A clinical study to evaluate mRNA-3705 in Patients with MMA

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 63

Inclusion Criteria

1. Participant is =1 year of age at the time of informed consent/assent. 2. Participant has a body weight of =11.0 kg at the Screening Visit. 3. Participant has a diagnosis of isolated MMA due to MUT deficiency confirmed by molecular genetic testing (see guidance in Section 8.1.1 for participants <23.3 kg). 4. Participant has a blood vitamin B12 level equal to or above the lower limit of normal (based on laboratory reference range) confirmed in the Screening Period. For those participants found to have an elevated blood vitamin B12 level, the participant may enter if, in the opinion of the Investigator, the cause of the elevation is secondary to B12 supplementation. 5. Participant or their legally authorized representative is willing and able to provide informed consent and/or assent as mandated by local regulations and is willing and able to comply with study-related assessments. 6. Sexually active females of childbearing potential and sexually active males of reproductive potential agree to use a highly effective method of contraception, consistent with local regulations, during the study and for 3 months after the last administration of study drug. 7. Participants with parameters that indicate MMA clinical severity as described in Section 10.2.3. 8. (Part 2 only) At least 1 documented MDE in the 12-month period before consent.

Exclusion Criteria

1. Participant has a diagnosis of isolated MMA cb1A, cb1B, or cb1D enzymatic subtypes or methylmalonyl-CoA epimerase deficiency or combined MMA with homocystinuria. 2. Participant has any individual laboratory abnormalities achieving exclusionary thresholds defined in Table 20. 3. Participant has previously received gene therapy for the treatment of MMA. 4. Participant has an eGFR <30 mL/min/1.73 m2, as estimated by the Schwartz formula for participants <18 years of age (Schwartz et al 2009), or by the Chronic Kidney Disease Epidemiology Collaboration creatinine-based formula for participants =18 years of age (Inker et al 2021), or receives long-term dialysis. 5. Participant has a corrected QT interval >480 ms using Bazett’s correction. 6. For female participants of reproductive potential, the participant has a positive pregnancy test at the Screening Visit. 7. Participant is pregnant or breastfeeding. 8. Participant has a history of organ transplantation or planned organ transplantation during the period of study participation. 9. Participant has a history of hypersensitivity to any components of the study drug. 10. Participant has a history of hypersensitivity or contraindication to acetaminophen/paracetamol and/or ibuprofen or H1/H2 receptor blockers. 11. Participation in another clinical trial of another investigational agent within 30 days before study entry or within 5 elimination half-lives of the investigational agent, whichever is longer. 12. Participant has undergone a major surgical procedure within 30 days before the Screening Visit (excludes central line, port, or feeding tube placement). 13. Participant has new uses or adjustments in dose within 2 weeks before first dose of study drug to antibiotic therapy used to reduce propionate production. 14. Any participant whose new or adjusted dose in antibiotics conflicts with the rules described above may enter the Treatment Period after stabilization of the antibiotic regimen. 15. Participant has an active, unstable, or clinically significant medical condition not related to MMA or history of noncompliance that, in the Investigator’s opinion, could potentiate the risk while participating in this study, interfere with the interpretation of study results, or limit the participant’s participation in the study. This may include, but is not limited to, history of relevant food or drug allergies; history of cardiovascular, central nervous, gastrointestinal, or infectious disease; history of clinically significant pathology; and/or history of cancer. 16. Participant has received coronavirus disease 2019 (COVID-19) vaccination (generally 2 doses or a booster) within 6 weeks between their last COVID-19 vaccination dose and first study drug administration. 17. Participant has any individual vital sign abnormalities achieving exclusionary thresholds as defined in Table 21. 18. Participant has a history of anaphylaxis/anaphylactoid reaction or severe hypersensitivity with infusions. 19. (Part 2 only) History of hepatitis B (known positive hepatitis B surface antigen [HbsAg]), hepatitis C virus (HCV), or HIV (positive HIV1/HIV-2 antibodies). Participants with a past or resolved hepatitis virus B (HBV) infection (defined as the presence of hepatitis B core antibody and absence of HbsAg) are eligible. Participants with history of positive results for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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