Effect of Oral Levosimendan (ODM-109) on Respiratory Function in Patients with ALS (REFALS)
The purpose of the study is to evaluate safety and the effectiveness of levosimendan in preserving respiratory function in patients with amyotrophic lateral sclerosis (ALS).
Disease:Amyotrophic Lateral Sclerosis (ALS), Familial ALS, Sporadic ALS
Study Type:Interventional Trial
Study Category:Drug Trial
Study Chair(s)/Principal Investigator(s):
Merit Cudkowicz, MD, Massachusetts General Hospital
Clinicaltrials.gov ID (11 digit #):NCT03505021
Coordinating Center Contact InformationMassachusetts General Hospital
Boston, Massachusetts 02114 United States
Full Study Summary:
This study will evaluate whether prolonged oral levosimendan can preserve respiratory function more effectively than placebo, resulting in better patient functionality as measured by the ALSFRS-R scale. In this randomized, double-blind, placebo-controlled, parallel-group, multicenter study, subjects are allocated in a 2:1 ratio to receive either levosimendan (1 -2 mg daily) or placebo for 48 weeks. The primary endpoint is slow vital capacity (SVC) at 12 weeks, with the impact on patient function assessed through 48 weeks, adjusted for patient outcome, using ALSFRS-R (combined assessment of function and survival, CAFS). Other important efficacy measures include time to respiratory events, clinical global impression (CGI), assessment of dyspnea using the Borg scale and sleep scales (Pittsburgh sleep quality index and Epworth sleepiness scale). Patient safety is monitored using conventional methods including adverse events, safety laboratory tests, vital signs and 12-lead EKG. Following screening and baseline visits, patients attend the clinic at 2, 4, 8, 12, 24, 36 and 48 weeks, with telephone assessments conducted at weeks 18, 30 and 42. An end of study visit is performed 14-25 days after the last study treatment administration. The study will be monitored by an independent data and safety monitoring board. A long-term extension study will be available for patients completing the study.
Study Sponsor:Orion Corporation, Orion Pharma
Total study duration for each subject will be 51-52 weeks, including the screening period, 48 weeks treatment and an end-of-study visit.
At screening, the visit length will be approximately 2 – 2.5hrs.
For visits 2, 3 and 8, the visit length will be approximately 3 – 5 hrs.
For visits 4 to 7, the visit length will be approximately 2 – 3hrs.
There will also be three telephone contacts made in-between sites visits that should not last longer than 30 minutes.
Depending on location of sites, the study participant may be required to travel.
Estimated Study Start Date:06/21/2018
Estimated Study Completion Date:10/30/2020
Posting Last Modified Date:10/22/2018
Date Study Added to alsconsortium.org:07/06/2018
Time since Symptom Onset:
Time since Diagnosis:
Can participants use Riluzole?Yes
Written or verbal informed consent (IC) for participation in the study
Diagnosis of laboratory supported probable, probable or definite ALS according to El Escorial revised criteria.
Able to swallow study treatment capsules, and in the opinion of the investigator, is expected to continue to do so during the study.
Disease duration from symptom onset (defined by first muscle weakness or dysarthria) 12-48 months at the time of visit 1 (baseline)
Able to perform supine SVC in an adequate and reliable way at screening and baseline visits as judged by the investigator.
Subjects with or without riluzole (up to 100mg/day, stable at least 4 weeks) and/or edaravone (at least one 28-day treatment cycle completed).
Other causes of neuromuscular weakness not excluded.
Diagnosis of another neurodegenerative disease (e.g. Parkinson’s or Alzheimer’s disease).
Assisted ventilation of any type within 3 months before the screening visit or at screening.
Any use of a diaphragm pacing system (DPS) within 3 months before the screening visit.
Any form of stem cell or gene therapy for the treatment of ALS.
Known hypersensitivity to levosimendan.
Administration of levosimendan within 3 months before the screening visit or previous participation in oral levosimenan trial.
Any use of tirasemtiv or reldesemtiv within 1 month before the screening visit.
Participation in a clinical trial with any experimental treatment within 30 days or within 5 half-lives of that treatment (whichever is longer) before the screening visit.
Any botulinum toxin use within 3 months before the screening visit.
Recorded diagnosis or evidence of major psychiatric diagnosis, significant cognitive impairment or clinically evident dementia that may interfere with the patient’s ability to comply with study procedures.
Pulmonary illness (e.g. asthma or COPD) requiring regular treatment.
Haemodynamically significant uncorrected valve disease or hypertrophic cardiomyopathy or restrictive cardiomyopathy.
Any cardiovascular event (e.g. myocardial infarction, HF, arrhythmia or stroke) requiring hospitalisation within 3 months before the screening visit.
History of Torsades de Pointes (TdP) or diagnosed long QT-syndrome.
History of life-threatening ventricular arrhythmia, unless treated with reliable measures to prevent recurrence (e.g. with placement of implantable cardioverter defibrillator [ICD] or catheter ablation).
History of second or third degree atrioventricular (AV) block or sinus node disease at screening, if not treated with pacemaker.
HR repeatedly > 100 bpm in the 12-lead ECG after a 5-minute rest at screening.
Systolic blood pressure (SBP) < 90 mmHg at screening.
Potassium < 3.7 mmol/l or > 5.5 mmol/l at screening.
Severe renal impairment (creatinine clearance < 30 ml/min at screening), creatinine > 170 μmol/l at screening or on dialysis.
Blood haemoglobin < 10 g/dl at screening or blood donation or loss of significant amount of blood within 60 days before the screening visit.
Clinically significant hepatic impairment at the discretion of the investigator.
Body mass index (BMI) ≤ 18.5kg/m2 (BMI = weight/height2).
Women who are lactating or of reproductive age without a negative pregnancy test and without a commitment to using a highly effective method of contraception (e.g. oral hormonal contraceptives associated with inhibition of ovulation, intrauterine devices and long acting progestin agents), if sexually active during the study, and for 1 month after the last dose of the study treatment. Women who are postmenopausal (1 year since last menstrual cycle), surgically sterilised or who have undergone a hysterectomy are considered not to be reproductive and can be included.
Patient judged to be actively suicidal by the investigator during 3 months before the screening visit.
Patients with known history of human immunodeficiency virus (HIV) infection.
Any other clinically significant cardiovascular, gastrointestinal, hepatic, renal, neurological or psychiatric disorder or any other major concurrent illness that in the opinion of the investigator could interfere with the interpretation of the study results or constitute a health risk for the subject if he/she took part in the study.
Site Contact Information
Neuromuscular Research Center and Neuromuscular Clinic of Arizona
Phoenix, Arizona 85028
Phoenix Neurological Associates
Phoenix, Arizona 85006
University of California San Diego
Colorado Springs Neurological Associates
Colorado Springs, Colorado 80907
Hospital for Special Care
New Britain, Connecticut 06053
The George Washington Medical Faculty Associates
Washington, District of Columbia 20037
University of Florida Health - Jacksonville
Jacksonville, Florida 32209
University of South Florida
Tampa, Florida 33612
Holy Cross Hospital
Fort Lauderdale, Florida 33308
Jacksonville, Florida 32224
Emory University School of Medicine
Northwestern University Feinberg School of Medicine
University of Kentucky Chandler Medical Center
Lexington, Kentucky 40536
Kentucky Neuroscience Research
Louisville, Kentucky 40202
Johns Hopkins Hospital
Baltimore, Maryland 21205
Massachuesetts General Hospital
Boston, Massachuesetts 02114
Mayo Clinic - Rochester
Rochester, Minnesota 55905
HealthPartners Specialty Center
Saint Paul, Minnesota 55130
Washington University School of Medicine
Lincoln, Nebraska 68506
Neurosciences Institute - Neurology Charlotte
Charlotte, North Carolina 28207
Duke University Medical Center
Durham, North Carolina 27705
Wake Forest University Baptist Medical Center
Winston-Salem, North Carolina 27157
The Ohio State University
Providence Brain and Spine Institute
Portland, Oregon 97213
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania 15213
University of Pennsylvania
Philadelphia, Pennsylvania 19107
Allegheny General Hospital
Pittsburgh, Pennsylvania 15212
Nerve and Muscle Center of Texas
Houston, Texas 77030
Daragh Heitzman / 214-827-3610
Dallas, Texas 75214
University of Utah
Salt Lake City, Utah 84108
Swedish Neuroscience Institute
Seattle, Washington 98122
Milwaukee, Wisconsin 53226
Brain and Mind Centre
Eleanor Ramsey / 02 9351 0976
Camperdown, New South Wales 2050
Perron Institute for Neurological and Translational Science
Calvary Health Care Bethlehem
Flinders Medical Centre
David Schultz / 61 8 8204 4187
Bedford Park, South Australia 5042
Royal Brisbane and Women's Hospital
Brisbane, Queensland 4029
Vöcklabruck, Upper Austria 4840
Universitaire Ziekenhuis Leuven
Philip Van Damme / 016 344280
Leuven, Flemish 3000
Algemeen Ziekenhuis St. Lucas Gent
Jan De Bleeker / 32-9-2246530
Gent, Oost-Vlaanderen 9000
Centre Hospitalier Régional de la Citadelle
Liège, Liege 4000
Stan Cassidy Centre for Rehabilitation
Fredericton, New Brunswick E3B 0C7
Centre De Recherche Du Centre Hospitalier de l'Universite de Montreal - Hopital Notre-Dame
Montreal, Quebec H2L 4M1
Alberta Health Services - Neuromuscular Clinic
Calgary, Alberta T3M1M4
Montreal Neurological Institute and Hospital
Montreal, Quebec H3A 2B4
University of Alberta
Edmondton, Alberta T6G 2G3
Moncton Hospital, Southeast Regional Health Authority
Moncton, New Brunswick E1C 2Z3
Sunnybrook Health Sciences Centre
Toronto, Ontario M4N 3M5
Turku University Hospital
Helsingin ja Uudenmaan sairaanhoitopiiri
Neurologian Poliklinikka - Meilahden Tornisairaala 3
Jena, Thuringen 07747
Deutsche Klinik für Diagnostik
Wiesbaden, Hessen 65191
Münster, Nordrhein-Westfalen 48149
Universitätsklinikum Carl Gustav Carus
Dresden, Sachsen 01307
Charité Universitätsmedizin Berlin - Campus Virchow-Klinikum
Beaumont Hospital - Ireland
Azienda Ospedaliera - Universitaria Città della Salute e della Scienza di Torino
Universitair Medisch Centrum Utrecht - Rudolf Magnus Instituut voor Neurowetenschappen
Utrecht, 3584 CG
Academisch Medisch Centrum
Amsterdam, 1105 AZ
Hospital San Rafael - Madrid
Hospital Universitari de Bellvitge
Berta Blanco Burguet / 34932607586
Hospital Universitario y Politécnico de La Fe
Hospital Universitario Reina Sofia
Hospital de Basurto
Bilbao, Vizcaya 48013
Karolina Palmback / 08 51771231
Karlstad, 651 85
The Walton Centre NHS Foundation Trust
Liverpool, England L9 7LJ
Barts Health NHS Trust
London, England E1 1BB
King's College Hospital NHS Foundation Trust
London , England SE5 9RS