Clinical trial NCT03948178: Effects of Oral Levosimendan on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS): Open-Label Extension
Official title: Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS: Open-Label Extension for Patients Completing Study 3119002
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Amyotrophic Lateral Sclerosis
Lead sponsor: Orion Corporation, Orion Pharma
Sponsor class: INDUSTRY
First posted: 2019-05-13
Enrollment: 227
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study provides an opportunity for subjects in the REFALS (3119002; NCT03505021) study to continue treatment with oral levosimendan. The study will also provide more information about long-term safety and effectiveness of oral levosimendan in patients with ALS.

This is an open-label study, so that all eligible subjects that complete the double-blind REFALS study (48-weeks of treatment) will have the opportunity to receive oral levosimendan treatment. The primary objective, in addition to continuing treatment for subjects enrolled in the REFALS study, is to evaluate long-term safety of oral levosimendan in ALS patients. Another important objective is to explore long-term effectiveness of oral levosimendan in the treatment of patients with ALS.

This study is open only to patients taking part in the REFALS study.


Eligibility criteria: Inclusion Criteria:

* Written or verbal informed consent (IC) for participation in the study
* Subjects who completed 48 weeks of treatment according to the REFALS study protocol
* Able to swallow study treatment capsules at the time of completing 48 weeks dosing in the REFALS study

Exclusion Criteria:

* Development (or significant worsening from baseline of the REFALS study) of serious cardiovascular disease (e.g.: myocardial infarction, heart failure, arrhythmia, stroke, or second or third degree atrioventricular (AV) block)
* Pulse/heart rate repeatedly \>100 bpm after 5-minute rest at baseline. If the pulse/heart rate is \>100 bpm in the first recording, then a second recording must be done after another 5 min rest to confirm pulse/heart rate \>100 bpm
* Systolic blood pressure (SBP) \<90 mmHg
* Severe renal impairment (creatinine clearance \< 30ml/min or creatine \>170 µmol/l at 48 week visit of the REFALS study, or on dialysis
* Severe hepatic impairment at the discretion of the investigator
* Women of reproductive age without a negative pregnancy test and without a commitment to using a highly effective method of contraception (e.g.: oral hormonal contraceptive associated with inhibition of ovulation, intrauterine devices and long acting progestin agent), 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
* Subject judged to be actively suicidal by the investigator
* Any other clinical 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

Primary outcomes:
measure: Adverse Events Recording
timeFrame: From signing informed consent until 14-25 days after the last study treatment for all patients, an average of 23.5 weeks.
measure: Pulse/Heart Rate Assessment
timeFrame: Change in pulse and heart rate(from ECG recording) from Baseline, week 2, week 4, week 6 (pulse rate only), Month 3, Month 6, end of study (subject's last visit, 2-48 weeks after study entry)
measure: 12-lead Electrocardiogram Assessments
timeFrame: Baseline, week 2, week 4, month 3, month 6, end-of-study(subject's last visit, 2-48 weeks after study entry)
Secondary outcomes:
measure: Disease Progression
timeFrame: From Baseline through study completion(subject's last visit, 2-48 weeks after study entry)
measure: Supine Slow Vital Capacity (SVC)
timeFrame: The change from Baseline, week 2, week 4, month 3, month 6, end-of-study (subject's last visit, 2-48 weeks after study entry)
measure: Revised ALS Functional Rating Scale (ALSFRS-R)
timeFrame: Change from Baseline in respiratory function of ALSFRS-R at study completion (subject's last visit, 2-48 weeks after study entry)
measure: Need for Respiratory Support Device
timeFrame: Time to event at study completion (subject's last visit, 2-48 weeks after study entry)
measure: Borg Category Ratio 10 Scale (CR 10)
timeFrame: Baseline through study completion (week 2, week 4, month 3, month 6, end of study (subject's last visit, 2-48 weeks after study entry)
measure: Number of Subjects Requiring Health and Home Care Resource Use
timeFrame: Baseline through study completion (2- 48 weeks after study entry)
measure: Subject's Status for Tracheostomy and Survival
timeFrame: Baseline to end of study (average 2-48 weeks after study entry
measure: Health Care Service Use During the Study(Stays in Hospital)
timeFrame: From baseline to the end of the study(2-48 weeks after study entry)
measure: Health Care Service Use During the Study(Visits to the Emergency Room)
timeFrame: From baseline to the end of the study(2-48 weeks after study entry)
measure: Health Care Service Use During the Study (Days Spent in an Institutional Facility)
timeFrame: From baseline to the end of the study(2-48 weeks after study entry)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Neuromuscular research Centre and Neuromuscular Clinic of Arizona
state: Arizona
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: New Britain
country: United States
facility: Hospital for Special Care
state: Connecticut
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Washington
country: United States
facility: The George Washington Medical Faculty Associates
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital Neuroscience Institute
state: Florida
city: Gainesville
country: United States
facility: University of Florida McKnight Brain Institute
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Tampa
country: United States
facility: University of South Florida/USF Health
state: Florida
city: Augusta
country: United States
facility: Augusta University, Medical Centre
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan, Michigan Medicine University Hospital
state: Michigan
city: Saint Paul
country: United States
facility: Health Partners Speciality Center
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Lincoln
country: United States
facility: Neurology Associates
state: Nebraska
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: New York
country: United States
facility: Columbia Presbyterian Hospital
state: New York
city: Charlotte
country: United States
facility: Neurosciences Institute - Neurology Charlotte
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Portland
country: United States
facility: Providence Brain and Spine Institute
state: Oregon
city: Pittsburgh
country: United States
facility: Alleghenay General hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: Nerve and Muscle Centre of Texas
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health-Imaging & Neurosciences Center in research Park
state: Utah
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Camperdown
country: Australia
facility: Brain and Mind Centre
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Parkdale
country: Australia
facility: Calvary Health Care Bethlehem
state: Victoria
city: Nedlands
country: Australia
facility: Perron Institute for Neurological and Translational Science
state: Western Australia
city: Innsbruck
country: Austria
facility: Medizinische Universitat Innsbruck
state: Tyrol
city: Vocklabruck
country: Austria
facility: Salzqammergut-klinikum Vocklabruck, Neurologie
state: Upper Austria
city: Wein
country: Austria
facility: Medizinische Universitat wein Universitatsklinik ffur Neurologie
city: Gent
country: Belgium
facility: Algemeen Ziekenhuis St Lucas Gent
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven
city: Liège
country: Belgium
facility: Centre Hospitalier Regional de la Vitadelle
city: Calgary
country: Canada
facility: Alberta Health Services-Neuromuscular Clinic
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta, Division of Neurology
state: Alberta
city: Fredericton
country: Canada
facility: Stan Cassidy Centre for Rehabilitation
state: New Brunswick
city: Hamilton
country: Canada
facility: McMaster University Medical Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Montréal
country: Canada
facility: Montreal Neurological Institute and Hospital
state: Quebec
city: Québec
country: Canada
facility: Centre Hospitalier Affilie Universitaire de Quebec
state: Quebec
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital, Neurology Outpatients Clinic
city: Turku
country: Finland
facility: Turku University Hospital
city: Limoges
country: France
facility: Centre Hospitalier Universitaire de Limoges Service de Neurologie
city: Montpellier
country: France
facility: Hopital Gui de Chauliac Service de Neurologie
city: Nice
country: France
facility: Hopital Pasteur Centre de reference des Malades Neuromusculaires et SLA
city: Berlin
country: Germany
facility: Charite Universitatmedizin Berlin- Campus Virchow-Klinikum
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Jena
country: Germany
facility: Universitatsklinikum Jena, Klinik fur Neurologie
city: Münster
country: Germany
facility: Universitatsklinikum Munster, Institut fur Schalfmedizin und Neuromuskalaire Erkrankungen
city: Rostock
country: Germany
facility: Universitatsmedizin Rostock, Klinik und Poliklinik fuer Neurologie
city: Ulm
country: Germany
facility: Universitatsklinikum Ulm, Poliklinik fur Neurologie
city: Wiesbaden
country: Germany
facility: Deutsche Klinik fur Daignostik
city: Dublin
country: Ireland
facility: Beaumont Hospital, Clinical Research Centre
city: Genova
country: Italy
facility: Azienda Policlinico San Martino
city: Milan
country: Italy
facility: ICS Maugeri Spa S UO Riabilitazione Nurologica
city: Novara
country: Italy
facility: Azienda Ospedaliera Universitaria-maggiore della Carita di Novara
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana Ospedale Santa Chiara
city: Rome
country: Italy
facility: Policlinico Umberto I di Roma Clinica Neurologica
city: Torino
country: Italy
facility: Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino
city: Utrecht
country: Netherlands
facility: Univeritair Medisch Centrum Utrech
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge
city: Bilbao
country: Spain
facility: Hospital Universitario de Basurto
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia Servicio Neurologia
city: Madrid
country: Spain
facility: Hospital San Rafael
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico de La Fe
city: Karlstad
country: Sweden
facility: Karlstad Central Hospital Neurology and Rehabilitation
city: Stockholm
country: Sweden
facility: Karolinska University Horpital Huddinge Neurology Clinic
city: Umeå
country: Sweden
facility: Norrlanda University Hospital Neuro-huvud-hals-centrum Vasterbotten
city: Liverpool
country: United Kingdom
facility: The Walton Centre NHs Foundation Trust, Neurology and Neurosurgery
city: London
country: United Kingdom
facility: Barts Health NHS Trust Royal London hospital
Study officials:
affiliation: Orion Corporation, Orion Pharma
name: Geneviève Nadeau, CSD
role: STUDY_DIRECTOR
References:
citation: Cudkowicz M, Genge A, Maragakis N, Petri S, van den Berg L, Aho VV, Sarapohja T, Kuoppamaki M, Garratt C, Al-Chalabi A; REFALS investigators. Safety and efficacy of oral levosimendan in people with amyotrophic lateral sclerosis (the REFALS study): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Neurol. 2021 Oct;20(10):821-831. doi: 10.1016/S1474-4422(21)00242-8.