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

NCT03977584 | Completed Phase 2 Results FDA Drug

• 1 other identifier: BN40199
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (3)

[^18F]GTP1 in Mutation Carriers: Crenezumab

EXPERIMENTAL

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; Other: [^18F]GTP1

[^18F]GTP1 in Mutation Carriers: Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo; Other: [^18F]GTP1

[^18F]GTP1 in Non-carriers of Mutation: Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo; Other: [^18F]GTP1

Interventions

Crenezumab DRUG

Crenezumab will be administered subcutaneously (every 2 weeks) or IV (every 4 weeks) for at least 260 weeks.

Also known as: MABT5102A

[^18F]GTP1 in Mutation Carriers: Crenezumab

Placebo DRUG

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

[^18F]GTP1 in Mutation Carriers: Placebo; [^18F]GTP1 in Non-carriers of Mutation: Placebo

[^18F]GTP1 OTHER

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.

[^18F]GTP1 in Mutation Carriers: Crenezumab; [^18F]GTP1 in Mutation Carriers: Placebo; [^18F]GTP1 in Non-carriers of Mutation: Placebo

Eligibility Criteria

• Age: 30 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• \- Enrolled in main Study NCT01998841 (GN28352).

You may not qualify if:

• \- 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• Banner Alzheimer's Institute: collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Grupo Neurociencias de Antioquia

Medellín, Colombia

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

crenezumab; (18F)GTP1

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: BN40199
• Organization: Hoffmann-La Roche

global-roche-genentech-trials@gene.com

888-662-6728 (U.S. Only)

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2019
• First Posted: June 6, 2019
• Study Start: June 10, 2019
• Primary Completion: April 19, 2022
• Study Completion: April 19, 2022
• Last Updated: March 15, 2024
• Results First Posted: March 15, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share

Locations

CO (1)