Clinical trial NCT05794139: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Spinal Muscular Atrophy
Keywords: Transmission Enhancer
Neuromuscular Junction Transmission
ClC-1
Lead sponsor: NMD Pharma A/S
Sponsor class: INDUSTRY
First posted: 2023-04-03
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 2-way crossover
Primary purpose: TREATMENT

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


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.

Primary outcomes:
measure: Change from baseline in 6 minute walk test (6MWT) total distance versus placebo
timeFrame: Baseline to day 21
Secondary outcomes:
measure: Change from baseline in muscle strength versus placebo
timeFrame: Baseline to day 21
measure: Change from baseline in 6 minute walk test (6MWT) fatigue index versus placebo
timeFrame: Baseline to day 21
measure: Change from baseline in Revised Hammersmith Scale (RHS) versus placebo
timeFrame: Baseline to day 21
measure: Change from baseline in jitter versus placebo
timeFrame: Baseline to day 21
measure: Change from baseline in blocking versus placebo
timeFrame: Baseline to day 21
measure: Incidence of treatment emergent adverse events
timeFrame: Over 21 days of dosing
measure: Incidence of serious treatment emergent adverse events
timeFrame: Over 21 days of dosing
measure: Incidence of clinically significant abnormalities on physical examinations
timeFrame: Over 21 days of dosing
measure: Incidence of clinically significant abnormalities on safety laboratory parameters
timeFrame: Over 21 days of dosing
measure: Incidence of clinically significant vital signs abnormalities
timeFrame: Over 21 days of dosing
measure: Incidence of clinically significant ECG abnormalities
timeFrame: Over 21 days of dosing
measure: Incidence of Suicidal Ideation or Suicidal Behavior
timeFrame: Over 21 days of dosing
measure: Incidence of clinically significant abnormalities on opthalmological examinations
timeFrame: Over 21 days of dosing
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA David Geffen School Of Medicine - Neurology
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Gainesville
country: United States
facility: UF Fixel Institute for Neurological Diseases
state: Florida
city: Atlanta
country: United States
facility: Rare Disease Center
state: Georgia
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Columbia
country: United States
facility: Roy Blunt NextGen Precision Health Institute
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Hillsborough
country: United States
facility: Rare Disease Research - Raleigh-Durham
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Denton
country: United States
facility: Neurology Rare Disease Center
state: Texas
city: Leuven
country: Belgium
facility: UZ Leuven - Neurochirurgie Campus Gasthuisberg
city: Liège
country: Belgium
facility: CHR de la Citadelle - Neurologie
city: Calgary
country: Canada
facility: Heritage Medical Research Clinic
city: Montréal
country: Canada
facility: Genge Partners Inc.
city: Aarhus
country: Denmark
facility: Aarhus Universitetshospital, Neurologisk Afdeling
city: København
country: Denmark
facility: Rigshospitalet - Neurologisk Afdeling
city: Berlin
country: Germany
facility: Charite - Campus Virchow-Klinikum (CVK)
city: Essen
country: Germany
facility: Universitätsklinikum Essen - Klinik Für Neurologie
city: Genova
country: Italy
facility: Istituto Giannina Gaslini, IRCCS
city: Milano
country: Italy
facility: Istituto Neurologico C. Besta, Fondazione IRCCS
city: Milano
country: Italy
facility: Ospedale Niguarda, ASST Grande Ospedale Metropolitano Niguarda
city: Pisa
country: Italy
facility: Università degli studi di Pisa
city: Roma
country: Italy
facility: PU A. Gemelli, Università Cattolica del Sacro Cuore
city: Torino
country: Italy
facility: AOU Città della Salute e della Scienza di Torino
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht, locatie Academisch Zie - Neurology
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D Hebron
city: Donostia
country: Spain
facility: H. Donostia
city: Madrid
country: Spain
facility: Hospital Materno Infantil La Paz
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
Study officials:
References: