A Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Phase 1 Study of CMP-CPS-001 in Healthy Volunteers and Participants With Abnormal Heterozygous Ornithine Transcarbamylase (OTC) Genotype
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 120
- 试验地点
- 3
- 主要终点
- Adverse events
研究概览
简要总结
The objective of this clinical study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple ascending doses of CMP-CPS-001 administered as a subcutaneous injection in adult healthy volunteers and participants with abnormal heterozygous OTC genotype.
详细描述
This is a randomized, double-blind (Sponsor-open), and placebo-controlled study.
The SAD part will be conducted in approximately 48 healthy volunteers, in 4 cohorts of 12, randomized 3:1 to receive a single subcutaneous dose of CMP-CPS-001 or placebo. Participants will be followed for 42 days after dosing.
The MAD part will be conducted in approximately 48 healthy volunteers, in 4 cohorts of 12, randomized 3:1 to receive 3 monthly doses of CMP-CPS-001 or placebo. Participants will be followed for 56 days after the last dose.
Up to 12 participants in Australia and up to 12 participants in EU with abnormal heterozygous OTC genotype will be randomized 3:1 to receive 3 monthly doses of CMP-CPS-001 or placebo. Participants will be followed for 56 days after the last dose.
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
- 16 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants 18 (SAD, MAD, OTC in AUS) or 16 (OTC in EU) to 65 years inclusive at time of informed consent
- •BMI ≥18.0 and ≤32 kg/m2 at screening, and ≤110 kg
- •Willing and able to sign informed consent form
- •OTC cohorts: female and must have confirmed heterozygous OTC genotype
排除标准
- •Any significant disease or disorder which, in the opinion of the Investigator, may either put the study participant at risk because of participation in the study, may influence the results of the study, or may affect the study participant's ability to participate in the study
- •Clinically relevant illness within 7 days before the first dose of study drug
- •History of intolerance to subcutaneous injection or relevant abdominal scarring
- •Laboratory results outside normal ranges at screening and judged as clinically relevant by the Investigator for liver function, kidney function, and platelets
- •Positive viral serology test results for human immunodeficiency virus type 1 or 2 antibodies, hepatitis B surface antigen or hepatitis C virus antibody
- •Any other safety laboratory result considered clinically significant and unacceptable by the Investigator
研究组 & 干预措施
Multiple Ascending Dose Part
Adult healthy volunteers in 4 cohorts of 12 will receive 3 monthly doses of either CMP-CPS-001 or placebo. Four dose levels will be evaluated.
干预措施: Placebo (Other)
Single Ascending Dose Part
Adult healthy volunteers in 4 cohorts of 12 will receive CMP-CPS-001 or placebo. Four dose levels will be evaluated.
干预措施: Placebo (Other)
OTC Heterozygous Participants in EU
Up to 12 clinically healthy female participants who have an abnormal heterozygous OTC genotype will receive 3 monthly doses of either CMP-CPS-001 or placebo.
干预措施: CMP-CPS-001 (Drug)
OTC Heterozygous Participants in Australia
Up to 12 clinically healthy female participants who have an abnormal heterozygous OTC genotype will receive 3 monthly doses of either CMP-CPS-001 or placebo.
干预措施: Placebo (Other)
OTC Heterozygous Participants in EU
Up to 12 clinically healthy female participants who have an abnormal heterozygous OTC genotype will receive 3 monthly doses of either CMP-CPS-001 or placebo.
干预措施: Placebo (Other)
Single Ascending Dose Part
Adult healthy volunteers in 4 cohorts of 12 will receive CMP-CPS-001 or placebo. Four dose levels will be evaluated.
干预措施: CMP-CPS-001 (Drug)
Multiple Ascending Dose Part
Adult healthy volunteers in 4 cohorts of 12 will receive 3 monthly doses of either CMP-CPS-001 or placebo. Four dose levels will be evaluated.
干预措施: CMP-CPS-001 (Drug)
OTC Heterozygous Participants in Australia
Up to 12 clinically healthy female participants who have an abnormal heterozygous OTC genotype will receive 3 monthly doses of either CMP-CPS-001 or placebo.
干预措施: CMP-CPS-001 (Drug)
结局指标
主要结局
Adverse events
时间窗: Screening (Day -36) until 42 days (SAD) or 112 days (MAD) after dosing
Incidence of adverse events, including dose limiting toxicities, after administration of CMP-CPS-001
Adverse events
时间窗: Screening until 42 days (SAD) or 112 days (MAD, OTC) after dosing
Incidence of adverse events, including dose limiting toxicities, after administration of CMP-CPS-001
次要结局
- Plasma PK(Pre-dose (Day 1) until 42 days (SAD) or 112 days (MAD) after dosing)
- Urinary excretion of CMP-CPS-001(42 days (SAD) or 111 days (MAD) after dosing)
- Pharmacodynamic effect of CMP-CPS-001 on ureagenesis(Run-in (Day -8) until 42 days (SAD) or 112 days (MAD) after dosing)
- Plasma PK(Pre-dose (Day 1) until 42 days (SAD) or 112 days (MAD, OTC) after dosing)
- Urinary excretion of CMP-CPS-001(42 days (SAD) or 111 days (MAD, OTC) after dosing)
- Pharmacodynamic effect of CMP-CPS-001 on ureagenesis(Run-in (Day -7) until 42 days (SAD) or 112 days (MAD, OTC) after dosing)