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

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.	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

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 (Actual): September 8, 2023
• Last Update Submitted That Met QC Criteria: September 7, 2023
• Last Verified: September 1, 2023

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: Nervous System Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Muscular Disorders, Atrophic; Heredodegenerative Disorders, Nervous System; Muscular Dystrophies; Myotonic Disorders; Myotonic Dystrophy
• 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