API Generation Study 1 (GS1)
Alzheimer's Prevention Initiative Generation Study 1 (CAD106 and umibecestat in APOE4 homozygotes, NCT02565511)
Brain MRI and amyloid, FDG and tau PET from a prevention trial of the amyloid vaccine CAD106 and the BACE inhibitor umibecestat in cognitively unimpaired people aged 60 to 75 who carry two copies of APOE4, with screening and longitudinal clinical data.
Overview
Generation Study 1 was a phase 2/3 prevention trial of the Alzheimer's Prevention Initiative, run by Banner Alzheimer's Institute with Novartis and Amgen. It enrolled cognitively unimpaired people aged 60 to 75 who carry two copies of APOE4, with or without raised brain amyloid. Cohort I received the active amyloid vaccine CAD106 or placebo, and Cohort II the BACE inhibitor umibecestat or placebo. Both cohorts stopped early in 2019 after people on umibecestat showed mild cognitive worsening that later reversed. Anonymized clinical data and images are requested through the LONI Image and Data Archive.
Composition
480 participants were randomized: 65 in Cohort I (42 on CAD106, 23 on placebo) and 415 in Cohort II. Cohort I came from 28 sites in five countries, and Cohort II from 10 countries. In Cohort I, 44 of the 65 were women, nearly all were White, and about two thirds were amyloid positive at baseline. The provider page says screening and longitudinal data are shared, so volunteers who were screened but not randomized are also part of the archive.
Acquisition
Screening included brain MRI, amyloid PET or a lumbar puncture, and tau PET. The study plan lists volumetric and resting-state functional MRI, amyloid PET, FDG PET (this study only) and tau PET. Safety MRI for ARIA was done every six months in the first year and yearly after that. In Cohort I, volumetric T1-weighted MRI was acquired on 3T systems at screening and at weeks 26, 52 and 104. Most amyloid PET in Cohort I used florbetapir, and a few participants had one of two other tracers.
Annotations
No image annotations are described. Central readers confirmed ARIA on safety MRI: three cases on CAD106 (one ARIA-E, two ARIA-H). Central MRI reads, volumetric measures and amyloid PET values such as SUVR come with the clinical data.
Known limitations
- The trial ended early, so treatment and follow-up fall far short of the planned 5 to 8 years. In Cohort I, treatment lasted 6 to 48 months.
- MRI sequences other than the volumetric T1-weighted scan, and the tau PET tracer, are not named in the open papers.
- The Data Transfer Agreement that approved requesters sign is not published.
- Sex, age and ARIA counts for Cohort II are reported only pooled with Generation Study 2.
Cohort
Aggregate numbers from the sources below. Bars are relative to the 480 subjects.
Age
range 60 to 75
No age bins reported.
Section 2.3 in Lopez Lopez et al. 2019, The API Generation Program: study design of two randomized controlled trials, Alzheimer's & Dementia: TRCI
Contrast / sequence
Groups can overlap
- T1-weighted 65 14%
Modality
- MRI 480 100%
Section 2.4 in Lopez Lopez et al. 2019, The API Generation Program: study design of two randomized controlled trials, Alzheimer's & Dementia: TRCI
Condition
Groups can overlap
- Amyloid-related imaging abnormalities 3 <1%
License and access
Our reading of the license, not legal advice. Before you use the data, read the original license and confirm that your use is allowed. We take no responsibility for how you use a dataset. Full disclaimer
A research proposal is reviewed and approved
API Generation Study 1 (GS1) Data Use Agreement
Anonymized data are requested for scientific investigation, teaching or planning clinical research. The Generation Program team reviews each request, and approved requesters must sign a Data Transfer Agreement, whose terms are not published.
The Generation Program team reviews each request and approved requesters sign a Data Transfer Agreement whose text is not published. The terms checked here are the ones shown on the LONI IDA application page. The clinical data without imaging can also be requested through the AD Workbench of the Alzheimer's Disease Data Initiative.
What you can do
- Not stated
- Not stated
- Not stated
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What you can share
- Not stated
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- Not stated
What you must do
- Not stated
- Share alike No
- Yes
- Not stated
- Not stated
- Release code No
- Not stated
- Not stated
Limits
- Not stated
- Not stated
Commercial license: Not stated No commercial license offer is published.
Citation
Lopez Lopez C, Tariot PN, Caputo A, et al. The Alzheimer's Prevention Initiative Generation Program: Study design of two randomized controlled trials for individuals at risk for clinical onset of Alzheimer's disease. Alzheimer's & Dementia: Translational Research & Clinical Interventions 5:216-227 (2019). doi:10.1016/j.trci.2019.02.005
Sources
Every number on this page comes from one of these documents. Each chart names the table or page it is taken from. The raw numbers are in stats.csv.
- Lopez Lopez et al. 2019, The API Generation Program: study design of two randomized controlled trials, Alzheimer's & Dementia: TRCI paper
- Riviere et al. 2024, Effects of the active amyloid beta immunotherapy CAD106 on PET measurements of amyloid plaque deposition in cognitively unimpaired APOE e4 homozygotes, Alzheimer's & Dementia paper
- Tariot et al. 2024, Reversibility of cognitive worsening observed with BACE inhibitor umibecestat in the API Generation Studies, Alzheimer's & Dementia paper
- Alzheimer's Prevention Initiative, Generation Program available data website