Clinical trial NCT05004129: Safety and Efficacy of Tideglusib in Congenital or Childhood Onset Myotonic Dystrophy
Official title: An Open-Label Study to Evaluate the Long-Term Safety and Efficacy of Tideglusib for the Treatment of Congenital or Childhood Onset DM1 (REACH CDM X)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Congenital Myotonic Dystrophy
Keywords: Tideglusib
AMO-02-MD-2-004
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: 2021-08-13
Enrollment: 76
Sex: ALL
Minimum age (years): 6
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label phase 2/3 study for individuals with Congenital Myotonic Dystrophy (Congenital DM1) who participated in the preceding AMO-02-MD-2-003 study or individuals with either Congenital or Childhood Onset DM1 who are treatment naïve.

Detailed description: This is an open-label study of either a weight-adjusted 1000 mg fixed dose or a weight banded fixed dose of tideglusib across a 52-week treatment period with an open-ended optional extended access period. The subjects are children and adolescents with Congenital DM1 who participated in the antecedent AMO-02-MD-2-003 study or individuals with either Congenital or Childhood onset DM1 who are treatment naïve.

Eligibility criteria: Inclusion Criteria:

Subjects who do not enter this study directly from completing the AMO-02-MD-2-003 study (i.e. subjects who did not complete AMO-02-MD-2-003, subjects who completed AMO-02-MD-2-003 but did not directly rollover or subjects who are re-entering AMO-02-MD-2-004), will not be considered eligible for the study without meeting all of the criteria below:

1. Subjects under study must be individuals with a diagnosis of Congenital or Childhood Onset DM1.
2. Diagnosis must be genetically confirmed
3. Subjects must be male or female aged ≥6 years to ≤45 years at Screening
4. Subjects must have a Clinical Global Impression - Severity (CGI-S) score of 3 or greater at Screening (V-1)
5. Written, voluntary informed consent must be obtained before any study related procedures are conducted. Where a parent or legally authorized representative (LAR) provides consent, there must also be assent from the subject (as required by local regulations)
6. Subject's caregiver must be willing and able to support participation for duration of study
7. Subject must be willing and able to comply with the required food intake restrictions as outlined per protocol

Subjects entering directly from completing the antecedent AMO-02-MD-2-003 study will not be considered eligible for the study without meeting all of the criteria below:

1. Subjects who have completed the antecedent AMO-02-MD-2-003 study through V11
2. 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 (as required by local regulations)
3. Subject's caregiver must be willing and able to support participation for duration of study
4. Subject must be willing and able to comply with the required food intake restrictions as outlined per protocol

Key Exclusion Criteria:

1. Body mass index (BMI) less than 13.5 kg/m² or greater than 40 kg/m²
2. New or change in medications/therapies within 4 weeks prior to Eligibility/Baseline Visit
3. Use within 4 weeks prior to Eligibility/Baseline Visit of strong CYP3A4 inhibitors (eg.clarithromycin, telithromycin, ketoconazole, itraconazole, posaconazole, nefazodone, idinavir and ritonavir)
4. Concurrent use of drugs metabolized by CYP3A4 with a narrow therapeutic window (e.g. warfarin and digitoxin)
5. 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 other than the AMO-02- MD-2-003 study
6. Existing or historical medical conditions or complications (eg. neurological, cardiovascular, renal, hepatic, gastrointestinal, endocrine or respiratory disease) that may impact the interpretability of the study results
7. Hypersensitivity to tideglusib or any components of its formulation including allergy to strawberry

Primary outcomes:
measure: Safety (Adverse Events)
timeFrame: 52 Weeks
measure: Safety (Adverse Events) - With Optional Expanded Access
timeFrame: Week 60 and every 8 weeks thereafter up until discontinuation or study closure, assessed up to Week 132
measure: Clinician-Completed Congenital DM1 Rating Scale (CDM1-RS)
timeFrame: 52 Weeks
Secondary outcomes:
measure: Clinician-Completed Congenital DM1 Rating Scale (CDM1-RS) - With Optional Expanded Access
timeFrame: Week 68 and every 16 weeks thereafter up until discontinuation or study closure, assessed up to Week 132
measure: Clinical Global Impressions Improvement Scale (CGI-I)
timeFrame: 54 Weeks
measure: Clinical Global Impressions Improvement Scale (CGI-I) - With Optional Expanded Access
timeFrame: Week 68 and every 16 weeks thereafter up until discontinuation or study closure, assessed up to Week 132
measure: Top 3 Caregiver Concerns Visual Analogue Scale (VAS) score
timeFrame: 54 weeks
measure: Top 3 Caregiver Concerns Visual Analogue Scale (VAS) score - With Optional Expanded Access
timeFrame: Week 68 and every 16 weeks thereafter up until discontinuation or study closure, assessed up to Week 132
measure: Caregiver Completed Congenital DM1 Rating Scale (CC-CDM1-RS)
timeFrame: 52 weeks
measure: Caregiver Completed Congenital DM1 Rating Scale (CC-CDM1-RS) - With Optional Expanded Access
timeFrame: Week 68 and every 16 weeks thereafter up until discontinuation or study closure, assessed up to Week 132
measure: Clinical Global Impressions Severity Scale (CGI-S)
timeFrame: 54 weeks
measure: Clinical Global Impressions Severity Scale (CGI-S) - With Optional Expanded Access
timeFrame: Week 68 and every 16 weeks thereafter up until discontinuation or study closure, assessed up to Week 132
measure: Autism Behavior Inventory- Clinician (ABI-C)
timeFrame: 52 Weeks
measure: Socialization, Communication, Daily Living, and Adaptive Behavior Composite standard scores of the Vineland Adaptive Behavior Scale - Survey Interview
timeFrame: 52 Weeks
measure: 10-meter walk-run test
timeFrame: 52 Weeks
measure: Plasma Troponin T levels
timeFrame: 52 Weeks
measure: Plasma Troponin T levels - With Optional Expanded Access
timeFrame: Week 68 and every 16 weeks thereafter up until discontinuation or study closure, assessed up to Week 132
measure: Blood Leukocytes CTG Repeats
timeFrame: Baseline and Week 52
measure: Blood Leukocytes CTG Repeats - With Optional Expanded Access
timeFrame: Week 52 or later
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: Lurie's Children's Hospital
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 Clinical Neurosciences Center
state: Utah
city: Norfolk
country: United States
facility: Children's Hospital of The King's Daughters
state: Virginia
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)
Study officials:
affiliation: AMO Pharma
name: Harriet Gray-Stephens, BM BCh, MA (Oxon), MFPM
role: STUDY_DIRECTOR
References: