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

Brief Title

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

Official 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

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.

Study Phase

Phase 1/Phase 2

Study Type


Primary Outcome

The incidence of treatment-emergent adverse events by treatment group

Secondary Outcome

 Pharmacokinetics parameters of MRT5201


Ornithine Transcarbamylase Deficiency



Study Arms / Comparison Groups

Description:  Single Ascending Low, Mid, and High doses of MRT5201


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

December 2019

Completion Date

July 2022

Primary Completion Date

July 2022

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

               -  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

          -  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.




18 Years - N/A

Accepts Healthy Volunteers



, , 

Administrative Informations



Organization ID


Secondary IDs


Responsible Party


Study Sponsor

Translate Bio, Inc.

Study Sponsor

, , 

Verification Date

September 2019