A Global, Phase 1/2, Open-Label, Dose Optimization Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of mRNA-3705 in Participants with Isolated Methylmalonic Acidemia Due to Methylmalonyl-CoA Mutase Deficiency

• Conditions: Deficiency of the enzyme methylmalonyl-coenzyme A (CoA) mutase (MUT); Isolated Methylmalonic Acidemia; 10000546

• Registration Number: NL-OMON55911
• Lead Sponsor: ModernaTX, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 9 April 2024

Recruitment & Eligibility

• Status: Pending
• Sex: Not specified
• Target Recruitment: 8

Inclusion Criteria

Participants are eligible to be included in the study only if all the following
criteria apply:
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
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 during the study and for 3 months after the last administration
of study drug (Section 11.5).
7. Participants with parameters that indicate MMA clinical severity as
described in Section 11.2.3.
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/H2receptor blockers.
11. Participation in another clinical study 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.
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 and reconfirmation of study eligibility.
14. 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.
15. Participant has received coronavirus disease 2019 vaccination (generally 2
doses or a booster) within 6 weeks between their last COVID 19 vaccination dose
and first study drug administration.
16. Participant has any individual vital sign abnormalities achieving
exclusionary thresholds as defined in Table 21.
17. Participant has a history of anaphylaxis/anaphylactoid reaction or severe
hypersensitivity with infusions.
18. (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

Study & Design

• Study Type: Interventional
• Study Design: Not specified