Efficacy and Safety of Tideglusib in Congenital Myotonic Dystrophy

Phase 2

Completed

Conditions: Congenital Myotonic Dystrophy

Interventions: Drug: Tideglusib
Drug: Placebo

Registration Number: NCT03692312

Lead Sponsor: AMO Pharma Limited

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 56

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tideglusib	Tideglusib	Weight adjusted tideglusib, orally, once daily
Tideglusib	Placebo	Weight adjusted tideglusib, orally, once daily
Placebo	Placebo	Matching placebo, orally, once daily

Primary Outcome Measures

Name	Time	Method
Change in Clinician-Completed Congenital DM1 Rating Scale (CDM1-RS)	Baseline and week 20	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. The severity of the clinician's concern in each domain is scored by using a 5-point Likert Scale. Scores range from 0 = Not present to 4 = Very severe.

Secondary Outcome Measures

Name	Time	Method
Change in Clinical Global Impression- Improvement Scale (CGI-I) Scores	Baseline and week 20	The clinician administered CGI-I rates how much the subject's illness has improved or worsened relative to a baseline state. A 7-point Likert type scale is used with ratings of 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse.
Change in Top 3 Caregiver Concerns Visual Analogue Scale (VAS) Score	Baseline and week 20	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. Caregivers were asked to rate three causes for concern by drawing a vertical mark on a 10 cm long VAS with anchors of "not at all severe" at the left end (0 cm) and "very severe" at the right end (10 cm). A score for each concern was to be determined by measuring the number of centimeters on the 10 cm VAS line from the anchor point on the left side of the line. A total VAS score for each subject was calculated as the sum of the scores for the 3 concerns (minimum = 0 cm, maximum = 30 cm). A higher score represents a worse outcome.
Caregiver Completed Congenital DM1 Rating Scale (CC-CDM1-RS)	Baseline and week 20	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. The symptoms are rated on a score from 0 to 4 based on overall severity where 0 = symptom not present or is no longer present during the relevant time frame, and 4 = very severe, symptom causes pronounced and consistent impairment and is highly disruptive with regard to daily life. A total CC-CDM1-RS score for each subject was calculated as the sum of the scores where 0 = min and 44 = max. A higher score represents a worse outcome.
Clinical Global Impression - Severity Scale (CGI-S)	Baseline and week 20	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. Subjects are assessed on severity of illness at the time of rating 1, normal, not at all ill; 2, borderline ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.
10-meter Walk-run Test	20 weeks	The 10-meter walk/run test is a performance measure used to assess walking speed in seconds over a short distance. It can be used as an assessment of functional mobility.
Number of Adverse Events (AEs), Including Serious Adverse Events (SAEs), Between Screening to End of Study.	Between Screening to End of Study, up to 28 weeks	Adverse events may be volunteered spontaneously by the subject, or discovered as a result of general, non-leading questioning by physician.
Number of Abnormal Findings in Objective Assessments (e.g. Laboratory Values, ECGs, Vital Signs and Bone Mineral Density) Between Screening and End of Study.	Between Screening to End of Study, up 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.
CDM1-RS Independent Central Rater Score (CDM1-RS)	Baseline to week 20	Change from baseline to end of treatment in the independent central rater CDM1-RS total score. CDM1 Rating Scale is an 11-item rating scale completed by the clinician to score the symptom severity that are clinically relevant in CDM1. The severity of the clinician's concern in each domain is scored by using a 5-point Likert Scale. Scores range from 0 = Not present to 4 = Very severe.
CGI-I Independent Central Rater Score (CGI-I)	Baseline and week 20	The CGI-I requires the clinician to rate how much the subject's illness has changed (improved, worsened or stayed the same) relative to a baseline state on a seven point scale. A 7-point Likert type scale is used with ratings of 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse.
Independent Rater Clinical Global Impression - Severity Scale (CGI-S)	Baseline and week 20	CGI-S is a 7-point Likert type scale. An independent central rater rated the CGI-S scales for both the in-clinic and telehealth interviews. Subjects are assessed on severity of illness at the time of rating 1, normal, not at all ill; 2, borderline ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.

Trial Locations

Locations (14): 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
Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸
Chicago, Illinois, United States
University of Iowa Hospitals and Clinics
🇺🇸
Iowa City, Iowa, United States
University of Rochester Medical Center
🇺🇸
Rochester, New York, United States
University of Pittsburgh Medical Center
🇺🇸
Pittsburgh, Pennsylvania, United States
University of Utah Hospital
🇺🇸
Salt Lake City, Utah, United States
Virginia Commonwealth University - Department of Neurology. Muscular Dystrophy Translational Research Program.
🇺🇸
Richmond, Virginia, United States
The Bright Alliance
🇦🇺
Randwick, New South Wales, Australia
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Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States