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

NCT03767270 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: MRT5201-1012018-004095-35
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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

Keywords

OTC; Urea Cycle Disorder; UCD

Outcome Measures

Primary Outcomes (1)

• The incidence of treatment-emergent adverse events by treatment group

  The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) for each dosing cohort by treatment group, assessed by severity and relationship to study product.

  Week 24

Secondary Outcomes (3)

• Pharmacokinetics parameters of MRT5201

  1 month after single dose

• Effect of a single dose of MRT5201 on ureagenesis

  Up to 1 month after single dose

• Effect of single dose of MRT5201 on metabolic markers of OTCD

  6 months after single dose

Study Arms (2)

MRT5201

EXPERIMENTAL

Single Ascending Low, Mid, and High doses of MRT5201

Biological: MRT5201

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

MRT5201 BIOLOGICAL

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

MRT5201

Placebo OTHER

5% dextrose in water

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Translate Bio, Inc.: lead

MeSH Terms

Conditions

Ornithine Carbamoyltransferase Deficiency Disease; Urea Cycle Disorders, Inborn

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2018
• First Posted: December 6, 2018
• Study Start: December 1, 2019
• Primary Completion: July 1, 2022
• Study Completion: July 1, 2022
• Last Updated: September 17, 2019

Record last verified: 2019-09