Spinal Muscular Atrophy
Conditions
Keywords
Transmission Enhancer, Neuromuscular Junction Transmission, ClC-1
Brief summary
The purpose of this study is to evaluate the efficacy, safety, tolerability and pharmacokinetics of NMD670 in the treatment of ambulatory adults with spinal muscular atrophy type 3
Interventions
DRUGNMD670
Tablets
DRUGPlacebo
Tablets
Sponsors
NMD Pharma A/S
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
2-way crossover
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Participants with a clinical diagnosis of Type 3 SMA. 2. Participants who are ambulatory, defined as being able to walk at least 50 metres without walking aids at screening during the 6-minute walk test. 3. Participant with genetic confirmation of diagnosis (e.g., homozygous deletion or compound heterozygous deletion and mutation of survival of motor neuron 1 gene \[SMN1\]) 4. Participant with 3 to 5 copies of survival of motor neuron 2 gene \[SMN2\]. 5. Participant has a body mass index (BMI) within the range 19-35 kg/m2 (inclusive). 6. Participant is male or female. 7. Contraceptive use by men and women must be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 8. Participant is capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
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. Participants with other significant clinical and/or laboratory safety findings that may interfere with the conduction or interpretation of the study 4. Participants received treatment with an investigational medical product (IMP) within 30 days (or 5 half-lives of the medication, whichever is longer) prior to Day 1. 5. Participants with history of poor compliance with relevant SMA therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in 6 minute walk test (6MWT) total distance versus placebo | Baseline to day 21 | Distance walked (meters) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in muscle strength versus placebo | Baseline to day 21 | Handgrip, knee flexor, elbow flexor, elbow extension and should abduction (Newton) |
| Change from baseline in 6 minute walk test (6MWT) fatigue index versus placebo | Baseline to day 21 | percentage change in distance walked in 6th minute compared to 1st minute |
| Change from baseline in Revised Hammersmith Scale (RHS) versus placebo | Baseline to day 21 | Total score. Scale goes from 0-69 and higher score indicates improvement of symptoms |
| Change from baseline in jitter versus placebo | Baseline to day 21 | Jitter (micro seconds) assessed with single fiber EMG |
| Change from baseline in blocking versus placebo | Baseline to day 21 | Blocking (%) assessed with single fiber EMG |
| Incidence of treatment emergent adverse events | Over 21 days of dosing | Summarised per treatment |
| Incidence of serious treatment emergent adverse events | Over 21 days of dosing | Summarised per treatment |
| Incidence of clinically significant abnormalities on physical examinations | Over 21 days of dosing | Summarised per treatment |
| Incidence of clinically significant abnormalities on safety laboratory parameters | Over 21 days of dosing | Summarised per treatment |
| Incidence of clinically significant vital signs abnormalities | Over 21 days of dosing | Summarised per treatment |
| Incidence of clinically significant ECG abnormalities | Over 21 days of dosing | Summarised per treatment |
| Incidence of Suicidal Ideation or Suicidal Behavior | Over 21 days of dosing | Summarised per treatment |
| Incidence of clinically significant abnormalities on opthalmological examinations | Over 21 days of dosing | Summarised per treatment |
Countries
Belgium, Canada, Denmark, Germany, Italy, Netherlands, Spain, United States
Outcome results
None listed