Clinical Study of DTX301 AAV-Mediated Gene Transfer for Ornithine Transcarbamylase (OTC) Deficiency

NCT05345171 | Active Not Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: DTX301-CL3012020-003384-252024-514337-38-00
• Study Type: interventional
• Target: 32
• Locations: 10 countries
• Sites: 16

Brief Summary

The primary objective is to evaluate the efficacy of DTX301 on the improvement of ornithine transcarbamylase (OTC) function by maintaining safe plasma ammonia levels.

Conditions

OTC Deficiency

Outcome Measures

Primary Outcomes (2)

• Plasma Ammonia as Measured by 24-Hour Ammonia (AUC0-24)

  Week 36

• Complete Responder Rate at the Final Study Visit After DTX301 Exposure

  Up to 64 Weeks Post DTX301 Infusion

Secondary Outcomes (11)

• Percentage of Complete Responders or Responders After DTX301 Exposure

  Up to 64 Weeks Post DTX301 Infusion

• Annualized Event Rate of Hyperammonemic Crises (HACs) Pre-DTX301 Exposure vs Post-DTX301 Exposure

  Pre-enrollment, Baseline, Up to 64 Weeks Post DTX301 Infusion

• Annualized Event Rate of Interim Clinical Events (ICEs) Pre-DTX301 Exposure vs Post-DTX301 Exposure

  Pre-enrollment, Baseline, Up to 64 Weeks Post DTX301 Infusion

• Change from Baseline in Plasma Ammonia (AUC0-24)

  Baseline, Up to Week 36

• Change in Plasma Ammonia (AUC0-24) After DTX301 Exposure

  Up to 64 Weeks Post DTX301 Infusion

Study Arms (2)

DTX301

EXPERIMENTAL

Participants receive single peripheral intravenous (IV) infusion of DTX301 in solution. Between Week 36 and Week 64, participants may receive single peripheral IV infusion of placebo.

Genetic: DTX301; Other: Placebo; Drug: Oral Corticosteroids; Drug: Placebo for oral corticosteroids; Drug: Sodium Acetate

Placebo, Then DTX301

EXPERIMENTAL

Participants receive single peripheral IV infusion of placebo. Between Week 36 and Week 64, participants receive single peripheral IV infusion of DTX301 in solution.

Genetic: DTX301; Other: Placebo; Drug: Oral Corticosteroids; Drug: Placebo for oral corticosteroids; Drug: Sodium Acetate

Interventions

DTX301 GENETIC

non-replicating, self-complementary recombinant adeno-associated virus serotype 8 (AAV8) vector

Also known as: avalotcagene ontaparvovec

DTX301; Placebo, Then DTX301

Placebo OTHER

normal saline infusion

DTX301; Placebo, Then DTX301

Oral Corticosteroids DRUG

Participants who receive DTX301 solution will receive oral corticosteroids.

Also known as: Prednisolone

DTX301; Placebo, Then DTX301

Placebo for oral corticosteroids DRUG

Participants who receive Placebo will receive placebo corticosteroids to maintain the study blind

DTX301; Placebo, Then DTX301

Sodium Acetate DRUG

A tracer for the Ureagenesis Rate Test (URT)

DTX301; Placebo, Then DTX301

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed clinical diagnosis of late-onset OTC deficiency with historical documentation by enzymatic (ie, liver biopsy), biochemical (ie, hyperammonemia in the presence of elevated plasma glutamine, low citrulline, and elevated spot urine orotic acid), or molecular testing (ie, OTC analysis)
• Free from symptomatic hyperammonemia and has not required emergent active intervention for hyperammonemia within 4 weeks before screening/baseline
• If on ongoing daily ammonia scavenger therapy, must be at stable daily dose(s) for ≥ 4 weeks prior to screening
• If on a protein-restricted diet, must be on a stable total daily protein intake that does not vary more than 20% for ≥ 4 weeks prior to screening
• From the time written informed consent through Visit 28, females of childbearing potential and fertile males must consent to use highly effective contraception. If female, agree not to become pregnant. If male, agree not father a child or donate sperm

You may not qualify if:

• Significant hepatic inflammation or cirrhosis
• Estimated glomerular filtration rate \< 60 mL/min/1.73 m2 at screening by the 2021 CKD-EPI creatinine-based formula (Inker et al., 2021) for patients ≥ 18 years of age or the Schwartz bedside formula (Schwartz and Work, 2009) for patients \< 18 years of age
• Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, documented by current use of antiviral therapy for HBV or HCV or by hepatitis B surface antigen (HBsAg) or HCV RNA positivity
• Active infection (viral or bacterial)
• Detectable pre-existing antibodies to the AAV8 capsid
• Presence or history of any condition that, in the view of the Investigator, would interfere with participation, pose undue risk, or would confound interpretation of results
• Participation (current or previous) in another gene transfer study

Sponsors & Collaborators

• Ultragenyx Pharmaceutical Inc: lead

Study Sites (16)

University of California

Los Angeles, California, 90095, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

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

Chicago, Illinois, 60611, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Hospital Italiano de Buenos Aires

Buenos Aires, C1199, Argentina

Location

Clinica Universitaria Reina Fabiola

Córdoba, X5004, Argentina

Location

Hospital de Clinicas de Porto Alegre

Porto Alegre, 90035-903, Brazil

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Hopital Femme Mere Enfant

Bron, 69500, France

Location

Necker-Enfants Maladas Hospital

Paris, 75015, France

Location

Universitatsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Kumamoto University Hospital

Kumamoto, 860-8556, Japan

Location

Fujita Health University Hospital

Toyoake, 470-1192, Japan

Location

Erasmus Universitair Medisch Centrum Rotterrdam

Rotterdam, 3015, Netherlands

Location

Centro Hospitalar Universitario de Sao Joao

Porto, 4200-319, Portugal

Location

Fundacio Hospital Universitari Vall D'Hebron-Institute de Recerca

Barcelona, 08035, Spain

Location

Related Publications (1)

• Baruteau J, Brunetti-Pierri N, Gissen P. Liver-directed gene therapy for inherited metabolic diseases. J Inherit Metab Dis. 2024 Jan;47(1):9-21. doi: 10.1002/jimd.12709. Epub 2024 Jan 3.

  PMID: 38171926 DERIVED

Related Links

• Ultragenyx Patient Advocacy/OTC Disease Information
• Ultragenyx Transparency Commitment

MeSH Terms

Conditions

Ornithine Carbamoyltransferase Deficiency Disease

Interventions

Adrenal Cortex Hormones; Prednisolone; Sodium Acetate

Condition Hierarchy (Ancestors)

Urea Cycle Disorders, Inborn; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Acetic Acid; Acetates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Medical Director

  Ultragenyx Pharmaceutical Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2022
• First Posted: April 25, 2022
• Study Start: October 18, 2022
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): March 1, 2031
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

JP (2); AR (2); PT (1); ES (1); BR (1); US (4); CA (1); DE (1); NL (1); FR (2)