A Phase 1/2, Multicenter Study Evaluating the Safety, Tolerability, and Biodistribution of RCT2100 With Single-Ascending Doses in Healthy Participants and Multiple-Ascending Doses and Proof-of-Concept in Participants With Cystic Fibrosis
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 128
- 试验地点
- 59
- 主要终点
- Part 1: The number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs).
研究概览
简要总结
This is the first-in-human study with RCT2100 and is designed to provide safety and tolerability data for future clinical studies.
详细描述
This is a multi-part study to assess the safety, tolerability, and biodistribution of a single ascending dose of inhaled RCT2100 administered via nebulizer to healthy participants (Part 1), the safety and tolerability of multiple-ascending doses of inhaled RCT2100 administered to participants with CF (Part 2), and the safety and tolerability of RCT2100 co-administered with ivacaftor in participants with CF (Part 3).
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
- Double (Participant, Investigator)
盲法说明
Participant and investigator masking only applies to Part 1 which is randomized. For Part 2 and Part 3, there is no masking, and this part is Open Label.
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Part 1 Major Inclusion Criteria:
- •Healthy, adult, male or female, 18-55 years of age, inclusive, at screening.
- •Body weight greater than or equal to 50 kg and body mass index (BMI) between 16-32 kg/m2, inclusive
- •The participant has a forced expiratory volume in one second (FEV1) of at least 80% predicted
- •The participant is considered by the investigator to be in good general health as determined by medical history, clinical laboratory test results, vital sign measurements, 12-lead ECG results, and physical examination findings at screening.
- •Understands the study procedures in the informed consent form (ICF), and is willing and able to comply with the protocol.
- •Part 1 Major
排除标准
- •History or presence of clinically significant medical, surgical, clinical laboratory, or psychiatric condition or disease.
- •The participant has supine blood pressure (BP) >150 mm Hg (systolic) or >90 mm Hg (diastolic), following at least 5 minutes of supine rest.
- •The participant has abnormal clinical laboratory tests at screening, as assessed by the study-specific laboratory.
- •The participant is a smoker or has used nicotine or nicotine-containing products 6 weeks before the first dose of study drug. Former smokers with greater than 10 pack years of smoking history are excluded.
- •Part 2 Major Inclusion Criteria:
- •Confirmed diagnosis of CF
- •Forced expiratory volume in 1 second ≥50% and ≤100% of predicted mean value for age, sex, and height
- •a) Not eligible for CFTR modulators based on having mutations of CFTR gene on both alleles that are not responsive to CFTR modulator therapy OR
- •b) Eligible for CFTR modulators (based on local prescribing information) but not using CFTR modulators due to intolerance or contraindications
- •Part 2 Major Exclusion Criteria:
- •Hepatic cirrhosis with portal hypertension, moderate hepatic impairment (Child Pugh Score 7 to 9), or severe hepatic impairment (Child Pugh Score 10 to 15)
- •An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for sinopulmonary disease within 4 weeks before the first dose of study drug
- •Lung infection with organisms associated with a more rapid decline in pulmonary status
- •Arterial oxygen saturation on room air less than 94% at screening
- •Treatment with a CFTR modulator (Kalydeco, Trikafta, Symdeko, Orkambi, or Alyftrek) within 12 weeks of Screening
- •Other protocol defined Inclusion/Exclusion criteria may apply.
- •Part 3 Major Inclusion Criteria:
- •Confirmed diagnosis of CF
- •Forced expiratory volume in 1 second ≥50% and ≤100% of predicted mean value for age, sex, and height
- •a) Not eligible for CFTR modulators based on having mutations of CFTR gene on both alleles that are not responsive to CFTR modulator therapy OR
- •b) Eligible for dual or triple CFTR modulators (based on local prescribing information) but not using CFTR modulators due to intolerance or contraindications
- •Part 3 Major Exclusion Criteria:
- •Hepatic cirrhosis with portal hypertension, moderate hepatic impairment (Child Pugh Score 7 to 9), or severe hepatic impairment (Child Pugh Score 10 to 15)
- •An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for sinopulmonary disease within 4 weeks before the first dose of study drug
- •Lung infection with organisms associated with a more rapid decline in pulmonary status
- •Arterial oxygen saturation on room air less than 94% at screening
- •Treatment with a CFTR modulator (Kalydeco, Trikafta, Symdeko, Orkambi, or Alyftrek) within 12 weeks of Screening
- •Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
RCT2100 (Part 2) 12 week
RCT2100 multiple dose
干预措施: RCT2100 (Drug)
Experimental: RCT2100 (Part 3) 6 week
RCT2100 multiple dose
干预措施: RCT2100 (Drug)
RCT2100 (Part 1)
RCT2100 single dose
干预措施: RCT2100 (Drug)
RCT2100 (Part 2) 4 week
RCT2100 multiple dose
干预措施: RCT2100 (Drug)
Experimental: RCT2100 (Part 3) 6 week
RCT2100 multiple dose
干预措施: Ivacaftor (Drug)
Placebo (Part 1)
Placebo single dose
干预措施: Placebo (Other)
结局指标
主要结局
Part 1: The number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs).
时间窗: From Baseline Through Day 29
Safety and tolerability as assessed by number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Part 2: The number of participants with CF with AEs and SAEs.
时间窗: From Day 1 through Safety Follow-up, Week 24
Safety and tolerability of multiple-ascending doses of inhaled RCT2100 administered to participants with CF
Part 3: The number of participants with CF with AEs and SAEs.
时间窗: From Day 1 through Safety Follow-up, Week 24
To assess the safety and tolerability of RCT2100 co-administered with ivacaftor in participants with CF.
次要结局
- Biodistribution parameters may be derived from concentrations of RCT2100 components in blood (where feasible). Parameters may include but are not limited to the following: AUC, Cmax, Tmax, and t1/2
- Absolute change in percent predicted FEV1 (ppFEV1) from baseline to Week 4 (escalation cohorts 1 to 3) or Week 12 (expansion cohort)
- Change from baseline in CF questionnaire-revised (CFQ-R) respiratory domain score through Week 4 (escalation cohorts 1 to 3) or Week 12 (expansion cohort)
- Incidence and titer of anti-CFTR binding antibodies
- Based on safety and tolerability at projected efficacious doses