Type 3 spinal muscular atrophy MedDRA version: 20.0 Level: LLT Classification code 10079415 Term: Spinal muscular atrophy type III System Organ Class: 100000004850
Conditions
Interventions
Product Code: NMD670
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: N/A
CAS Number: 2354321-33-6
Current Sponsor code: NMD670
Other descriptive name: NMD670
Concentration unit: mg millig
Sponsors
NMD Pharma A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant must be 18 to 60 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]). 8. Participant has a body mass index (BMI) within the range 19-30 kg/m2 (inclusive). 9. Participant is male or female. 10. Contraceptive use by men and women must be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male Participants: • A male participant must agree to use a highly effective contraception as detailed in Appendix 4 of this protocol during the intervention period and for at least 14 days after the last dose of study intervention (corresponding to time needed to eliminate study intervention) and refrain from donating sperm during this period. Female Participants: • A female participant is eligible to participate if she is not pregnant (see Appendix 4), not breastfeeding, and at least one of the following conditions applies: o Not a woman of childbearing potential (WOCBP) as defined in Appendix 4. OR o A WOCBP who agrees to follow the contraceptive guidance in Appendix 4 during the intervention period and for at least 14 days after the last dose of study intervention (corresponding to time needed to eliminate study intervention). 11. Participant is capable of giving signed informed consent as described in Appendix 1, Section 10.1.3 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 54 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
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. 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 is not limited to) hepatitis virus infections, drug- or alcohol-related liver disease, non-alcoholic steatohepatitis, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-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 for 5 years. 9. Participants with ongoing significant psychiatric disorder (e.g., uncontrolled depression, anxiety). 10. Participants with positive drug screen (cocaine, heroin, ketamine [unless medically prescribed], opiates) at screening. 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.
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 - ESNHP 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 Department
Parexel International
Outcome results
None listed