DIAN-TU Trial Interim Analysis

By DIAN Trials Unit, Washington University School of Medicine · June 6, 2018

Notice to DIAN-TU Investigational Sites and Participants

RE: DIAN-TU-001 INTERIM ANALYSIS

April 25, 2018

DIAN-TU Site Leaders and Participants,

The original goal and intent of the biomarker interim analysis was to determine if the investigational drugs at the dosages used were modifying the amyloid-beta targets.  The biomarker Interim Analysis was designed to allow the DIAN-TU trial to adapt to the biomarker results by continuing, stopping, or modifying the dosage of a drug.  Several actions both inside and outside our clinical trial have changed the purpose of the biomarker Interim Analysis, as the aims to adapt dosing have already been met.

• Findings from other studies for both solanezumab and gantenerumab indicate that higher doses increase target engagement by binding more amyloid-beta or removing more amyloid-beta plaque (what the drug is designed to do) ^{1, 2}. Further, the lower doses tested in late onset Alzheimer’s disease (AD) did not significantly improve dementia.  Therefore, implementation of dose adjustment to higher doses has already occurred for each drug in the DIAN-TU trial.
• Upon review of the primary aims, the DIAN-TU trial has already met the goal of the interim analysis by increasing doses in both drugs by adapting to external data prior to the availability of the internal trial data.
• Therefore, the DIAN-TU Data Safety Monitoring Board (DSMB) (our external safety committee), leadership, and partners have unanimously agreed to continue the solanezumab and gantenerumab arms without stopping. Safety and biomarker data will continue to be monitored by the DIAN-TU DSMB on a quarterly basis for recommendations on how to continue the planned study.  However, no formal data will be released at this time to the DIAN-TU investigators or participants. The DIAN-TU trial of solanezumab and gantenerumab is scheduled to complete at the end of 2019.

Sincerely,

Randall J. Bateman, M.D.

Charles F. and Joanne Knight Distinguished Professor of Neurology
Principle Investigator, Department of Neurology
Director, Dominantly Inherited Alzheimer’s Network Trials Unit