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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04899310




Registration number
NCT04899310
Ethics application status
Date submitted
19/05/2021
Date registered
24/05/2021
Date last updated
1/05/2024

Titles & IDs
Public title
A Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of mRNA-3705 in Participants With Isolated Methylmalonic Acidemia
Scientific title
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
Secondary ID [1] 0 0
2020-004980-24
Secondary ID [2] 0 0
mRNA-3705-P101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Methylmalonic Acidemia 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Renal and Urogenital 0 0 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - mRNA-3705

Experimental: mRNA-3705 - Participants in Part 1 will receive a weight based dose of mRNA-3705, administered intravenously (IV), once every 2 weeks (Q2W) or once every 3 weeks (Q3W) for up to 10 doses over approximately 40 weeks. Participants in Part 2 will receive mRNA 3705 at the selected dose level and frequency for up to 12 months.


Treatment: Other: mRNA-3705
A sterile liquid for injection
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Study Drug-related TEAES, Serious Adverse Events (SAEs), and TEAEs Leading to Treatment Discontinuation
Timepoint [1] 0 0
Up to 144 weeks
Primary outcome [2] 0 0
Part 2: Annualized Frequency of Metabolic Decompensation Events (MDEs)
Timepoint [2] 0 0
Baseline up to Week 52
Secondary outcome [1] 0 0
Change in Blood Methylmalonic Acid Level
Timepoint [1] 0 0
Baseline up to Week 40
Secondary outcome [2] 0 0
Maximum Observed Effect (Emax) for Plasma Methylmalonic Acid Measurement after Single and Repeated Administrations of mRNA-3705
Timepoint [2] 0 0
Baseline up to Week 40
Secondary outcome [3] 0 0
Area Under the Effect Curve (AUEC) for Plasma Methylmalonic Acid Measurement after Single and Repeated Administrations of mRNA-3705
Timepoint [3] 0 0
Baseline up to Week 40
Secondary outcome [4] 0 0
Duration of Response for Plasma Methylmalonic Acid Measurement after Single and Repeated Administrations of mRNA-3705
Timepoint [4] 0 0
0 (predose) up to 336 hours postdose
Secondary outcome [5] 0 0
Change in Blood 2-Methylcitric Acid (2-MC ) Levels
Timepoint [5] 0 0
Baseline up to Week 40
Secondary outcome [6] 0 0
Maximum Observed Concentration (Cmax) of human Methylmalonyl-Coenzyme A Mutase (hMUT) mRNA-3705
Timepoint [6] 0 0
0 (predose) to 336 hours postdose
Secondary outcome [7] 0 0
Area Under the Concentration-Time Curve (AUC) of hMUT mRNA-3705
Timepoint [7] 0 0
0 (predose) to 336 hours postdose
Secondary outcome [8] 0 0
Titer of Anti-Polyethylene Glycol (PEG) Antibodies
Timepoint [8] 0 0
0 (predose) to 336 hours postdose

Eligibility
Key inclusion criteria
Key

* Participant has a body weight of =11.0 kilograms (kg) at the Screening Visit.
* Participant has a diagnosis of isolated MMA due to MUT deficiency confirmed by molecular genetic testing.
* 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.
* 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.
* 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.
* (Part 2 only) At least 1 documented MDE in the 12-month period before consent.

Key
Minimum age
1 Year
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Participant has a diagnosis of isolated MMA cb1A, cb1B, or cb1D enzymatic subtypes or methylmalonyl-CoA epimerase deficiency or combined MMA with homocystinuria.
* Participant has previously received gene therapy for the treatment of MMA.
* Participant has a history of organ transplantation or planned organ transplantation during the period of study participation.
* 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.
* (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
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/08/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/08/2028
Actual
Sample size
Target
63
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 0 0
Royal Children's Hospital Melbourne - Parkville
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Pennsylvania
Country [3] 0 0
Canada
State/province [3] 0 0
Alberta
Country [4] 0 0
Canada
State/province [4] 0 0
Ontario
Country [5] 0 0
France
State/province [5] 0 0
Paris
Country [6] 0 0
Netherlands
State/province [6] 0 0
Rotterdam
Country [7] 0 0
Netherlands
State/province [7] 0 0
Utrecht
Country [8] 0 0
Spain
State/province [8] 0 0
Barcelona
Country [9] 0 0
Spain
State/province [9] 0 0
Barakaldo
Country [10] 0 0
Spain
State/province [10] 0 0
Madrid
Country [11] 0 0
Spain
State/province [11] 0 0
Santiago de Compostela
Country [12] 0 0
Spain
State/province [12] 0 0
Sevilla
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Birmingham
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
ModernaTX, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a study of mRNA-3705 in participants with isolated elevated methylmalonic acid (MMA) due to methylmalonyl-coenzyme A (CoA) mutase (MUT) deficiency. The main goal of the study is to assess safety, pharmacokinetics, and pharmacodynamics of mRNA-3705.
Trial website
https://clinicaltrials.gov/study/NCT04899310
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Moderna Clinical Trials Support Center
Address 0 0
Country 0 0
Phone 0 0
1-877-777-7187
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04899310