Efficacy and Safety of Tideglusib in Congenital Myotonic Dystrophy

Sponsor

AMO Pharma Limited (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03692312

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

3.7

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Congenital Myotonic Dystrophy	Drug: Tideglusib Drug: Placebo	Phase 2/Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

56 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Mar 3, 2021

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Feb 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tideglusib Weight adjusted tideglusib, orally, once daily	Drug: Tideglusib Tideglusib for oral suspension, weight-adjusted at 400mg, 600mg or 1000 mg dose levels, once daily Drug: Placebo Matching placebo formulation
Placebo Comparator: Placebo Matching placebo, orally, once daily	Drug: Placebo Matching placebo formulation

Arm

Intervention/Treatment

Experimental: Tideglusib

Weight adjusted tideglusib, orally, once daily

Drug: Tideglusib

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

Drug: Placebo

Matching placebo formulation

Placebo Comparator: Placebo

Matching placebo, orally, once daily

Drug: Placebo

Matching placebo formulation

Outcome Measures

Primary Outcome Measures

Change in Clinician-Completed Congenital DM1 Rating Scale (CDM1-RS) [22 weeks]
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 [22 weeks]
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 [22 Weeks]
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) [22 weeks]
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) [22 weeks]
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 [22 weeks]
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. [22 to 28 weeks]
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. [22 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 16 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202
2	University of California, Los Angeles (UCLA)	Los Angeles	California	United States	90095
3	Stanford University	Palo Alto	California	United States	94304
4	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
5	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
6	University of Rochester Medical Center	Rochester	New York	United States	14642
7	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
8	University of Utah Hospital	Salt Lake City	Utah	United States	84112
9	Children's Hospital of the King's Daughters	Norfolk	Virginia	United States	23507
10	Virginia Commonwealth University - Department of Neurology. Muscular Dystrophy Translational Research Program.	Richmond	Virginia	United States	23219
11	The Bright Alliance	Randwick	New South Wales	Australia	2031
12	Children's Hospital London Health Sciences Centre (LHSC)	London	Ontario	Canada	N6A4G5
13	Children's Hospital of Eastern Ontario	Ottawa	Ontario	Canada	K1H 8L1
14	New Zealand Clinical Research (NZCR)	Auckland		New Zealand	1010
15	Newcastle University	Newcastle Upon Tyne		United Kingdom	NE2 4HH