Study of CMP-CPS-001 in Healthy Volunteers and Participants With Abnormal Heterozygous OTC Genotype

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

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.

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.

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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