A Phase I/II Open-label Safety and Efficacy Study of LNP.UCD.ABE in Patients With Urea Cycle Disorders.
Trial statusNot yet recruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age24-5
SponsorRebecca Ahrens-Nicklas
About this trial
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.
Eligibility criteria
Qualifiers
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 a urea cycle disorder gene (CPS1, OTC, ASS1, ASL, ARG, NAGS, or SLC25A15) that is targeted by a variant-specific version LNP.UCD.ABE;
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;
Disqualifiers
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;
Trial design
Treatments tested in this trial
- LNP.UCD.ABE
Treatment groups
7 Participants
are divided into 1 treatment groupSponsors and collaborators
Rebecca Ahrens-Nicklas
Lead sponsor
Children's Hospital of Philadelphia
Sponsor institution
Source ClinicalTrials.gov