Study to investigate the safety and activity of Pegzilarginase in children under two years of age with Arginase 1 Deficiency

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Immedica Pharma AB

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

18 Dec 2024 → 18 Jun 2025

Decision date (initial)

2024-12-12

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Immedica Pharma AB

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic, Efficacy, Safety

To evaluate the effect of pegzilarginase on plasma arginine concentrations in subjects < 24 months of age with arginase 1 deficiency (ARG1-D)

Secondary objectives 4

1. To evaluate the safety of pegzilarginase
2. To characterize the pharmacokinetic (PK) profile of pegzilarginase
3. To evaluate the pharmacodynamic (PD) response of pegzilarginase
4. To describe changes in physical function

Conditions and MedDRA coding

Arginase 1 deficiency (ARG1-D)

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001925-PIP02-19

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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: a. elevated plasma arginine levels; b. a mutation analysis revealing a pathogenic variant; c. 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: a. attempt to maintain a stable, age-appropriate level of protein consumption, including natural protein, and EAA supplementation within approximately ± 15 % of dietitian recommended diet; b. attempt to maintain current use of ammonia scavengers, if prescribed
6. Subjects must weigh > 8 kg due to clinical trial related blood collection volumes required

Exclusion criteria 8

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in plasma arginine after 12 weeks of pegzilarginase treatment

Secondary endpoints 4

1. Safety assessments will include: a. adverse events (AEs), including hypersensitivity reactions (HSRs), injection site reactions (ISRs), and hyperammonaemic events; b. laboratory tests; c. vital signs, physical examinations, growth assessments, and electrocardiograms (ECGs)
2. PK parameters evaluation including half-life (T½), time to maximum observed concentration (Tmax), maximum observed concentration (Cmax), area under the plasma drug concentration-time curve from time 0 to time t (AUC0-t), area under the plasma drug concentration-time curve from time 0 extrapolated to infinite time (AUC0-∞), extravascular clearance (CL/F), and apparent volume of distribution at steady state after non-intravenous administration (Vss/F)
3. PD response evaluation including anti-drug antibodies (ADAs), levels of plasma arginine and ornithine
4. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Immedica Pharma AB

Sponsor organisation

Immedica Pharma AB

Address

Solnavagen 3 H

City

Stockholm

Postcode

113 63

Country

Sweden

Scientific contact point

Organisation

Immedica Pharma AB

Contact name

Clinical trial information

Public contact point

Organisation

Immedica Pharma AB

Contact name

Clinical trial information

Third parties 4

Locations

2 EU/EEA countries · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications