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

• Sponsor: Avidity Biosciences, Inc. (Industry)
• Overall Status: Enrolling by invitation
• CT.gov ID: NCT05479981
• Collaborator: (none)
• Enrollment: 44
• Locations: 8
• Arms: 2
• Anticipated Duration (Months): 33
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
DM1; Muscular Dystrophies; Myotonic Dystrophy; Myotonic Dystrophy 1; Myotonic Disorders; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases	Drug: Placebo; Drug: AOC 1001	Phase 2

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) 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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 44 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• 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 so that participants who did not receive active drug on Day 43 in AOC 1001-CS1 will received active drug on Day 43 in AOC 1001-CS2.
• Primary Purpose: Treatment
• Official Title: 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
• Anticipated Study Start Date: Jul 1, 2022
• Anticipated Primary Completion Date: Apr 1, 2025
• Anticipated Study Completion Date: Apr 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AOC 1001 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; AOC 1001 will be administered by intravenous (IV) infusion.
Experimental: AOC 1001 (with Placebo at Day 43) 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; Placebo will be administered by intravenous (IV) infusion.; Other Names: Saline ; Drug: AOC 1001; AOC 1001 will be administered by intravenous (IV) infusion.

Outcome Measures

Primary Outcome Measures

1. Number and severity of treatment-emergent adverse events (TEAEs) [Through study completion, up to Day 729]

Secondary Outcome Measures

1. Plasma pharmacokinetic (PK) parameters [Through study completion, up to Day 729]

   Maximum and trough plasma concentration

2. AOC 1001 levels in muscle tissue [Through Day 183]

3. Change and percentage change from baseline in DMPK mRNA knockdown [Through Day 183]

4. Change and percentage change from baseline in Spliceopathy [Through Day 183]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 66 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Los Angeles	Los Angeles	California	United States	90095
2	Stanford University	Palo Alto	California	United States	94304
3	University of Colorado	Denver	Colorado	United States	80045
4	University of Florida	Gainesville	Florida	United States	32608
5	Kansas University Medical Center	Kansas City	Kansas	United States	66205
6	University of Rochester Medical Center	Rochester	New York	United States	14642
7	Ohio State University	Columbus	Ohio	United States	43221
8	Virginia Commonwealth University	Richmond	Virginia	United States	23298

Sponsors and Collaborators

• Avidity Biosciences, Inc.

Investigators

• Study Director: Li Tai, MD, Avidity Biosciences, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Avidity Biosciences, Inc.
• ClinicalTrials.gov Identifier: NCT05479981
• Other Study ID Numbers: AOC 1001-CS2
• First Posted: Jul 29, 2022
• Last Update Posted: Jul 29, 2022
• Last Verified: Jul 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Avidity Biosciences, Inc.: 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
• Additional relevant MeSH terms: Muscular Dystrophies; Musculoskeletal Diseases; Myotonic Dystrophy; Muscular Diseases; Myotonic Disorders; Muscular Disorders, Atrophic; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Genetic Diseases, Inborn; Disease

Study Results

No Results Posted as of Jul 29, 2022