Study of AOC 1001 in Adult Myotonic Dystrophy Type 1 (DM1) Patients

Study Overview
=================
Brief Summary
-----------------
AOC 1001-CS1 is a randomized, double-blind, placebo-controlled, Phase 1/2 study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple-doses of AOC 1001 Administered Intravenously to Adult Myotonic Dystrophy Type 1 (DM1) patients (MARINA). Part A is a single dose design with 1 cohort (dose level). In Part A, the patient duration is 6 months as the treatment period is 1 day followed by a 6 month follow-up period. Part B is a multiple-ascending dose design with 2 cohorts (dose levels). In Part B, the patient duration is 6 months as the treatment period is 3 months followed by a 3 month follow-up period.

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled, Phase 1/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple-Doses of AOC 1001 Administered Intravenously to Adult Myotonic Dystrophy Type 1 (DM1) Patients

Conditions
-----------------
DM1, Myotonic Dystrophy 1, Myotonic Dystrophy, Myotonic Dystrophy Type 1 (DM1), Dystrophy Myotonic, Myotonic Disorders, Steinert Disease, Myotonic Muscular Dystrophy

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Genetic diagnosis of DM1 (CTG repeat length ≥ 100) Clinician assessed signs of DM1 Ability to walk independently (orthoses and ankle braces allowed) for at least 10 meters at screening Key Exclusion Criteria: Diabetes that is not adequately controlled BMI > 35 kg/m2 Uncontrolled hypertension Congenital DM1 History of tibialis anterior (TA) biopsy within 3 months of Day 1 or planning to undergo TA biopsies during study period Recently treated with an investigational drug Treatment with anti-myotonic medication within 14 days of Day 1 Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A Single Dose: AOC 1001 Dose Level 1<br>AOC 1001 will be administered once. | Drug: AOC 1001<br>* AOC 1001 will be administered by intravenous (IV) infusion.<br>|
| Placebo Comparator: Part A Single Dose: Placebo<br>Saline will be administered once. | Drug: Placebo<br>* Placebo will be administered by intravenous (IV) infusion.<br>|
| Experimental: Part B Multiple Ascending Dose: AOC 1001 Dose Levels 2 & 3<br>AOC 1001 will be administered three times. | Drug: AOC 1001<br>* AOC 1001 will be administered by intravenous (IV) infusion.<br>|
| Placebo Comparator: Part B Multiple Ascending Dose: Placebo<br>Saline will be administered three times. | Drug: Placebo<br>* Placebo will be administered by intravenous (IV) infusion.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of treatment emergent adverse events (TEAEs) |  | Through study completion, up to Day 183 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma pharmacokinetic (PK) parameters | Maximum plasma concentration (Cmax) | Through study completion, up to Day 183 | 
| Plasma pharmacokinetic (PK) parameters | Time to maximum plasma concentration (Tmax) | Through study completion, up to Day 183 | 
| Plasma pharmacokinetic (PK) parameters | Terminal Half-life (t1/2) | Through study completion, up to Day 183 | 
| Plasma pharmacokinetic (PK) parameters | Area Under the Concentration-time Curve (AUC) | Through study completion, up to Day 183 | 
| Urine pharmacokinetic (PK) parameters | fraction excreted (fe) in urine | Through study completion, up to Day 183 | 
| AOC 1001 levels in muscle tissue |  | Through study completion, up to Day 183 | 
| Change and percentage change from baseline in DMPK mRNA knockdown |  | Through study completion, up to Day 183 | 
| Change and percentage change from baseline in Spliceopathy |  | Through study completion, up to Day 183 | 

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