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Can neurofilament lightchain as endpoint in Phase 2 derisk clinical disability worsening in Phase 3 in multiple sclerosis?

  • 0GSK 980 Great West Rd London TW8 9GS, United Kingdom.
Multiple Sclerosis and Related Disorders +

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November 4, 2024

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November 4, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

A positive Phase 2 trial using neurofilament lightchain (NfL) can reduce the risk for Phase 3 multiple sclerosis trials. More stringent success criteria in Phase 2 trials significantly improve the probability of Phase 3 success.

Area Of Science

  • Neurology
  • Clinical Trials
  • Biomarkers

Background

  • Neurofilament lightchain (NfL) is a potential biomarker for multiple sclerosis (MS) clinical trials.
  • NfL is being considered as a Phase 2 endpoint in MS studies.
  • This study investigates the predictive value of NfL in Phase 2 trials for Phase 3 success.

Purpose Of The Study

  • To evaluate how a positive Phase 2 trial using NfL as an endpoint can de-risk a subsequent Phase 3 trial.
  • To assess the impact of Phase 2 success criteria on Phase 3 trial outcomes.
  • To determine the influence of sample size in Phase 2 trials on de-risking Phase 3.

Main Methods

  • Simulations were used to compute the probability of success for Phase 2 and Phase 3 trials.
  • A model linking NfL treatment effects to clinical disability worsening was developed using FREEDOMS trial data in relapsing-remitting MS (RRMS) patients.
  • Prior distributions of treatment effects on NfL were incorporated.

Main Results

  • The correlation between treatment effects and Phase 2 success criteria significantly impacts the de-risking of Phase 3 trials.
  • Implementing more stringent success criteria in Phase 2 trials can increase Phase 3 probability of success (PoS) by over 20% after a positive Phase 2 result.
  • Increasing Phase 2 sample size had a negligible effect on de-risking Phase 3.

Conclusions

  • A positive Phase 2 trial with NfL as the primary endpoint can, under certain assumptions, de-risk a Phase 3 trial focused on clinical disability worsening.
  • Stringent Phase 2 success criteria are more effective in de-risking than larger sample sizes.
  • NfL shows promise as a surrogate endpoint for predicting Phase 3 success in MS clinical trials.

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