| Eligibility |
Inclusion Criteria:
- Ambulatory and non-ambulatory patients from age 5 - 16 years (5 years old and <17
years old) at time of screening with a clinical picture (see below) consistent with
COL6-related dystrophy (COL6-RD) or LAMA2-related dystrophy (LAMA2-RD)
- Under regular review at a neuromuscular center
- On adequate double-barrier contraception (if of child-bearing potential)
- Stable on any allowed concomitant medications for 1 month prior to run in Phase
- Forced Vital Capacity (FVC) 30-80% of the predicted value and confirmed at Screening
and Baseline visit(s)
For patients with Collagen VI-related dystrophy (COL6-RD)- required clinical picture:
• Muscle weakness: inability to walk or, if patient is still ambulatory, inability to run
and > 5 s for 10 m walk
Genetic and Pathology:
• Molecular diagnosis of COL6-RD, defined by one dominant or two recessive mutation(s) in
COL6A1, COL6A2 or COL6A3 known to cause the clinical picture,,
OR
• Histological diagnosis showing (i) absent or significantly decreased expression of
collagen VI in muscle (overall reduction or basal lamina specific) or (ii) absent or
significantly abnormal matrix in skin fibroblast culture
For patients with Laminin alpha 2 related dystrophy (LAMA2-RD) - required clinical picture:
• Muscle weakness: Inability to walk; if patient is still ambulatory, inability to run and
> 5 s for 10 m walk.
Genetics and Pathology:
• Either: 2 identified pathologic or probable pathologic mutations in LAMA2 gene
OR:
• 1 identified pathologic or probable pathologic mutation in LAMA 2 gene with evidence of
decrease in laminin alpha 2 staining on muscle or skin biopsy
OR:
• Evidence of decrease in laminin alpha 2 staining on muscle or skin biopsy with matching
clinical phenotype and no suspicion of alpha dystroglycanopathy (aDG-RD) (clinically or by
staining on muscle biopsy)
Exclusion Criteria:
- Use of any investigational drug other than the study medication within 12 weeks of
study start.
- Recurrent hospitalisation for chest infections in previous 2 years (=2 per year)
- Patients with respiratory parameters (eg: low pulmonary function test value i.e. <30%
or need for brief course of daytime non-invasive ventilation) currently affected by
short term medications, or acute illness/ conditions (conduct baseline assessments
when the patient has recovered and no longer taking acute medication)
- Any need for surgery (scoliosis, gastrostomy, other) in the preceding 24 weeks or
foreseen during the course of the study.
- Patient has an intercurrent significant medical condition or situation which in the
opinion of the Investigator or the study Medical Monitor may put the patient at
significant risk, confound the study results or interfere significantly with the
patient's participation in the study
- Failure to thrive, defined as:
- Falling 20 percentiles (20/100) in body weight in the 12 weeks preceding
Screening/Baseline (based on family report of weight loss and acquiring relevant
medical records)
- In patients below the 3rd percentile, any further drop in body weight percentile in
the 12 weeks preceding Screening/Baseline (based on family report of weight loss and
acquiring relevant medical records)
- Weight less than 17kg at Baseline
- Morbidly obese or grossly overweight (=86 percentile BMI in children)
- History of epilepsy or on antiepileptic medication at Screening/Baseline
- Diabetes
- On daytime Non Invasive Ventilation (NIV)
- Intake of prohibited medication (as listed in Appendix I)
- Anticipated need for anesthesia during the course of this study
- Patients with renal impairment defined as urinary protein concentration = 0.2 g/L
- Patients with moderate to severe hepatic impairment
- ALT = 8x upper limit of normal (ULN) and total bilirubin 2x ULN (plus >35% 'direct'
bilirubin), or
- ALT = 8x ULN and INR >1.5 or ALT >2x baseline levels, and total bilirubin > 2x ULN
(plus >35% 'direct' bilirubin), or
- ALT >2x baseline levels, and INR greater than 1.5,
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