Safety, Tolerability and Pharmacokinetics of ERX-963 in Adults With Myotonic Dystrophy Type 1
Primary Purpose
Myotonic Dystrophy, Type 1 (DM1), Myotonic Dystrophy
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ERX-963
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Myotonic Dystrophy, Type 1 (DM1) focused on measuring Excessive Daytime Sleepiness, hypersomnia
Eligibility 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
Sites / Locations
- Stanford Neurosciences Health Center
- Sleep Medicine Specialists of South Florida
- University of Iowa
- The Center for Sleep & Wake Disorders
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
ERX-963 then placebo
Placebo then ERX-963
Arm Description
Participants in this arm will receive ERX-963 followed by a washout period. After the washout period, participants will receive placebo.
Participants in this arm will receive placebo followed by a washout period. After the washout period, participants will receive ERX-963.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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).
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.
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.
Full Information
NCT ID
NCT03959189
First Posted
May 16, 2019
Last Updated
June 22, 2021
Sponsor
Expansion Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03959189
Brief Title
Safety, Tolerability and Pharmacokinetics of ERX-963 in Adults With Myotonic Dystrophy Type 1
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
June 17, 2019 (Actual)
Primary Completion Date
March 31, 2020 (Actual)
Study Completion Date
April 30, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Expansion Therapeutics, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myotonic Dystrophy, Type 1 (DM1), Myotonic Dystrophy
Keywords
Excessive Daytime Sleepiness, hypersomnia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ERX-963 then placebo
Arm Type
Experimental
Arm Description
Participants in this arm will receive ERX-963 followed by a washout period. After the washout period, participants will receive placebo.
Arm Title
Placebo then ERX-963
Arm Type
Experimental
Arm Description
Participants in this arm will receive placebo followed by a washout period. After the washout period, participants will receive ERX-963.
Intervention Type
Drug
Intervention Name(s)
ERX-963
Intervention Description
Active medicine
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Comparator
Primary Outcome Measure Information:
Title
Incidence of Adverse Events, Serious Adverse Events, and Drug-related Adverse Events [Safety and Tolerability] After a Single Dose of ERX-963 vs. Placebo
Description
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.
Time Frame
Adverse Events were collected from screening to the End of Study Visit, up to 57 days
Secondary Outcome Measure Information:
Title
Assess the Effect of ERX-963 on the Stanford Sleepiness Scale Score Compared to the Effect of Placebo
Description
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.
Time Frame
From dosing to approximately 2 hours
Title
Assess the Effect of ERX-963 on the Change in Patient Global Impression - Improvement Scale (PGI-I) Compared to Placebo
Description
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.
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.
Title
Assess the Effect of ERX-963 on the Clinical Global Impressment - Improvement (CGI-I) Scale Compared to Placebo
Description
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).
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.
Title
Assess the Effect of ERX-963 on the Psychomotor Vigilance Task (PVT)
Description
Participants will be tested for their response time and number of lapses during the PVT.
Time Frame
From dosing to approximately 2 hours
Title
Assess the Effect of ERX-963 on the One-back Task
Description
Participants will be tested for the proportion of correct response to the One-back task.
Time Frame
From dosing to approximately 2 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elliot Ehrich, MD
Organizational Affiliation
Chief Medical Officer
Official's Role
Study Director
Facility Information:
Facility Name
Stanford Neurosciences Health Center
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Sleep Medicine Specialists of South Florida
City
Miami
State/Province
Florida
ZIP/Postal Code
33126
Country
United States
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
The Center for Sleep & Wake Disorders
City
Chevy Chase
State/Province
Maryland
ZIP/Postal Code
20815
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://www.expansionrx.com/
Description
Expansion Therapeutics Corporate Website
Learn more about this trial
Safety, Tolerability and Pharmacokinetics of ERX-963 in Adults With Myotonic Dystrophy Type 1
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