Generation Program
Generation Study 1 (GS1) and Generation Study 2 (GS2)
Program Overview
Alzheimer’s Prevention Initiative (API) Generation Program was made up of two clinical trials – Generation Study 1 and Generation Study 2 (clinicaltrials.gov NCT02565511 and NCT03131453) – testing investigational study medications, CAD106 and umibecestat, which aimed to prevent or delay the onset of symptoms associated with Alzheimer’s disease in cognitively healthy people whose genetic makeup put them at particularly high risk for developing the disease.
Generation Study 1
A randomized, double-blind, placebo-controlled, two-cohort, parallel group study to evaluate the efficacy of CAD106 and CNP520 in participants at risk for the onset of clinical symptoms of Alzheimer’s disease.
This trial was a randomized, double-blind, placebo-controlled, parallel group, adaptive design with variable treatment duration planned in cognitively unimpaired APOE4 homozygotes aged 60 to 75 years. Participants were enrolled into Cohort I (CAD106) or Cohort II (CNP520). The planned treatment period of 5 to 8 years was not achieved due to early study termination.
Generation Study 2
A randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of CNP520 in participants at risk for the onset of clinical symptoms of Alzheimer’s disease.
This trial was a randomized, double-blind, placebo-controlled, parallel group, adaptive design with variable treatment duration planned in cognitively unimpaired participants aged 60 to 75 with one or two copies of APOE4 allele. Participants with one copy (heterozygotes) were also required to have elevated brain amyloid as determined by PET or CSF. Participants were randomized to either umibecestat 50 mg, umibecestat 15 mg, or placebo using a 2:1:2 ratio, stratifying on amyloid status.
Genetic Disclosure Materials
As part of the Generation Program, materials were developed to help guide participants through the APOE and amyloid disclosure sessions, including:
- Educational handout summarizing considerations for undergoing APOE and amyloid disclosure,
- Handouts used by providers of disclosure to walk participants through the APOE and amyloid disclosure sessions,
- Results summary sheets for each possible APOE genotype, and
- Amyloid results summary sheet.
Development of these materials was supported by funding to Banner Alzheimer’s Institute from the National Institute on Aging (1UF1AG046150). To request access to and use of these materials, see our Resources page.
Our Partners
We gratefully acknowledge the participants and their family members.
Design and implementation of the Generation Program was led collaboratively by Banner Alzheimer’s Institute, Novartis Pharma AG and Amgen. The National Institute on Aging served in an advisory capacity in the design of the trial and in oversight of the Data Monitoring Committee (DMC). In addition, advisors from numerous institutions played key roles and provided invaluable contributions to the design and implementation of the Generation Program.
This Generation Program was funded by Novartis Pharma AG, Basel, Switzerland, and Amgen, Thousand Oaks, CA, USA, in collaboration with the Banner Alzheimer’s Institute located in Phoenix, AZ, USA. Generation Study 1 was supported by funding from the National Institute on Aging (1UF1AG0461501), part of the National Institutes of Health, as well as the Alzheimer’s Association, FBRI, GHR Foundation and Banner Alzheimer’s Foundation.