Myotonic Dystrophy, Myotonic Dystrophy, Type 1 (DM1)
Conditions
Keywords
Excessive Daytime Sleepiness, hypersomnia
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.
Interventions
DRUGERX-963
Active medicine
DRUGPlacebo
Comparator
Sponsors
Expansion Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events, Serious Adverse Events, and Drug-related Adverse Events [Safety and Tolerability] After a Single Dose of ERX-963 vs. Placebo | 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
| Measure | Time frame | Description |
|---|---|---|
| Assess the Effect of ERX-963 on the Stanford Sleepiness Scale Score Compared to the Effect of Placebo | 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. |
| Assess the Effect of ERX-963 on the Change in Patient Global Impression - Improvement Scale (PGI-I) Compared to Placebo | 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. |
| Assess the Effect of ERX-963 on the Clinical Global Impressment - Improvement (CGI-I) Scale Compared to Placebo | 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). |
| Assess the Effect of ERX-963 on the Psychomotor Vigilance Task (PVT) | From dosing to approximately 2 hours | 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 | From dosing to approximately 2 hours | Participants will be tested for the proportion of correct response to the One-back task. |
Countries
United States
Participant flow
Recruitment details
Between June 2019 and March 2020, 12 patients were enrolled and treated with ERX-963 at three sites in the United States (Stanford University Neurosciences Health Center, University of Iowa Hospitals and Clinics, and Sleep Specialists of South Florida).
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: 1 mg ERX-963 Sequence 1: Participants will receive placebo followed by a washout period. After the washout period, participants will receive 1 mg of ERX-963.
Sequence 2: Participants will receive 1 mg of ERX-963 followed by a washout period. After the washout period, participants will receive placebo. | 7 |
| Cohort 2: 2 mg ERX-963 Sequence 1: Participants will receive placebo followed by a washout period. After the washout period, participants will receive 2 mg of ERX-963.
Sequence 2: Participants will receive 2 mg of ERX-963 followed by a washout period. After the washout period, participants will receive placebo. | 5 |
| Total | 12 |
Baseline characteristics
| Characteristic | Cohort 1: 1 mg ERX-963 | Total | Cohort 2: 2 mg ERX-963 |
|---|---|---|---|
| Age, Continuous | 54.0 years | 51.5 years | 44.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 12 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 12 Participants | 5 Participants |
| Region of Enrollment United States | 7 participants | 12 participants | 5 participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 1 Participants |
| Sex: Female, Male Male | 2 Participants | 6 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 7 | 0 / 5 | 0 / 5 |
| other Total, other adverse events | 0 / 7 | 1 / 7 | 2 / 5 | 1 / 5 |
| serious Total, serious adverse events | 0 / 7 | 0 / 7 | 0 / 5 | 0 / 5 |
Outcome results
Primary
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.
Time frame: Adverse Events were collected from screening to the End of Study Visit, up to 57 days
Population: The safety population is defined as all participants who sign the study-specific informed consent documents and received at least 1 dose of ERX-963 or placebo.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: 1 mg ERX-963 | Incidence of Adverse Events, Serious Adverse Events, and Drug-related Adverse Events [Safety and Tolerability] After a Single Dose of ERX-963 vs. Placebo | Drug-related AEs in Placebo period | 1 Participants |
| Cohort 1: 1 mg ERX-963 | Incidence of Adverse Events, Serious Adverse Events, and Drug-related Adverse Events [Safety and Tolerability] After a Single Dose of ERX-963 vs. Placebo | TEAEs in Placebo period | 0 Participants |
| Cohort 1: 1 mg ERX-963 | Incidence of Adverse Events, Serious Adverse Events, and Drug-related Adverse Events [Safety and Tolerability] After a Single Dose of ERX-963 vs. Placebo | Drug-related AEs in ERX-963 period | 0 Participants |
| Cohort 1: 1 mg ERX-963 | Incidence of Adverse Events, Serious Adverse Events, and Drug-related Adverse Events [Safety and Tolerability] After a Single Dose of ERX-963 vs. Placebo | TEAEs in ERX-963 period | 1 Participants |
| Cohort 1: 1 mg ERX-963 | Incidence of Adverse Events, Serious Adverse Events, and Drug-related Adverse Events [Safety and Tolerability] After a Single Dose of ERX-963 vs. Placebo | Serious Adverse Events | 0 Participants |
| Cohort 2: 2 mg ERX-963 | Incidence of Adverse Events, Serious Adverse Events, and Drug-related Adverse Events [Safety and Tolerability] After a Single Dose of ERX-963 vs. Placebo | TEAEs in ERX-963 period | 1 Participants |
| Cohort 2: 2 mg ERX-963 | Incidence of Adverse Events, Serious Adverse Events, and Drug-related Adverse Events [Safety and Tolerability] After a Single Dose of ERX-963 vs. Placebo | Serious Adverse Events | 0 Participants |
| Cohort 2: 2 mg ERX-963 | Incidence of Adverse Events, Serious Adverse Events, and Drug-related Adverse Events [Safety and Tolerability] After a Single Dose of ERX-963 vs. Placebo | Drug-related AEs in Placebo period | 1 Participants |
| Cohort 2: 2 mg ERX-963 | Incidence of Adverse Events, Serious Adverse Events, and Drug-related Adverse Events [Safety and Tolerability] After a Single Dose of ERX-963 vs. Placebo | Drug-related AEs in ERX-963 period | 0 Participants |
| Cohort 2: 2 mg ERX-963 | Incidence of Adverse Events, Serious Adverse Events, and Drug-related Adverse Events [Safety and Tolerability] After a Single Dose of ERX-963 vs. Placebo | TEAEs in Placebo period | 2 Participants |
Secondary
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.
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.
Population: All treated participants who completed all the protocol specified assessments in both treatment periods were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 1 mg ERX-963 | Assess the Effect of ERX-963 on the Change in Patient Global Impression - Improvement Scale (PGI-I) Compared to Placebo | 3.4 Score of a scale | Standard Deviation 1.27 |
| Cohort 2: 2 mg ERX-963 | Assess the Effect of ERX-963 on the Change in Patient Global Impression - Improvement Scale (PGI-I) Compared to Placebo | 3.4 Score of a scale | Standard Deviation 1.13 |
| Cohort 2: Placebo Period | Assess the Effect of ERX-963 on the Change in Patient Global Impression - Improvement Scale (PGI-I) Compared to Placebo | 4.0 Score of a scale | Standard Deviation 2 |
| Cohort 2: 2 mg ERX-963 Period | Assess the Effect of ERX-963 on the Change in Patient Global Impression - Improvement Scale (PGI-I) Compared to Placebo | 4.2 Score of a scale | Standard Deviation 1.92 |
Secondary
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).
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.
Population: All treated participants who completed all the protocol specified assessments in both treatment periods were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: 1 mg ERX-963 | Assess the Effect of ERX-963 on the Clinical Global Impressment - Improvement (CGI-I) Scale Compared to Placebo | 3.7 Score on a scale | Standard Deviation 1.25 |
| Cohort 2: 2 mg ERX-963 | Assess the Effect of ERX-963 on the Clinical Global Impressment - Improvement (CGI-I) Scale Compared to Placebo | 3.9 Score on a scale | Standard Deviation 0.9 |
| Cohort 2: Placebo Period | Assess the Effect of ERX-963 on the Clinical Global Impressment - Improvement (CGI-I) Scale Compared to Placebo | 4.0 Score on a scale | Standard Deviation 1.22 |
| Cohort 2: 2 mg ERX-963 Period | Assess the Effect of ERX-963 on the Clinical Global Impressment - Improvement (CGI-I) Scale Compared to Placebo | 4.4 Score on a scale | Standard Deviation 1.67 |
Secondary
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.
Time frame: From dosing to approximately 2 hours
Population: One-back task analysis was not performed for this study as this outcome measure analysis requirement was removed in the amended statistical plan. At the end of the clinical study, the project was terminated and the development group was disbanded. The entire team that worked on this project departed and moved on to their new companies. Therefore, this Outcome Measure has zero total analyzed.
Secondary
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.
Time frame: From dosing to approximately 2 hours
Population: PVT analysis was not performed for this study as this outcome measure analysis requirement was removed in the amended statistical plan. At the end of the clinical study, the project was terminated and the development group was disbanded. The entire team that worked on this project departed and moved on to their new companies. Therefore, this Outcome Measure has zero total analyzed.
Secondary
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.
Time frame: From dosing to approximately 2 hours
Population: All treated participants who completed all the protocol specified assessments in both treatment periods were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 1 mg ERX-963 | Assess the Effect of ERX-963 on the Stanford Sleepiness Scale Score Compared to the Effect of Placebo | 1 hr., 10 min. after end of infusion, SSS | 3.7 score on a scale | Standard Deviation 1.98 |
| Cohort 1: 1 mg ERX-963 | Assess the Effect of ERX-963 on the Stanford Sleepiness Scale Score Compared to the Effect of Placebo | 10 min. after end of infusion, SSS | 3.0 score on a scale | Standard Deviation 0.82 |
| Cohort 1: 1 mg ERX-963 | Assess the Effect of ERX-963 on the Stanford Sleepiness Scale Score Compared to the Effect of Placebo | 1 hr., 40 min. after end of infusion, SSS | 3.6 score on a scale | Standard Deviation 1.4 |
| Cohort 1: 1 mg ERX-963 | Assess the Effect of ERX-963 on the Stanford Sleepiness Scale Score Compared to the Effect of Placebo | 40 min. after end of infusion, SSS | 3.1 score on a scale | Standard Deviation 1.57 |
| Cohort 1: 1 mg ERX-963 | Assess the Effect of ERX-963 on the Stanford Sleepiness Scale Score Compared to the Effect of Placebo | baseline Stanford Sleepiness Score | 3.4 score on a scale | Standard Deviation 0.79 |
| Cohort 2: 2 mg ERX-963 | Assess the Effect of ERX-963 on the Stanford Sleepiness Scale Score Compared to the Effect of Placebo | 40 min. after end of infusion, SSS | 2.9 score on a scale | Standard Deviation 1.68 |
| Cohort 2: 2 mg ERX-963 | Assess the Effect of ERX-963 on the Stanford Sleepiness Scale Score Compared to the Effect of Placebo | 1 hr., 10 min. after end of infusion, SSS | 3.1 score on a scale | Standard Deviation 1.57 |
| Cohort 2: 2 mg ERX-963 | Assess the Effect of ERX-963 on the Stanford Sleepiness Scale Score Compared to the Effect of Placebo | baseline Stanford Sleepiness Score | 3.4 score on a scale | Standard Deviation 0.79 |
| Cohort 2: 2 mg ERX-963 | Assess the Effect of ERX-963 on the Stanford Sleepiness Scale Score Compared to the Effect of Placebo | 1 hr., 40 min. after end of infusion, SSS | 3.3 score on a scale | Standard Deviation 0.76 |
| Cohort 2: 2 mg ERX-963 | Assess the Effect of ERX-963 on the Stanford Sleepiness Scale Score Compared to the Effect of Placebo | 10 min. after end of infusion, SSS | 2.7 score on a scale | Standard Deviation 1.6 |
| Cohort 2: Placebo Period | Assess the Effect of ERX-963 on the Stanford Sleepiness Scale Score Compared to the Effect of Placebo | 40 min. after end of infusion, SSS | 4.2 score on a scale | Standard Deviation 1.92 |
| Cohort 2: Placebo Period | Assess the Effect of ERX-963 on the Stanford Sleepiness Scale Score Compared to the Effect of Placebo | baseline Stanford Sleepiness Score | 4.0 score on a scale | Standard Deviation 2.12 |
| Cohort 2: Placebo Period | Assess the Effect of ERX-963 on the Stanford Sleepiness Scale Score Compared to the Effect of Placebo | 10 min. after end of infusion, SSS | 4.0 score on a scale | Standard Deviation 1.87 |
| Cohort 2: Placebo Period | Assess the Effect of ERX-963 on the Stanford Sleepiness Scale Score Compared to the Effect of Placebo | 1 hr., 10 min. after end of infusion, SSS | 4.0 score on a scale | Standard Deviation 1.73 |
| Cohort 2: Placebo Period | Assess the Effect of ERX-963 on the Stanford Sleepiness Scale Score Compared to the Effect of Placebo | 1 hr., 40 min. after end of infusion, SSS | 4.6 score on a scale | Standard Deviation 1.82 |
| Cohort 2: 2 mg ERX-963 Period | Assess the Effect of ERX-963 on the Stanford Sleepiness Scale Score Compared to the Effect of Placebo | 1 hr., 10 min. after end of infusion, SSS | 5.0 score on a scale | Standard Deviation 2.45 |
| Cohort 2: 2 mg ERX-963 Period | Assess the Effect of ERX-963 on the Stanford Sleepiness Scale Score Compared to the Effect of Placebo | 10 min. after end of infusion, SSS | 3.8 score on a scale | Standard Deviation 2.39 |
| Cohort 2: 2 mg ERX-963 Period | Assess the Effect of ERX-963 on the Stanford Sleepiness Scale Score Compared to the Effect of Placebo | baseline Stanford Sleepiness Score | 4.2 score on a scale | Standard Deviation 2.17 |
| Cohort 2: 2 mg ERX-963 Period | Assess the Effect of ERX-963 on the Stanford Sleepiness Scale Score Compared to the Effect of Placebo | 40 min. after end of infusion, SSS | 4.0 score on a scale | Standard Deviation 2.45 |
| Cohort 2: 2 mg ERX-963 Period | Assess the Effect of ERX-963 on the Stanford Sleepiness Scale Score Compared to the Effect of Placebo | 1 hr., 40 min. after end of infusion, SSS | 5.6 score on a scale | Standard Deviation 1.82 |
Comparison: A mixed effects model will be used to compare SSS effects following ERX-963 versus placebo. In the primary analysis of SSS, the cohort 1 and cohort 2 data were combined for ERX-963 and placebo treatments.p-value: 0.774695% CI: [-0.6, 0.5]Mixed Models Analysis
Comparison: A mixed effects model will be used to compare SSS effects following 1 mg ERX-963 versus placebo. In this analysis of SSS, the effect of 1 mg ERX-963 treatment was compared to the effect of placebo treatment.p-value: 0.4795% CI: [-1, 0.5]Mixed Models Analysis
Comparison: A mixed effects model will be used to compare SSS effects following 2 mg ERX-963 versus placebo. In this analysis of SSS, the effect of 2 mg ERX-963 treatment was compared to the effect of placebo treatment.p-value: 0.812795% CI: [-0.8, 1]Mixed Models Analysis