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| ID | Type | Description | Link |
|---|---|---|---|
| 2022-502492-32-00 | Other Identifier | Clinical Trials Information System (CTIS) |
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As part of ongoing efforts to refine the MMA program strategy, we are reevaluating clinical study plans for mRNA-3705, in order to further optimize the development program. As part of this process, Moderna will be closing the mRNA-3705-P101 study.
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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, efficacy, pharmacokinetics, and pharmacodynamics of intravenously (IV)-infused mRNA-3705.
This study comprises 3 parts and is designed to evaluate multiple doses and dosing intervals of mRNA-3705.
Parts 1 and 3 are designed to characterize the safety, tolerability, and pharmacological activity of mRNA-3705 administered via intravenous infusion to participants with isolated MMA due to MUT deficiency. Part 2 will evaluate the efficacy of mRNA-3705 as assessed by the change in plasma methylmalonic acid levels.
Participants who complete the treatment period in any part of the study, including the end of treatment (EOT) visit, will be offered participation in the mRNA-extension study (mRNA-3705-P101-EXT; NCT05295433) or may transition to the follow-up period of the study. All participants, including those randomized to placebo in Part 2, will receive mRNA-3705 in the extension study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| mRNA-3705 | Experimental | Participants in Part 1 will receive a weight-based dose of mRNA-3705, administered IV, once every 2 weeks or once every 3 weeks for up to 10 doses over approximately 40 weeks. Participants in Part 2 and Part 3 will receive mRNA-3705 at the selected dose level and frequency for 3 months. |
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| Placebo | Placebo Comparator | Participants only in Part 2 will receive placebo at the selected frequency for 3 months. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| mRNA-3705 | Biological | Sterile liquid for infusion |
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| Measure | Description | Time Frame |
|---|---|---|
| Parts 1 and 3: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Study Drug-related TEAEs, Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and TEAEs Leading to Treatment Discontinuation | Up to 134 weeks | |
| Part 2: Percentage Change in Plasma MMA Levels at Month 3 | Baseline, Month 3 |
| Measure | Description | Time Frame |
|---|---|---|
| Parts 1 and 3: Percentage Change in Plasma MMA Level | Baseline up to Week 30 | |
| Part 1: Maximum Observed Effect (Emax) for Plasma MMA Measurement after Single and Repeated Administrations of mRNA-3705 | Baseline up to Week 30 |
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Key Inclusion Criteria:
Key Exclusion Criteria:
Note: Additional inclusion/exclusion criteria may apply, per protocol.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCLA Medical Center | Los Angeles | California | 90095 | United States | ||
| Lucile Packard Children's Hospital at Stanford |
Parts 2 and 3 run in parallel and occur after Part 1.
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Parts 1 and 3 are open label and non-randomized. Part 2 is blinded and randomized.
| Placebo | Biological | Sterile liquid for infusion |
|
| Part 1: Area Below the Baseline and Above the Response Curve (AUC_Below_B) for Plasma MMA Measurement after Single and Repeated Administrations of mRNA-3705 | Baseline up to Week 30 |
| Part 1: Area Under the Curve that is the Area Under the Response Curve Above the Baseline (AUC_Above_B)-AUC_Below_B (AUC_Net_B) for Plasma MMA Measurement after Single and Repeated Administrations of mRNA-3705 | Baseline up to Week 30 |
| Parts 1-3: Percentage Change in Plasma 2-Methylcitric Acid (2-MC) Levels | Baseline up to Week 30 |
| Parts 1-3: Maximum Observed Concentration (Cmax) of human Methylmalonyl-Coenzyme A Mutase (hMUT) mRNA-3705 | 0 (predose) to 264 hours postdose |
| Parts 1-3: Area Under the Concentration-Time Curve (AUC) of hMUT mRNA-3705 | 0 (predose) to 264 hours postdose |
| Parts 1-3: Titer of Anti-Polyethylene Glycol (PEG) Antibodies | 0 (predose) to 336 hours postdose |
| Parts 2 and 3: Titer of Anti-hMUT Antibodies | 0 (predose) to 336 hours postdose |
| Parts 2 and 3: Change from Baseline in Pediatric Quality of Life Inventory (PedsQL) Physical Function Score | Baseline, Month 3 |
| Parts 2 and 3: Annualized Frequency of MMA-related Hospitalizations | Baseline up to Month 3 |
| Parts 2 and 3: Annualized Frequency of Metabolic Decompensation Events | Baseline up to Month 3 |
| Parts 2 and 3: Change from Baseline in PedsQL Total Score | Baseline, Week 47 |
| Parts 2 and 3: Change from Baseline in Investigator Global Assessment of Severity (IGA-S) | Baseline, Week 47 |
| Parts 2 and 3: Change from Baseline in Caregiver-Reported Global Impression of Severity (CrGI-S) | Baseline, Week 47 |
| Parts 2 and 3: Change from Baseline in Investigator Global Assessment of Improvement (IGA-I) | Week 3 (Dose 2), Week 47 |
| Parts 2 and 3: Change from Baseline in Caregiver-Reported Global Impression of Improvement (CrGI-I) | Week 3 (Dose 2), Week 47 |
| Part 2: Number of Participants with TEAEs, SAEs, AESIs, and TEAEs Leading to Treatment Discontinuation | Up to 47 weeks |
| Part 2: Plasma Concentration of SM-86 | 0 (predose) to 48 hours postdose |
| Palo Alto |
| California |
| 94304 |
| United States |
| The Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| Stollery Children's Hospital University of Alberta | Edmonton | Alberta | T6G 2R7 | Canada |
| Hospital For Sick Children | Toronto | Ontario | M5G 1X8 | Canada |
| Hôpital Necker - Enfants Malades | Paris | 75015 | France |
| Erasmus MC | Rotterdam | 3015 AA | Netherlands |
| Universitair Medisch Centrum Utrecht | Utrecht | 3584 CX | Netherlands |
| Hospital Universitario Cruces | Barakaldo | 48903 | Spain |
| Hospital Universitario 12 de Octubre | Madrid | 28041 | Spain |
| Royal Manchester Children's Hospital | Manchester | M13 9WL | United Kingdom |
| ID | Term |
|---|---|
| C537358 | Methylmalonic acidemia |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| ID | Term |
|---|---|
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D008765 | Methylmalonyl-CoA Mutase |
| ID | Term |
|---|---|
| D019751 | Intramolecular Transferases |
| D007535 | Isomerases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
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