Treatment of child and adolescent congenital myotonic dystrophy. MedDRA version: 20.0 Level: PT Classification code 10068871 Term: Myotonic dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 20.0 Level: PT Classification code 10068871 Term: Myotonic dystrophy System Organ Class: 10010331
Conditions
Interventions
Product Name: Tideglusib
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: Tideglusib
CAS Number: 865854-05-3
Current
Sponsors
AMO Pharma Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The subject will not be considered eligible for the study without meeting all of the criteria below: 1. Subjects under study must be children or adolescents with a diagnosis of DM1. For the purposes of this study, the following definitions apply. In addition to the genetic confirmation of DM1, one or more of the following clinically relevant (e.g. requiring medical intervention) signs or symptoms was evident within the first week after birth: • Hypotonia • Generalized weakness • Respiratory insufficiency • Feeding difficulties • Clubfoot or another musculoskeletal deformity 2. Diagnosis must be genetically confirmed 3. Subjects must be male or female children and adolescents aged =6 years and =16 years at Screening 4. Subjects must have a Clinical Global Impression – Severity (CGI-S) score of 4 or greater at Screening and start of Run-in (V2) 5. Subjects must be ambulatory and able to complete the 10-meter walk-run test (orthotics/splints allowed, forearm crutches are not allowed) 6. 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) 7. Subject’s caregiver must be willing and able to support participation for duration of study 8. Subject must be willing and able to comply with the required food intake restrictions as outlined per protocol Are the trial subjects under 18? yes Number of subjects for this age range: 56 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Non-ambulatory (full time) wheel chair use 2. BMI less than 13.5 kg/m² or greater than 40 kg/m² 3. Receiving other medications/therapies not stable (i.e. changed) within 4 weeks prior to Screening. For each enrollee, every effort should be made to maintain stable regimens (i.e. dose, as applicable, and frequency) of allowed concomitant medications (e.g. concomitant mexiletine or stimulants) and allowed non-medicine based therapies (e.g. occupational or physiotherapy) throughout the course of the study, from the time of commencement of Screening until the last study assessment 4. Use within 4 weeks prior to Baseline (V3) of strong CYP3A4 inhibitors. Examples include clarithromycin, telithromycin, ketoconazole, itraconazole, posaconazole, nefazodone, idinavir and ritonavir 5. Concurrent use of drugs metabolized by CYP3A4 with a narrow therapeutic window e.g. warfarin and digitoxin 6. Medical illness or other concern 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 7. 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 8. Gastrointestinal disease which, in the opinion of the investigator, may interfere with the absorption, distribution, metabolism or excretion of the study medication and impact the interpretability of the study results 9. Current clinically significant (as determined by the investigator) neurological, cardiovascular, renal, hepatic, endocrine or respiratory disease that may impact the interpretability of the study results 10. Clinically significant heart disease (in the opinion of the investigator) or second or third degree heart block, atrial flutter, atrial fibrillation, ventricular arrhythmias, or is receiving medication for treatment of a cardiac arrhythmia 11. Implantation of a cardiac pacemaker within the 12 months preceding Screening 12. Average QTcF value of >450 msec at Screening or at Run-In (V2) (may repeat to confirm) 13. Clinically significant abnormalities in safety laboratory tests, vital signs or ECG, as determined by the Investigator at Screening or Run-In (V2) as applicable (may repeat to confirm) 14. Females of child-bearing potential who are pregnant, lactating or not willing to use a protocol-defined acceptable contraception method if sexually active and not surgically sterile 15. Males, engaged in sexual relations with a female of child-bearing potential, not using an acceptable contraceptive method if not surgically sterile 16. Kidney disease requiring ongoing treatment 17. A history of chronic liver disease with current out of range values for ALT, clinically relevant hepatic steatosis or other clinical manifestations of liver disease 18. ALT value > 2X ULN reference range at Screening (may repeat to confirm) 19. Total bilirubin value greater than the upper limit of the normal reference range at Screening (unless due to Gilbert’s syndrome) (may repeat to confirm). For subjects with a well known/well documented diagnosis of Gilbert's syndrome a total bilirubin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: A blinded sample size re-estimation, based on the observed variance in the primary outcome measure, will occur when approximately 50% of subjects are enrolled and have completed week 20 (Visit 11). The variability of key secondary and secondary endpoints may be assessed as well, if feasible. This endpoint will be fully evaluated once a full data set is acquired. ;Main Objective: To evaluate the efficacy, between start and end of treatment, of tideglusib compared to placebo in children and adolescents with Congenital Myotonic Dystrophy (DM1).; Secondary Objective: To evaluate the safety and tolerability of tideglusib compared to placebo in children and adolescents with Congenital DM1 To evaluate the blood levels of tideglusib in children and adolescents with Congenital DM1. ;Primary end point(s): Clinician-Completed Congenital DM1 Rating Scale (CDM1-RS) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Efficacy Endpoint: • Clinical Global Impression- Improvement Scale (CGI-I) Secondary Efficacy Endpoints: • Top 3 Caregiver Concerns VAS score • Caregiver Completed Congenital DM1 Rating Scale (CC-CDM1-RS) • Clinical Global Impression - Severity Scale (CGI-S) • DXA Scan measurement of total body lean/muscle mass ; Timepoint(s) of evaluation of this end point: When approximately 50% of subjects are enrolled and have completed week 20 (Visit 11). The variability of key secondary and secondary endpoints may be assessed, if feasible. All secondary endpoints will be evaluated once a full data set is acquired. | — |
Countries
Canada, United Kingdom, United States
Contacts
Public ContactGeneral Enquiries
AMO Pharma Ltd
Outcome results
None listed