Adaptive phase II study of BAN2401 in early Alzheimer’s disease continues toward 18-month endpoint

Study 201 (ClinicalTrials.gov identifier NCT01767311) is a placebo-controlled, double-blind, parallel-group, randomized study in patients with prodromal or mild Alzheimer’s disease (collectively known as early Alzheimer’s disease) and with positive biomarkers for brain amyloid pathology. The study design included 16 interim analyses that assessed potential for futility or stopping for safety. Neither of these conditions was met and the study continues to a full analysis at 18 months. The efficacy of five dose groups of BAN2401 was evaluated at 12 months based on Eisai’s in-house developed novel endpoint Alzheimer’s disease Composite Score (ADCOMS). According to the Bayesian analysis at 12 months, success was judged as an 80% or higher probability of achieving a Clinically Significant Difference (CSD: a 25% or greater reduction in the rate of decline in ADCOMS compared to placebo).

In the final analysis at 18 months, a comprehensive evaluation which includes assessing changes from baseline in the clinical evaluation indicators ADCOMS and Clinical Dementia Rating Sum of Boxes (CDR-SB), as well as changes in biomarkers such as brain amyloid levels as measured by amyloid PET and total hippocampal volume using vMRI, will be assessed.

“By using Bayesian statistics in this uniquely-designed trial we had hoped that it would enable us to demonstrate clinical success faster than more traditional study designs. We now await the final study analysis which will be conducted after 18 months of treatment, which represents an amount of treatment time that is considered as appropriate for assessing efficacy in disease modifying agents for Alzheimer’s disease,” said Lynn Kramer, MD, chief clinical officer and chief medical officer, Neurology Business Group, Eisai.

BAN2401 is a humanized monoclonal antibody for Alzheimer’s disease that is the result of a strategic research alliance between Eisai and BioArctic AB (Headquarters: Stockholm, Sweden, CEO: Gunilla Osswald, “BioArctic”). Since March 2014, Eisai and Biogen have been jointly developing BAN2401.

Study 201 is a placebo-controlled, double-blind, parallel-group study to evaluate safety, tolerability and efficacy of BAN2401 in patients with prodromal or mild Alzheimer’s disease (collectively known as early Alzheimer’s disease) and with positive biomarkers for brain amyloid pathology, using Bayesian Adaptive Randomization Design which allows for automatic changes to the design during the study, including adaptively changing the subject allocation ratio to treatment arms with higher probabilities based on the results of interim analyses in order to more efficiently identify the effectiveness and optimal dose regimen of BAN2401. The study will explore efficacy and the dose response of BAN2401 with 16 interim analyses for early success, a 12-month evaluation based on ADCOMS and an 18-month comprehensive assessment of treatment with placebo or 5 active arms. The 5 treatment arms consist of 3 dose levels (2.5 mg/kg, 5 mg/kg, 10mg/kg) given biweekly and 2 dose levels (5 mg/kg, 10 mg/kg) given monthly.

After 12 months of treatment, change from baseline in the ADCOMS is evaluated. In the final analysis at 18 months, comprehensive evaluation including changes from baseline in ADCOMS and Clinical Dementia Rating Sum of Boxes (CDR-SB), as well as changes in brain amyloid levels as measured by amyloid PET and in total hippocampal volume using vMRI, will be conducted.

Adaptive, alzheimer’s disease continues toward 18-month endpoint