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.

Study Overview

• Status: Completed
• Conditions: Arginase 1 Deficiency
• Intervention / Treatment: Drug: Pegzilarginase

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 Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, A-8036
    • Univ. Klinik für Kinder- und Jugendheilkunde Medizinische Universität
• Portugal
  • Lisbon, Portugal
    • Unidade de Doenças Metabólicas Pediatria, Hospital Santa Maria
• United Kingdom
  • Bradford, United Kingdom, BD9 6RJ
    • Bradford Royal Infirmary Duckworth Lane

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Weekly subcutaneous (SC) administration of pegzilarginase; All subjects will receive a once weekly (QW) SC dose of pegzilarginase for 12 weeks	Drug: Pegzilarginase; SC administration of pegzilarginase over 12 weeks in subjects with ARG1-D who are < 24 months of age; Other Names: Loargys

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Plasma Arginine Concentrations in Subjects <24 Months of Age With Arginase 1 Deficiency (ARG1-D).	To evaluate the effect of pegzilarginase on plasma arginine concentrations in subjects <24 months of age with arginase 1 deficiency (ARG1-D).	From baseline up to 12 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) Profile of Pegzilarginase: Half-life (T½).	PK parameters with evaluation of half-life (T½).	From baseline up to 12 weeks. Within 1 hour pre-dose a sample was taken on visits 1, 2, 4, 6, 8, 10, and 13. A post-dose sample was taken 12 - 48 hours after dosing on visits 2, 4, and 10.
Pharmacokinetic (PK) Profile of Pegzilarginase: Maximum Observed Concentration (Tmax).	PK parameters with evaluation on time to maximum observed concentration (Tmax).	From baseline up to 12 weeks. Within 1 hour pre-dose a sample was taken on visits 1, 2, 4, 6, 8, 10, and 13. A post-dose sample was taken 12 - 48 hours after dosing on visits 2, 4, and 10.
Pharmacokinetic (PK) Profile of Pegzilarginase: Maximum Observed Concentration (Cmax).	PK parameters with evaluation of maximum observed concentration (Cmax).	From baseline up to 12 weeks. Within 1 hour pre-dose a sample was taken on visits 1, 2, 4, 6, 8, 10, and 13. A post-dose sample was taken 12 - 48 hours after dosing on visits 2, 4, and 10.
Pharmacokinetic (PK) Profile of Pegzilarginase: Area Under the Plasma Drug Concentration-time Curve.	PK parameters with evaluation on area under the plasma drug concentration-time curve.	From baseline up to 12 weeks. Within 1 hour pre-dose a sample was taken on visits 1, 2, 4, 6, 8, 10, and 13. A post-dose sample was taken 12 - 48 hours after dosing on visits 2, 4, and 10.
Pharmacodynamic (PD) Response of Pegzilarginase: Anti-drug Antibodies (ADAs).	PD response evaluation, anti-drug antibodies (ADAs).	From baseline up to 12 weeks. Samples taken on visit 1, 2, 4, 8 and 13 (pre-dose if on a dosing day).
Pharmacodynamic (PD) Response of Pegzilarginase: Levels of Plasma Arginine.	PD response evaluation, levels of plasma arginine. Arginine within guidance level.	From baseline up to 12 weeks. Samples taken on visit 1, 2, 4, 8 and 13 (pre-dose if on a dosing day).
Changes From Baseline in Physical Function: GMFM-66.	Changes in physical function after 12 weeks of pegzilarginase treatment as measured by Gross Motor Function Measure (GMFM)-66 Parts A through E (total score). The Gross Motor Function Measure (GMFM) utilize a 4-point scoring system for each item across dimensions A-E. The minimum score is 0; the maximum score is 198, with a higher score representing better gross motor function.	From baseline up to 12 weeks.

Collaborators and Investigators

• Sponsor: Immedica Pharma AB
• Investigators: Study Director: Mattias Rudebeck, PhD MSc BMedSc, Immedica Pharma AB

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2024
• Primary Completion (Actual): June 17, 2025
• Study Completion (Actual): June 17, 2025

Study Registration Dates

• First Submitted: August 20, 2024
• First Submitted That Met QC Criteria: August 30, 2024
• First Posted (Actual): September 3, 2024

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Amino Acid Metabolism, Inborn Errors; Urea Cycle Disorders, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Hyperargininemia
• Other Study ID Numbers: CAEB1102-301A (Europe)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No