COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03767270
Recruitment Status : Withdrawn (Program was discontinued.)
First Posted : December 6, 2018
Last Update Posted : September 17, 2019
Information provided by (Responsible Party):
Translate Bio, Inc.

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.

Condition or disease Intervention/treatment Phase
Ornithine Transcarbamylase Deficiency Biological: MRT5201 Other: Placebo Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Estimated Study Start Date : December 2019
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : July 2022

Arm Intervention/treatment
Experimental: MRT5201
Single Ascending Low, Mid, and High doses of MRT5201
Biological: MRT5201
Codon-optimized human ornithine transcarbamylase messenger ribonucleic acid with lipid-based nanoparticles

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

Primary Outcome Measures :
  1. The incidence of treatment-emergent adverse events by treatment group [ Time Frame: Week 24 ]
    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.

Secondary Outcome Measures :
  1. Pharmacokinetics parameters of MRT5201 [ Time Frame: 1 month after single dose ]
    Pharmacokinetics of MRT5201 as measured by levels of mRNA

  2. Effect of a single dose of MRT5201 on ureagenesis [ Time Frame: Up to 1 month after single dose ]
    Change from Baseline in 4-hour ureagenesis AUC at weeks 2, 3, 4, and 5 after a single dose of MRT5201

  3. Effect of single dose of MRT5201 on metabolic markers of OTCD [ Time Frame: 6 months after single dose ]
    Change from Baseline in 8-hour ammonia AUC

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.
Layout table for additonal information
Responsible Party: Translate Bio, Inc. Identifier: NCT03767270    
Other Study ID Numbers: MRT5201-101
2018-004095-35 ( EudraCT Number )
First Posted: December 6, 2018    Key Record Dates
Last Update Posted: September 17, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Translate Bio, Inc.:
Urea Cycle Disorder
Additional relevant MeSH terms:
Layout table for MeSH terms
Ornithine Carbamoyltransferase Deficiency Disease
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
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Metabolic Diseases