Safety and Efficacy of NMD670 in Ambulatory Adult Patients With Type 3 Spinal Muscular Atrophy

Study Overview
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Brief Summary
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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

Official Title
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A Phase 2, Randomised, Double-blind, Placebo-controlled, 2-way Crossover Study to Evaluate the Efficacy, Safety, and Tolerability of NMD670 in Ambulatory Adults With Type 3 Spinal Muscular Atrophy

Conditions
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Spinal Muscular Atrophy

Intervention / Treatment
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* Drug: NMD670
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who are with a clinical diagnosis of Type 3 SMA. Participants who are ambulatory, defined as being able to walk at least 50 metres without walking aids. Participant with genetic confirmation of diagnosis (i.e., homozygous deletion of survival of motor neuron 1 gene [SMN1]). Participant with 3 to 5 copies of survival of motor neuron 2 gene [SMN2]. Participant has a body mass index (BMI) within the range 19-30 kg/m2 (inclusive). Participant is male or female. Contraceptive use by men and women must be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 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: Participants with prior surgery or fixed deformity (scoliosis, contractures) which would restrict ability to perform study-related tasks. Participants with other significant disease that may interfere with the interpretation of study data (e.g., other neuromuscular or muscular diseases). Participants with other significant clinical and/or laboratory safety findings that may interfere with the conduction or interpretation of the study 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. Participants with history of poor compliance with relevant SMA therapy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 2-way crossover
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Experimental drug followed by placebo | Drug: NMD670<br>* Tablets<br>Drug: Placebo<br>* Tablets<br>|
| Experimental: Cohort 2<br>Placebo followed by experimental drug | Drug: NMD670<br>* Tablets<br>Drug: Placebo<br>* Tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in 6 minute walk test (6MWT) total distance versus placebo | Distance walked (meters) | Baseline to day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in muscle strength versus placebo | Handgrip, knee flexor, elbow flexor, elbow extension and should abduction (Newton) | Baseline to day 21 | 
| Change from baseline in 6 minute walk test (6MWT) fatigue index versus placebo | percentage change in distance walked in 6th minute compared to 1st minute | Baseline to day 21 | 
| Change from baseline in Revised Hammersmith Scale (RHS) versus placebo | Total score. Scale goes from 0-69 and higher score indicates improvement of symptoms | Baseline to day 21 | 
| Change from baseline in time to dropout in the endurance shuttle 9-hole peg test (ESNHPT) versus placebo | time to dropout (seconds) | Baseline to day 21 | 
| Change from baseline in proportion of patients that drops out in the endurance shuttle 9-hole peg test (ESNHPT) versus placebo | Proportion of patient dropout (%) | Baseline to day 21 | 
| Change from baseline in jitter versus placebo | Jitter (micro seconds) assessed with single fiber EMG | Baseline to day 21 | 
| Change from baseline in blocking versus placebo | Blocking (%) assessed with single fiber EMG | Baseline to day 21 | 
| Incidence of treatment emergent adverse events | Summarised per treatment | Over 21 days of dosing | 
| Incidence of serious treatment emergent adverse events | Summarised per treatment | Over 21 days of dosing | 
| Incidence of clinically significant abnormalities on physical examinations | Summarised per treatment | Over 21 days of dosing | 
| Incidence of clinically significant abnormalities on safety laboratory parameters | Summarised per treatment | Over 21 days of dosing | 
| Incidence of clinically significant vital signs abnormalities | Summarised per treatment | Over 21 days of dosing | 
| Incidence of clinically significant ECG abnormalities | Summarised per treatment | Over 21 days of dosing | 
| Incidence of Suicidal Ideation or Suicidal Behavior | Summarised per treatment | Over 21 days of dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transmission Enhancer, Neuromuscular Junction Transmission, ClC-1