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

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

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).

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: Crenezumab; Other: [^18F]GTP1; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 114
• Phase: Phase 2

Contacts and Locations

Study Locations

• Colombia
  • Medellin, Colombia
    • Grupo Neurociencias de Antioquia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [^18F]GTP1 in Mutation Carriers: Crenezumab; Mutation-carrying participants receiving crenezumab in the main study NCT01998841 (GN28352) will receive up to three IV injections of [^18F]GTP1 and will undergo a tau PET scan after each IV injection of [^18F]GTP1.	Drug: Crenezumab; Crenezumab will be administered subcutaneously (every 2 weeks) or IV (every 4 weeks) for at least 260 weeks.; Other Names: MABT5102A; 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.
Placebo Comparator: [^18F]GTP1 in Mutation Carriers: Placebo; Mutation-carrying participants receiving placebo in the main study NCT01998841 (GN28352) will receive up to three IV injections of [^18F]GTP1 and will undergo a tau PET scan after each IV injection of [^18F]GTP1.	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.; Drug: Placebo; Placebo matched to crenezumab will be administered subcutaneously (every 2 weeks) or IV (every 4 weeks) for at least 260 weeks.
Placebo Comparator: [^18F]GTP1 in Non-carriers of Mutation: Placebo; Non-carriers of the mutation receiving placebo in the main study NCT01998841 (GN28352) will receive up to three IV injections of [^18F]GTP1 and will undergo a tau PET scan after each IV injection of [^18F]GTP1.	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.; Drug: Placebo; Placebo matched to crenezumab will be administered subcutaneously (every 2 weeks) or IV (every 4 weeks) for at least 260 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Collaborators: National Institute on Aging (NIA); Banner Alzheimer's Institute
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2019
• Primary Completion (Actual): April 19, 2022
• Study Completion (Actual): April 19, 2022

Study Registration Dates

• First Submitted: June 5, 2019
• First Submitted That Met QC Criteria: June 5, 2019
• First Posted (Actual): June 6, 2019

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: BN40199

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes