An open label extension for patients completing study 3119002 to study the effects of oral Levosimendan on breathing function in patients with the disease Amyotrophic Lateral Sclerosis (ALS)

• Register: EUCTR
• Last refreshed on: 7 September 2020
• Main ID: EUCTR2018-004180-31-IE
• Date of registration: 02/08/2019
• Prospective Registration: Yes
• Primary sponsor: Orion Corporation
• Public title: An open label extension for patients completing study 3119002 to study the effects of oral Levosimendan on breathing function in patients with the disease Amyotrophic Lateral Sclerosis (ALS)
• Scientific title: Effects of oral Levosimendan (ODM-109) on respiratory function in patients with ALS: open label extension for patients completing study 3119002 - REFALS-ES
• Date of first enrolment: 16/12/2019
• Target sample size: 450
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-004180-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Canada, Finland, France, Germany, Ireland, Italy, Netherlands, Spain, Sweden, United Kingdom, United States

Contacts

• Name: Senior Regulatory Affairs Manager
• Affiliation: Orion Organization

• Name: Senior Regulatory Affairs Manager
• Affiliation: Orion Organization

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must meet all of the following criteria to be included into the study:
1.Written or verbal informed consent (IC) for participation in the study will be obtained from the subject. In case that the study subject him/herself cannot sign the IC, a witness may sign the consent form to indicate that the subject has given verbal consent.
2. Subjects who completed 48 weeks of treatment according to the REFALS study protocol.
3. Able to swallow study treatment capsules at the time of completing 48 weeks dosing in the REFALS study
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 440
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
Subjects will not be included into this study if they meet any of the following criteria:
1. 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).
2. 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.
3. Systolic blood pressure (SBP) < 90 mmHg.
4. Severe renal impairment (creatinine clearance < 30 ml/min or creatinine > 170 µmol/l at 48 week visit of the REFALS study, or on dialysis.
5. Severe hepatic impairment at the discretion of the investigator.
6. 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 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.
7. Subject judged to be actively suicidal by the investigator.
8. 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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Amyotrophic Lateral Sclerosis (ALS)
MedDRA version: 21.1 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: Oral LEVOSIMENDAN
Product Code: ODM-109
Pharmaceutical Form: Capsule
INN or Proposed INN: LEVOSIMENDAN
CAS Number: 141505-33-1
Current Sponsor code: ODM-109
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.0-

Primary Outcome(s)

Primary end point(s): This study is not endpoint driven. The primary and secondary objectives are summarized below. Safety will be assessed by adverse events (AEs), vital signs, 12-lead electrocardiogram (ECG) and by assessment of suicidality.

Timepoint(s) of evaluation of this end point: The analysis will take place at end of the study, and be summarized with and without data from REFALS 3119002 study.

Main Objective: The primary objective, in addition to continuing treatment for subjects in this study, is to evaluate long-term safety of oral levosimendan in amyotrophic lateral sclerosis (ALS) patients.

Secondary Objective: The secondary objective is to explore long-term effectiveness of oral levosimendan in the treatment of patients with ALS, by continuing to observe rate of disease progression during the treatment.

Secondary Outcome(s)

Secondary end point(s): Secondary objectives is efficacy and include:
Slope of decline in sitting and supine SVC and ALSFRS-R will be estimated using a random slope model.
Median time to non-invasive mask ventilation (NIV) or death and to decline (by at least 1 point) in the ALSFRS-R
respiratory domain will be evaluated using Kaplan-Meier estimates.
Borg CR10 (sitting, supine and orthostatic changes) will be evaluated using mixed model for repeated measures.
Health and home care resource use data will be summarized in the study report, but any further analysis for potential pharmacoeconomic purposes will be reported separately.

Timepoint(s) of evaluation of this end point: The analysis will take place at end of the study, and be summarized with and without data from REFALS 3119002 study.

Secondary ID(s)

NCT03948178

2018-004180-31-ES

3119003

Source(s) of Monetary Support

Orion Corporation

Ethics review

Status: Approved
Approval date: 16/12/2019
Contact: