Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia: A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation

Alzheimer's disease (AD) is defined by the presence of abnormal accumulations of amyloid protein (plaques) and tau protein (tangles) in the brain. The double-blind arm of DIAN-TU-001 Master protocol (NCT01760005) tested whether gantenerumab provided a clinical benefit by slowing the onset or the worsening of the disease. A clinical benefit was not observed in the double-blind part of the DIAN-TU-001 study. However, gantenerumab was associated with improvements in measures of amyloid and tau and an improvement in an overall measure of neurodegeneration (when nerve cells in the brain lose function over time). It is not known whether these changes may provide future clinical benefits. Based on this information, an exploratory Open Label Extension (OLE) will further study the effect of gantenerumab on these Alzheimer-related proteins and their relationship to disease progression.

After this final evaluation of study treatment with gantenerumab used in the gantenerumab / solanezumab double-blind arm of the Master protocol (NCT01760005), eligible participants from the placebo, solanezumab, and gantenerumab treatment groups in double-blind period were invited to participate in an OLE period to receive active gantenerumab study treatment as part of the DIAN-TU-001 Master protocol. The OLE period of the study planned to provide study treatment with gantenerumab for up to 3 years (36 months).

This study collected brain scans, blood, and spinal fluid tests (also called biomarkers), as well as safety, clinical and cognitive testing. The goal is to determine if gantenerumab has favorable effects on these tests to determine if and how much treatment may prevent or delay the symptoms of AD.

Update:

Based on the results of the completed studies of gantenerumab in sporadic AD in late 2022, it was decided to determine if dominantly inherited Alzheimer's disease (DIAD) participants in the DIAN-TU-001 OLE study were substantially clinically benefiting from gantenerumab high-dose treatment before the trial reached completion as the Gant program was being stopped.

An interim efficacy analysis of the DIAN-TU-001 OLE was performed to:

1. determine if gantenerumab OLE treatment and/or long-term treatment results in clinical benefit and determine the extent of amyloid removal compared to the double-blind period. 2. determine the potential effects of gantenerumab on clinical and cognitive measures to support decision-making regarding next steps for the DIAN-TU-001 OLE.