Back to resultsEfficacy and Safety of Tideglusib in Congenital Myotonic Dystrophy
Primary Purpose
Congenital Myotonic Dystrophy
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Tideglusib
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Congenital Myotonic Dystrophy focused on measuring 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
Eligibility Criteria
Inclusion Criteria:
- Male or female children and adolescents aged ≥6 years and ≤16 years
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
- Subject must be able to walk and complete the 10-meter walk-run test (orthotics/splints allowed, forearm crutches are not allowed)
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
- Subject's caregiver must be willing and able to support participation for duration of study
- Subject must be willing and able to comply with the required food intake restrictions as outlined per protocol
Exclusion Criteria:
- Not able to walk; (full time wheel chair use)
- Body mass index (BMI) less than 13.5 kg/m² or greater than 40 kg/m²
- New or change in medications/therapies within 4 weeks prior to Screening
- Use of strong CYP3A4 inhibitors (e.g clarithromycin, telithromycin, ketoconazole, itraconazole, posaconazole, nefazodone, idinavir and ritonavir) within 4 weeks prior to Baseline
- Concurrent use of drugs metabolized by CYP3A4 with a narrow therapeutic window (e.g. warfarin and digitoxin)
- 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
- 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
- Hypersensitivity to tideglusib and its excipients including allergy to strawberry
Sites / Locations
- Arkansas Children's Hospital
- University of California, Los Angeles (UCLA)
- Stanford University
- Ann & Robert H. Lurie Children's Hospital of Chicago
- University of Iowa Hospitals and Clinics
- University of Rochester Medical Center
- University of Pittsburgh Medical Center
- University of Utah Hospital
- Virginia Commonwealth University - Department of Neurology. Muscular Dystrophy Translational Research Program.
- The Bright Alliance
- Children's Hospital London Health Sciences Centre (LHSC)
- Children's Hospital of Eastern Ontario
- New Zealand Clinical Research (NZCR)
- Newcastle University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Tideglusib
Placebo
Arm Description
Weight adjusted tideglusib, orally, once daily
Matching placebo, orally, once daily
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03692312
Brief Title
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
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
March 3, 2021 (Actual)
Primary Completion Date
April 4, 2023 (Actual)
Study Completion Date
April 4, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AMO Pharma Limited
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
56 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tideglusib
Arm Type
Experimental
Arm Description
Weight adjusted tideglusib, orally, once daily
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo, orally, once daily
Intervention Type
Drug
Intervention Name(s)
Tideglusib
Intervention Description
Tideglusib for oral suspension, weight-adjusted at 400mg, 600mg or 1000 mg dose levels, once daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo formulation
Primary Outcome Measure Information:
Title
Change in Clinician-Completed Congenital DM1 Rating Scale (CDM1-RS)
Description
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.
Time Frame
22 weeks
Secondary Outcome Measure Information:
Title
Change in Clinical Global Impression- Improvement Scale (CGI-I) scores
Description
The clinician administered CGI-I rates how much the subject's illness has improved or worsened relative to a baseline state.
Time Frame
22 weeks
Title
Change in Top 3 Caregiver Concerns Visual Analogue Scale (VAS) score
Description
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.
Time Frame
22 Weeks
Title
Caregiver Completed Congenital DM1 Rating Scale (CC-CDM1-RS)
Description
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.
Time Frame
22 weeks
Title
Clinical Global Impression - Severity Scale (CGI-S)
Description
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.
Time Frame
22 weeks
Title
10-meter walk-run test
Description
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.
Time Frame
22 weeks
Title
Incidence of Adverse events (AEs), including serious adverse events (SAEs), between Screening to end of study.
Description
Adverse events may be volunteered spontaneously by the subject, or discovered as a result of general, non-leading questioning by physician.
Time Frame
22 to 28 weeks
Title
Incidence of abnormal findings in objective assessments (e.g. laboratory values, ECGs, vital signs and bone mineral density) between Screening and end of study.
Description
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.
Time Frame
22 to 28 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female children and adolescents aged ≥6 years and ≤16 years
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
Subject must be able to walk and complete the 10-meter walk-run test (orthotics/splints allowed, forearm crutches are not allowed)
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
Subject's caregiver must be willing and able to support participation for duration of study
Subject must be willing and able to comply with the required food intake restrictions as outlined per protocol
Exclusion Criteria:
Not able to walk; (full time wheel chair use)
Body mass index (BMI) less than 13.5 kg/m² or greater than 40 kg/m²
New or change in medications/therapies within 4 weeks prior to Screening
Use of strong CYP3A4 inhibitors (e.g clarithromycin, telithromycin, ketoconazole, itraconazole, posaconazole, nefazodone, idinavir and ritonavir) within 4 weeks prior to Baseline
Concurrent use of drugs metabolized by CYP3A4 with a narrow therapeutic window (e.g. warfarin and digitoxin)
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
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
Hypersensitivity to tideglusib and its excipients including allergy to strawberry
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joseph P Horrigan, MD
Organizational Affiliation
AMO Pharma
Official's Role
Study Director
Facility Information:
Facility Name
Arkansas Children's Hospital
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
Facility Name
University of California, Los Angeles (UCLA)
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Ann & Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Iowa Hospitals and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
University of Utah Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Virginia Commonwealth University - Department of Neurology. Muscular Dystrophy Translational Research Program.
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23219
Country
United States
Facility Name
The Bright Alliance
City
Randwick
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Facility Name
Children's Hospital London Health Sciences Centre (LHSC)
City
London
State/Province
Ontario
ZIP/Postal Code
N6A4G5
Country
Canada
Facility Name
Children's Hospital of Eastern Ontario
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L1
Country
Canada
Facility Name
New Zealand Clinical Research (NZCR)
City
Auckland
ZIP/Postal Code
1010
Country
New Zealand
Facility Name
Newcastle University
City
Newcastle Upon Tyne
ZIP/Postal Code
NE2 4HH
Country
United Kingdom
12. IPD Sharing Statement
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Efficacy and Safety of Tideglusib in Congenital Myotonic Dystrophy
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