A clinical trial to investigate how safe and effective tideglusib is, as treatment for adolescents and adults with myotonic dystrophy diagnosed before they were 12 years old.
- Conditions
- Treatment of adolescent and adult congenital and juvenile onset myotonic dystrophyMedDRA version: 19.1Level: PTClassification code 10068871Term: Myotonic dystrophySystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- EUCTR2016-000067-16-GB
- Lead Sponsor
- AMO Pharma Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 16
1. Subjects under study must be adolescent or adults with a diagnosis of congenital or juvenile-onset type 1 myotonic dystrophy (DM-1). For the purposes of this study, the following definitions apply:
Congenital: in addition to the genetic confirmation of DM-1, one or more of the following signs or symptoms was evident within the first week after birth:
a) Hypotonia
b) Generalized weakness
c) Respiratory insufficiency
d) Feeding difficulties
e) Clubfoot or another musculoskeletal deformity
Childhood/juvenile-onset: in addition to the genetic confirmation of DM-1, at least 2 signs or symptoms (not caused by another, unrelated condition) were evident prior to 12 years of age that can be clearly assigned to DM-1, for example:
a) Muscle weakness
b) Myotonia (delayed muscle relaxation)
c) Difficulty using hands, including fine motor problems
d) Excessive daytime sleepiness
e) Problems with upper or lower gastrointestinal functioning
f) Problems with concentration or focusing (including symptoms of attention-deficit/hyperactivity disorder)
g) Learning difficulties (including dyslexia)
2. Diagnosis must be genetically confirmed
3. Subjects must be male or female aged 12 years to 45 years (the first 3 subjects in Cohort 1 must be =18 years)
4. Subjects must have a Clinical Global Impression – Severity (CGI-S) score of 4 or greater at Screening and Run-in (V2)
5. Subjects must be ambulatory and able to complete the 10 metre walk/run test (splints allowed)
6. Subject’s legally authorised representative (LAR) must provide written informed consent and there must be written consent or assent (as age applicable and developmentally appropriate) by the subject before any study-related procedures are conducted
7. Subject’s caregiver must be willing and able to support subject’s participation for duration of study and if different from the LAR, must consent to this in writing
Are the trial subjects under 18? yes
Number of subjects for this age range: 8
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 8
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Non-ambulatory (full time) wheel chair user
2. Receiving stimulant medication
3. Receiving other medications/therapies not stable (changed) within 4 weeks prior to Run-in (V2)
4. Medical illness or other concern which would cause investigator to conclude subjects will not be able to perform the study procedures or assessments or would confound interpretation of data obtained during assessment
5. Current enrolment in a clinical trial of an investigational drug or enrolment in a clinical trial of an investigational drug in the last 6 months
6. Women 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
7. Men, if engaged in sexual relations with a female of child-bearing potential, not using an acceptable contraceptive method if not surgically sterile
8. Gastrointestinal disease which 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) cardiovascular, renal, hepatic, endocrine or respiratory disease
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. Average QTcF value of >450msec at screening
12. Kidney disease requiring ongoing treatment
13. A history of chronic liver disease with current out of range value for ALT, clinically relevant hepatic steatosis or other clinical manifestations of ongoing liver disease
14. Current ALT value > 2X the upper limit of the normal reference range at Screening or Run-in (V2) (may repeat to confirm)
15. Current total bilirubin value greater than the upper limit of the normal reference range at Screening or Run-in (V2) (unless due to Gilbert’s syndrome) (may repeat to confirm)
16. HbA1c values greater than 6% or 42.0mmol/mol at Screening (may repeat to confirm)
17. TSH values outside of the normal reference range at Screening or Run-in (V2) (may repeat to confirm)
18. Serum creatinine >150 umol/L and creatinine clearance = 60 mL/m (according to Cockcroft-Gault formula) at Screening (may repeat to confirm)
19. Clinical history of hepatitis, previous or current positive serological evidence for hepatitis B or C
20. Serological evidence of Hepatitis A at Screening or in the 6 months preceding Screening
21. A history of significant drug allergy (such as Steven-Johnson syndrome, anaphylaxis)
22. A history of alcohol or substance use disorders
23. Current malignancy or any history of malignancy except for surgically-cured skin cancer or pilomatricoma (benign tumor of the hair follicle that is associated with DM-1).
24. Severe arthritis or other medical condition (besides DM-1) that would significantly impact ambulation
25. Use within 4 weeks prior to baseline (V3) of strong CYP3A4 inhibitors e.g. clarithyromycin, telithromycin, ketoconazole, itarconazole, posaconazole, nefazadone, indinavir, ritonavir
26. Concurrent use of drugs metabolised by CYP3A4 with a narrow therapeutic window e.g. warfarin and digitoxin
27. Judged clinically to be at risk of suicide (suicidal ideation, severe depression, or other factors) over the last three months, as assessed by the Investigator.
28. Hypersensitivity to tideglusib or any components of i
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method