Safety and Efficacy of Tideglusib in Congenital or Childhood Onset Myotonic Dystrophy

Study Overview
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Brief Summary
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This is an open-label phase 2/3 study for individuals with Congenital Myotonic Dystrophy (Congenital DM1) who participated in the preceding AMO-02-MD-2-003 study or individuals with either Congenital or Childhood Onset DM1 who are treatment naïve.

Detailed Description
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This is an open-label study of weight-adjusted 1000 mg tideglusib, once daily for 52 weeks with an open-ended optional extended access period in children and adolescents with a diagnosis of Congenital DM1 who participated in the AMO-02-MD-2-003 study or individuals with either Congenital or Childhood Onset DM1 who are treatment naïve.

Official Title
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An Open-Label Study to Evaluate the Long-Term Safety and Efficacy of Tideglusib for the Treatment of Congenital or Childhood Onset DM1 (REACH CDM X)

Conditions
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Congenital Myotonic Dystrophy

Intervention / Treatment
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* Drug: Tideglusib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who do not enter this study directly from completing the AMO-02-MD-2-003 study (i.e. subjects who did not complete AMO-02-MD-2-003, subjects who completed AMO-02-MD-2-003 but did not directly rollover or subjects who are re-entering AMO-02-MD-2-004), will not be considered eligible for the study without meeting all of the criteria below: Subjects under study must be individuals with a diagnosis of Congenital or Childhood Onset DM1. Diagnosis must be genetically confirmed Subjects must be male or female aged ≥6 years to ≤45 years at Screening Subjects must have a Clinical Global Impression - Severity (CGI-S) score of 3 or greater at Screening (V-1) Written, voluntary informed consent must be obtained before any study related procedures are conducted. Where a parent or legally authorized representative (LAR) provides consent, there must also be assent from the subject (as required by local regulations) 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 Subjects entering directly from completing the antecedent AMO-02-MD-2-003 study will not be considered eligible for the study without meeting all of the criteria below: Subjects who have completed the antecedent AMO-02-MD-2-003 study through V11 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 (as required by local regulations) 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 Key Exclusion Criteria: 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 Eligibility/Baseline Visit Use within 4 weeks prior to Eligibility/Baseline Visit of strong CYP3A4 inhibitors (eg.clarithromycin, telithromycin, ketoconazole, itraconazole, posaconazole, nefazodone, idinavir and ritonavir) 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 other than the AMO-02- MD-2-003 study Existing or historical medical conditions or complications (eg. neurological, cardiovascular, renal, hepatic, gastrointestinal, endocrine or respiratory disease) that may impact the interpretability of the study results Hypersensitivity to tideglusib or any components of its formulation including allergy to strawberry

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 45 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tideglusib<br>Weight adjusted tideglusib, orally, once daily | Drug: Tideglusib<br>* All subjects will receive weight-adjusted 1000 mg tideglusib following a titration period of 2 weeks at a weight-adjusted dose of 400 mg and 2 weeks at a weight-adjusted dose of 600 mg tideglusib.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (Adverse Events) | The incidence of AEs, including SAEs, and abnormal findings in objective assessments (e.g. laboratory values, ECGs and vital signs) from Screening to Enrolment (where applicable), from Enrolment to End of Treatment (52 Weeks), and End of Treatment to the End of Follow-up period. | 52 Weeks | 
| Safety (Adverse Events) - With Optional Expanded Access | The incidence of AEs, including SAEs, and abnormal findings in objective assessments (e.g. laboratory values, ECGs and vital signs) from End of Treatment to End of Optional Extended Access, and End of Optional Extended Access to the End of Follow-up period. | Week 60 and every 8 weeks thereafter up until discontinuation or study closure, assessed up to Week 132 | 
| Clinician-Completed Congenital DM1 Rating Scale (CDM1-RS) | The Clinician-completed Congenital DM1 Rating Scale is an 11-item rating scale completed by the clinician to score the symptom severity of domains that are clinically relevant in Congenital DM1. | 52 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinician-Completed Congenital DM1 Rating Scale (CDM1-RS) - With Optional Expanded Access | The Clinician-completed Congenital DM1 Rating Scale is an 11-item rating scale completed by the clinician to score the symptom severity of domains that are clinically relevant in Congenital DM1. | Week 68 and every 16 weeks thereafter up until discontinuation or study closure, assessed up to Week 132 | 
| Clinical Global Impressions Improvement Scale (CGI-I) | The CGI-I requires the clinician to rate how much the subject's illness has changed (improved, worsened or stayed the same) relative to a baseline state. | 54 Weeks | 
| Clinical Global Impressions Improvement Scale (CGI-I) - With Optional Expanded Access | The CGI-I requires the clinician to rate how much the subject's illness has changed (improved, worsened or stayed the same) relative to a baseline state. | Week 68 and every 16 weeks thereafter up until discontinuation or study closure, assessed up to Week 132 | 
| 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. | 54 weeks | 
| Top 3 Caregiver Concerns Visual Analogue Scale (VAS) score - With Optional Expanded Access | 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. | Week 68 and every 16 weeks thereafter up until discontinuation or study closure, assessed up to Week 132 | 
| Caregiver Completed Congenital DM1 Rating Scale (CC-CDM1-RS) | CC-CDM1-RS provides a caregiver assessment of the subject on symptoms that may occur in individuals with CDM1. There are a total of 11 symptoms that the caregiver is asked to rate from 0 to 4 based on overall severity. | 52 weeks | 
| Caregiver Completed Congenital DM1 Rating Scale (CC-CDM1-RS) - With Optional Expanded Access | CC-CDM1-RS provides a caregiver assessment of the subject on symptoms that may occur in individuals with CDM1. There are a total of 11 symptoms that the caregiver is asked to rate from 0 to 4 based on overall severity. | Week 68 and every 16 weeks thereafter up until discontinuation or study closure, assessed up to Week 132 | 
| Clinical Global Impressions Severity Scale (CGI-S) | The CGI-S is a 7-point Likert type 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. | 54 weeks | 
| Clinical Global Impressions Severity Scale (CGI-S) - With Optional Expanded Access | The CGI-S is a 7-point Likert type 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. | Week 68 and every 16 weeks thereafter up until discontinuation or study closure, assessed up to Week 132 | 
| Autism Behavior Inventory- Clinician (ABI-C) | ABI-C is a 14 item rating scale requires the clinician to assess the core features of Autism Spectrum Disorder as well as common associated behaviors. | 52 Weeks | 
| Socialization, Communication, Daily Living, and Adaptive Behavior Composite standard scores of the Vineland Adaptive Behavior Scale - Survey Interview | The Vineland Adaptive Behavior Scales require the clinician to measure personal and social skills needed for everyday living. It provides a targeted assessment of adaptive behavior via a semi-structured parent or caregiver interview. | 52 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. | 52 Weeks | 
| Plasma Troponin T levels | Troponin T can be used as a biomarker for cardiac dysfunction but can also be elevated in DM1 patients without evident cardiac dysfunction. | 52 Weeks | 
| Plasma Troponin T levels - With Optional Expanded Access | Troponin T can be used as a biomarker for cardiac dysfunction but can also be elevated in DM1 patients without evident cardiac dysfunction. | Week 68 and every 16 weeks thereafter up until discontinuation or study closure, assessed up to Week 132 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tideglusib, AMO-02-MD-2-004, Congenital Myotonic Dystrophy, Myotonic Dystrophy, Dystrophia Myotonica, Myotonia Atrophica, Myotonia Dystrophica, Myotonic Dystrophy, Congenital, Steinert Disease, Steinert Myotonic Dystrophy, Steinert's Disease