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Trial record 3 of 11 for:    Methylmalonic Acidemia

Open Label Study of mRNA-3704 in Patients With Isolated Methylmalonic Acidemia

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ClinicalTrials.gov Identifier: NCT03810690
Recruitment Status : Recruiting
First Posted : January 21, 2019
Last Update Posted : July 19, 2019
Sponsor:
Information provided by (Responsible Party):
ModernaTX, Inc.

Tracking Information
First Submitted Date  ICMJE January 14, 2019
First Posted Date  ICMJE January 21, 2019
Last Update Posted Date July 19, 2019
Actual Study Start Date  ICMJE May 28, 2019
Estimated Primary Completion Date November 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 16, 2019)
  • Incidence of treatment-emergent adverse events [ Time Frame: Day 1 (initial mRNA-3704 dose) through 52 weeks after final mRNA-3704 dose ]
  • Change in plasma methylmalonic acid levels [ Time Frame: Week -4 through 36 weeks after initial mRNA-3704 dose ]
    Baseline (pre-dose levels) to post-dose levels measured after single and after repeated administrations of mRNA-3704
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03810690 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 16, 2019)
  • Maximum observed concentration (Cmax) after administration of mRNA-3704 [ Time Frame: Baseline through 36 weeks after initial mRNA-3704 dose ]
  • Time of Cmax (Tmax) [ Time Frame: Baseline through 36 weeks after initial mRNA-3704 dose ]
  • Area under the plasma concentration-time curve (AUC) [ Time Frame: Baseline through 36 weeks after initial mRNA-3704 dose ]
  • Change in plasma 2-methylcitrate levels [ Time Frame: Week -4 through 36 weeks after initial mRNA-3704 dose ]
    Baseline (pre-dose levels) to levels measured after single and after repeated administrations of mRNA-3704
  • Measurement of anti-PEG antibodies [ Time Frame: Pre-dose through up to 52 weeks after final mRNA-3704 dose ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Open Label Study of mRNA-3704 in Patients With Isolated Methylmalonic Acidemia
Official Title  ICMJE A Global, Phase 1/2, Open Label, Dose Escalation Study to Evaluate the Safety, Pharmacodynamics, and Pharmacokinetics of mRNA-3704 in Patients With Isolated Methylmalonic Acidemia Due to Methylmalonyl-CoA Mutase Deficiency
Brief Summary

This First-in-Human (FIH) Phase 1/2 study will evaluate mRNA-3704 in patients with methylmalonic acidemia/aciduria (MMA) due to methylmalonyl-coenzyme A mutase (MUT) deficiency between 1 to 18 years of age with elevated plasma methylmalonic acid. The study is designed to characterize baseline biomarker levels followed by assessment of safety, pharmacokinetics, and pharmacodynamics of different doses of mRNA-3704 in patients affected by MMA as part of the Dose Escalation phase.

During the Dose Escalation phase, three dose levels of mRNA-3704 are planned to be investigated in this study among patients with MMA due to MUT deficiency: low dose, mid dose, and high dose. An additional cohort to evaluate a fourth dose level may be considered jointly by the independent SMC and the Sponsor.

Upon establishment of a dose with acceptable safety and pharmacodynamic activity, additional patients will be enrolled in a Dose Expansion phase to allow for further characterization of the safety and pharmacodynamics of mRNA-3704.

Patients in both phases of study will participate in a pre-dosing observational period, followed by a treatment period, and then a follow-up period after withdrawal of treatment.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Methylmalonic Acidemia (MMA)
  • Metabolism, Inborn Errors
Intervention  ICMJE Biological: mRNA-3704
mRNA-3704 dispersion for intravenous (IV) infusion
Study Arms  ICMJE
  • Experimental: Dose Escalation Phase: Dose Level 1
    mRNA-3704
    Intervention: Biological: mRNA-3704
  • Experimental: Dose Escalation Phase: Dose Level 2
    mRNA-3704
    Intervention: Biological: mRNA-3704
  • Experimental: Dose Escalation Phase: Dose Level 3
    mRNA-3704
    Intervention: Biological: mRNA-3704
  • Experimental: Dose Escalation Phase: Dose Level 4 (optional)
    mRNA-3704
    Intervention: Biological: mRNA-3704
  • Experimental: Dose Expansion Phase: mRNA-3704
    Intervention: Biological: mRNA-3704
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 16, 2019)
34
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2024
Estimated Primary Completion Date November 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Patients are eligible to be included in the study only if all of the following criteria apply:

  • Confirmed diagnosis of isolated MMA due to MUT deficiency based on the following criteria:

    • Elevated plasma methylmalonic acid concentrations (≥ 100 µmol/L)
    • Presence of normal serum/plasma Vitamin B12 and plasma homocysteine levels
    • Confirmed diagnosis by molecular genetic testing
  • Patient must be ≥ 1 to ≤ 18 years of age at the time of consent/assent (Inclusion of the first three patients will be restricted to individuals age ≥ 12 to ≤18 years)

Exclusion Criteria:

Patients are excluded from the study if any of the following criteria apply:

  • Diagnosis of isolated MMA cblA, cblB, or cblD enzymatic subtypes or methylmalonyl-CoA epimerase deficiency or combined MMA with homocystinuria
  • History of organ transplantation
  • Previously received gene therapy for the treatment of MMA.
  • Estimated glomerular filtration rate (GFR) < 30 mL/min/1.73 m2; or patients who receive chronic dialysis
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Moderna Clinical Trials 855-663-6762 clinicaltrials@modernatx.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03810690
Other Study ID Numbers  ICMJE mRNA-3704-P101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party ModernaTX, Inc.
Study Sponsor  ICMJE ModernaTX, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account ModernaTX, Inc.
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP