Managing Background Therapies in the NIMBLE Phase III Trial

In a recent video interview with Applied Clinical Trials, Umesh Chaudhari, executive medical director, global program head of the C5 programs, Regeneron, discussed recently released data from the Phase III NIMBLE clinical trial (NCT05070858), which evaluated the efficacy of cemdisiran monotherapy and a combination of cemdisiran and pozelimab in generalized myasthenia gravis (gMG). The study showed a 2.3-point reduction in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score, indicating improved daily functioning. The combination therapy had a 17% worsening rate, compared to 1% in the cemdisiran monotherapy group. Chaudhari highlighted the trial's robust design, including double-blind, double-dummy protocols, and standardized assessments, which ensured high data quality. The findings suggest that lower complement inhibition levels may be optimal for efficacy, with implications for future research in autoimmune diseases.

ACT: Given that the trial allowed standard-of-care immunosuppressants at the investigator's discretion, how did the team manage variability in background therapies to ensure consistent efficacy assessments?

Chaudhari: The trial, as I mentioned previously, was one of the largest Phase III trials, that is one of the more powerful aspects of this that allows balance across treatment arms and manage the issues associated with some variability in physician, investigator, site to site, prescription prescribing habits, or regional prescribing habits. That was one critical aspect. The other second thing is we had what's called a stratification factor on the basis of background immunosuppressive therapy use. That allows also to ensure comparability and balance across these treatment arms.