Efficacy and Safety of Tideglusib in Congenital Myotonic Dystrophy

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)

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).

Study Overview

• Status: Completed
• Conditions: Congenital Myotonic Dystrophy
• Intervention / Treatment: Drug: Tideglusib; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2; Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • The Bright Alliance
• Canada
  • Ontario
    • London, Ontario, Canada, N6A4G5
      • Children's Hospital London Health Sciences Centre (LHSC)
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
• New Zealand
  • Auckland, New Zealand, 1010
    • New Zealand Clinical Research (NZCR)
• United Kingdom
  • Newcastle upon Tyne, United Kingdom, NE2 4HH
    • Newcastle University
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
  • California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles (UCLA)
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah Hospital
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University - Department of Neurology. Muscular Dystrophy Translational Research Program.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 16 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female children and adolescents aged ≥6 years and ≤16 years

2. 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
3. Subject must be able to walk and complete the 10-meter walk-run test (orthotics/splints allowed, forearm crutches are not allowed)

4. 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
5. Subject's caregiver must be willing and able to support participation for duration of study
6. Subject must be willing and able to comply with the required food intake restrictions as outlined per protocol

Exclusion Criteria:

1. Not able to walk; (full time wheel chair use)
2. Body mass index (BMI) less than 13.5 kg/m² or greater than 40 kg/m²
3. New or change in medications/therapies within 4 weeks prior to Screening
4. Use of strong CYP3A4 inhibitors (e.g clarithromycin, telithromycin, ketoconazole, itraconazole, posaconazole, nefazodone, idinavir and ritonavir) within 4 weeks prior to Baseline
5. Concurrent use of drugs metabolized by CYP3A4 with a narrow therapeutic window (e.g. warfarin and digitoxin)
6. 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
7. 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
8. Hypersensitivity to tideglusib and its excipients including allergy to strawberry

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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. The severity of the clinician's concern in each domain is scored by using a 5-point Likert Scale. Scores range from 0 = Not present to 4 = Very severe.	Baseline and week 20

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. A 7-point Likert type scale is used with ratings of 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse.	Baseline and week 20
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. Caregivers were asked to rate three causes for concern by drawing a vertical mark on a 10 cm long VAS with anchors of "not at all severe" at the left end (0 cm) and "very severe" at the right end (10 cm). A score for each concern was to be determined by measuring the number of centimeters on the 10 cm VAS line from the anchor point on the left side of the line. A total VAS score for each subject was calculated as the sum of the scores for the 3 concerns (minimum = 0 cm, maximum = 30 cm). A higher score represents a worse outcome.	Baseline and week 20
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. The symptoms are rated on a score from 0 to 4 based on overall severity where 0 = symptom not present or is no longer present during the relevant time frame, and 4 = very severe, symptom causes pronounced and consistent impairment and is highly disruptive with regard to daily life. A total CC-CDM1-RS score for each subject was calculated as the sum of the scores where 0 = min and 44 = max. A higher score represents a worse outcome.	Baseline and week 20
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. Subjects are assessed on severity of illness at the time of rating 1, normal, not at all ill; 2, borderline ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.	Baseline and week 20
10-meter Walk-run Test	The 10-meter walk/run test is a performance measure used to assess walking speed in seconds over a short distance. It can be used as an assessment of functional mobility.	20 weeks
Number 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.	Between Screening to End of Study, up to 28 weeks
Number 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.	Between Screening to End of Study, up to 28 weeks
CDM1-RS Independent Central Rater Score (CDM1-RS)	Change from baseline to end of treatment in the independent central rater CDM1-RS total score. CDM1 Rating Scale is an 11-item rating scale completed by the clinician to score the symptom severity that are clinically relevant in CDM1. The severity of the clinician's concern in each domain is scored by using a 5-point Likert Scale. Scores range from 0 = Not present to 4 = Very severe.	Baseline to week 20
CGI-I Independent Central Rater Score (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 on a seven point scale. A 7-point Likert type scale is used with ratings of 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse.	Baseline and week 20
Independent Rater Clinical Global Impression - Severity Scale (CGI-S)	CGI-S is a 7-point Likert type scale. An independent central rater rated the CGI-S scales for both the in-clinic and telehealth interviews. Subjects are assessed on severity of illness at the time of rating 1, normal, not at all ill; 2, borderline ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.	Baseline and week 20

Collaborators and Investigators

• Sponsor: AMO Pharma Limited
• Investigators: Study Director: Joseph P Horrigan, MD, AMO Pharma

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2021
• Primary Completion (Actual): April 4, 2023
• Study Completion (Actual): April 4, 2023

Study Registration Dates

• First Submitted: March 16, 2018
• First Submitted That Met QC Criteria: September 26, 2018
• First Posted (Actual): October 2, 2018

Study Record Updates

• Last Update Posted (Estimated): October 8, 2025
• Last Update Submitted That Met QC Criteria: September 25, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Myotonic Dystrophy; Tideglusib; AMO-02-MD-2-003; Congenital Myotonic Dystrophy; Dystrophia Myotonica; Myotonia Atrophica; Myotonia Dystrophica; Myotonic Dystrophy, Congenital; Steinert Disease; Steinert Myotonic Dystrophy; Steinert's Disease
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Muscular Disorders, Atrophic; Muscular Dystrophies; Myotonic Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Myotonic Dystrophy; Substandard Drugs; Pharmaceutical Preparations; tideglusib
• Other Study ID Numbers: AMO-02-MD-2-003; 2016-004623-23 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No