DM1, Genetic Diseases, Inborn, Heredodegenerative Disorders, Nervous System, Muscular Diseases, Muscular Disorders, Atrophic, Muscular Dystrophies, Musculoskeletal Diseases, Myotonic Disorders, Myotonic Dystrophy, Myotonic Dystrophy 1, Nervous System Diseases, Neurodegenerative Diseases, Neuromuscular Diseases
Conditions
Keywords
DM1, Myotonic Dystrophy 1, Myotonic Dystrophy Type 1 (DM1), Myotonic Dystrophy, DM, Dystrophy Myotonic, Myotonic Disorders, Steinert Disease, MARINA-OLE, MARINA, Avidity Biosciences, Avidity, AOC 1001, Myotonic Muscular Dystrophy
Brief summary
AOC 1001-CS2 (MARINA-OLE) (NCT05479981) is a Phase 2 extension of the AOC 1001-CS1 (MARINA) (NCT05027269) study to evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of multiple-doses of AOC 1001 Administered Intravenously to Adult Myotonic Dystrophy Type 1 (DM1) patients
Detailed description
This study will continue to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of AOC 1001 in participants that enrolled in the randomized, placebo-controlled, First-In-Human Phase 1/2 AOC 1001-CS1 (MARINA) (NCT05027269) clinical study. Participants from AOC 1001-CS1 (NCT05027269) are eligible to enroll in AOC 1001-CS2 (NCT05479981) if they have satisfactorily completed AOC 1001-CS1 (NCT05027269). After completion of Q8W (once every 8 weeks) Visit 6 assessments, participants will have the option to enroll in another AOC 1001 open-label extension (OLE) study - AOC 1001-CS4 (HARBOR-OLE) (NCT07008469). Participants who do not enroll in an AOC 1001 OLE study will be monitored for safety for a total of 8 weeks from the last dose of study drug. Total duration on study is up to 37 months (3 years 1 month). As of September 2024, the dosing regimen was updated to every 8 weeks.
Interventions
DRUGPlacebo
Placebo will be administered by intravenous (IV) infusion.
DRUGAOC 1001
AOC 1001 will be administered by intravenous (IV) infusion.
Sponsors
Avidity Biosciences, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Participants will receive one blinded treatment at Day 43. Treatment assignment on this day will be based on treatment received in AOC 1001-CS1 (NCT05027269) so that participants who did not receive active drug on Day 43 in AOC 1001-CS1 (NCT05027269) will receive active drug on Day 43 in AOC 1001-CS2 (NCT05479981).
Eligibility
Sex/Gender
ALL
Age
18 Years to 66 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Completion of AOC 1001-CS1 (MARINA) study with satisfactory compliance and no significant tolerability issues Key
Exclusion criteria
* Pregnancy, intent to become pregnant, or active breastfeeding * Unwilling or unable to continue to comply with contraceptive requirements * Any new conditions or worsening of existing conditions that in the opinion of the investigator or sponsor would make the participant unsuitable for the study or could interfere with participation or completion of the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number and severity of treatment-emergent adverse events (TEAEs) | Through study completion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AOC 1001 levels in muscle tissue | Through Day 183 | — |
| Change and percentage change from baseline in DMPK mRNA knockdown | Through Day 183 | — |
| Change and percentage change from baseline in Spliceopathy | Through Day 183 | — |
| Plasma pharmacokinetic (PK) parameters | Up to Day 729 | Maximum and trough plasma concentration |
Countries
United States
Outcome results
None listed