Safety and Efficacy of Tideglusib in Congenital or Childhood Onset Myotonic Dystrophy
- Registration Number
- NCT05004129
- Lead Sponsor
- AMO Pharma Limited
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 76
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Tideglusib Tideglusib Weight adjusted tideglusib, orally, once daily
- Primary Outcome Measures
Name Time Method Safety (Adverse Events) 52 Weeks 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.
Safety (Adverse Events) - With Optional Expanded Access Week 60 and every 8 weeks thereafter up until discontinuation or study closure, assessed up to Week 132 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.
Clinician-Completed Congenital DM1 Rating Scale (CDM1-RS) 52 Weeks 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.
- Secondary Outcome Measures
Name Time Method Caregiver Completed Congenital DM1 Rating Scale (CC-CDM1-RS) - With Optional Expanded Access Week 68 and every 16 weeks thereafter up until discontinuation or study closure, assessed up to Week 132 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.
Clinical Global Impressions Severity Scale (CGI-S) 54 weeks 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.
Top 3 Caregiver Concerns Visual Analogue Scale (VAS) score - With Optional Expanded Access Week 68 and every 16 weeks thereafter up until discontinuation or study closure, assessed up to Week 132 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.
Caregiver Completed Congenital DM1 Rating Scale (CC-CDM1-RS) 52 weeks 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.
Clinician-Completed Congenital DM1 Rating Scale (CDM1-RS) - With Optional Expanded Access Week 68 and every 16 weeks thereafter up until discontinuation or study closure, assessed up to Week 132 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.
Clinical Global Impressions Improvement Scale (CGI-I) 54 Weeks 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.
Clinical Global Impressions Improvement Scale (CGI-I) - With Optional Expanded Access Week 68 and every 16 weeks thereafter up until discontinuation or study closure, assessed up to Week 132 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.
Top 3 Caregiver Concerns Visual Analogue Scale (VAS) score 54 weeks 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.
Autism Behavior Inventory- Clinician (ABI-C) 52 Weeks 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.
Socialization, Communication, Daily Living, and Adaptive Behavior Composite standard scores of the Vineland Adaptive Behavior Scale - Survey Interview 52 Weeks 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.
10-meter walk-run test 52 Weeks 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.
Clinical Global Impressions Severity Scale (CGI-S) - With Optional Expanded Access Week 68 and every 16 weeks thereafter up until discontinuation or study closure, assessed up to Week 132 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.
Plasma Troponin T levels 52 Weeks Troponin T can be used as a biomarker for cardiac dysfunction but can also be elevated in DM1 patients without evident cardiac dysfunction.
Plasma Troponin T levels - With Optional Expanded Access Week 68 and every 16 weeks thereafter up until discontinuation or study closure, assessed up to Week 132 Troponin T can be used as a biomarker for cardiac dysfunction but can also be elevated in DM1 patients without evident cardiac dysfunction.
Trial Locations
- Locations (14)
Children's Hospital of Eastern Ontario
🇨🇦Ottawa, Ontario, Canada
New Zealand Clinical Research (NZCR)
🇳🇿Auckland, New Zealand
University of California, Los Angeles (UCLA)
🇺🇸Los Angeles, California, United States
Lurie's Children's Hospital
🇺🇸Chicago, Illinois, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
Stanford University
🇺🇸Palo Alto, California, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
The Bright Alliance
🇦🇺Randwick, New South Wales, Australia
Children's Hospital of The King's Daughters
🇺🇸Norfolk, Virginia, United States
University of Utah Clinical Neurosciences Center
🇺🇸Salt Lake City, Utah, United States
Children's Hospital London Health Sciences Centre (LHSC)
🇨🇦London, Ontario, Canada
Virginia Commonwealth University-Department of Neurology - Muscular Dystrophy Translational Research Program
🇺🇸Richmond, Virginia, United States
University of Rochester - Medical Center
🇺🇸Rochester, New York, United States