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Can neurofilament lightchain as endpoint in Phase 2 derisk clinical disability worsening in Phase 3 in multiple
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Background:
Neurofilament lightchain has been proposed as a Phase 2 endpoint in clinical trials for multiple sclerosis. We evaluated via simulations the extent to which a positive Phase 2 trial would derisk a Phase 3 trial where the primary endpoint is time to confirmed clinical disability worsening.
Methods:
Using a prior distribution of the treatment effect on neurofilament lightchain and a model linking it with clinical disability worsening constructed using the FREEDOMS trial in RRMS patients, the probability of success of two randomized controlled Phase 2 and Phase 3 trials were computed for different scenarios.
Results:
The strength of the correlation between both treatment effects and the success criteria of the Phase 2 trial impact the ability of the Phase 2 to derisk Phase 3. Being more stringent with the success criteria in Phase 2 can increase the Phase 3 PoS by more than 20% after a positive Phase 2 study. Increasing the sample size of the Phase 2 has no substantial impact on the derisking.
Conclusion:
Under some assumptions a positive Phase 2 trial with neurofilament lightchain as primary endpoint can to a certain extent derisk a Phase 3 trial with clinical disability worsening as primary endpoint.
