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

NCT ID: NCT03767270

Last Updated: 2019-09-17

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-31
• Study Completion Date: 2022-07-31

Brief Summary

This Phase 1/2, first-in-human study will evaluate the safety and tolerability of single escalating doses of MRT5201 administered intravenously to subjects with OTC Deficiency (OTCD). This study will also evaluate the effect of a single dose of MRT5201 on metabolic markers of OTCD and ureagenesis; and determine an acceptable dosing interval of MRT5201.

Conditions

Ornithine Transcarbamylase Deficiency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

MRT5201

Single Ascending Low, Mid, and High doses of MRT5201

Group Type: EXPERIMENTAL

MRT5201

Intervention Type: BIOLOGICAL

Codon-optimized human ornithine transcarbamylase messenger ribonucleic acid with lipid-based nanoparticles

Placebo

Placebo comparator using 5% dextrose in water at the same administration rate as study drug.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

5% dextrose in water

Interventions

MRT5201

Codon-optimized human ornithine transcarbamylase messenger ribonucleic acid with lipid-based nanoparticles

Intervention Type: BIOLOGICAL

Placebo

5% dextrose in water

Intervention Type: OTHER

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Translate Bio, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

2018-004095-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MRT5201-101

Identifier Type: -

Identifier Source: org_study_id