Tau Positron Emission Tomography (PET) Longitudinal Substudy Associated With: Study of Crenezumab Versus Placebo in Preclinical Presenilin1 (PSEN1) E280A Mutation Carriers in the Treatment of Autosomal-Dominant Alzheimer's Disease

Alzheimer Disease Clinical Trial

Official title:

Tau PET Longitudinal Substudy Associated With: A Double-Blind, Placebo-Controlled Parallel-Group Study in Preclinical PSEN1 E280A Mutation Carriers Randomized to Crenezumab or Placebo, and in Non-randomized, Placebo-treated Non-carriers From the Same Kindred, to Evaluate the Efficacy and Safety of Crenezumab in the Treatment of Autosomal-Dominant Alzheimer's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03977584
• Other study ID #: BN40199
• Status: Completed
• Phase: Phase 2
• Start date: June 10, 2019
• Est. completion date: April 19, 2022

Study information

• Verified date: March 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This substudy will evaluate the effect of crenezumab on the longitudinal tau burden in a subgroup of preclinical Presenilin1 (PSEN1) E280A mutation carriers and non-carriers, who were enrolled in study NCT01998841 (GN28352). Participants will receive up to three intravenous (IV) injections of [^18F] Genentech Tau Probe 1 (GTP1) and will undergo a tau positron emission tomography (PET) scan after each IV injection of [18^F]GTP1. The purpose of this substudy is to increase the understanding of disease progression in the preclinical stage of familial Alzheimer's Disease (AD).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 114
• Est. completion date: April 19, 2022
• Est. primary completion date: April 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 60 Years

Eligibility

Inclusion Criteria:

• Enrolled in main Study NCT01998841 (GN28352).

Exclusion Criteria:

• Contraindication to PET scan procedures, possibly including, but not limited to current, past, or planned participation in studies involving radioactive agents, including the main Study NCT01998841 (GN28352) and this Tau PET substudy, such that the total research-related radiation dose to the participant in any given year would exceed the limits set forth in the U.S. Code of Federal Regulations (CFR) Title 21 Section 361.

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• Crenezumab
Crenezumab will be administered subcutaneously (every 2 weeks) or IV (every 4 weeks) for at least 260 weeks.
• Placebo
Placebo matched to crenezumab will be administered subcutaneously (every 2 weeks) or IV (every 4 weeks) for at least 260 weeks.

Other:
• [^18F]GTP1
IV [^18F]GTP1 will be administered up to three times. The first primary [^18F]GTP1 tau PET scan will occur during any visit in the main protocol NCT01998841 (GN28352) from Week 130 to Week 224 and the second [^18F]GTP1 tau PET scan from Week 248 to Week 260. The third and optional [^18F]GTP1 tau PET scan will supplement the two primary scans.

Locations

Country	Name	City	State
Colombia	Grupo Neurociencias de Antioquia	Medellin

Sponsors (3)

Lead Sponsor	Collaborator
Hoffmann-La Roche	Banner Alzheimer's Institute, National Institute on Aging (NIA)

Country where clinical trial is conducted

Colombia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized Rate of Change in Tau Burden	Tau is a protein that accumulates in Alzheimer's disease and damages brain cells including those essential for learning and memory. The effect of crenezumab on tau burden was assessed using [18F]GTP1 Tau PET. The annualized rate of change in tau burden from the first [18F]GTP1 scan of the standardized uptake ratio (SUVR) in the entorhinal cortex (Braak Stage 1) with an inferior cerebellum reference region was analyzed using a random coefficient regression model (RCRM). Braak staging classifies the degree of pathology in Alzheimer's disease. Braak stages 1 and 2 are used when neurofibrillary tangle involvement is confined mainly to the transentorhinal region of the brain, stages 3 and 4 when there is also involvement of limbic regions such as the hippocampus, and 5 and 6 when there is extensive neocortical involvement.	Baseline up to Week 149