Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS
Status: | Recruiting |
---|---|
Conditions: | Neurology, Neurology |
Therapuetic Areas: | Neurology |
Healthy: | No |
Age Range: | 18 - 120 |
Updated: | 2/8/2019 |
Start Date: | June 21, 2018 |
End Date: | October 30, 2020 |
Contact: | Merit E Cudkowicz, MD |
Email: | Cudkowicz.Merit@mgh.harvard.edu |
Phone: | +1 617 726 2383 |
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.
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.
Inclusion Criteria:
- Written or verbal informed consent (IC) for participation in the study
- Male or female subjects with diagnosis of laboratory supported probable, probable or
definite ALS according to El Escorial revised criteria. Full electromyogram (EMG)
report available consistent with ALS (but not necessarily fulfilling the
electrodiagnostic criteria for ALS) from an experienced neurophysiologist
- Able to swallow study treatment capsules, and in the opinion of the investigator, is
expected to continue to do so during the study
- Sitting SVC between 60-90% of the predicted value for age, height and sex at screening
visit
- 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 and/or edaravone. If using riluzole (any daily dose
up to 100 mg), the dose must have been stable for at least 4 weeks before the
screening visit and should not be changed during the study. If using edaravone, the
treatment should have been started at least 4 weeks before the screening visit (at
least one 28-day treatment cycle as indicated) and should not be changed during the
study. If not on riluzole and/or edaravone, the respective treatments should not be
started during the study
Exclusion Criteria:
- Subject in whom other causes of neuromuscular weakness have not been excluded
- Subject with a 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 the present phase III study or earlier study with oral levosimendan
in ALS patients (LEVALS)
- 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. If the
HR is > 100 bpm in the first recording, then the second recording must be done after
another 5 min rest to confirm HR > 100 bpm
- 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
We found this trial at
48
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Emory University School of Medicine Emory University School of Medicine has 2,359 full- and part-time...
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185 Cambridge Street
Boston, Massachusetts 02114
Boston, Massachusetts 02114
617-724-5200
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University of Florida The University of Florida (UF) is a major, public, comprehensive, land-grant, research...
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8700 Beverly Blvd # 8211
Los Angeles, California 90048
Los Angeles, California 90048
(1-800-233-2771)
Phone: 310-423-8497
Cedars Sinai Med Ctr Cedars-Sinai is known for providing the highest quality patient care. Our...
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3400 Spruce St
Philadelphia, Pennsylvania 19104
Philadelphia, Pennsylvania 19104
(215) 662-4000
Phone: 215-829-5041
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3181 Southwest Sam Jackson Park Road
Portland, Oregon 97239
Portland, Oregon 97239
503 494-8311
Phone: 503-494-7394
Oregon Health and Science University In 1887, the inaugural class of the University of Oregon...
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4202 E Fowler Ave
Tampa, Florida 33620
Tampa, Florida 33620
(813) 974-2011
Phone: 813-974-9413
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University of Michigan The University of Michigan was founded in 1817 as one of the...
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Johns Hopkins Hospital Patients are the focus of everything we do at The Johns Hopkins...
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303 E Chicago Ave
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Chicago, Illinois 60611
(312) 503-8194
Northwestern University Feinberg School of Medicine Northwestern University Feinberg School of Medicine, founded in 1859,...
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Ohio State University The Ohio State University’s main Columbus campus is one of America’s largest...
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535 E 70th St
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New York, New York 10021
(212) 606-1000
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Phoenix, Arizona 85028
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660 S Euclid Ave
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Saint Louis, Missouri 63110
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Washington University School of Medicine Washington University Physicians is the clinical practice of the School...
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California Pacific Medical Center California Pacific Medical Center is one of the largest private, not-for-profit,...
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1959 NE Pacific St
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3700 O St NW
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1 Medical Center Blvd
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