Safety and Efficacy of NMD670 in Ambulatory Adult Patients With Type 3 Spinal Muscular Atrophy (SYNAPSE-SMA)

• ClinicalTrials.gov Identifier: NCT05794139
• Recruitment Status: Recruiting
• First Posted: April 3, 2023
• Last Update Posted: April 26, 2024
• Sponsor: NMD Pharma A/S
• Information provided by (Responsible Party): NMD Pharma A/S

Tracking Information

• First Submitted Date: March 15, 2023
• First Posted Date: April 3, 2023
• Last Update Posted Date: April 26, 2024
• Actual Study Start Date: September 21, 2023
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 29, 2023)

Change from baseline in 6 minute walk test (6MWT) total distance versus placebo [ Time Frame: Baseline to day 21 ]

Distance walked (meters)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 24, 2024)

• Change from baseline in muscle strength versus placebo [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline to day 21 ]
  Jitter (micro seconds) assessed with single fiber EMG
• Change from baseline in blocking versus placebo [ Time Frame: Baseline to day 21 ]
  Blocking (%) assessed with single fiber EMG
• Incidence of treatment emergent adverse events [ Time Frame: Over 21 days of dosing ]
  Summarised per treatment
• Incidence of serious treatment emergent adverse events [ Time Frame: Over 21 days of dosing ]
  Summarised per treatment
• Incidence of clinically significant abnormalities on physical examinations [ Time Frame: Over 21 days of dosing ]
  Summarised per treatment
• Incidence of clinically significant abnormalities on safety laboratory parameters [ Time Frame: Over 21 days of dosing ]
  Summarised per treatment
• Incidence of clinically significant vital signs abnormalities [ Time Frame: Over 21 days of dosing ]
  Summarised per treatment
• Incidence of clinically significant ECG abnormalities [ Time Frame: Over 21 days of dosing ]
  Summarised per treatment
• Incidence of Suicidal Ideation or Suicidal Behavior [ Time Frame: Over 21 days of dosing ]
  Summarised per treatment
• Incidence of clinically significant abnormalities on opthalmological examinations [ Time Frame: Over 21 days of dosing ]
  Summarised per treatment

Original Secondary Outcome Measures (submitted: March 29, 2023)

• Change from baseline in muscle strength versus placebo [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline to day 21 ]
  Total score
• Change from baseline in time to dropout in the endurance shuttle 9-hole peg test (ESNHPT) versus placebo [ Time Frame: Baseline to day 21 ]
  time to dropout (seconds)
• Change from baseline in proportion of patients that drops out in the endurance shuttle 9-hole peg test (ESNHPT) versus placebo [ Time Frame: Baseline to day 21 ]
  Proportion of patient dropout (%)
• Change from baseline in jitter versus placebo [ Time Frame: Baseline to day 21 ]
  Jitter (micro seconds) assessed with single fiber EMG
• Change from baseline in blocking versus placebo [ Time Frame: Baseline to day 21 ]
  Blocking (%) assessed with single fiber EMG
• Incidence of treatment emergent adverse events [ Time Frame: Over 21 days of dosing ]
  Summarised per treatment
• Incidence of serious treatment emergent adverse events [ Time Frame: Over 21 days of dosing ]
  Summarised per treatment
• Incidence of clinically significant abnormalities on physical examinations [ Time Frame: Over 21 days of dosing ]
  Summarised per treatment
• Incidence of clinically significant abnormalities on safety laboratory parameters [ Time Frame: Over 21 days of dosing ]
  Summarised per treatment
• Incidence of clinically significant vital signs abnormalities [ Time Frame: Over 21 days of dosing ]
  Summarised per treatment
• Incidence of clinically significant ECG abnormalities [ Time Frame: Over 21 days of dosing ]
  Summarised per treatment
• Incidence of Suicidal Ideation or Suicidal Behavior based on the Columbia-Suicide Severity Rating Scale [ Time Frame: Over 21 days of dosing ]
  Summarised per treatment

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy of NMD670 in Ambulatory Adult Patients With Type 3 Spinal Muscular Atrophy
• Official Title: 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
• 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
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:

2-way crossover

Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: Spinal Muscular Atrophy

Intervention

• Drug: NMD670
  Tablets
• Drug: Placebo
  Tablets

Study Arms

• Experimental: Cohort 1
  Experimental drug followed by placebo
  Interventions:

  • Drug: NMD670
  • Drug: Placebo
• Experimental: Cohort 2
  Placebo followed by experimental drug
  Interventions:

  • Drug: NMD670
  • Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 29, 2023): 54
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2024
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: NMD Pharma A/S; contact@nmdpharma.com; contact@nmdpharma.com

• Listed Location Countries: Belgium, Canada, Denmark, Germany, Italy, Netherlands, Spain, United States

Administrative Information

• NCT Number: NCT05794139
• Other Study ID Numbers: NMD670-02-0001; 2022-002301-24 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: NMD Pharma A/S
• Original Responsible Party: Same as current
• Current Study Sponsor: NMD Pharma A/S
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: NMD Pharma A/S
• Verification Date: April 2024