Efficacy and Safety of Tideglusib in Congenital Myotonic Dystrophy

Congenital Myotonic Dystrophy Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03692312
• Other study ID #: AMO-02-MD-2-003
• Secondary ID: 2016-004623-23
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: March 3, 2021
• Est. completion date: April 4, 2023

Study information

• Verified date: September 2023
• Source: AMO Pharma Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: April 4, 2023
• Est. primary completion date: April 4, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 16 Years

Eligibility

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

Related Conditions & MeSH terms

• Congenital Myotonic Dystrophy
• Myotonic Dystrophy

Intervention

Drug:
• Tideglusib
Tideglusib for oral suspension, weight-adjusted at 400mg, 600mg or 1000 mg dose levels, once daily
• Placebo
Matching placebo formulation

Locations

Country	Name	City	State
Australia	The Bright Alliance	Randwick	New South Wales
Canada	Children's Hospital London Health Sciences Centre (LHSC)	London	Ontario
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
New Zealand	New Zealand Clinical Research (NZCR)	Auckland
United Kingdom	Newcastle University	Newcastle Upon Tyne
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	University of California, Los Angeles (UCLA)	Los Angeles	California
United States	Stanford University	Palo Alto	California
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	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	University of Utah Hospital	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
AMO Pharma Limited

Countries where clinical trial is conducted

United States,  Australia,  Canada,  New Zealand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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