DIAN-TU Amyloid Removal Trial (ART) in Dominantly Inherited Alzheimer's Disease

Phase 3

Recruiting

• Conditions: Dementia; Alzheimer's Disease, Familial; Alzheimer's Disease
• Interventions: Drug: lecanemab

• Registration Number: NCT06384573
• Lead Sponsor: Washington University School of Medicine

Brief Summary

This is an open label study to treat dominantly inherited Alzheimer's disease (DIAD) mutation carrier participants from the DIAN-TU-001 gantenerumab Open Label Extension (OLE) period with lecanemab to determine the effects of amyloid removal on age of onset and clinical progression compared to external controls, if amyloid plaque as measured by amyloid PET c...

Detailed Description

The Dominantly Inherited Alzheimer Network (DIAN) and the DIAN Trials Unit (DIAN-TU) have established a global network that has increased understanding of Alzheimer's disease (AD) and identified a reliable cohort of individuals available for clinical trials. Over the past 12 years, the DIAN-TU has conducted a trial with the monoclonal antibody gantenerumab (...

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2024-04-22
• Study First Submitted QC: 2024-04-22
• Study First Posted: 2024-04-25
• Study Start: 2024-06-10
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-01
• Last Update Posted: 2024-07-03
• Primary Completion: 2029-11
• Study Completion: 2029-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 65

Inclusion Criteria

• Previously participated in the DIAN-TU-001 gantenerumab OLE period.
• Willing to participate in ongoing anti-amyloid therapy with informed consent by participant or legally authorized representative.
• People of childbearing potential (POCBP), if partner is not sterilized, must agree to use highly effective contraceptive measures (e.g., hormonal contraception, intra-uterine device, sexual abstinence, vasectomized partner) from Consent (V1) until five (5) halflives after last dose of any study drug. Refer to the study procedures manual for acceptable methods of contraception.
• Co-enrollment in the DIAN Observational Study (DIAN Obs, NCT00869817) and is willing to complete DIAN Obs procedures and assessments.
• Able to undergo safety MRI scans as required.
• Vascular access adequate for study drug administration and safety monitoring.

Key

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Exclusion Criteria

• Has any significantly increased risks associated with amyloid-related imaging abnormalities characterized by edema/effusion (ARIA-E), ARIA characterized by microhemorrhage (ARIA-H MCH) or superficial siderosis (ARIA-H SS) and vascular factors reviewed by the medical monitoring team. Risks to be reviewed include:

  1. History of recurrent ARIA-E (2 or more episodes regardless of location).
  2. More than 20 ARIA-H MCH.
  3. More than one area of ARIA-H SS.
  4. More than 2 lacunar infarcts or stroke involving a major vascular territory.

• Requiring full anticoagulation or on high dose or dual antiplatelet therapy (daily aspirin 325 mg or less allowed).

• History of macrohemorrhages >1 cm.

• Intolerance for lecanemab.

• Pregnancy.

• Breastfeeding.

• Uncontrolled medical condition that is life threatening or precludes interpretation of AD.

• Uncontrolled blood pressure including mean arterial pressure exceeding 97 mm Hg.

• Uncontrolled seizure disorder.

• Ongoing auto-immune condition, bleeding diathesis, or neutropenia (platelets lower than 50,000) major depression or psychiatric condition.

• Exposure to other AD investigational agents within the past six months, or five half-lives from Visit 2 (Entry Visit) whichever is longer.

• Active cancer/malignancy that could interfere with study evaluations.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
lecanemab	lecanemab	Starting at Week 0, participants will receive open-label lecanemab administered intravenously approximately every 2 weeks for a minimum of 5 years utilizing a common close design.

Primary Outcome Measures

Name	Time	Method
The primary endpoint for the final analysis is the time to recurrent progression of Clinical Dementia Rating - Sum of Boxes (CDR-SB).	Week 0, Week 52, Week 104, Week 156, Week 208, Week 260, Week 312, Week 364

Trial Locations

Locations (6)

Indiana University School of Medicine; 🇺🇸 Indianapolis, Indiana, United States

Neuroscience Research Australia; 🇦🇺 Randwick, New South Wales, Australia

University of Alabama in Birmingham; 🇺🇸 Birmingham, Alabama, United States

University of Washington; 🇺🇸 Seattle, Washington, United States

The National Hospital for Neurology and Neurosurgery; 🇬🇧 London, Greater London, United Kingdom

Washington University in St. Louis; 🇺🇸 Saint Louis, Missouri, United States