Congenital myopathy intervention study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vaestra Goetalandsregionen, Vaestra Goetalandsregionen

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

27 Sep 2021 → 17 Mar 2025

Decision date (initial)

2024-04-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-512027-36-00

EudraCT number

2019-001147-51

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective of this study is to increase the muscle strength and muscle function of congenital myopathy subjects. This will be evaluated using MFM 32 where an increase of the total score needs to be observed after 6 months of treatment compared to the baseline.

Secondary objectives 10

1. Evaluate changes from screening/evaluation B to evaluation A/C visit at week 24 between treatment group vs non-treatment group on total distance travelled in completing the 6 minute walking test.
2. Evaluate changes from screening/evaluation B to evaluation A/C visit at week 24 between treatment group vs non-treatment group on the velocity (meters/minute) to complete 6MWT.
3. Evaluate changes from screening/evaluation B to evaluation A/C visit at week 24 between treatment group vs non-treatment group on Time to Stand Test (TTSTAND) velocity (rise/second).
4. Evaluate changes from screening/evaluation B to evaluation A/C visit at week 24 between treatment group vs non-treatment group on Time to Climb (4 Steps) Test (TTCLIMB) velocity (tasks/second).
5. Evaluate changes from screening/evaluation B to evaluation A/C visit at week 24 between treatment group vs non-treatment group on Time to Run/Walk Test (TTRW) velocity (meters/second) to complete 10 meters of a 14 meter course.
6. Evaluate changes from screening/evaluation B to evaluation A/C visit at week 24 between treatment group vs non-treatment group on hand held myometry.
7. Evaluate changes from screening/evaluation B to evaluation A/C visit at week 24 between treatment and non-treatment group on the change in time (seconds) needed to complete 5 consecutive 9-whole peg test with the dominant hand.
8. Evaluate changes from screening/evaluation B to evaluation A/C visit at week 24 between treatment group vs non-treatment group on FVC values in sitting and lying down positions.
9. Evaluate changes from screening/evaluation B to evaluation A/C visit at week24 between treatment group vs non-treatment group on quality of life as measured on QOL tests.
10. Determine if some genetic mutations are genetic modifiers leading to better effect of salbutamol compared to other genetic mutation.

Conditions and MedDRA coding

Congenital myopathy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Signed informed consent from legal guardians/patients and patient (where applicable).
2. 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.
3. Stable MFM32 over at least 6 months (between baseline and screening). An increase or decrease of the score with max two points will be allowed.
4. If on other medications- stabile dose for at least 3 months prior to start.
5. At least 1 point on MFM32 at screening visit.
6. 6 years of age to 30 years of age.
7. Women of fertile age can be on oral contraceptives.
8. Underwent cardiac evaluation with ECG and 2D echocardiography in the last 2 years and has no signs or symptoms of cardiac abnormality.

Exclusion criteria 19

1. Subject with clinical symptoms consistent with CM but has no confirmed genetic mutation and only unspecific changes on muscle biopsy that are not confined to just CM but can be seen in other disorders.
2. Younger than 6 years of age and older than 30 years.
3. Subject receives 94 or more points on MFM32 test at screening visit.
4. Subject doesn’t not speak Swedish and a translator is needed in order to perform the tests included in the study.
5. Subject smokes more than 10 cigarettes a day or has smoked more than 10 cigarettes in the last year.
6. Subject has tracheostomy.
7. Subject receives no points on MFM 32 test at screening.
8. Subject has other concomitant chronic diagnosis that can affect the patients motor function, in the opinion of the investigator.
9. Subject is currently or has been on oral corticosteroids in the last 6 months.
10. Subject has arrhythmia as seen on ECG, confirmed by cardiologist.
11. Subject has cardiomyopathy as seen on ultrasound, confirmed by cardiologist.
12. Subject has severe behavioral and/ cognitive problems that preclude participation in the study, in the opinion of the investigator;
13. Subject is allergic or hypersensitive to study drug or any of its constituents.
14. 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;
15. 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.
16. Subject is planning on participating in any other study during the duration of this study.
17. Female subjects of fertile age that are or are planning to become pregnant during the study.
18. Female subjects that have given birth up to 1 year prior to baseline visit and/or are nursing up to 1 month prior of baseline visit.
19. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Increase of MFM32 test after 6 months of treatment as compared to no treatment.

Secondary endpoints 7

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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vaestra Goetalandsregionen

Sponsor organisation

Vaestra Goetalandsregionen

Address

Regionens Hus

City

Vänersborg

Postcode

462 80

Country

Sweden

Scientific contact point

Organisation

Vaestra Goetalandsregionen

Contact name

Niklas Darin

Public contact point

Organisation

Vaestra Goetalandsregionen

Contact name

Niklas Darin

Vaestra Goetalandsregionen

Sponsor organisation

Vaestra Goetalandsregionen

Address

Regionens Hus

City

Vänersborg

Postcode

462 80

Country

Sweden

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications