MMA in kids up to 16 with MMUT mutations (MMUT-related isolated MMA) observational

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is an observational, non-interventional study enrolling pediatric participants up to 16 years old with confirmed MMUT-related isolated methylmalonic acidemia. The study aims to understand clinical outcomes across a spectrum of disease severity, including participants with and without a prior organ transplant. Eligibility requires a confirmed MMUT mutation and a severe MMA phenotype for untransplanted participants, defined by clinical and biochemical criteria. Sites include CHOP, UPMC, and OSR in Milan, with a capped subcohort of transplanted participants. Details on specific interventions are not provided in the protocol.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. Aged ≤16 years at screening visit
2. With or without previous liver (or combined liver/kidney) transplantation at time of screening (note: number of transplanted participants capped at n=15) 3. Confirmed laboratory diagnosis of Isolated MMA caused by mutations in the MMUT gene (NOTE: if a historical genetic mutational analysis report was available at Screening visit but was not from a CLIA/ISO15189 approved laboratory, a confirmatory sample will be taken during the study. However the original lab report will be adequate for study eligibility consideration)..

4\. Severe MMA phenotype.

* For untransplanted participants, all of the following criteria (a-c) must be met to qualify as "severe" MMA phenotype:

  1. Serum methylmalonic acid (sMMA) level of \>100 µmol/L at the Screening visit
  2. An unscheduled ER visit, hospitalization or requirement for use of the sick day diet regimen in the 12 months prior to the screening visit
  3. Considered to potentially require future liver transplantation to improve metabolic stability in accordance with MMA transplantation guidelines (Baumgartner 2014, Forny 2021, Sen 2023)
* For participants with previous liver or combined liver and kidney transplantation, the phenotype of the participant will be judged by the Investigator to be severe if both of the following were applicable prior to transplantation:

  1. Pre-transplant serum methylmalonic acid (sMMA) level of \>100 µmol/L AND
  2. Transplantation was conducted to improve metabolic stability in accordance with MMA transplantation guidelines (Baumgartner 2014, Forny 2021, Sen 2023).

NOTE: sMMA pre-transplant measure must have been obtained within 6 months prior to transplant. An alternative blood MMA concentration may be used (e.g. plasma MMA, or dry blood spot), if sMMA is unavailable. Details of the assay used must be provided and additional samples will be collected during the study to allow comparison to sMMA results.

Exclusion Criteria:

1. Participant/parent/legal guardian/caregiver not willing to consent to participate
2. Current participation in another interventional or therapeutic study
3. Prior participation in a gene therapy clinical trial including mRNA therapy
4. Participants who, in the opinion of the Site Investigator, would be unable or unsuitable to participate in the demands of the study, for example but not limited to participants unable to travel to protocol study visits or participants under palliative care.
5. For participants who are post-liver transplant only, participant will be excluded if no prior pre-liver transplant measurements of blood MMA are available.

Where it's running

• GOSH NHS (Great Ormond Street Hospital for Children)
  London, United Kingdom Recruiting
• CHOP (Children's hospital of Philadelphia)
  Philadelphia, Pennsylvania, United States Not yet recruiting
• UPMC (Children's hospital of Pittsburgh)
  Pittsburgh, Pennsylvania, United States Not yet recruiting
• OSR_San Raffaele
  Milan, Italy Not yet recruiting
• OBGP (Bambino Gesu Ospedale Pediatrico)
  Roma, Italy Not yet recruiting
• SJD_San Joan de Deù Children's Hospital
  Barcelona, Spain Not yet recruiting

Study contacts

• Study coordinator: Gwenaelle roguet, MD
• Email: clinical.operations@genespire.com
• Phone: +33 0745017668

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Long-term evaluation of mRNA-3705 for treating methylmalonic acidemia

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• Long-term management of organic acidemia with CARBAGLU®

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• Observational study of Methylmalonic Acidemia

  This study looks at how often complications like metabolic stroke and developmental delays happen in people of all ages with Methylmalonic Acidemia to help improve future treatments.

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.