5q spinal muscular atrophy Autosomal recessive proximal spinal muscular atrophy
Conditions
Interventions
After a screening period of up to 4 weeks, each treatment period in the 2-way
crossover design will last 21 days (preceded 1 day before dosing by a baseline
visit), separated by a 7-day inter-treatm
Sponsors
NMD Pharma
Eligibility
Inclusion criteria
Inclusion criteria: 1. Participant must be 18 to 75 years of age inclusive, at the time of signing the informed consent. 2. Participants who are with a clinical diagnosis of Type 3 SMA. 3. Participants who are ambulatory, defined as being able to walk at least 50 metres without walking aids. 4. Participant with genetic confirmation of diagnosis (i.e., homozygous deletion of survival of motor neuron 1 gene [SMN1]). 5. Participant with 3 to 5 copies of survival of motor neuron 2 gene [SMN2]. 6. Participants with a MFM-32 dimension 1 score =7% CMAP amplitude decrement at screening (recorded from the trapezius muscle during repeated nerve stimulation [RNS]).
Exclusion criteria
Exclusion criteria: 1. Participants with prior surgery or fixed deformity (scoliosis, contractures) which would restrict ability to perform study-related tasks. 2. Participants with other significant disease that may interfere with the interpretation of study data (e.g., other neuromuscular or muscular diseases). 3. Participant with a clinical diagnosis of gout, or with serum uric acid >6.5 mg/dL at screening. 4. Participant with clinically significant ECG abnormalities at screening including PR interval >=220 msec, irregular rhythms (other than sinus arrhythmia or occasional, rare supraventricular or rare ventricular ectopic beats) in the judgement of the Investigator, or T-wave configurations are not of sufficient quality for assessing QT interval duration.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Objective: To assess changes in muscle strength and function after NMD670 400 mg bid for 21 days, compared with placebo, in participants with SMA. Primary Endpoint Change from baseline in 6MWT (total distance, without walking aids) after 21-day dosing | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Objective: To assess changes in muscle strength after NMD670 400 mg bid for 21 days, compared with placebo, in participants with SMA. Secondary Endpoint: Change from baseline in individual muscle groups maximum strength (measured with a dynamometer) after 21-day dosing. Secondary Objective: To further assess changes in muscle strength and function after NMD670 400 mg bid for 21 days, compared with placebo, in participants with SMA Secondary Endpoint: Change from baseline after 21-day dosing in: • 6MWT (fatigue index) • revised Hammersmith scale score Secondary Objective: To assess changes in neuromuscular junction transmission after NDM670 400 mg bid for 21 days, compared with placebo, in participants with SMA Secondary Endpoint: Change from baseline in jitter and blocking measured via sfEMG after 21-day dosing Secondary Objective: To assess the safety and tolerability of NMD670, compared with placebo, over 21-day dosing, in participants with SMA Secondary Endpoint: AEs, physical examinations, ophthalmological examinations, clinical laboratory parameters, vital signs, ECG, C-SSRS | — |
Countries
Netherlands
Outcome results
None listed