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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ERX-963 then placebo | Experimental | Participants in this arm will receive ERX-963 followed by a washout period. After the washout period, participants will receive placebo. |
|
| Placebo then ERX-963 | Experimental | Participants in this arm will receive placebo followed by a washout period. After the washout period, participants will receive ERX-963. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ERX-963 | Drug | Active medicine |
| |
| Placebo |
| 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 |
| 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 |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Elliot Ehrich, MD | Chief Medical Officer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford Neurosciences Health Center | Palo Alto | California | 94305 | United States | ||
| Sleep Medicine Specialists of South Florida |
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| Label | URL |
|---|---|
| Expansion Therapeutics Corporate Website | View source |
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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).
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Count of Participants | Participants | Adverse Events were collected from screening to the End of Study Visit, up to 57 days |
Adverse Events were collected from screening to the End of Study Visit, which was a period of up to 57 days
The adverse event and serious adverse event definition for this study did not differ from the clinicaltrials.gov definitions.
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1: Placebo Period | The crossover design tests each subject under different treatment conditions allowing for each subject to serve as their own control. 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diplopia | Eye disorders | Systematic Assessment |
The 0.5 mg dose level was not tested in this study.
The analyses of the effect of ERX-963 on the Psychomotor Vigilance Task and the One-Back task were removed from the final analysis and documented accordingly in a Statistical Analysis Plan memo.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Expansion Therapeutics, Inc. | 858-764-4290 | info@expansionrx.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 31, 2019 | Jan 11, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 2, 2020 | Jan 11, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D009223 | Myotonic Dystrophy |
| D006970 | Disorders of Excessive Somnolence |
| ID | Term |
|---|---|
| D009136 | Muscular Dystrophies |
| D020966 | Muscular Disorders, Atrophic |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
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| Drug |
Comparator |
|
| 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 |
| Miami |
| Florida |
| 33126 |
| United States |
| University of Iowa | Iowa City | Iowa | 52242 | United States |
| The Center for Sleep & Wake Disorders | Chevy Chase | Maryland | 20815 | United States |
| 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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | Cohort 1: 1 mg ERX-963 | The crossover design tests each subject under different treatment conditions allowing for each subject to serve as their own control. 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. |
| OG001 | Cohort 2: 2 mg ERX-963 | The crossover design tests each subject under different treatment conditions allowing for each subject to serve as their own control. 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. |
|
|
| 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. | All treated participants who completed all the protocol specified assessments in both treatment periods were analyzed. | Posted | Mean | Standard Deviation | score on a scale | From dosing to approximately 2 hours |
|
|
|
|
| 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. | All treated participants who completed all the protocol specified assessments in both treatment periods were analyzed. | Posted | Mean | Standard Deviation | Score of a scale | Administered at the end of the dosing visit day, upon completion of the other outcome measures. Approximately 2 hours after the end of infusion. |
|
|
|
| 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). | All treated participants who completed all the protocol specified assessments in both treatment periods were analyzed. | Posted | Mean | Standard Deviation | Score on a scale | Administered at the end of the dosing visit day, upon completion of the other outcome measures. Approximately 2 hours after the end of infusion. |
|
|
|
| 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. | 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. | Posted | From dosing to approximately 2 hours |
|
|
| 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. | 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. | Posted | From dosing to approximately 2 hours |
|
|
| 0 |
| 7 |
| 0 |
| 7 |
| 0 |
| 7 |
| EG001 | Cohort 1: 1 mg ERX-963 Period | The crossover design tests each subject under different treatment conditions allowing for each subject to serve as their own control. 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. | 0 | 7 | 0 | 7 | 1 | 7 |
| EG002 | Cohort 2: Placebo Period | The crossover design tests each subject under different treatment conditions allowing for each subject to serve as their own control. 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. | 0 | 5 | 0 | 5 | 2 | 5 |
| EG003 | Cohort 2: 2 mg ERX-963 Period | The crossover design tests each subject under different treatment conditions allowing for each subject to serve as their own control. 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. | 0 | 5 | 0 | 5 | 1 | 5 |
| Infusion site pain | General disorders | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Hypersomnia | Nervous system disorders | Systematic Assessment |
|
Expansion Therapeutics reserves the right to embargo communications regarding trial results prior to public release for a period ≤ 60 days in order to protect patentable information. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed company confidential information other than study results.
| D020967 | Myotonic Disorders |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D009422 | Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D020919 | Sleep Disorders, Intrinsic |
| D020920 | Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D001523 | Mental Disorders |
| 10 min. after end of infusion, SSS |
|
| 40 min. after end of infusion, SSS |
|
| 1 hr., 10 min. after end of infusion, SSS |
|
| 1 hr., 40 min. after end of infusion, SSS |
|
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. |
| Mixed Models Analysis |
| 0.4700 |
| mixed effects model |
| -0.2608 |
| Standard Error of the Mean |
| 0.3589 |
| 2-Sided |
| 95 |
| -1.0 |
| 0.5 |
| Superiority |
| 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. | Mixed Models Analysis | 0.8127 | mixed effects model | 0.1016 | Standard Error of the Mean | 0.4272 | 2-Sided | 95 | -0.8 | 1.0 | Superiority |