| Title: |
Efficacy and safety of low-dose IL-2 as an add-on therapy to riluzole (MIROCALS): a phase 2b, double-blind, randomised, placebo-controlled trial |
| Authors: |
Bensimon, G.; Leigh, P.N.; Tree, T.; Malaspina, A.; Payan, C.A.M.; Pham, H.-P.; Klaassen, P.; Shaw, P.J.; Al Khleifat, A.; Amador, M.D.M.; Attarian, S.; Bell, S.M.; Beltran, S.; Bernard, E.; Camu, W.; Corcia, P.; Corvol, J.-C.; Couratier, P.; Danel, V.; Debs, R.; Desnuelle, C.; Dimitriou, A.; Ealing, J.; Esselin, F.; Fleury, M.-C.; Gorrie, G.H.; Grapperon, A.-M.; Hesters, A.; Juntas-Morales, R.; Kolev, I.; Lautrette, G.; Le Forestier, N.; McDermott, C.J.; Pageot, N.; Salachas, F.; Sharma, N.; Soriani, M.-H.; Sreedharan, J.; Svahn, J.; Verber, N.; Verschueren, A.; Yildiz, O.; Suehs, C.M.; Saker-Delye, S.; Muller, C.; Masseguin, C.; Hajduchova, H.; Kirby, J.; Garlanda, C.; Locati, M.; Zetterberg, H.; Asselain, B.; Al-Chalabi, A. |
| Publisher Information: |
Elsevier BV |
| Publication Year: |
2025 |
| Collection: |
White Rose Research Online (Universities of Leeds, Sheffield & York) |
| Description: |
Background Amyotrophic lateral sclerosis (ALS) is a life-threatening disease characterised by progressive loss of motor neurons with few therapeutic options. The MIROCALS study tested the hypothesis that low-dose interleukin-2 (IL-2LD) improves survival and function in ALS. Methods In this randomised, double-blind, placebo-controlled trial, male and female riluzole-naive participants, with either a possible, laboratory-supported probable, probable, or definite ALS diagnosis (revised El Escorial criteria), aged 18–76 years, with symptom duration of 24 months or fewer, and slow vital capacity of 70% or more, underwent a riluzole-only 12–18 week run-in period before randomisation in a 1:1 ratio to either 2 million international units (MIU) IL-2LD or placebo by subcutaneous injection daily for 5 days every 28 days over 18 months. The primary endpoint was survival at 640 days (21 months). Secondary outcomes included safety, ALS Functional Rating Scale-Revised (ALSFRS-R) score, and biomarker measurements including regulatory T-cells (Tregs), cerebrospinal fluid (CSF)-phosphorylated-neurofilament heavy-chain (CSF-pNFH), and plasma and CSF-chemokine ligand 2 (CCL2). The primary endpoint analysis used unadjusted log-rank and Cox's model adjusted analyses using pre-defined prognostic covariates to control for the disease and treatment response heterogeneity. The study was 80% powered to detect a two-fold decrease in the risk of death by the log-rank test in the intention-to-treat (ITT) population, including all randomly allocated participants. MIROCALS is registered with ClinicalTrials.gov (NCT03039673) and is complete. Findings From June 19, 2017, to Oct 16, 2019, 304 participants were screened, of whom 220 (72%) met all criteria for random allocation after the 12-to-18-week run-in period on riluzole. 136 (62%) of participants were male and 84 participants (38%) were female. 25 (11%) of the 220 randomly allocated participants were defined as having possible ALS under El Escorial criteria. At the cutoff date there was no ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| ISSN: |
0140-6736 |
| Relation: |
https://eprints.whiterose.ac.uk/id/eprint/226796/1/PIIS0140673625002624.pdf; Bensimon, G., Leigh, P.N., Tree, T. et al. (50 more authors) (2025) Efficacy and safety of low-dose IL-2 as an add-on therapy to riluzole (MIROCALS): a phase 2b, double-blind, randomised, placebo-controlled trial. The Lancet, 405 (10492). pp. 1837-1850. ISSN: 0140-6736 |
| Availability: |
https://eprints.whiterose.ac.uk/id/eprint/226796/; https://eprints.whiterose.ac.uk/id/eprint/226796/1/PIIS0140673625002624.pdf |
| Rights: |
cc_by_4 |
| Accession Number: |
edsbas.C0B3E407 |
| Database: |
BASE |