Extension of AOC 1001-CS1 (MARINA) Study in Adult Myotonic Dystrophy Type 1 (DM1) Patients

Study Overview
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Brief Summary
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AOC 1001-CS2 (MARINA-OLE) is a Phase 2 extension of the AOC 1001-CS1 (MARINA) 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
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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) clinical study. Participants from AOC 1001-CS1 are eligible to enroll in AOC 1001-CS2 if they have satisfactorily completed AOC 1001-CS1. The total duration of active treatment in AOC 1001-CS2 is approximately 24 months. Once participants have completed active treatment, they will be followed through a 9-month safety follow-up period. The sponsor may extend active treatment beyond 24 months at a future timepoint.

Official Title
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A Phase 2 Extension Study to Evaluate the Long-Term Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of AOC 1001 Administered Intravenously to Adult Myotonic Dystrophy Type 1 (DM1) Patients

Conditions
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DM1, Heredodegenerative Disorders, Nervous System, Neurodegenerative Diseases, Muscular Dystrophies, Myotonic Dystrophy, Myotonic Dystrophy 1, Myotonic Disorders, Muscular Disorders, Atrophic, Muscular Diseases, Musculoskeletal Diseases, Neuromuscular Diseases, Nervous System Diseases, Genetic Diseases, Inborn

Intervention / Treatment
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* Drug: Placebo
* Drug: AOC 1001


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 66 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AOC 1001<br>AOC 1001 will be administered quarterly. On Day 43 patients will receive an additional dose. Treatment assignment will be based on treatment received in AOC 1001-CS1. If participant did not receive AOC 1001 on Day 43 in AOC 1001-CS1, participant will receive AOC 1001 treatment on Day 43 in AOC 1001-CS2. | Drug: AOC 1001<br>* AOC 1001 will be administered by intravenous (IV) infusion.<br>|
| Experimental: AOC 1001 (with Placebo at Day 43)<br>AOC 1001 will be administered quarterly. On Day 43 patients will receive an additional dose. Treatment assignment will be based on treatment received in AOC 1001-CS1. If participant received AOC 1001 on Day 43 in AOC 1001-CS1, participant will receive blinded placebo treatment on Day 43 in AOC 1001-CS2. | Drug: Placebo<br>* Placebo will be administered by intravenous (IV) infusion.<br>* Other names: Saline;Drug: AOC 1001<br>* AOC 1001 will be administered by intravenous (IV) infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and severity of treatment-emergent adverse events (TEAEs) |  | Through study completion, up to Day 729 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma pharmacokinetic (PK) parameters | Maximum and trough plasma concentration | Through study completion, up to Day 729 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DM, Dystrophy Myotonic, DM1, Myotonic Dystrophy 1, Myotonic Dystrophy Type 1 (DM1), Myotonic Dystrophy, Myotonic Disorders, Steinert Disease, MARINA-OLE, MARINA, Avidity Biosciences, Avidity, AOC 1001, Myotonic Muscular Dystrophy