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Recruiting NCT05295433

An Extension Study to Evaluate the Long-Term Safety and Clinical Activity of mRNA-3705 in Participants Previously Enrolled in Other Clinical Studies of mRNA-3705

Phase I / Phase II Interventional Methylmalonic Acidemia

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An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: mRNA-3705.
Who it may be relevant to
Registry conditions: Methylmalonic Acidemia. Basic parameters: from 1 year · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States, Canada, France, Netherlands, Spain +1
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

A Phase 1/2, Global, Open-Label, Extension Study to Evaluate the Long-Term Safety and Clinical Activity of mRNA-3705 in Participants Previously Enrolled in Other Clinical Studies of mRNA-3705

Overview

The primary objective of this study is to evaluate the long-term safety and clinical activity of mRNA-3705 administered to participants with isolated methylmalonic acidemia (MMA) due to methylmalonyl-coenzyme A mutase (MUT) deficiency who have previously participated in other clinical studies of mRNA-3705.

Detailed description

Participants with isolated MMA due to MUT deficiency who were previously enrolled in other clinical studies of mRNA-3705 will have the option to enroll into this extension study provided all eligibility criteria have been met. The study will include 2 periods: 1) Treatment Period and 2) Follow-up Period (up to 6 months after the last dose of study drug).

Treatment Period will continue unless one of the following occurs: mRNA-3705 receives marketing approval and reimbursement in the country of origin of the participant (following market approval and access being in place, all participants who wish to continue treatment will be offered mRNA-3705 through market access, with the intention of preventing treatment interruption. Other appropriate access program is offered as allowed by local regulation to continue treatment with mRNA-3705. Safety monitoring will be performed for all participants under treatment per market access requirements), the participant discontinues study drug, the participant is no longer receiving clinical benefit in the opinion of the Investigator, or Sponsor discontinues the development of mRNA-3705.

Interventions

  • Drug mRNA-3705
    A sterile liquid for injection

Primary outcome measures

  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Drug-Related TEAEs, Unrelated TEAEs, Adverse Events of Special Interests (AESIs), Serious Adverse Events (SAEs) and TEAEs Leading to Discontinuation [Time frame: Baseline up to follow-up period (up to 6 years + 6 months)]
Secondary outcome measures (11)
  • Percent Change in Plasma Methylmalonic Acid and 2-Methylcitric Acid (2-MC) Levels (Primary Biomarkers) From Baseline up to 18 Months [Time frame: Baseline, Year 6 (Treatment Period) + Month 6 (Follow up)]
  • Pre- and Postdose Human Methylmalonyl-Coenzyme A Mutase (hMUT) mRNA and SM-86 Levels [Time frame: Baseline up to 6 years]
  • Change From Baseline in Pretreatment and Post-treatment Annualized Metabolic Decompensation Events (MDEs) Rate [Time frame: Baseline, Year 6 (Treatment Period) + Month 6 (Follow up)]
  • Number of Healthcare Resource Utilization Visits [Time frame: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)]
  • Number of Annualized MMA-related Hospitalizations [Time frame: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)]
  • Number of Annualized MMA-related Healthcare Visits [Time frame: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)]
  • Number of Anti-Polyethylene Glycol (PEG) and Anti-hMUT Antibodies [Time frame: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)]
  • Change in Health-Related Quality of Life (HRQoL) as Measured Using the Pediatric Quality of Life Inventory (PedsQL™) at Month 3 up to 18 Months [Time frame: Month 3, Year 6 (Treatment Period) + Month 6 (Follow up)]
  • Change in Investigator Global Assessment of Improvement (IGA-I) Score [Time frame: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)]
  • Change in Investigator Global Assessment of Severity (IGA-S) Score [Time frame: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)]
  • Change in EuroQoL 5-Dimensions 5-level/Youth Questionnaire (EQ-5D-5L/Y) Score [Time frame: Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up)]

Eligibility criteria

Inclusion criteria

  • Completed the assigned dose regimen treatment time period in other clinical studies of mRNA-3705 or is eligible for early transition to this study because they missed more than 3 consecutive doses of study drug due to coronavirus disease 2019 (COVID-19) vaccination during Study mRNA-3705-P101 Part 1.
  • Completed the End of treatment (EOT) Visit (or End of Study Visit in the case of unscheduled dosing) in Study mRNA-3705-P101 within 10 days of their first dose of mRNA-3705 in this extension study.

Exclusion criteria

  • Not expected to receive clinical benefit from continued mRNA-3705 administration, in the opinion of the Investigator.
  • Any clinical or laboratory abnormality or medical condition that, at the discretion of the Investigator, may put the individual at increased risk by participating in this study.
  • History of liver and/or kidney transplant.

NOTE: Other inclusion and exclusion criteria may apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
N/A
Model
Single group
Masking
Open label
Primary purpose
Treatment

Study locations

United States · 3 centers
  • UCLA Medical Center — Los Angeles
  • Lucile Packard Children's Hospital at Stanford — Palo Alto
  • Altman Clinical and Translational Research Institution — San Diego
Canada · 2 centers
  • Stollery Children's Hospital University of Alberta — Edmonton
  • Hospital For Sick Children — Toronto
Netherlands · 2 centers
  • Erasmus MC — Rotterdam
  • Universitair Medisch Centrum Utrecht — Utrecht
Spain · 2 centers
  • Hospital Universitario Cruces — Barakaldo
  • Hospital Universitario 12 de Octubre — Madrid
United Kingdom · 2 centers
  • Birmingham Children's Hospital NHS Foundation Trust — Birmingham
  • Royal Manchester Childrens Hospital — Manchester
France · 1 center
  • Hôpital Necker - Enfants Malades APHP — Paris

Identifiers

NCT: NCT05295433 · mRNA-3705-P101-EXT · 2021-000446-17 · 2022-501997-20-00

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗