DIAN Trials Unit Research Updates

Here are the latest research updates related to our clinical trials:

Update: Feb 10, 2020

Investigational drugs didn’t slow memory loss, cognitive decline in rare, inherited Alzheimer’s, initial analysis indicates

DIAN-TU-001

Update: Feb 7, 2020

A message from Dr. Bateman to DIAN-TU trial participants

Update: July 2018

Update on the DIAN-TU-001 TRIAL:  Janssen BACE Inhibitor (JNJ-54861911/atabecestat) DRUG ARM DISCONTINUATION

The statement below is an update to the May 25th announcement found on Janssen’s website.

Previously, Janssen observed elevations of liver enzymes in some study participants who received atabecestat, including two patients who had high elevations of liver enzymes, placing them at increased risk for severe liver injury. These patients remain clinically stable, and their liver enzyme levels have normalized.

After further consideration and consultation, Janssen has concluded that the benefit-risk balance of JNJ‑54861911 (atabecestat) is no longer favorable to continue development of atabecestat (Read more here). Therefore, all randomized participants in the DIAN-TU-001 trial’s atabecestat arm will be instructed to stop dosing with study drug.  The DIAN-TU is informing study participants, health authorities, the study ethics committees, and institutional review boards about this decision.

To facilitate transitioning the trial arm to another study drug, the DIAN-TU is modifying the current protocol to include a cognitive run-in period prior to randomization into study drug arms. This run-in period is intended to improve power, continue engagement of participants, and decrease total duration of the trial.  This cognitive run-in period was included in the funded NIH DIAN-TU NexGen trial grant (NIH R01AG053267, DIAN-TU Next Generation Prevention Trials).

We are in the process of considering the next drug for the third drug arm.  The DIAN-TU trial platform was designed to quickly adapt to new information about drugs as they are developed, and we plan to be doing this soon.

Thank you and the participants for your continued commitment.

Best regards,

Randall J. Bateman, MD

Director, DIAN and DIAN-TU

David Clifford, MD

Medical Director, DIAN-TU

Lon Schneider, MD

Atabecestat Project Arm Leader, DIAN-TU

Update: April 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

1  Safety and biomarker effects of solanezumab in patients with Alzheimer’s disease. Farlow, Martin et al. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, Volume 8, Issue 4, 261 – 271 https://doi.org/10.1016/j.jalz.2011.09.224

2  Higher dose Gantenerumab leads to Significant Reduction in Amyloid Plaque Burden – Results for the Marguerite and Scarlet Road Open Label Extension Studies. https://www.youtube.com/watch?v=yT-u7Ct6-Hc

Update: December 2015
The Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) has completed the first stage of participant enrollment in the first Alzheimer’s prevention trial for autosomal dominant Alzheimer’s disease (ADAD), also referred to as early-onset Alzheimer’s disease. The goal of the first stage of the study is to determine the biomarker and cognitive effects of two different drugs targeting amyloid beta. With this enrollment milestone, first biomarker results may be available at the end of 2016 with the final cognitive endpoint data expected in late 2019.

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