| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| Congenital myopathy is a muscle disorder that presents with low muscle tone and generalised hypotonia. Symptoms present during childhood but in severe cases they appear from birth |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10062547 |
| E.1.2 | Term | Congenital myopathy |
| E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
We want to investigate if daily intake of oral salbutamol can increase the
total score of muscle function measure 32 test in a group of congenital
myopathy subjects after 6 months on treatment as compared to having
no treatment. |
|
| E.2.2 | Secondary objectives of the trial |
1) Increased walking distance during 6-minute walking test after 6 months of treatment
2) Less fatigability during physical activity after 6 months of treatment: assessed by comparing subjects speed (m/min) during the first and last minute of 6 minute walking test
3) Decreased time needed to complete timed function tests (10 m walk/run, 4 steps and down) after 6 months treatment
4) Increased hand strength on hand held myometry after 6 months on treatment.
5) Less fatigability in upper extremities during physical examination: assessed with 5 consecutive 9 hole peg tests, where time of completion of first set is compared with time of completion of the last set.
6) Increase in forced vital capacity both sitting and lying down after 6 months of treatment
7) Improvement of quality of life after 6 months of treatment
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
a) Signed informed consent from legal guardians/patients and patient (where applicable)
b) Subject must have a confirmed CM diagnosis defined as:
• Clinical symptoms consistent with CM with pathohistological findings on muscle biopsy and known genetic mutation consistent with CM
OR
• Clinical symptoms consistent with CM with unspecific pathohistological changes but known genetic mutation consistent with CM
c. Stabile on MFM 32 over at least 6 months ( between baseline and screening visit. An increase or decrease of the total score of max 2 points between baseline and screening visit will be allowed.
d. At least 1 point on MFM32 on screening visit
e. If on other medications that can affect motor function in the opinion of the investigator- stabile dose for 2 months prior to start
f. 6 years of age to 30 years of age
g. Women of fertile age can be on oral contraceptives
h. Subjects must have had cardiac evaluation with ECG and 2D echocardiography in the last 2 years, with no signs or symptoms of cardiac abnormality.
|
|
| E.4 | Principal exclusion criteria |
a) Subject with clinical symptoms consistent with congenital myopathy but has no confirmed genetic mutation and only unspecific changes on muscle biopsy that are not confined to just congenital myopathy but can be seen in other disorders.
b) Younger than 6 years of age and older than 30 years.
c) Subject receives 94 or more points on MFM32 test at screening visit.
d) Subject doesn’t not speak Swedish and a translator is needed in order to perform the tests included in the study.
e) Subject receives no point on MFM 32 test at screening (baseline 2)
f) Subject smokes more than 10 cigarettes a day or has smoked more that 10 cigarettes in the last year before the study start
g) Subject has tracheostomy
h) Subject has other concomitant chronic diagnosis that can affect the patients motor function, in the opinion of the investigator
i) Subject is currently or has been on oral corticosteroids in the last 6 months
j) Subject has arrhythmia as seen on ECG, confirmed by cardiologist
k) Subject has cardiomyopathy as seen on ultrasound, confirmed by cardiologist
l) Subject has severe behavioral and/ cognitive problems that preclude participation in the study, in the opinion of the investigator;
m) Subject is allergic or hypersensitive to study drug or any of its constituents
n) Subject has previous or ongoing medical condition, medical history, physical findings or laboratory abnormalities that could affect safety, make it unlikely that treatment and follow-up will be correctly completed or impair the assessment of study results, in the opinion of the Investigator;
o) Subject is currently taking any other investigational drug or has taken any other investigational drug within 3 months prior to the first dose of study medication.
p) Subject is planning on participating in any other study during the duration of this study.
q) Female subjects of fertile age that are pregnant or are planning to become pregnant during the study.
r) Female subjects that have given birth upto 1 year prior to first baseline visit and/or are nursing upto 1 month prior to first baseline visit.
s)Subject has a fracture in the last 6 months before the study start or has acquired a fracture during the study.The fracture needs to be on a body part that can affect our study tests and results, in the opinion of the investigator. .
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Increase of MFM32 test with at least 3 points after 6 months of treatment as compared to no treatment |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
-6months, 0 (randomization, study start), 6 months, 7 months and 13
months after randomization
E. |
|
| E.5.2 | Secondary end point(s) |
1) Increased walking distance during 6-minute walking test after 6 months of treatment
2) Less fatigability during physical activity after 6 months of treatment: assessed by comparing subjects speed (m/min) during the first and last minute of 6 minute walking test
3) Decreased time needed to complete timed function tests (10 m walk/run, 4 steps and down) after 6 months treatment
4) Increased hand strength on hand held myometry after 6 months on treatment.
5) Less fatigability in upper extremities during physical examination: assessed with 5 consecutive 9 hole peg tests, where time of completion of first set is compared with time of completion of the last set.
6) Increase in forced vital capacity both sitting and lying down after 6 months of treatment
7) Improvement of quality of life after 6 months of treatment |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
-6months, 0 (randomization, study start), 6 months, 7 months and 13
months after randomization
E. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | No |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| the clinical evaluators will be blinded |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | |
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