Efficacy and Safety of Tideglusib in Congenital Myotonic Dystrophy

AMO Pharma Limited56 enrolled

Overview

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).

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Congenital Myotonic Dystrophy

Interventions

TideglusibDRUG

Tideglusib for oral suspension, weight-adjusted at 400mg, 600mg or 1000 mg dose levels, once daily

PlaceboDRUG

Matching placebo formulation

Eligibility

Sex: ALLMin age: 6 YearsMax age: 16 Years

Medical Language ↔ Plain English

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

Locations (14)

Arkansas Children's Hospital

Little Rock, Arkansas, United States

University of California, Los Angeles (UCLA)

Los Angeles, California, United States

Outcomes

Primary Outcomes

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. 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.

Time frame: Baseline and week 20

Secondary Outcomes

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. 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.

Time frame: Baseline and week 20

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. 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.

Time frame: Baseline and week 20

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. 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.

Data from ClinicalTrials.gov

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