Ongoing Clinical Trials for Ornithine Transcarbamoylase Deficiency
There are currently 3 clinical trials investigating gene therapy treatments for Ornithine Transcarbamoylase Deficiency, targeting both neonatal-onset cases in infants and late-onset forms in adolescents and adults. These trials are taking place across several European countries including Spain, France, Italy, Netherlands, Portugal, and Germany.
Clinical trial locations
- France
- Germany
- Italy
- Netherlands
- Portugal
- Spain
- Long-Term Study on the Safety of Avalotcagene Ontaparvovec for Adults with Late-Onset Ornithine Transcarbamylase Deficiency
- Study of Avalotcagene Ontaparvovec for Patients Aged 12 and Older with Late-onset Ornithine Transcarbamylase Deficiency
- Study on ECUR-506A and ECUR-506D for Male Infants Under 9 Months with Neonatal Onset Ornithine Transcarbamylase Deficiency
Study on ECUR-506A and ECUR-506D for Male Infants Under 9 Months with Neonatal Onset Ornithine Transcarbamylase Deficiency
This trial is testing a gene therapy called ECUR-506 for very young male infants with severe neonatal-onset disease. The treatment uses a specially modified virus to deliver a healthy version of the OTC gene directly into the body through a single intravenous infusion.
Inclusion criteria: To participate, infants must be male, at least 37 weeks gestational age, and between 24 hours and 7 months old at screening. They must weigh between 3.5 kg and 10.0 kg and have genetically confirmed diagnosis. The condition must be severe, shown by either a past or current hyperammonemic crisis in the first week of life, or a family history with genetic confirmation of a harmful mutation. Participants must be receiving current treatment including dietary protein restriction and scavenger therapy, and have received all age-appropriate vaccinations.
Exclusion criteria: The trial excludes female patients and those outside the specified age range. Infants who are part of vulnerable populations may also be excluded.
Focus and goals: The primary goal is to evaluate the safety and tolerability of ECUR-506. The study lasts 24 weeks with regular monitoring including physical exams and blood tests to check liver function and other safety measures. After completing the initial phase, participants move into a long-term follow-up lasting up to 14.5 years to assess ongoing safety and effectiveness, including tracking the frequency of hyperammonemic crises.
Investigational drug: ECUR-506 is delivered as a single intravenous dose using an adeno-associated virus serotype rh79 to carry the healthy human OTC gene to liver cells.
Long-Term Study on the Safety of Avalotcagene Ontaparvovec for Adults with Late-Onset Ornithine Transcarbamylase Deficiency
This trial focuses on the long-term safety of avalotcagene ontaparvovec (also known as DTX301), a gene therapy for adults with late-onset disease. It is a follow-up study for participants who completed an earlier trial.
Inclusion criteria: Participants must have completed the Week 52 visit in the previous Study 301OTC01. They need to be willing and able to provide written informed consent and commit to following the study schedule for visits, procedures, and requirements over an extended monitoring period.
Exclusion criteria: The trial excludes individuals with severe allergies to study medication components, those who received another investigational drug within 30 days, people with uncontrolled medical conditions, pregnant or breastfeeding women, those with recent drug or alcohol abuse, individuals with liver disease other than OTC deficiency, those who had major surgery within 3 months, patients with cancer history (except certain skin cancers), people infected with HIV, Hepatitis B, or Hepatitis C, and those unable to comply with study procedures.
Focus and goals: The study monitors participants for up to 416 weeks after receiving a single dose of the gene therapy. Researchers track side effects, measure changes in blood ammonia levels, and assess the body’s ability to produce urea. This long-term monitoring helps determine whether the treatment can safely manage the condition over time.
Investigational drug: DTX301 uses adeno-associated virus serotype 8 (AAV8) to deliver a healthy copy of the OTC gene to liver cells through a single intravenous infusion.
Study of Avalotcagene Ontaparvovec for Patients Aged 12 and Older with Late-onset Ornithine Transcarbamylase Deficiency
This is a randomized, double-blind trial testing avalotcagene ontaparvovec in adolescents and adults aged 12 and older with late-onset disease. Participants receive either the active gene therapy or a placebo.
Inclusion criteria: Participants must be 12 years or older and agree to use highly effective contraception if they are females of childbearing potential or fertile males. They must have a confirmed diagnosis of late-onset disease through previous liver biopsy, blood tests, or genetic testing. A history of at least one episode of symptomatic hyperammonemia (confirmed ammonia level of 100 micromoles per liter or more) is required. Participants must currently be on ammonia scavenger therapy or protein-restricted diet without symptoms and no emergency treatment for high ammonia in the past 4 weeks. Their plasma 24-hour ammonia level must be 4800 micromoles per hour per liter or less at screening. If taking scavenger therapy, the dose must be stable for at least 4 weeks. If on a protein-restricted diet, daily protein intake should not vary by more than 20% for at least 4 weeks. Participants must be willing to attend hospital stays, undergo frequent testing, and complete questionnaires.
Exclusion criteria: Individuals without a diagnosis of late-onset disease, those outside the eligible age ranges, and people from certain vulnerable populations cannot participate.
Focus and goals: The study evaluates how well the gene therapy improves OTC function and maintains safe ammonia levels in the blood. The treatment involves a one-time intravenous infusion, followed by oral prednisolone to manage potential immune responses. Participants attend regular follow-up visits for up to 128 weeks, including blood and urine tests, physical examinations, and questionnaires. At the end of the study, results are compared between the gene therapy and placebo groups to determine effectiveness.
Investigational drug: DTX301 uses adeno-associated virus serotype 8 (AAV8) to deliver a functional copy of the human OTC gene into liver cells, aiming to restore normal enzyme activity and maintain safe plasma ammonia levels.
Summary
All three clinical trials focus on gene therapy approaches using adeno-associated viruses to deliver healthy copies of the OTC gene. Two different investigational products are being tested: ECUR-506 for neonatal-onset cases in male infants, and avalotcagene ontaparvovec (DTX301) for late-onset cases in older patients.
Spain stands out as the only country hosting all three trials, making it a significant hub for this research. France also hosts two trials, while Italy, Netherlands, Portugal, and Germany each participate in one trial focused on late-onset disease in patients aged 12 and older.
The trials address different patient populations based on disease severity and age of onset. The neonatal trial targets the most severe early-onset cases in very young infants, while the late-onset trials serve adolescents and adults with milder forms. The long-term follow-up study demonstrates the commitment to understanding safety over extended periods, with monitoring lasting up to 14.5 years in one trial.
