Safety, Tolerability and PK/PD Evaluation of Intravenous Administration of MRT5201 in Patients With OTC Deficiency

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03767270
• Date of registration: 28/11/2018
• Prospective Registration: Yes
• Primary sponsor: Translate Bio, Inc.
• Public title: Safety, Tolerability and PK/PD Evaluation of Intravenous Administration of MRT5201 in Patients With OTC Deficiency STEP-OTC
• Scientific title: A Phase 1/2 Single Ascending Dose Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenously Administered MRT5201 in Subjects With Ornithine Transcarbamylase Deficiency
• Date of first enrolment: December 2019
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: https://clinicaltrials.gov/show/NCT03767270
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1/Phase 2

Key inclusion & exclusion criteria

Inclusion Criteria:

- Have a documented diagnosis of OTCD.

- Documented history of =1 symptomatic hyperammonemia event with ammonia =100 µmol/L

- Subject's OTCD is stable as evidenced by meeting the following criteria:

- Ammonia level <175 µmol/L during the Screening Period and at Baseline (Day -1)

- No clinical symptoms of hyperammonemia during the Screening Period and at
Baseline (Day -1)

- If using nitrogen scavenger therapy, must be on a stable regimen for =28 days prior to
signing informed consent

- Subject has maintained a stable protein restricted diet (which may or may not include
medical foods) and/or amino acid supplementation with no changes in calorie or protein
goals and no changes in medical food and/or amino acid supplementation for = 28 days
prior to signing informed consent.

Exclusion Criteria:

- Any laboratory abnormality that may put the subject at increased risk by participating
in this study.

- Have any significant concurrent or past medical condition that would represent an
unacceptable risk to the subject or might jeopardize the collection of high-quality
data from the study. These include but are not limited to:

- History of liver transplant, including hepatocyte therapy/transplant

- History of liver disease

- Positive viral serology test results for HIV type 1 or 2 antibodies, hepatitis B
surface antigen (HBsAg) or hepatitis C virus (HCV) antibody

- Type I or Type II diabetes that is poorly controlled, in the opinion of the
Investigator

- Poorly controlled hypertension (defined as systolic blood pressure [BP] > 150 mm
Hg or diastolic BP > 90 mm Hg)

- Use of anticoagulants or platelet inhibitors, including but not limited to
heparin and non-steroidal anti-inflammatory drugs (NSAIDS). Acetaminophen is
permitted

- Participation in previous clinical studies evaluating investigational OTCD therapies
directed at expressing functional OTC protein (eg, OTC gene therapy studies, other
mRNA replacement therapy) that has led to the presence of anti-OTC antibodies.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Ornithine Transcarbamylase Deficiency

Intervention(s)

Other: Placebo

Biological: MRT5201

Primary Outcome(s)

The incidence of treatment-emergent adverse events by treatment group [Time Frame: Week 24]

Secondary Outcome(s)

Effect of single dose of MRT5201 on metabolic markers of OTCD [Time Frame: 6 months after single dose]

Pharmacokinetics parameters of MRT5201 [Time Frame: 1 month after single dose]

Effect of a single dose of MRT5201 on ureagenesis [Time Frame: Up to 1 month after single dose]

Secondary ID(s)

MRT5201-101

2018-004095-35

Source(s) of Monetary Support

Please refer to primary and secondary sponsors