Baseline characteristics and status update of REFALS: a phase 3 study comparing oral levosimendan to placebo in patients with ALS


Clinical Trials

Poster Number: 33


Merit Cudkowicz, Angela Genge, Nicholas Maragakis, MD, Susanne Petri, Leonard van den Berg, Valtteri V. Aho, Toni Sarapohja, Ammar Al-Chalabi


1. Massachusetts General Hospital, Boston, USA, 2. Montreal Neurological Institute and Hospital, Montreal, Canada, 3. Johns Hopkins University, Baltimore, USA, 4. Medizinische Hochschule Hannover, Hannover, Germany, 5. University Medical Center Utrecht, Utrecht, Netherlands, 6. Orion Pharma, Orion Corporation, Espoo, Finland, 7. Orion Pharma, Orion Corporation, Espoo, Finland, 8. King’s College London, London, UK

Levosimendan is a calcium sensitizing drug that improves force generation in both cardiac and skeletal muscle. Levosimendan was shown to have positive effects on supine slow vital capacity (SVC) in the LEVALS pilot study in patients with amyotrophic lateral sclerosis (ALS).

In the ongoing REFALS phase 3 trial (NCT03505021) randomized patients with ALS are treated with oral levosimendan (target dose 2mg daily) or placebo for 48 weeks in a double-blind, parallel group design. The primary endpoint is supine SVC, and secondary endpoints include ALSFRS-R adjusted for patient survival, occurrence of respiratory events, clinical global impression, Borg scale for dyspnea and scales assessing sleep and sleepiness. The safety profile of oral levosimendan is being assessed using standard measures including adverse events, vital signs, 12-lead electrocardiogram and laboratory safety tests at regular intervals throughout the 48 week treatment period. Patients record changes in level of care received in a diary.

REFALS trial enrolled 496 adult patients with definite, probable or laboratory supported probable ALS and some degree of respiratory dysfunction (sitting SVC 60-90%) at 94 clinical sites in 14 countries in EU, North America and Australia. The baseline characteristics of the patients were similar to those of other recent large clinical trials in ALS. The patients (mean age 59.3 y, 61.9% male) had experienced symptoms more than 2 years and had substantial disability based on ALSFRS-R. Most patients were receiving riluzole and almost 1/3 of patients in North America had started edaravone. Safety labs revealed relatively common increases in liver tests, low creatinine and frequently increased markers of muscle injury including CRP, creatine kinase and troponin T. Baseline characteristics of the study population, including demographics, ALS diagnosis and treatment, respiratory function and ALSFRS-R will be presented.