LNP.UCD.ABE for severe urea cycle disorders in young children

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a phase 1/2, open-label, single-site study evaluating a gene-editing therapy delivered by lipid nanoparticles in pediatric patients with severe UCDs. Eligible participants have a confirmed enzyme or transporter deficiency and a disease-causing mutation that is amenable to base editing by LNP.UCD.ABE. The study uses a master protocol to enroll subjects whose specific mutations could be corrected by the adenine base editor and administers a one-time intravenous dose. Safety, tolerability, and preliminary efficacy data will be collected, focusing on ammonia control and clinical outcomes relevant to UCDs. The trial is conducted at the Children’s Hospital of Philadelphia, with collaboration from NINDS and ARPA-H.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. Diagnosis of a severe urea cycle disorder, in the judgement of the investigators.
2. Molecular testing demonstrating homozygosity or compound heterozygosity for a disease-causing mutation in CPS1 that is targeted by a variant-specific version of the LNP.UCD.ABE drug product.
3. Current or historical biochemical testing consistent with a urea cycle disorder
4. At least one of the subject's alleles must be amenable to base editing by LNP.UCD.ABE, as assessed in vitro
5. A history of an ammonia level of ≥400 μmol/L prior to age 12 months, unless a diagnosis was made prenatally and care was initiated immediately after birth

   * If the patient is taking a nitrogen scavenger medication, their ammonia level may currently be in the normal range
   * If the patient is diagnosed prenatally, then personal history, family history, or analysis of mutations should indicate a high likelihood of a severe UCD.
6. Subjects more than 8 weeks from the initial diagnosis of a UCD must have demonstrated:

   * a persistent need for dietary protein restriction and chronic administration of a nitrogen scavenger medication, AND / OR
   * a recurrent hyperammonemic event AND / OR
   * a history of a hyperammonemia-induced seizure
7. Weight \>3.5 kg at the time of screening
8. Legal guardian(s) capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria:

1. Abnormal liver function, electrolyte, coagulation, or blood count laboratory values thought not attributable to the underlying urea cycle disorder;
2. Demonstrated need for urgent liver transplantation due to liver failure, in the opinion of the investigators;
3. Participation in a prior gene therapy trial or participation in a trial of an investigational product in the last 12 months;
4. History of liver transplantation;
5. Any other diseases or conditions that the investigators would consider to pose unacceptable risk to the subject;
6. Inability or unwillingness to comply with the visit schedule and study assessments;
7. Any genetic variation in the causative urea cycle disorder gene that, in the opinion of the investigators, may decrease the potential efficacy of the drug product;
8. History of severe hypersensitivity or anaphylaxis to polyethylene glycol (PEG)-containing products, such as PEG-containing vaccines or laxatives

Where it's running

• Children's Hospital of Philadelphia
  Philadelphia, Pennsylvania, United States Recruiting

Study contacts

• Principal investigator: Rebecca Ahrens-Nicklas, M.D., Ph.D. — Children's Hospital of Philadelphia
• Study coordinator: Sarah McCague
• Email: cigt@chop.edu
• Phone: 267-426-1464

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• KRRO-121 for hyperammonemia in urea cycle disorders: a first-in-human study

  This study tests KRRO-121, a treatment designed to help clear ammonia, in adults with urea cycle disorders and in healthy volunteers to see if it is safe and how it acts in the body.

  Recruiting Phase 1/2 Korro Bio, Inc. · Melbourne, Victoria · NCT07773246

• Home Ammonia Monitoring for People with Metabolic Ammonia Disorders

  This study tests whether people with certain ammonia metabolism disorders can successfully measure their ammonia levels at home every day.

  Recruiting Sequitur Health Corp. · Portland, Oregon · NCT06953505

• Glycerol phenylbutyrate for Chinese children and teens with urea cycle disorders

  This project will try glycerol phenylbutyrate in children and teens in China who have urea cycle disorders to see if it lowers ammonia and reduces hyperammonemic crises over five years.

  Recruiting at 5 sites Tongji Hospital · Beijing, Beijing Municipality and 4 other locations · NCT06904027

• Analyzing urea production in healthy individuals and patients with urea cycle disorders

  This study is testing how well the body makes urea in healthy people and those with urea cycle disorders to better understand these conditions and improve treatments.

  Recruiting University Children's Hospital, Zurich · Zurich, Canton of Zurich · NCT05671666

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.