Pegzilarginase in Subjects <24 Months Old with Arginase 1 Deficiency

Phase 3

Recruiting

• Conditions: Arginase 1 Deficiency
• Interventions: Drug: Pegzilarginase

• Registration Number: NCT06582524
• Lead Sponsor: Immedica Pharma AB

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2024-08-20
• Study Start: 2024-08-30
• Study First Submitted QC: 2024-08-30
• Study First Posted: 2024-09-03
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-13
• Last Update Posted: 2025-01-14
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 3

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. 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

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

5. 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Weekly subcutaneous (SC) administration of pegzilarginase	Pegzilarginase	All subjects will receive a once weekly (QW) SC dose of pegzilarginase for 12 weeks

Primary Outcome Measures

Name	Time	Method
To evaluate the effect of pegzilarginase	From baseline up to 12 weeks	To evaluate the effect of pegzilarginase on plasma arginine concentrations in subjects \<24 months of age with arginase 1 deficiency (ARG1-D)

Secondary Outcome Measures

Name	Time	Method
To evaluate the safety of pegzilarginase	From baseline up to 12 weeks	Safety assessments will include electrocardiograms (ECGs) to evalute P Wave, QRS Complex, QT Interval
To characterize the pharmacokinetic (PK) profile of pegzilarginase	From baseline up to 12 weeks	PK parameters with evaluation on area under the plasma drug concentration-time curve
To evaluate the pharmacodynamic (PD) response of pegzilarginase	From baseline up to 12 weeks	PD response evaluation including anti-drug antibodies (ADAs), levels of plasma arginine and ornithine
To describe changes in physical function	From baseline up to 12 weeks	Changes in physical function after 12 weeks of pegzilarginase treatment as measured by Gross Motor Function Measure (GMFM)-66 Parts A through E, as age appropriate and feasible

Trial Locations

Locations (3)

Univ. Klinik für Kinder- und Jugendheilkunde Medizinische Universität; 🇦🇹 Graz, Austria

Bradford Royal Infirmary Duckworth Lane; 🇬🇧 Bradford, United Kingdom

Unidade de Doenças Metabólicas Pediatria, Hospital Santa Maria; 🇵🇹 Lisboa, Portugal