Can an enzyme replacement tame a rare metabolic disorder?

NCT ID NCT03921541

Disease control Sponsor: Immedica Pharma AB Source: ClinicalTrials.gov ↗

First seen Aug 21, 2026 · Last updated Aug 21, 2026

Summary

This phase 3 trial is testing whether pegzilarginase, an enzyme replacement therapy, can lower plasma arginine levels and improve mobility in children and adults with arginase 1 deficiency, a rare genetic condition that causes high arginine levels and neurological problems. Participants receive either pegzilarginase or a placebo, alongside standard care like protein restriction and ammonia scavengers. The main goal is to see if the treatment reduces arginine levels after 24 weeks, with a key secondary goal of improving walking ability.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: Pegzilarginase (also known as Co-ArgI-PEG or AEB1102), an enzyme replacement therapy, given alongside standard care like protein restriction and ammonia scavengers.
What this could lead to: If successful, pegzilarginase could become a targeted treatment to lower harmful arginine levels and improve mobility in people with arginase 1 deficiency.
What could go wrong: This is a small phase 3 trial, and results may not confirm benefit. Risks include potential side effects from the enzyme therapy, and the need for ongoing management remains.

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Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 3

Large-scale testing in a bigger group. Usually the last step before a treatment can be approved.

Participants

32 people

The number who actually took part.

Started

May 2019

Finished

Feb 2023

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

2 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: Subjects are eligible to be included in the study only if all the following criteria apply: 1. The subject and/or parent/guardian provides written informed consent/assent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol 2. A current diagnosis of ARG1 D as documented in medical records, which must include 1 of the following: elevated plasma arginine levels, a mutation analysis that results in a pathogenic variant, or reduced RBC arginase activity. For entry into this study, subjects must also fulfill the following plasma arginine criteria: 1. The average of all measured values of plasma arginine during the screening period prior to the randomization visit (Visit 1, Study Day 1) is ≥ 250 µmol/L 2. If a subject is re-screened, the only values that are considered for eligibility assessment are those in the current screening period 3. Subjects must be ≥ 2 years of age on the date of informed consent/assent 4. The subject must be assessable for clinically meaningful within-subject change (clinical response) on at least one component of one assessment included in the key secondary/other secondary endpoints. To be considered assessable, the subject must be able to complete the assessment, and must have a baseline deficit in at least one component as defined in the protocol 5. Have received documented confirmation from the investigator and/or dietician that the subject can maintain their diet in accordance with dietary information presented in the protocol, ie, can maintain the current level of protein consumption, including natural protein and EAA supplementation 6. Subjects receiving ammonia scavenger therapy, anti-epileptic drugs, and/or medications for spasticity (eg, baclofen) must be on a stable dose of the medication for at least 4 weeks prior to randomization and be willing to remain on a stable dose during the double-blind portion and blinded follow-up portions of the study 7. Female and male subjects may participate. Female subjects of childbearing potential must have a negative serum pregnancy test during the screening period before receiving the first dose of study treatment, and a negative urine pregnancy test on the day of the first dose, prior to the first dose. If the subject (male or female) is engaging in sexual activity that could lead to pregnancy, must be surgically sterile, postmenopausal (no menses for 12 months without an alternative medical cause or a high FSH level in the postmenopausal range in women not using hormonal contraception or hormonal replacement therapy), or must agree to use a highly effective method of birth control during the study and for a minimum of 30 days after the last study drug administration. Highly effective methods of contraception include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation; progesterone-only hormonal contraception associated with inhibition of ovulation; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); or abstinence (refraining from heterosexual intercourse during the entire period of risk associated with study treatment). Exclusion Criteria: 1. Hyperammonemic episode (defined as an event in which a subject has an ammonia level ≥100 µM with one or more symptoms related to hyperammonemia requiring hospitalization or emergency room management) within the 6 weeks before the first dose of study drug is administered 2. Active infection requiring anti-infective therapy within 3 weeks prior to first dose 3. Known active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C 4. Extreme mobility deficit, defined as either the inability to be assessed on the GFAQ or a score of 1 on the GFAQ 5. Other medical conditions or comorbidities that, in the opinion of the investigator would interfere with study compliance or data interpretation (eg, severe intellectual disability precluding required study assessments) 6. Has participated in a previous interventional study with pegzilarginase 7. Has a history of hypersensitivity to polyethylene glycol (PEG) that, in the judgment of the investigator, puts the subject at unacceptable risk for adverse events 8. Subject is being treated with botulinum toxin-containing regimens or plans to initiate such regimens during the double-blind or blinded follow-up portions of the study or received surgical or botulinum-toxin treatment for spasticity-related complications within the 16 weeks prior to the first dose of study treatment in this study 9. Is currently participating in another therapeutic clinical trial or has received any investigational agent within 30 days (or 5 half-lives whichever is longer) prior to the first dose of study treatment in this study 10. Previous liver or hematopoietic transplant procedure.

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Conditions

The condition(s) this trial relates to.

arginase deficiency

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Arginase I deficiency Hyperargininemia

Contacts and locations

Locations

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States
Azienda Ospedaliera Città della Salute e della Scienza di Torino

Torino, Italy
Birmingham Children's Hospital

Birmingham, United Kingdom
Children's Hospital of Orange County

Orange, California, 92868, United States
Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States
Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States
Cohen Children's Medical Center (Northwell Health)

Queens, New York, 11040, United States
Duke University Medical Center

Durham, North Carolina, 27710, United States
Emory University

Atlanta, Georgia, 30322, United States
Fondazione MBBM

Monza, Italy
Great Ormond Street Hospital for Children

London, United Kingdom
Harvey Pediatrics

Rogers, Arkansas, 72758, United States
Hopital des Enfants

Talence, France
Hôpital Necker - Enfants Malades

Paris, France
Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States
LKH Bregenz

Bregenz, Austria
McGill University Health Center

Montreal, Quebec, Canada
Medizinische Universität Innsbruck

Innsbruck, Austria
Ospedale Pediatrico Bambino Gesù

Roma, Italy
Salford Royal

Salford, United Kingdom
Seattle Children's Hospital

Seattle, Washington, 98105, United States
Stanford University School of Medicine

Stanford, California, 94305, United States
UT Southwestern Medical Center

Dallas, Texas, 75390, United States
Universitaetsklinikum Muenster

Münster, North Rhine-Westphalia, Germany
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz

Mainz, Rhineland-Palatinate, Germany
University Hospital of Wales

Cardiff, United Kingdom
University of Florida College of Medicine

Gainesville, Florida, 32610, United States
University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15224, United States
University of Texas Health Science Center Medical School at Houston

Houston, Texas, 77030, United States
University of Utah Hospitals & Clinics

Salt Lake City, Utah, 84108, United States
Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States
Willink Biochemical Genetics Unit

Manchester, United Kingdom

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