Alzheimer's Tau Platform: Master Protocol
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age50-80
SponsorPaul S. Aisen
About this trial
The goal of the Alzheimer's Tau Platform (ATP) is to evaluate the safety and effectiveness of tau-directed therapies, alone or in combination with the anti-amyloid monoclonal antibody, donanemab, in adults aged 50-80 with late preclinical or early prodromal Alzheimer's disease.
This platform trial allows for the simultaneous testing of multiple tau therapies under a shared master protocol. This means that multiple investigational products will be tested simultaneously or sequentially. Each investigational product will be tested in a regimen.
The main questions the platform trial aims to answer are:
* Does a tau-directed therapy, alone or in combination with donanemab, reduce tau buildup in the brain compared to donanemab alone? * Does a tau-directed therapy, alone or in combination with donanemab, slow disease progression based on brain imaging, fluid biomarkers, and measures of memory and thinking?
Participants will:
* Be randomized to a treatment regimens, each containing different tau therapies. The exact number of treatment regimens that will active at the time of screening will change over time. * Receive donanemab or placebo for 6 months, followed by 24 months of tau therapy alone or in combination with donanemab. * Undergo regular cognitive testing, brain scans (MRI/PET), and biomarker assessments over 30 months
Participants will have an equal chance to be randomized to all regimens that are active at the time of screening. Once randomized to a regimen, participants will be randomized to one of three arms: (1) tau therapy alone, (2) a combination of donanemab and tau therapy, or (3) donanemab alone.
New regimens will be continuously added as new investigational products become available. The Alzheimer's Tau Platform Trial will enroll additional participants as each new regimen becomes available.
ATP will launch with one regimen: Regimen A: AADvac1. In the future, Regimen B ("Tau2") will launch with a second tau directed therapy.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Documentation of the participant's informed consent to study procedures (including APOE genotyping).
Ages 50-80 years (inclusive). Participants between the ages of 50 and 60 (inclusive) must be mildly impaired at screening (global CDR=0.5 and maximum CDR-SB <1.5
Cognitively unimpaired (preclinical AD with a global CDR=0) or mildly impaired (prodromal AD with a global CDR=0.5 and maximum CDR-SB <1.5).
If <12 years of education, MMSE required to be >20.
Disqualifiers
Females who are lactating or pregnant (as documented by a urine pregnancy test) during screening, or plan to become pregnant during the study.
Females of childbearing potential who did not use a highly effective method of contraception within 28 days of screening and/or are not willing to use highly effective method of contraception for the duration of their participation in the study. Males who are sexually active with a female of childbearing potential and do not agree to use barrier methods of contraception (condoms with spermicide) during the trial and for 6 months after the last dose of study drug unless the female is using a highly effective method of contraception.
Lacks good venous access such that multiple blood draws would be precluded.
Weighs less than 40kg, or more than 136kg at screening.
Trial design
Design model
Parallel
Treatments tested in this trial
AADvac1
DrugAADvac1 tau directed therapy
Tau2
DrugTau2 directed therapy
Treatment groups
900 Participants
are divided into 2 treatment groupsGroup A: Regimen A: AADvac1Experimental treatment 1 intervention
Group B: Regimine B: Tau2Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Reduction of brain tau deposition as measured by tau positron emission tomography (PET)
To determine whether at least one tau therapy, either alone or in combination with donanemab, will produce a greater reduction in brain tau deposition as measured by 18F-MK-6240 PET compared to donanemab alone.
Time frame
0, 6, 18 and 30 monthsSecondary outcomes
1
Disease progression as measured by plasma biomarkers
To assess whether at least one tau therapy, either alone or in combination with donanemab slows disease progression as measured by plasma biomarkers. Plasma biomarkers are measured by the ratio of amyloid-beta 42 to amyloid-beta 40 (Aβ42/40), phosphorylated tau at threonine 217 (ptau217), neurofilament light chain (NfL), or glial fibrillary acid protein (GFAP).
Time frame
30 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Paul S. Aisen
Lead sponsor
University of Southern California
Sponsor institution
National Institute on Aging (NIA)
Collaborator
University of California, San Francisco
Collaborator
Massachusetts General Hospital
Collaborator
Alzheimer's Therapeutic Research Institute
Collaborator
Alzheimer's Clinical Trials Consortium
Collaborator
Source ClinicalTrials.gov