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

Prior treatment

• Exposure to other AD investigational agents within the past six months, or five half-lives from Visit 2 (Entry Visit) whichever is longer.
• Requiring full anticoagulation or on high dose or dual antiplatelet therapy (daily aspirin 325 mg or less allowed).

Other illness

• 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.
• Uncontrolled medical condition that is life threatening or precludes interpretation of AD.
• Uncontrolled seizure disorder.
• 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.
• Active cancer/malignancy that could interfere with study evaluations.
• History of macrohemorrhages >1 cm.
• Hypersensitivity to lecanemab or any of the excipient, or to any monoclonal antibody treatment.

Lab values

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

Other

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

• 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 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
• 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.
• Body Mass Index (BMI) greater than 17 and less than 35 at Visit 2 (Entry Visit).
• 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.