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

• ClinicalTrials.gov Identifier: NCT03959189
• Recruitment Status: Completed
• First Posted: May 22, 2019
• Results First Posted: June 23, 2021
• Last Update Posted: June 23, 2021
• Sponsor: Expansion Therapeutics, Inc.
• Information provided by (Responsible Party): Expansion Therapeutics, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Myotonic Dystrophy, Type 1 (DM1); Myotonic Dystrophy	Drug: ERX-963; Drug: Placebo	Phase 1

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Double-Blind, Placebo-Controlled, Dose-Range-Finding, Crossover Trial of Single Day Administration of ERX-963 in Adults With Myotonic Dystrophy Type 1
• Actual Study Start Date: June 17, 2019
• Actual Primary Completion Date: March 31, 2020
• Actual Study Completion Date: April 30, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: ERX-963 then placebo; Participants in this arm will receive ERX-963 followed by a washout period. After the washout period, participants will receive placebo.	Drug: ERX-963; Active medicine
Experimental: Placebo then ERX-963; Participants in this arm will receive placebo followed by a washout period. After the washout period, participants will receive ERX-963.	Drug: Placebo; Comparator

Outcome Measures

Primary Outcome Measures :

1. Incidence of Adverse Events, Serious Adverse Events, and Drug-related Adverse Events [Safety and Tolerability] After a Single Dose of ERX-963 vs. Placebo [ Time Frame: Adverse Events were collected from screening to the End of Study Visit, up to 57 days ]
   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.

Secondary Outcome Measures :

1. Assess the Effect of ERX-963 on the Stanford Sleepiness Scale Score Compared to the Effect of Placebo [ Time Frame: From dosing to approximately 2 hours ]
   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.
2. Assess the Effect of ERX-963 on the Change in Patient Global Impression - Improvement Scale (PGI-I) Compared to Placebo [ Time Frame: Administered at the end of the dosing visit day, upon completion of the other outcome measures. Approximately 2 hours after the end of infusion. ]
   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.
3. Assess the Effect of ERX-963 on the Clinical Global Impressment - Improvement (CGI-I) Scale Compared to Placebo [ Time Frame: Administered at the end of the dosing visit day, upon completion of the other outcome measures. Approximately 2 hours after the end of infusion. ]
   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).
4. Assess the Effect of ERX-963 on the Psychomotor Vigilance Task (PVT) [ Time Frame: From dosing to approximately 2 hours ]
   Participants will be tested for their response time and number of lapses during the PVT.
5. Assess the Effect of ERX-963 on the One-back Task [ Time Frame: From dosing to approximately 2 hours ]
   Participants will be tested for the proportion of correct response to the One-back task.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

Stanford Neurosciences Health Center

Palo Alto, California, United States, 94305

United States, Florida

Sleep Medicine Specialists of South Florida

Miami, Florida, United States, 33126

United States, Iowa

University of Iowa

Iowa City, Iowa, United States, 52242

United States, Maryland

The Center for Sleep & Wake Disorders

Chevy Chase, Maryland, United States, 20815

Sponsors and Collaborators

Expansion Therapeutics, Inc.

Investigators

• Study Director: Elliot Ehrich, MD; Chief Medical Officer

  Study Documents (Full-Text)

Documents provided by Expansion Therapeutics, Inc.:

Study Protocol  [PDF] October 31, 2019

Statistical Analysis Plan  [PDF] April 2, 2020

More Information

Additional Information:

Expansion Therapeutics Corporate Website 

• Responsible Party: Expansion Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03959189
• Other Study ID Numbers: ERX-963-001
• First Posted: May 22, 2019
• Results First Posted: June 23, 2021
• Last Update Posted: June 23, 2021
• Last Verified: May 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Expansion Therapeutics, Inc.:

Excessive Daytime Sleepiness; hypersomnia

Additional relevant MeSH terms:

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