Pegzilarginase in Subjects <24 Months Old With Arginase 1 Deficiency

A Phase 3 Open-Label Study of Safety, Pharmacokinetics, and Activity of Weekly Subcutaneous Pegzilarginase in Subjects <24 Months Old With Arginase 1 Deficiency

This is an open-label, multicentre study to evaluate the safety, PK, and activity (PD) of weekly subcutaneous (SC) administration of pegzilarginase in subjects with ARG1-D who are < 24 months of age. The study consists of a screening period of up to 4 weeks, a subsequent 12-week treatment period, and a safety follow-up period of 8 weeks.

CAEB1102-301A is an open-label, single-arm, non-controlled, repeat dosing, multicentre study to evaluate the safety, PK, and activity (PD) of weekly SC administration of pegzilarginase over 12 weeks in subjects with ARG1-D who are < 24 months of age.

This study will consist of:

• A screening period of up to 4 weeks to ensure the subjects meet the study eligibility criteria and establish baseline plasma arginine
• A treatment period of 12 weeks
• A safety follow-up period of 8 weeks with visits 1 week and 8 weeks after the last dose.

Inclusion Criteria:

1. Subjects must be < 24 months of age on the date of informed consent

2. Confirmed diagnosis of ARG1-D documented in medical records by at least 1 of the following methods:

   1. elevated plasma arginine levels
   2. a mutation analysis revealing a pathogenic variant
   3. red blood cell (RBC) arginase activity

3. Subjects must weigh > 8 kg due to clinical trial related blood collection volumes required

4. Written informed consent by parent/legal guardian, in accordance with national stipulations, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol

5. At least one value of plasma arginine ≥ 180 μM during screening

6. Documented confirmation from the Investigator and/or dietitian that the subject can:

   1. attempt to maintain a stable, age-appropriate level of protein consumption, including natural protein, and EAA supplementation within approximately ± 15% of dietitian recommended diet
   2. attempt to maintain current use of ammonia scavengers, if prescribed

Exclusion Criteria:

1. Other medical condition(s) or comorbidity(ies) that, in the opinion of the Investigator, would interfere with study compliance or data interpretation
2. Hyperammonaemic episode (plasma ammonia levels > 100 μM) with ≥ 1 symptom related to hyperammonaemia requiring hospitalisation or emergency room management within the 4 weeks before the first dose of study drug
3. Active infection requiring anti-infective therapy within < 2 weeks before first dose of study drug
4. Known active infection with human immunodeficiency virus, hepatitis B, or hepatitis C
5. History of hypersensitivity to polyethylene glycol (PEG) or any of the excipients included in the study drug that, in the judgment of the Investigator, puts the subject at unacceptable risk for AEs
6. Currently participating in another therapeutic clinical study or has received any investigational agent within 30 days (or 5 half-lives, whichever is longer) prior to first dose of study drug
7. Previous liver or haematopoietic stem cell transplant
8. Use of botulinum toxin within 16 weeks prior to first dose