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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03948178




Registration number
NCT03948178
Ethics application status
Date submitted
7/05/2019
Date registered
13/05/2019
Date last updated
9/03/2023

Titles & IDs
Public title
Effects of Oral Levosimendan on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS): Open-Label Extension
Scientific title
Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS: Open-Label Extension for Patients Completing Study 3119002
Secondary ID [1] 0 0
3119003
Universal Trial Number (UTN)
Trial acronym
REFALS-ES
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Amyotrophic Lateral Sclerosis 0 0
Condition category
Condition code
Neurological 0 0 0 0
Neurodegenerative diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Levosimendan

Experimental: Levosimendan - 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.


Treatment: Drugs: Levosimendan
Levosimendan 1 mg capsule for oral administration
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Adverse Events Recording
Timepoint [1] 0 0
From signing informed consent until 14-25 days after the last study treatment for all patients, an average of 23.5 weeks.
Primary outcome [2] 0 0
Pulse/Heart Rate Assessment
Timepoint [2] 0 0
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)
Primary outcome [3] 0 0
12-lead Electrocardiogram Assessments
Timepoint [3] 0 0
Baseline, week 2, week 4, month 3, month 6, end-of-study(subject's last visit, 2-48 weeks after study entry)
Secondary outcome [1] 0 0
Disease Progression
Timepoint [1] 0 0
From Baseline through study completion(subject's last visit, 2-48 weeks after study entry)
Secondary outcome [2] 0 0
Supine Slow Vital Capacity (SVC)
Timepoint [2] 0 0
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)
Secondary outcome [3] 0 0
Revised ALS Functional Rating Scale (ALSFRS-R)
Timepoint [3] 0 0
Change from Baseline in respiratory function of ALSFRS-R at study completion (subject's last visit, 2-48 weeks after study entry)
Secondary outcome [4] 0 0
Need for Respiratory Support Device
Timepoint [4] 0 0
Time to event at study completion (subject's last visit, 2-48 weeks after study entry)
Secondary outcome [5] 0 0
Borg Category Ratio 10 Scale (CR 10)
Timepoint [5] 0 0
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)
Secondary outcome [6] 0 0
Number of Subjects Requiring Health and Home Care Resource Use
Timepoint [6] 0 0
Baseline through study completion (2- 48 weeks after study entry)
Secondary outcome [7] 0 0
Subject's Status for Tracheostomy and Survival
Timepoint [7] 0 0
Baseline to end of study (average 2-48 weeks after study entry
Secondary outcome [8] 0 0
Health Care Service Use During the Study(Stays in Hospital)
Timepoint [8] 0 0
From baseline to the end of the study(2-48 weeks after study entry)
Secondary outcome [9] 0 0
Health Care Service Use During the Study(Visits to the Emergency Room)
Timepoint [9] 0 0
From baseline to the end of the study(2-48 weeks after study entry)
Secondary outcome [10] 0 0
Health Care Service Use During the Study (Days Spent in an Institutional Facility)
Timepoint [10] 0 0
From baseline to the end of the study(2-48 weeks after study entry)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
120 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/06/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/11/2020
Sample size
Target
Accrual to date
Final
227
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Brain and Mind Centre - Camperdown
Recruitment hospital [2] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [3] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [4] 0 0
Calvary Health Care Bethlehem - Parkdale
Recruitment hospital [5] 0 0
Perron Institute for Neurological and Translational Science - Nedlands
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
5042 - Bedford Park
Recruitment postcode(s) [4] 0 0
3195 - Parkdale
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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United States of America
State/province [2] 0 0
California
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State/province [3] 0 0
Connecticut
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District of Columbia
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Florida
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Georgia
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Illinois
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Missouri
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Nebraska
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New York
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North Carolina
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Oregon
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Utah
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Washington
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Austria
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Tyrol
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Upper Austria
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Wein
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Gent
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Leuven
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Liège
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Helsinki
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Turku
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Nice
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Jena
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Rostock
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Ulm
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Wiesbaden
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Ireland
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Dublin
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Genova
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Milan
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Novara
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Pisa
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Italy
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Rome
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Torino
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Utrecht
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Barcelona
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Bilbao
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Córdoba
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Madrid
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Valencia
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Sweden
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Karlstad
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Sweden
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Stockholm
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Sweden
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Umeå
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United Kingdom
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Liverpool
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United Kingdom
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London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Orion Corporation, Orion Pharma
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT03948178
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
Geneviève Nadeau, CSD
Address 0 0
Orion Corporation, Orion Pharma
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03948178