Efficacy and Safety of Tideglusib in Congenital Myotonic Dystrophy

• ClinicalTrials.gov Identifier: NCT03692312
• Recruitment Status: Active, not recruiting
• First Posted: October 2, 2018
• Last Update Posted: February 24, 2023
• Sponsor: AMO Pharma Limited
• Information provided by (Responsible Party): AMO Pharma Limited

Study Description

Brief 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).

Condition or disease	Intervention/treatment	Phase
Congenital Myotonic Dystrophy	Drug: Tideglusib; Drug: Placebo	Phase 2; Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: March 3, 2021
• Estimated Primary Completion Date: April 2023
• Estimated Study Completion Date: April 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Change in Clinician-Completed Congenital DM1 Rating Scale (CDM1-RS) [ Time Frame: 22 weeks ]
   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.

Secondary Outcome Measures :

1. Change in Clinical Global Impression- Improvement Scale (CGI-I) scores [ Time Frame: 22 weeks ]
   The clinician administered CGI-I rates how much the subject's illness has improved or worsened relative to a baseline state.
2. Change in Top 3 Caregiver Concerns Visual Analogue Scale (VAS) score [ Time Frame: 22 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.
3. Caregiver Completed Congenital DM1 Rating Scale (CC-CDM1-RS) [ Time Frame: 22 weeks ]
   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.
4. Clinical Global Impression - Severity Scale (CGI-S) [ Time Frame: 22 weeks ]
   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.
5. 10-meter walk-run test [ Time Frame: 22 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.
6. Incidence of Adverse events (AEs), including serious adverse events (SAEs), between Screening to end of study. [ Time Frame: 22 to 28 weeks ]
   Adverse events may be volunteered spontaneously by the subject, or discovered as a result of general, non-leading questioning by physician.
7. Incidence of abnormal findings in objective assessments (e.g. laboratory values, ECGs, vital signs and bone mineral density) between Screening and end of study. [ Time Frame: 22 to 28 weeks ]
   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Arkansas

Arkansas Children's Hospital

Little Rock, Arkansas, United States, 72202

United States, California

University of California, Los Angeles (UCLA)

Los Angeles, California, United States, 90095

Stanford University

Palo Alto, California, United States, 94304

United States, Illinois

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States, 60611

United States, Iowa

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States, 52242

United States, New York

University of Rochester Medical Center

Rochester, New York, United States, 14642

United States, Pennsylvania

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States, 15213

United States, Utah

University of Utah Hospital

Salt Lake City, Utah, United States, 84112

United States, Virginia

Virginia Commonwealth University - Department of Neurology. Muscular Dystrophy Translational Research Program.

Richmond, Virginia, United States, 23219

Australia, New South Wales

The Bright Alliance

Randwick, New South Wales, Australia, 2031

Canada, Ontario

Children's Hospital London Health Sciences Centre (LHSC)

London, Ontario, Canada, N6A4G5

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada, K1H 8L1

New Zealand

New Zealand Clinical Research (NZCR)

Auckland, New Zealand, 1010

United Kingdom

Newcastle University

Newcastle Upon Tyne, United Kingdom, NE2 4HH

Sponsors and Collaborators

AMO Pharma Limited

Investigators

• Study Director: Joseph P Horrigan, MD; AMO Pharma

More Information

• Responsible Party: AMO Pharma Limited
• ClinicalTrials.gov Identifier: NCT03692312
• Other Study ID Numbers: AMO-02-MD-2-003; 2016-004623-23 ( EudraCT Number )
• First Posted: October 2, 2018
• Last Update Posted: February 24, 2023
• Last Verified: February 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AMO Pharma Limited:

AMO-02-MD-2-003; Tideglusib; Congenital Myotonic Dystrophy; Myotonic Dystrophy; Dystrophia Myotonica; Myotonia Atrophica; Myotonia Dystrophica; Myotonic Dystrophy, Congenital; Steinert Disease; Steinert Myotonic Dystrophy; Steinert's Disease

Additional relevant MeSH terms:

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