Safety, Tolerability and Pharmacokinetics of ERX-963 in Adults With Myotonic Dystrophy Type 1

Study Overview
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Brief Summary
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Participants in this study will receive two treatments, placebo and ERX-963, on different days in a randomized fashion. The primary purpose of this study is to investigate the safety and tolerability of ERX-963 in participants diagnosed with Myotonic Dystrophy, Type 1 (DM1). The secondary purpose is to evaluate the potential of ERX-963 treatment to reduce excessive daytime sleepiness / hypersomnia and improve cognitive function in DM1 participants compared to placebo treatment.

Detailed Description
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This study is evaluating single administration of two dose levels of ERX-963 to explore the relationship between dose, safety, tolerability, exposure and clinical benefit. This is a multi-center, randomized, double-blind, placebo-controlled, two-treatment period crossover study in two cohorts of participants with DM1. Participants who have consented and meet eligibility criteria will receive two treatments, placebo and ERX-963, in a randomized crossover fashion with a washout period between the treatments. On treatment days, participants will receive treatment followed by repeated blood collection for pharmacokinetic analysis and administration of a battery of outcome measures relevant to sleep and cognition.

Official Title
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Double-Blind, Placebo-Controlled, Dose-Range-Finding, Crossover Trial of Single Day Administration of ERX-963 in Adults With Myotonic Dystrophy Type 1

Conditions
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Myotonic Dystrophy, Type 1 (DM1), Myotonic Dystrophy

Intervention / Treatment
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* Drug: ERX-963
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 18 to 65 years of age DM1 defined by genetic testing or clinical-confirmation Epworth Sleepiness Scale (ESS) of > 11 or participants who have long sleep periods of an average of > 10 hours a day Age of onset of DM1 greater than 16 years Key Exclusion Criteria: Significant respiratory compromise Significant cardiac disease Diagnosis of symptomatic Restless Leg Syndrome or significant untreated nocturnal hypoxias Significant moderate to severe hepatic insufficiency Clinically active depression, anxiety, or other medical condition that, in the investigator's opinion, would interfere with the safety and efficacy assessments History of seizures History of panic disorders

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ERX-963 then placebo<br>Participants in this arm will receive ERX-963 followed by a washout period. After the washout period, participants will receive placebo. | Drug: ERX-963<br>* Active medicine<br>|
| Experimental: Placebo then ERX-963<br>Participants in this arm will receive placebo followed by a washout period. After the washout period, participants will receive ERX-963. | Drug: Placebo<br>* Comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events, Serious Adverse Events, and Drug-related Adverse Events [Safety and Tolerability] After a Single Dose of ERX-963 vs. Placebo | An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. Treatment-emergent AEs were AEs which started between the date and time of study drug dosing and through Study Day 2, within each period. Drug-related AEs were assessed by the investigator to determine the relationship (related or unrelated) between the study intervention and each AE occurrence. | Adverse Events were collected from screening to the End of Study Visit, up to 57 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the Effect of ERX-963 on the Stanford Sleepiness Scale Score Compared to the Effect of Placebo | Participants will self-report their level of sleepiness by self-rated questionnaire Stanford Sleepiness Scale (SSS). This is a single item questionnaire on a 7-point scale (1-7). Higher values indicate worse outcome. | From dosing to approximately 2 hours | 
| Assess the Effect of ERX-963 on the Change in Patient Global Impression - Improvement Scale (PGI-I) Compared to Placebo | The PGI-I is a 7-point rating system used by the patient to rate their overall clinical condition after intervention relative to before intervention where 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse, and 7=very much worse. | Administered at the end of the dosing visit day, upon completion of the other outcome measures. Approximately 2 hours after the end of infusion. | 
| Assess the Effect of ERX-963 on the Clinical Global Impressment - Improvement (CGI-I) Scale Compared to Placebo | The CGI-I is a 7-point rating system used by the clinician or investigator to compare the patient's overall clinical condition after intervention relative to before intervention where 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse, and 7=very much worse (Guy, 1976; Busner, 2007). | Administered at the end of the dosing visit day, upon completion of the other outcome measures. Approximately 2 hours after the end of infusion. | 
| Assess the Effect of ERX-963 on the Psychomotor Vigilance Task (PVT) | Participants will be tested for their response time and number of lapses during the PVT. | From dosing to approximately 2 hours | 
| Assess the Effect of ERX-963 on the One-back Task | Participants will be tested for the proportion of correct response to the One-back task. | From dosing to approximately 2 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Excessive Daytime Sleepiness, hypersomnia