Ornithine Transcarbamylase DeficiencyPhase 1/2STEP-OTCNCT03767270
Safety, Tolerability and PK/PD Evaluation of Intravenous Administration of MRT5201 in Patients With OTC Deficiency
A Phase 1/2 study testing MRT5201 in people with Ornithine Transcarbamylase Deficiency, run by Translate Bio, Inc..
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ornithine Transcarbamylase Deficiency
- What is being tested?
- MRT5201
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Dec 2019to Jul 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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.
About this study
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
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
- Being tested
- MRT5201, Placebo
- Keywords
- OTC, Urea Cycle Disorder, UCD
- Medical subject headings
- Ornithine Carbamoyltransferase Deficiency Disease, Urea Cycle Disorders, Inborn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRT5201Biological
Codon-optimized human ornithine transcarbamylase messenger ribonucleic acid with lipid-based nanoparticles
PlaceboOther
5% dextrose in water
| Study group | Role | What they receive |
|---|---|---|
| MRT5201 | Experimental | Single Ascending Low, Mid, and High doses of MRT5201 Receives: Biological: MRT5201 |
| Placebo | Placebo comparator | Placebo comparator using 5% dextrose in water at the same administration rate as study drug. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 24
Secondary outcomes (3)
Pharmacokinetics parameters of MRT5201
Pharmacokinetics of MRT5201 as measured by levels of mRNA
Measured: 1 month after single dose
Effect of a single dose of MRT5201 on ureagenesis
Change from Baseline in 4-hour ureagenesis AUC at weeks 2, 3, 4, and 5 after a single dose of MRT5201
Measured: Up to 1 month after single dose
Effect of single dose of MRT5201 on metabolic markers of OTCD
Change from Baseline in 8-hour ammonia AUC
Measured: 6 months after single dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2018
- Study startDec 2019 (estimated)
- Primary completionJul 2022 (estimated)
- Study completionJul 2022 (estimated)
Why it stopped: Program was discontinued.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ornithine Transcarbamylase DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Translate Bio, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03767270
- Sponsor's protocol ID
- MRT5201-101
- Other IDs
- 2018-004095-35, 2018
- Acronym
- STEP-OTC
- Status last verified
- Sep 2019
- First submitted
- 28 Nov 2018
- Last updated
- 17 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03767270
- Acronym / sponsor ID
- STEP-OTC / MRT5201-101
- Conditions
- Ornithine Transcarbamylase Deficiency
- Keywords
- OTC, Urea Cycle Disorder, UCD
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Program was discontinued.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Translate Bio, Inc.Industry (pharma, biotech, devices)
- Study start
- Dec 2019 (estimated)
- Primary completion
- Jul 2022 (estimated)
- Study completion
- Jul 2022 (estimated)
- First posted
- 6 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MRT5201 | Experimental | Biological: MRT5201Single Ascending Low, Mid, and High doses of MRT5201 |
| Placebo | Placebo comparator | Other: PlaceboPlacebo comparator using 5% dextrose in water at the same administration rate as study drug. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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:
- 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.
Key exclusion criteria (9 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MRT5201Codon-optimized human ornithine transcarbamylase messenger ribonucleic acid with lipid-based nanoparticles | Biological | MRT5201 |
| Placebo5% dextrose in water | Other | Placebo |
Primary outcome
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.
3 secondary outcomes
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
Effect of single dose of MRT5201 on metabolic markers of OTCD
Time frame: 6 months after single dose
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2019.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MRT5201 in people with Ornithine Transcarbamylase Deficiency, run by Translate Bio, Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 17 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The incidence of treatment-emergent adverse events by treatment group (time frame: Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2019.