Type 3 spinal muscular atrophy MedDRA version: 20.0 Level: LLT Classification code 10079415 Term: Spinal muscular atrophy type III System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Code: NMD670
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: NA
CAS Number: 2354321-33-6
Current Sponsor code: NMD670
Other descriptive name: NMD670
Concentration unit: mg milligr
Sponsors
NMD Pharma A/S
Eligibility
Sex/Gender
All
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 at screening during the 6-minute walk test. 4. Participant with genetic confirmation of diagnosis (e.g., homozygous deletion or compound heterozygous deletion and mutation 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 an MFM-32 dimension 1 (D1) score =65 years) yes F.1.3.1 Number of subjects for this age range 5
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 >ULN at screening. 4. Participant with clinically significant electrocardiogram (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. 5. Participant with any of the following abnormalities in QT interval corrected for heart rate using Fridericia's correction (QTcF) at screening: a. QTcF >450 msec for male participants without bundle branch block. b. QTcF >470 msec for female participants without bundle branch block. c. QTcF >480 msec in participants with bundle branch block. 6. Participant with any of the following: a. Abnormal liver function test defined as total bilirubin >1.5×ULN (participants with Gilbert's syndrome can be included with total bilirubin >1.5×ULN if direct bilirubin is =1.5×ULN and =35% of total bilirubin). b. Current or chronic history of liver disease including (but not limited to) hepatitis virus infections, drug- or alcohol-related liver disease, nonalcoholic steatohepatitis, autoimmune hepatitis, hemochromatosis, Wilson's disease, a-1 antitrypsin deficiency, primary biliary cholangitis, primary sclerosing cholangitis, or any other liver disease considered clinically significant by the Investigator. c. Known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). 7. Participant with clinically significant laboratory test abnormalities at screening. 8. Participant with breast cancer within the past 10 years or lymphoma, leukaemia, or any malignancy within the past 5 years. An exception of this 5-year requirement is basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease. 9. Participants with ongoing significant psychiatric disorder (e.g., uncontrolled depression, anxiety). 10. Participants with positive drug screen (cocaine, heroin, opiates, and ketamine at screening. Participants will not be excluded from the study if they showed a positive drug screen due to medically prescribed, opiates or ketamine. 11. Participants with positive human immunodeficiency virus (HIV) antibody test. 12. Participants with presence of hepatitis B surface antigen (HBsAg) [or hepatitis B core antibody (HBcAb)] at screening or within 3 months prior to first dose of investigational intervention. 13. Participants with positive hepatitis C antibody or ribonucleic acid (RNA) test result at screening or within 3 months prior to Day 1. NOTE: Participants with hepatitis C with positive hepatitis C antibody could be enrolled, if a negative hepatitis C RNA test is obtained. 14. Participants with a clinically significant history of allergic conditions (including drug allergies and anaphylactic reactions) or hypersensitivity to any component of the study intervention. 15. Participants with evidence of a lens opacity or cataract, or an inability to undergo the ophthalmologic evaluation, at screening. 16. Participants who
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess changes in muscle strength and function after NMD670 400 mg bid for 21 days, compared with placebo, in participants with SMA;Secondary Objective: - To assess changes in muscle strength after NMD670 400 mg bid for 21 days, compared with placebo, in participants with SMA - To further assess changes in muscle strength and function after NMD670 400 mg bid for 21 days, compared with placebo, in participants with SMA - To assess changes in neuromuscular junction transmission after NDM670 400 mg bid for 21 days, compared with placebo, in participants with SMA - To assess the safety and tolerability of NMD670, compared with placebo, over 21-day dosing, in participants with SMA Exploratory objectives: - To assess changes in patient-reported quality of life and fatigue severity after 21-day dosing of NMD670, compared with placebo, in participants with SMA - To explore drug exposure after NMD670 400 mg bid for 21 days in participants with SMA;Primary end point(s): Change from baseline in 6MWT (total distance) after 21-day dosing;Timepoint(s) of evaluation of this end point: After 21 day dosing | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change from baseline in individual muscle groups maximum strength (measured with a dynamometer) after 21-day dosing Change from baseline after 21-day dosing in: • 6MWT (fatigue index) • revised Hammersmith scale score Change from baseline in jitter and blocking measured via sfEMG after 21-day dosing AEs, physical examinations, clinical laboratory parameters, vital signs, ECG, C-SSRS Exploratory: Change from baseline after 21-day dosing in: • INQoL score • FSS Plasma levels of NMD670 and its metabolite NMD1190 ;Timepoint(s) of evaluation of this end point: After 21 day dosing During study participation | — |
Countries
Belgium, Canada, Denmark, Germany, Italy, Netherlands, Spain, United States
Contacts
Public ContactClinical Trials Information
Parexel International
Outcome results
None listed