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A clinical study to evaluate mRNA-3704 in Patients with MMA

Phase 1
Conditions
Isolated Methylmalonic Acidemia Due to Methylmalonyl-CoA Mutase Deficiency
Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]
Registration Number
EUCTR2019-001061-32-GB
Lead Sponsor
ModernaTX, Inc.
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
34
Inclusion Criteria

Patients are eligible to be included in the study only if all of the following criteria apply:
1. Confirmed diagnosis of isolated MMA due to MUT deficiency based on the following criteria:
o Elevated plasma methylmalonic acid concentrations of =100 µmol/L, confirmed by 2 values drawn at least 24 hours apart during the Screening Period or within the past 6 months;
o Presence of normal serum/plasma vitamin B12 and plasma homocysteine levels (local laboratory reference range) confirmed in the Screening Period (values may be from historical data); and
o Confirmed diagnosis by molecular genetic testing.
2. Patient must be =1 years of age at the time of consent/assent. (inclusion of the first three patients will be restricted to individuals 8 years of age or older).
3. Patient or legally authorized representative is willing and able to provide informed consent and/or assent as mandated by local regulations.
4. The patient’s caregiver (and the patient) must be willing and able to comply with study-related assessments.
5. Values for ALT, AST, and direct serum bilirubin =1.25x of ULN.
6. Platelet count within a range of =150,000/mm3 to 450,000/mm3.
7. Hemoglobin levels >9 g/dL
8. 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 12 weeks following study participation.
Are the trial subjects under 18? yes
Number of subjects for this age range: 33
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Patients are excluded from the study if any of the following criteria apply:
1. Diagnosis of isolated MMA cblA, cblB, or cblD enzymatic subtypes or methylmalonyl-CoA epimerase deficiency or combined MMA with homocystinuria.
2. Previously received gene therapy for the treatment of MMA.
3. Estimated glomerular filtration rate (GFR) <30 mL/min/1.73 m2, as estimated by the Schwartz formula (based on serum creatinine); or patients who receive chronic dialysis.
4. QTc including Bazett's correction >450 msec.
5. In female patients of reproductive potential: a positive pregnancy test at Screening or at the end of the Observational Period.
6. Pregnant or lactating.
7. aPTT, PT, or INR greater than ULN or history of clinically significant bleeding abnormality.
8. Absolute neutrophil count (ANC) below the following:
• 1000/mm3 for patients =1 year of age to <2 years of age
• 1500/mm3 for patients =2 years of age
9. History of organ transplantation.
10. History of hypersensitivity to any components of the study drug.
11. Participated in another clinical trial of another investigational agent within 30 days prior to study entry (or within 5 elimination half-lives of the investigational agent), whichever is longer.
12. Major surgical procedure within 30 days prior to study entry (excludes central line, port, or feeding tube placement).
13. Known history of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection.
14. Have any other clinically significant medical condition that in the Investigator’s opinion could interfere with the interpretation of study results or limit the patient’s participation in the study.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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