Study of LNP.UCD.ABE in Patients With Urea Cycle Disorders

NCT07667387 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: UCD-101
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-site Phase 1/2 open-label umbrella clinical trial designed to evaluate the safety, tolerability, and efficacy of a single intravenous dose of LNP.UCD.ABE in 5 pediatric subjects with severe infantile-onset UCDs. This is a master clinical protocol in which subjects with a variant in a urea cycle disorder (UCD) gene (CPS1, OTC, ASS1, ASL, ARG, NAGS, or SLC25A15) that is demonstrated to be amenable to corrective editing by an adenine base editor (ABE) would be eligible for enrollment.

Conditions

Urea Cycle Disorders; Carbamoyl-Phosphate Synthase I Deficiency

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of a single intravenous dose of LNP.UCD.ABE

  Incidence of treatment-emergent adverse events as assessed by CTCAE version 6.0 criteria at 52 weeks after LNP.UCD.ABE administration.

  52 weeks

Secondary Outcomes (1)

• Clinical efficacy of a single intravenous dose of LNP.UCD.ABE

  16 weeks

Study Arms (1)

Experimental

EXPERIMENTAL

Biological: LNP.UCD.ABE

Interventions

LNP.UCD.ABE BIOLOGICAL

Each subject will have a personalized variant-specific LNP.UCD.ABE developed and evaluated in real time. Each member of the LNP.UCD.ABE drug product (DP) family is a lipid nanoparticle (LNP)-based editing therapeutic comprising lipid excipients, a messenger RNA (mRNA) drug substance (DS) encoding an adenine base editor (ABE), and a single guide RNA (gRNA) DS.

Experimental

Eligibility Criteria

• Age: 24 Hours - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Diagnosis of a severe urea cycle disorder, in the judgement of the investigators.
• 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.
• Current or historical biochemical testing consistent with a urea cycle disorder
• At least one of the subject's alleles must be amenable to base editing by LNP.UCD.ABE, as assessed in vitro
• 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.
• 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
• Weight \>3.5 kg at the time of screening
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Rebecca Ahrens-Nicklas: lead

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Urea Cycle Disorders, Inborn

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Rebecca Ahrens-Nicklas, M.D., Ph.D.

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarah McCague

CONTACT

267-426-1464; cigt@chop.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Chief for Research, Division of Human Genetics; Director, Gene Therapy for Inherited Metabolic Disorders Frontier Program

Study Record Dates

• First Submitted: June 18, 2026
• First Posted: June 25, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: July 31, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)