The Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) Amyloid Removal Trial (ART): A Phase IIIb/IV Open-Label Study of Lecanemab to Evaluate Prevention and Progression of Dominantly Inherited Alzheimer’s Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Washington University School Of Medicine

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

completed 2 May 2025

Decision date (initial)

2024-10-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

The Alzheimer's Association · National Institutes of Health (NIH) · Eisai Co. Ltd. · Washington University in St. Louis

External identifiers

EU CT number

2024-513458-31-00

ClinicalTrials.gov

NCT06384573

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic

To determine the effects of amyloid removal on age of onset and clinical progression compared to external controls.

Secondary objectives 2

1. To determine if amyloid plaque as measured by amyloid PET can be fully removed in DIAD.
2. To determine the effects of amyloid removal on biomarkers of disease progression.

Conditions and MedDRA coding

Dominantly Inherited Alzheimer Disease (DIAD)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Previously participated in the DIAN-TU-001 gantenerumab OLE period.
2. Willing to participate in ongoing anti-amyloid therapy with informed consent by participant or legally authorized representative.
3. People of childbearing potential (POCBP), if partner is not sterilized, must agree to use highly effective contraceptive measures methods that can achieve a failure rate of less than 1% per year when used consistently and correctly from Consent (V1) until eight (8) weeks after last dose of any study drug. Such methods include: a. combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: o oral o intravaginal o transdermal b. progestogen-only hormonal contraception associated with inhibition of ovulation: o oral o injectable o implantable c. intrauterine device (IUD) d. intrauterine hormone-releasing system (IUS) e. bilateral tubal occlusion f. vasectomized partner g. sexual abstinence
4. Co-enrollment in the DIAN Observational Study (DIAN Obs, NCT00869817) and is willing to complete DIAN Obs procedures and assessments.
5. Able to undergo safety MRI scans as required.
6. Vascular access adequate for study drug administration and safety monitoring.
7. Body Mass Index (BMI) greater than 17 and less than 35 at Visit 2 (Entry Visit).
8. Have an identified study partner (defined as a person able to support the subject for the duration of the study and who spends at least 8 hours per week with the subject). The study partner must provide separate written informed consent. In addition, this person must be willing and able to provide follow-up information on the subject throughout the course of the study. This person must, in the opinion of the investigator, spend sufficient time with the subject on a regular basis such that the study partner can reliably fulfil the study requirements. A permanent study partner need not be living in the same residence with the subject. For such a study partner not residing with the subject, the investigator has to be satisfied that the subject can contact the study partner readily during the times when the study partner is not with the subject.

Exclusion criteria 14

1. 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 (see Section 7.4.1). Risks to be reviewed include: a. History of recurrent ARIA-E (2 or more episodes regardless of location). b. More than 4 ARIA-H MCH. c. History of ARIA-H SS. d. More than 2 lacunar infarcts or stroke involving a major vascular territory.
2. Ongoing auto-immune condition, bleeding diathesis, or neutropenia (platelets lower than 50,000) major depression or psychiatric condition.
3. Exposure to other AD investigational agents within the past six months, or five half-lives from Visit 2 (Entry Visit) whichever is longer.
4. Active cancer/malignancy that could interfere with study evaluations.
5. Requiring full anticoagulation or on high dose or dual antiplatelet therapy (daily aspirin 325 mg or less allowed).
6. History of macrohemorrhages >1 cm.
7. Hypersensitivity to lecanemab or any of the excipient, or to any monoclonal antibody treatment.
8. Pregnancy.
9. Breastfeeding.
10. Uncontrolled medical condition that is life threatening or precludes interpretation of AD.
11. Uncontrolled blood pressure including mean arterial pressure exceeding 97 mm Hg.
12. Uncontrolled seizure disorder.
13. Presence of certain implanted medical devices, such as some pacemakers, aneurysm clips, artificial heart valves, ear implants, or foreign metal objects in the eyes, skin, or body which would preclude MRI scan.
14. Answer “yes” to C-SSRS suicidal ideation Type 4 or 5, or any suicidal behavior assessment within 6 months of Visit 2 (Entry Visit), or has been hospitalized or treated for suicidal behavior in the past 5 years before Entry.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary and secondary endpoints measures will be collected through the DIAN Obs protocol. The primary endpoint for the interim analysis is the change from ART baseline to year 1 or year 2 in amyloid Pittsburgh compound B (PiB) PET standardized uptake value ratio (SUVR). The primary endpoint for the final analysis is the time to recurrent progression of Clinical Dementia Rating – Sum of Boxes (CDR-SB).

Secondary endpoints 1

1. The secondary endpoint analysis will be the change from ART baseline to year 5 in the following assessments: imaging (amyloid PET, tau PET), clinical (Functional Assessment Scale), plasma and CSF biomarkers of disease progression including Aβ42/40, tau species (%phosphorylated tau217, 205, 231), total tau, and microtubule-binding region (MTBR) species, e.g. MTBR-243. These assessments are collected at the initial DIAN Obs Visit (which coincides with DIAN‐TU‐003 V2) and...Truncated due to limit

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Washington University School Of Medicine

Sponsor organisation

Washington University School Of Medicine

Address

660 South Euclid Avenue 8056

City

Saint Louis

Postcode

63110-1010

Country

United States

Scientific contact point

Organisation

Washington University School Of Medicine

Contact name

Susan Mills, Sr. Director, Clin O

Public contact point

Organisation

Washington University School Of Medicine

Contact name

Susan Mills, Sr. Director, Clin O

Third parties 6

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 26 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications