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

Phase 2

Recruiting

• Conditions: Spinal Muscular Atrophy
• Interventions: Drug: NMD670; Drug: Placebo

• Registration Number: NCT05794139
• Lead Sponsor: NMD Pharma A/S

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 available

Study Timeline

• Study First Submitted: 2023-03-15
• Study First Submitted QC: 2023-03-29
• Study First Posted: 2023-04-03
• Study Start: 2023-09-21
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-12
• Last Update Posted: 2025-03-13
• Primary Completion: 2026-01
• Study Completion: 2026-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 54

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Cohort 2	Placebo	Placebo followed by experimental drug
Cohort 1	NMD670	Experimental drug followed by placebo
Cohort 2	NMD670	Placebo followed by experimental drug
Cohort 1	Placebo	Experimental drug followed by placebo

Primary Outcome Measures

Name	Time	Method
Change from baseline in 6 minute walk test (6MWT) total distance versus placebo	Baseline to day 21	Distance walked (meters)

Secondary Outcome Measures

Name	Time	Method
Incidence of treatment emergent adverse events	Over 21 days of dosing	Summarised per treatment
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
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
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 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 serious treatment emergent adverse events	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
Incidence of clinically significant abnormalities on physical examinations	Over 21 days of dosing	Summarised per treatment

Trial Locations

Locations (29)

Roy Blunt NextGen Precision Health Institute; 🇺🇸 Columbia, Missouri, United States

The Ohio State University Wexner Medical Center; 🇺🇸 Columbus, Ohio, United States

H. Donostia; 🇪🇸 Donostia, Spain

Hospital Universitari Vall D Hebron; 🇪🇸 Barcelona, Spain

Hospital Materno Infantil La Paz; 🇪🇸 Madrid, Spain

Hospital Universitario y Politécnico La Fe; 🇪🇸 Valencia, Spain

UCLA David Geffen School Of Medicine - Neurology; 🇺🇸 Los Angeles, California, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Rare Disease Research - Raleigh-Durham; 🇺🇸 Hillsborough, North Carolina, United States

Aarhus Universitetshospital, Neurologisk Afdeling; 🇩🇰 Aarhus, Denmark

Rigshospitalet - Neurologisk Afdeling; 🇩🇰 København, Denmark

UZ Leuven - Neurochirurgie Campus Gasthuisberg; 🇧🇪 Leuven, Belgium

Ospedale Niguarda, ASST Grande Ospedale Metropolitano Niguarda; 🇮🇹 Milano, Italy

Charite - Campus Virchow-Klinikum (CVK); 🇩🇪 Berlin, Germany

Genge Partners Inc.; 🇨🇦 Montréal, Canada

Istituto Giannina Gaslini, IRCCS; 🇮🇹 Genova, Italy

CHR de la Citadelle - Neurologie; 🇧🇪 Liège, Belgium

Istituto Neurologico C. Besta, Fondazione IRCCS; 🇮🇹 Milano, Italy

Universitair Medisch Centrum Utrecht, locatie Academisch Zie - Neurology; 🇳🇱 Utrecht, Netherlands

Universitätsklinikum Essen - Klinik Für Neurologie; 🇩🇪 Essen, Germany

Università degli studi di Pisa; 🇮🇹 Pisa, Italy

PU A. Gemelli, Università Cattolica del Sacro Cuore; 🇮🇹 Roma, Italy

AOU Città della Salute e della Scienza di Torino; 🇮🇹 Torino, Italy

Rare Disease Center; 🇺🇸 Atlanta, Georgia, United States

Stanford University Medical Center; 🇺🇸 Palo Alto, California, United States

Heritage Medical Research Clinic; 🇨🇦 Calgary, Canada

UF Fixel Institute for Neurological Diseases; 🇺🇸 Gainesville, Florida, United States

Neurology Rare Disease Center; 🇺🇸 Denton, Texas, United States

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States