Clinical trial NCT06582524: Pegzilarginase in Subjects <24 Months Old with Arginase 1 Deficiency
Official title: A Phase 3 Open-Label Study of Safety, Pharmacokinetics, and Activity of Weekly Subcutaneous Pegzilarginase in Subjects <24 Months Old with Arginase 1 Deficiency
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Arginase 1 Deficiency
Lead sponsor: Immedica Pharma AB
Sponsor class: INDUSTRY
First posted: 2024-09-03
Enrollment: 3
Sex: ALL
Minimum age (years): 1
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: To evaluate the effect of pegzilarginase
timeFrame: From baseline up to 12 weeks
Secondary outcomes:
measure: To evaluate the safety of pegzilarginase
timeFrame: From baseline up to 12 weeks
measure: To characterize the pharmacokinetic (PK) profile of pegzilarginase
timeFrame: From baseline up to 12 weeks
measure: To characterize the pharmacokinetic (PK) profile of pegzilarginase
timeFrame: From baseline up to 12 weeks
measure: To characterize the pharmacokinetic (PK) profile of pegzilarginase
timeFrame: From baseline up to 12 weeks
measure: To characterize the pharmacokinetic (PK) profile of pegzilarginase
timeFrame: From baseline up to 12 weeks
measure: To evaluate the pharmacodynamic (PD) response of pegzilarginase
timeFrame: From baseline up to 12 weeks
measure: To describe changes in physical function
timeFrame: From baseline up to 12 weeks
measure: To evaluate the safety of pegzilarginase
timeFrame: From baseline up to 12 weeks
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Univ. Klinik für Kinder- und Jugendheilkunde Medizinische Universität
city: Lisboa
country: Portugal
facility: Unidade de Doenças Metabólicas Pediatria, Hospital Santa Maria
city: Bradford
country: United Kingdom
facility: Bradford Royal Infirmary Duckworth Lane
Study officials:
affiliation: Immedica Pharma AB
name: Mattias Rudebeck, PhD MSc BMedSc
role: STUDY_DIRECTOR
References: