COURAGE-ALS (study NCT04944784) is being conducted at five Australia sites and recruitment is currently underway. The details of the Phase 3 trial can be found here.
The global Phase 3 COURAGE-ALS trial (NCT04944784) will enrol approximately 555 adults who are within two years of their first symptom of muscle weakness. Participants must have moderate lung function loss and mild disability, which is defined as an ALS Functional Rating Scale Revised (ALSFRS-R) score of no more than 44 at the time of screening.
To enhance patient participation, the trial has been designed to include remote clinic visits, home nursing visits, and mobile-app based endpoint measurements. These elements were implemented following feedback from Cytokinetics’ ALS Patient and Caregiver Advisory Council (ALS-PAC), as well as meetings with patients, caregivers, healthcare professionals, advocates, and payers.
Also, at least one patient representative will join the steering committee of COURAGE-ALS, to provide a patient perspective throughout the trial and when interpreting results.
After entering COURAGE-ALS, patients will be assigned randomly to receive either a placebo or 300 mg of oral reldesemtiv twice daily over 24 weeks (nearly six months). Following that part, all participants will receive reldesemtiv for another 24 weeks.
Patients who are receiving standard MND therapies, such as riluzole, can continue doing so during the trial.
The trial’s primary goal is to measure changes in ALSFRS-R over the initial 24 weeks. Secondary goals include total ALSFRS-R scores and time to respiratory insufficiency and survival, as well as changes in respiratory function, quality of life, and muscle strength.
A data monitoring committee will conduct two planned interim analyses. The first is a futility study — meant to determine if the trial can meet its goals — that will take place 12 weeks after one-third or more of the participants are assigned randomly to receive the medication or a placebo. A second analysis also will assess for futility and determine whether the trial needs to enrol more patients.
Continued access to reldesemtiv will be available to patients who complete COURAGE-ALS, as well as those who participated in prior reldesemtiv clinical trials, the company said.
The trial commenced in June 2021 and is currently recruiting. Primary completion is expected end of 2023.
FORTITUDE-ALS (NCT03160898) was a phase 2, double-blind, randomised, dose-ranging, placebo-controlled, parallel group study that assessed reldesemtiv in 458 eligible patients with MND. Investigators used change from baseline in the percent predicted slow vital capacity (SVC), a measure of respiratory function, as the primary end point. After 12 weeks of dosing, the study did not achieve statistical significance for a pre-specified dose-response relationship in change from baseline in SVC (P = .11). The full press release from the American Academy of Neurology is available here.
Similar analyses of ALSFRS-R and COURAGE slope of Muscle Strength Mega-Score, key secondary end points, yielded P values of 0.09 and 0.31, respectively. Investigators did note that patients across all dose groups (150 mg, 300 mg, and 450 mg) declined less than patients on placebo for SVC and ALSFRS-R, with larger and clinically meaningful differences emerging over time.
A post-hoc analysis of FORTITUDE-ALS showed that the differences between reldesemtiv and placebo on SVC and ALSFRS-R total score following the 12-week study period remained evident at follow-up, 4 weeks after the last dose of the study drug.
A spokesperson from Cytokenetics said: “While FORTITUDE-ALS did not meet the primary endpoint, we are encouraged by the results of the trial as they further validate the potential of skeletal muscle activation in treating patients battling ALS … This Phase II trial of reldesemtiv demonstrated consistency of effect for doses, endpoints, and time points and we believe the results support progression of reldesemtiv in further clinical trials toward potential registration.”
Following the results from the phase 2 FORTITUDE clinical trial, Cytokinetics announced open enrolment for a new phase 3 trial, dubbed COURAGE-ALS, which will evaluate the efficacy and safety of reldesemtiv in patients with MND.
Reldesemtiv is an investigational medication not currently approved for use in patients with ALS in any country worldwide. A possible treatment resulting from this study is likely years away.
New South Wales
Brain and Mind Centre
Camperdown, New South Wales, Australia, 2050
Contact: Matthew Kiernan
+61 2 9351 0976, hannah.timmins@sydney.edu.au
Concord Repatriation General Hospital
Concord, New South Wales, Australia, 2139
Contact: Steve Vucic
+61 (02) 9767 8461, SLHD-BNRC@health.nsw.gov.au
Queensland
Royal Brisbane and Women's Hospital
Herston, Queensland, Australia, 4029
Contact: Susan Heggie
+61 7 36468111, Susan.Heggie@health.qld.gov.au
South Australia
Flinders Medical Centre
Bedford Park, South Australia, Australia, 5042
Contact: David Schultz
Western Australia
The Perron Institute
Nedlands, Western Australia, Australia, 6009
Contact: Merrilee Needham
+61 (08) 6457 0312, info@perron.uwa.edu.au
