Effects of Oral Levosimendan on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS): Open-Label Extension

NCT03948178 | Terminated Phase 3 Results FDA Drug

• 1 other identifier: 3119003
• Study Type: interventional
• Target: 227
• Locations: 13 countries
• Sites: 74

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.

Conditions

Amyotrophic Lateral Sclerosis

Outcome Measures

Primary Outcomes (3)

• Adverse Events Recording

  Adverse Events as subject counts and proportions (%) of subject per Adverse Event

  From signing informed consent until 14-25 days after the last study treatment for all patients, an average of 23.5 weeks.

• Pulse/Heart Rate Assessment

  Actual values and changes from baseline in supine pre-dose pulse/heart rate were summarised using descriptive statistics .

  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)

• 12-lead Electrocardiogram Assessments

  Summarisation of any abnormal 12-lead ECG findings using descriptive statistics.

  Baseline, week 2, week 4, month 3, month 6, end-of-study(subject's last visit, 2-48 weeks after study entry)

Secondary Outcomes (10)

• Disease Progression

  From Baseline through study completion(subject's last visit, 2-48 weeks after study entry)

• Supine Slow Vital Capacity (SVC)

  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)

• Revised ALS Functional Rating Scale (ALSFRS-R)

  Change from Baseline in respiratory function of ALSFRS-R at study completion (subject's last visit, 2-48 weeks after study entry)

• Need for Respiratory Support Device

  Time to event at study completion (subject's last visit, 2-48 weeks after study entry)

• Borg Category Ratio 10 Scale (CR 10)

  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)

Study Arms (1)

Levosimendan

EXPERIMENTAL

Oral Levosimendan; Levosimendan 1mg capsules for oral administration, once to twice a day, continued as long as clinically beneficial. The total study duration is up to 3 years.

Drug: Levosimendan

Interventions

Levosimendan DRUG

Levosimendan 1 mg capsule for oral administration

Also known as: ODM-109

Levosimendan

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Orion Corporation, Orion Pharma: lead

Study Sites (79)

Neuromuscular research Centre and Neuromuscular Clinic of Arizona

Phoenix, Arizona, 85028, United States

Location

University of California San Diego

La Jolla, California, 92037-0886, United States

Location

University of California Irvine Medical Center

Orange, California, 92868, United States

Location

Hospital for Special Care

New Britain, Connecticut, 06053, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

The George Washington Medical Faculty Associates

Washington D.C., District of Columbia, 20037, United States

Location

Holy Cross Hospital Neuroscience Institute

Fort Lauderdale, Florida, 33308, United States

Location

University of Florida McKnight Brain Institute

Gainesville, Florida, 32611, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

University of South Florida/USF Health

Tampa, Florida, 33612, United States

Location

Augusta University, Medical Centre

Augusta, Georgia, 30912, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan, Michigan Medicine University Hospital

Ann Arbor, Michigan, 48109, United States

Location

Health Partners Speciality Center

Saint Paul, Minnesota, 55130-5302, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Neurology Associates

Lincoln, Nebraska, 68506, United States

Location

Hospital for Special Surgery

New York, New York, 10021, United States

Location

Columbia Presbyterian Hospital

New York, New York, 10032, United States

Location

Neurosciences Institute - Neurology Charlotte

Charlotte, North Carolina, 28207, United States

Location

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27157-1023, United States

Location

The Ohio State University Wexner Medical center

Columbus, Ohio, 43210, United States

Location

Oregon Health and Science University

Portland, Oregon, 97201-3098, United States

Location

Providence Brain and Spine Institute

Portland, Oregon, 97213, United States

Location

Alleghenay General hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Nerve and Muscle Centre of Texas

Houston, Texas, 77030, United States

Location

University of Utah Health-Imaging & Neurosciences Center in research Park

Salt Lake City, Utah, 84132, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Brain and Mind Centre

Camperdown, New South Wales, 2050, Australia

Location

Royal Brisbane and Women's Hospital

Herston, Queensland, 4029, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

Calvary Health Care Bethlehem

Parkdale, Victoria, 3195, Australia

Location

Perron Institute for Neurological and Translational Science

Nedlands, Western Australia, 6009, Australia

Location

Medizinische Universitat Innsbruck

Innsbruck, Tyrol, 6020, Austria

Location

Salzqammergut-klinikum Vocklabruck, Neurologie

Vöcklabruck, Upper Austria, 4840, Austria

Location

Medizinische Universitat wein Universitatsklinik ffur Neurologie

Wein, 1090, Austria

Location

Algemeen Ziekenhuis St Lucas Gent

Ghent, 9000, Belgium

Location

Universitair Ziekenhuis Leuven

Leuven, 3000, Belgium

Location

Centre Hospitalier Regional de la Vitadelle

Liège, 4000, Belgium

Location

Alberta Health Services-Neuromuscular Clinic

Calgary, Alberta, T3M 1M4, Canada

Location

University of Alberta, Division of Neurology

Edmonton, Alberta, T6G 2G3, Canada

Location

Stan Cassidy Centre for Rehabilitation

Fredericton, New Brunswick, E3B 0C7, Canada

Location

McMaster University Medical Centre

Hamilton, Ontario, L8N 3Z5, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Montreal Neurological Institute and Hospital

Montreal, Quebec, H3A 2B4, Canada

Location

Centre Hospitalier Affilie Universitaire de Quebec

Québec, Quebec, G1J 1Z4, Canada

Location

Helsinki University Central Hospital, Neurology Outpatients Clinic

Helsinki, 00029, Finland

Location

Turku University Hospital

Turku, 20521, Finland

Location

Centre Hospitalier Universitaire de Limoges Service de Neurologie

Limoges, France

Location

Hopital Gui de Chauliac Service de Neurologie

Montpellier, 34295, France

Location

Hopital Pasteur Centre de reference des Malades Neuromusculaires et SLA

Nice, 06202, France

Location

Charite Universitatmedizin Berlin- Campus Virchow-Klinikum

Berlin, 13353, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitatsklinikum Jena, Klinik fur Neurologie

Jena, 07747, Germany

Location

Universitatsklinikum Munster, Institut fur Schalfmedizin und Neuromuskalaire Erkrankungen

Münster, 48149, Germany

Location

Universitatsmedizin Rostock, Klinik und Poliklinik fuer Neurologie

Rostock, 18147, Germany

Location

Universitatsklinikum Ulm, Poliklinik fur Neurologie

Ulm, 89081, Germany

Location

Deutsche Klinik fur Daignostik

Wiesbaden, 65191, Germany

Location

Beaumont Hospital, Clinical Research Centre

Dublin, Ireland

Location

Azienda Policlinico San Martino

Genova, 16132, Italy

Location

ICS Maugeri Spa S UO Riabilitazione Nurologica

Milan, 20138, Italy

Location

Azienda Ospedaliera Universitaria-maggiore della Carita di Novara

Novara, 28100, Italy

Location

Azienda Ospedaliero Universitaria Pisana Ospedale Santa Chiara

Pisa, 56126, Italy

Location

Policlinico Umberto I di Roma Clinica Neurologica

Rome, 00161, Italy

Location

Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino

Torino, 10126, Italy

Location

Univeritair Medisch Centrum Utrech

Utrecht, 3584, Netherlands

Location

Hospital Universitari de Bellvitge

Barcelona, 08207, Spain

Location

Hospital Universitario de Basurto

Bilbao, 48013, Spain

Location

Hospital Universitario Reina Sofia Servicio Neurologia

Córdoba, 14011, Spain

Location

Hospital San Rafael

Madrid, 28016, Spain

Location

Hospital Universitario y Politecnico de La Fe

Valencia, 46026, Spain

Location

Karlstad Central Hospital Neurology and Rehabilitation

Karlstad, Sweden

Location

Karolinska University Horpital Huddinge Neurology Clinic

Stockholm, 14186, Sweden

Location

Norrlanda University Hospital Neuro-huvud-hals-centrum Vasterbotten

Umeå, 90185, Sweden

Location

The Walton Centre NHs Foundation Trust, Neurology and Neurosurgery

Liverpool, L9 7LJ, United Kingdom

Location

Barts Health NHS Trust Royal London hospital

London, E1 1BB, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 34536404 DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Simendan

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Hydrazones; Hydrazines; Organic Chemicals; Pyridazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Head of Compliance and UK Study Management, Clinical Operations
• Organization: Orion Corporation

clinicaltrials@orionpharma.com

+441159487100

Study Officials

• Geneviève Nadeau, CSD

  Orion Corporation, Orion Pharma

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2019
• First Posted: May 13, 2019
• Study Start: June 26, 2019
• Primary Completion: November 18, 2020
• Study Completion: November 18, 2020
• Last Updated: March 9, 2023
• Results First Posted: March 9, 2023

Record last verified: 2023-02

Locations

GB (2); AU (3); DE (7); FR (3); IE (1); FI (2); US (31); CA (7); NL (1); SE (3); ES (5); BE (3); IT (6)