Efficacy and Safety of Tideglusib in Congenital Myotonic Dystrophy

Study Overview
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Brief Summary
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This is a randomized, multicenter, double-blind, placebo-controlled, Phase 2/3 study of patients (aged 6 to 16 years) diagnosed with Congenital Myotonic Dystrophy (Congenital DM1).

Detailed Description
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This is a randomized, double-blind, placebo controlled study of weight adjusted dose 1000 mg/day tideglusib versus placebo in the treatment of children and adolescents 6-16 years of age with Congenital DM1.

Official Title
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A Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Tideglusib Versus Placebo for the Treatment of Children and Adolescents With Congenital Myotonic Dystrophy (REACH CDM)

Conditions
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Congenital Myotonic Dystrophy

Intervention / Treatment
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* Drug: Tideglusib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female children and adolescents aged ≥6 years and ≤16 years Diagnosis of Congenital DM1 (also known as Steinert's disease) Diagnosis must be genetically confirmed One or more of the following clinically relevant (e.g. requiring medical intervention) signs or symptoms was evident within the first month after birth: Hypotonia Generalized weakness Respiratory insufficiency Feeding difficulties Clubfoot or another musculoskeletal deformity Subject must be able to walk and complete the 10-meter walk-run test (orthotics/splints allowed, forearm crutches are not allowed) Written, voluntary informed consent must be obtained before any study related procedures are conducted. Where a parent or LAR provides consent, there must also be assent from the subject Subject's caregiver must be willing and able to support participation for duration of study Subject must be willing and able to comply with the required food intake restrictions as outlined per protocol Exclusion Criteria: Not able to walk; (full time wheel chair use) Body mass index (BMI) less than 13.5 kg/m² or greater than 40 kg/m² New or change in medications/therapies within 4 weeks prior to Screening Use of strong CYP3A4 inhibitors (e.g clarithromycin, telithromycin, ketoconazole, itraconazole, posaconazole, nefazodone, idinavir and ritonavir) within 4 weeks prior to Baseline Concurrent use of drugs metabolized by CYP3A4 with a narrow therapeutic window (e.g. warfarin and digitoxin) Current enrollment in a clinical trial of an investigational drug or enrollment in a clinical trial of an investigational drug in the last 6 months Existing or historical medical conditions or complications (e.g. neurological, cardiovascular, renal, hepatic, endocrine, gastrointestinal or respiratory disease) which would cause the investigator to conclude that the subject will not be able to perform the study procedures or assessments or would confound interpretation of data obtained during assessment Hypersensitivity to tideglusib and its excipients including allergy to strawberry

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 16 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tideglusib<br>Weight adjusted tideglusib, orally, once daily | Drug: Tideglusib<br>* Tideglusib for oral suspension, weight-adjusted at 400mg, 600mg or 1000 mg dose levels, once daily<br>Drug: Placebo<br>* Matching placebo formulation<br>|
| Placebo Comparator: Placebo<br>Matching placebo, orally, once daily | Drug: Placebo<br>* Matching placebo formulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Clinician-Completed Congenital DM1 Rating Scale (CDM1-RS) | The Clinician-Completed Congenital DM1 Scale is an 11-item rating scale completed by the clinician that scores the symptom severity of domains that are clinically relevant in Congenital DM1. | 22 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Clinical Global Impression- Improvement Scale (CGI-I) scores | The clinician administered CGI-I rates how much the subject's illness has improved or worsened relative to a baseline state. | 22 weeks | 
| Change in Top 3 Caregiver Concerns Visual Analogue Scale (VAS) score | The Top 3 concerns VAS allows caregivers to identify their main three causes of concern, related to the subject's myotonic dystrophy, rather than these being pre-specified within a scale and then rating how these concerns have changed at specific time-points during the study. | 22 Weeks | 
| Caregiver Completed Congenital DM1 Rating Scale (CC-CDM1-RS) | The Caregiver-Completed Congenital DM1 Scale is a caregiver assessment of the subject on symptoms that may occur in individuals with CDM1. There are a total of 11 clinically relevant symptoms that the caregiver is asked to rate the severity of. | 22 weeks | 
| Clinical Global Impression - Severity Scale (CGI-S) | The Clinical Global Impression - Severity Scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the subject's illness at the time of assessment, relative to the clinician's past experience with subjects who have the same diagnosis. | 22 weeks | 
| 10-meter walk-run test | The 10-meter walk/run test is a performance measure used to assess walking speed in meters per second over a short distance. It can be used as an assessment of functional mobility. | 22 weeks | 
| Incidence of Adverse events (AEs), including serious adverse events (SAEs), between Screening to end of study. | Adverse events may be volunteered spontaneously by the subject, or discovered as a result of general, non-leading questioning by physician. | 22 to 28 weeks | 
| Incidence of abnormal findings in objective assessments (e.g. laboratory values, ECGs, vital signs and bone mineral density) between Screening and end of study. | Abnormal laboratory findings (e.g. hematology, liver function, biochemistry, urinalysis) or other abnormal assessments (e.g. ECGs, vital signs) that are judged by the Investigator as clinically significant will be recorded as AEs or SAEs if they meet the definition of an AE. The Investigator will exercise his or her medical and scientific judgment in deciding whether an abnormal laboratory finding or other abnormal assessment is clinically significant. | 22 to 28 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tideglusib, AMO-02-MD-2-003, Congenital Myotonic Dystrophy, Myotonic Dystrophy, Dystrophia Myotonica, Myotonia Atrophica, Myotonia Dystrophica, Myotonic Dystrophy, Congenital, Steinert Disease, Steinert Myotonic Dystrophy, Steinert's Disease