Clinical trial NCT03692312: Efficacy and Safety of Tideglusib in Congenital Myotonic Dystrophy
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Congenital Myotonic Dystrophy
Keywords: Tideglusib
AMO-02-MD-2-003
Congenital Myotonic Dystrophy
Myotonic Dystrophy
Dystrophia Myotonica
Myotonia Atrophica
Myotonia Dystrophica
Myotonic Dystrophy, Congenital
Steinert Disease
Steinert Myotonic Dystrophy
Steinert's Disease
Lead sponsor: AMO Pharma Limited
Sponsor class: INDUSTRY
First posted: 2018-10-02
Enrollment: 56
Sex: ALL
Minimum age (years): 6
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Eligibility 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

Primary outcomes:
measure: Change in Clinician-Completed Congenital DM1 Rating Scale (CDM1-RS)
timeFrame: 22 weeks
Secondary outcomes:
measure: Change in Clinical Global Impression- Improvement Scale (CGI-I) scores
timeFrame: 22 weeks
measure: Change in Top 3 Caregiver Concerns Visual Analogue Scale (VAS) score
timeFrame: 22 Weeks
measure: Caregiver Completed Congenital DM1 Rating Scale (CC-CDM1-RS)
timeFrame: 22 weeks
measure: Clinical Global Impression - Severity Scale (CGI-S)
timeFrame: 22 weeks
measure: 10-meter walk-run test
timeFrame: 22 weeks
measure: Incidence of Adverse events (AEs), including serious adverse events (SAEs), between Screening to end of study.
timeFrame: 22 to 28 weeks
measure: Incidence of abnormal findings in objective assessments (e.g. laboratory values, ECGs, vital signs and bone mineral density) between Screening and end of study.
timeFrame: 22 to 28 weeks
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Los Angeles
country: United States
facility: University of California, Los Angeles (UCLA)
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University - Department of Neurology. Muscular Dystrophy Translational Research Program.
state: Virginia
city: Randwick
country: Australia
facility: The Bright Alliance
state: New South Wales
city: London
country: Canada
facility: Children's Hospital London Health Sciences Centre (LHSC)
state: Ontario
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Auckland
country: New Zealand
facility: New Zealand Clinical Research (NZCR)
city: Newcastle Upon Tyne
country: United Kingdom
facility: Newcastle University
Study officials:
affiliation: AMO Pharma
name: Joseph P Horrigan, MD
role: STUDY_DIRECTOR
References: