator (CFTR) mutations in Class I or II (genotype confirmed at the screening visit).
- •Chronic sinopulmonary disease and/or gastrointestinal/nutritional abnormalities consistent with CF disease.
- •Clinically stable CF disease, as judged by the investigator.
- •Forced expiratory volume in 1 second (FEV1) ≥50% and ≤90% of the predicted normal for age, gender, and height at screening.
- •Resting oxygen saturation ≥92% on room air (pulse oximetry).
排除标准
- •An acute upper or lower respiratory infection, pulmonary exacerbation, or clinically significant episode of hemoptysis or change in chronic respiratory medications (including antibiotics) for CF lung disease within 28 days prior to dosing with investigational product on Day
- •Participants were receiving treatment with ivacaftor monotherapy (KALYDECO).
- •Parts A and B only: Were receiving treatment with triple combination therapy (TRIKAFTA).
- •Participants with a Class III, IV, or V CFTR gene mutation in at least 1 allele.
- •Infection with highly virulent bacteria associated with accelerated decline in pulmonary function and/or decreased survival (e.g., Burkholderia cenocepacia, Burkholderia dolosa, Mycobacterium abscessus).
- •Treatment with ORKAMBI or SYMDEKO was not an exclusion for this study.
研究组 & 干预措施
Part A - SAD Group 1: MRT5005 8 mg
Participants received single dose of MRT5005 8 milligrams (mg) by nebulization on Day 1.
干预措施: MRT5005 (Drug)
Part A - SAD Group 2: MRT5005 16 mg
Participants received single dose of MRT5005 16 mg by nebulization on Day 1.
干预措施: MRT5005 (Drug)
Part A - SAD Group 3: MRT5005 20 mg
Participants received single dose of MRT5005 20 mg by nebulization on Day 1.
干预措施: MRT5005 (Drug)
Part A - SAD Group 4: MRT5005 24 mg
Participants received single dose of MRT5005 24 mg by nebulization on Day 1.
干预措施: MRT5005 (Drug)
Part A - SAD Groups: Pooled Placebo
Participants received single dose of placebo (normal saline) by nebulization on Day 1. Data were analyzed as a pooled population for all participants who received placebo in Part A SAD groups and reported in this arm.
干预措施: Normal saline (Drug)
Part B - MAD Group 1: MRT5005 8 mg
Participants received MRT5005 8 mg once weekly by nebulization for 5 weeks (i.e., on Day 1, Day 8, Day 15, Day 22 and Day 29).
干预措施: MRT5005 (Drug)
Part B - MAD Group 2: MRT5005 12 mg
Participants received MRT5005 12 mg once weekly by nebulization for 5 weeks (i.e., on Day 1, Day 8, Day 15, Day 22 and Day 29).
干预措施: MRT5005 (Drug)
Part B - MAD Group 3: MRT5005 16 mg
Participants received MRT5005 16 mg once weekly by nebulization for 5 weeks (i.e., on Day 1, Day 8, Day 15, Day 22 and Day 29).
干预措施: MRT5005 (Drug)
Part B - MAD Group 4: MRT5005 20 mg
Participants received MRT5005 20 mg once weekly by nebulization for 5 weeks (i.e., on Day 1, Day 8, Day 15, Day 22 and Day 29).
干预措施: MRT5005 (Drug)
Part B - MAD Groups: Pooled Placebo
Participants received placebo (normal saline) once weekly by nebulization for 5 weeks (i.e., on Day 1, Day 8, Day 15, Day 22 and Day 29). Data were analyzed as a pooled population for all participants who received placebo in Part B MAD groups and reported in this arm.
干预措施: Normal saline (Drug)
Part D: MRT5005 4 mg
Participants received MRT5005 4 mg once daily by nebulization from Day 1 to Day 5.
干预措施: MRT5005 (Drug)
Part D: Placebo
Participants received placebo (normal saline) once daily by nebulization from Day 1 to Day 5.
干预措施: Normal saline (Drug)
结局指标
主要结局
Parts A, B and D: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events
时间窗: From the first dose of study treatment administration (Day 1) up to 48 weeks (end of the follow-up period) after the last dose of study treatment administration (Part A: Day 337, Part B: Day 365 and Part D: Day 341)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that did not necessarily had a causal relationship with the study treatment. A serious adverse event (SAE) was any untoward medical occurrence (whether considered to be related to study treatment or not) that at any dose: resulted in death; or was life-threatening; or required inpatient hospitalization or prolongation of existing hospitalization; or resulted in persistent or significant disability/incapacity; or was a congenital abnormality/birth defect; or was an important medical event. The TEAEs were defined as events that were newly reported or reported to worsen in severity after the start of study treatment up to 48 weeks (end of follow-up period) after the last dose of study treatment administration.
次要结局
- Parts A, B and D: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)(Part A:BL, D1(8hPD), D2(24hPD), D3, D8, D15 and D29; Part B:BL, D1(6hPD), D2, D8(PrD and 6hPD), D9, D15(PrD and 6hPD), D16, D22(PrD and 6hPD), D23, D29(PrD and 6hPD), D30, D36, D43 and D57; Part D:BL, D1(2hPD), PrD on D2, D3, D4 and D5, D11, D18 and D32)