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Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation (DIAN-TU) (DIAN-TU)

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ClinicalTrials.gov Identifier: NCT05269394
Recruitment Status : Recruiting
First Posted : March 8, 2022
Last Update Posted : March 8, 2022
Sponsor:
Collaborators:
Alzheimer's Association
National Institute on Aging (NIA)
Accelerating Medicines Partnership (AMP)
Eisai Inc.
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:
To assess the safety, tolerability, biomarker, cognitive, and clinical efficacy of investigational products in participants with an Alzheimer's disease-causing mutation by determining if treatment with the study drug improves disease-related biomarkers and slows the rate of progression of cognitive or clinical impairment.

Condition or disease Intervention/treatment Phase
Alzheimers Disease Dementia Alzheimers Disease, Familial Drug: E2814 Drug: Lecanemab Drug: Matching Placebo (E2814) Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 168 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Interventional
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II/III Multicenter Randomized, Double-Blind, Placebo-Controlled Platform Trial of Potential Disease Modifying Therapies Utilizing Biomarker, Cognitive, and Clinical Endpoints in Dominantly Inherited Alzheimer's Disease
Actual Study Start Date : December 22, 2021
Estimated Primary Completion Date : July 2027
Estimated Study Completion Date : October 2027

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: E2814 plus lecanemab

Symptomatic Population (Cohort 1)

At Week 0, participants will receive open-label lecanemab administered intravenously for the full treatment period.

At Week 24, participants randomized to E2814 will receive intravenously in a blinded fashion for the remainder of their treatment period.

Asymptomatic Population (Cohort 2)

At Week 0, participants randomized to E2814 will receive intravenously in a blinded fashion for the full treatment period.

At Week 52, all participants will initiate open-label lecanemab administered intravenously for the remainder of their treatment period.

Drug: E2814
Administered intravenously in a blinded fashion

Drug: Lecanemab
Administered intravenously
Other Name: BAN2401

Placebo Comparator: Matching placebo (E2814) plus lecanemab

Symptomatic Population (Cohort 1)

At Week 0, participants will receive open-label lecanemab administered intravenously for the full treatment period.

At Week 24, participants randomized to E2814 placebo will receive placebo intravenously in a blinded fashion for the remainder of their treatment period.

Asymptomatic Population (Cohort 2)

At Week 0, participants randomized to E2814 placebo will receive placebo intravenously in a blinded fashion for the full treatment period.

At Week 52, all participants will initiate open-label lecanemab administered intravenously for the remainder of their treatment period.

Drug: Lecanemab
Administered intravenously
Other Name: BAN2401

Drug: Matching Placebo (E2814)
Placebo administered intravenously in a blinded fashion.




Primary Outcome Measures :
  1. The primary end point is the change from Week 24 to Week 104 and Week 208 in tau PET in the Symptomatic Population (Cohort 1). [ Time Frame: Weeks 24, 104, and 208 ]
    To determine whether E2814 is superior to placebo, when each is concurrently administered with lecanemab, in the change from Week 24 to Week 104 (interim analysis) and Week 208 (final analysis) in tau spread as measured by tau PET in the symptomatic population (Cohort 1).


Secondary Outcome Measures :
  1. Symptomatic Population (Cohort 1): Key Secondary: Change from Week 24 to Week 208 in Clinical Dementia Scale - Sum of Boxes (CDR-SB). [ Time Frame: Weeks 24, 52, 104, 156 and 208 ]

    To determine whether E2814 is superior to placebo, when each is concurrently administered with lecanemab, in change from Week 24 to Week 208 in CDR-SB

    Scores range from 0-18 with lower scores showing better outcomes


  2. Asymptomatic Population (Cohort 2): Key Secondary: Change from Week 0 to Week 104 and Week 208 in CSF ptau217/total tau [ Time Frame: Weeks 0, 104 and 208 ]
    To determine whether E2814 is superior to placebo, when each is administered alone and then concurrently with lecanemab, in change from Week 0 to Week 104 (interim analysis) and Week 208 (final analysis) in cerebrospinal fluid (CSF) phosphorylated tau (ptau217)/total tau

  3. Symptomatic Population (Cohort 1): Change from Week 24 to Week 104 and Week 208 in the cognitive composite score [ Time Frame: Weeks 24, 52, 76, 104, 128, 156, 180 and 208 ]
  4. Symptomatic Population (Cohort 1): Change from Week 0 to Week 24 in amyloid PET [ Time Frame: Week 0 to Week 24 ]
  5. Asymptomatic Population (Cohort 2): Change from Week 0 to Week 52 in CSF ptau217/total tau [ Time Frame: Week 0 to Week 52 ]
  6. Symptomatic population (Cohort 1): Change from Week 24 to Week 104 and Week 208 in CSF neurofilament light chain (NfL) [ Time Frame: Weeks 24, 104 and 208 ]
  7. Asymptomatic Population (Cohort 2): Change from Week 52 to Week 104 and Week 208 in CSF neurofilament light chain (NfL) [ Time Frame: Weeks 52, 104 and 208 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Between 18-80 years of age
  • Individuals who know they have an Alzheimer's disease-causing mutation.
  • Are within -10 to + 10 years of the predicted or actual age of cognitive symptom onset.
  • Cognitively normal or with mild cognitive impairment or mild dementia, Clinical Dementia Rating (CDR) of 0-1 (inclusive)
  • Fluency in DIAN-TU trial approved language and evidence of adequate premorbid intellectual functioning
  • Able to undergo Magnetic Resonance Imaging (MRI), Lumbar Puncture (LP), Positron Emission Tomography (PET), and complete all study related testing and evaluations.
  • For women of childbearing potential, if partner is not sterilized, participant must agree to use effective contraceptive measures (hormonal contraception, intra-uterine device, sexual abstinence, barrier method with spermicide).
  • Adequate visual and auditory abilities to perform all aspects of the cognitive and functional assessments.
  • Has a Study Partner who in the investigator's judgment is able to provide accurate information as to the subject's cognitive and functional abilities, who agrees to provide information at the study visits which require informant input for scale completion.

Key Exclusion Criteria:

  • Significant neurologic disease (other than AD) or psychiatric disease that may currently or during the course of the study affect cognition or participant's ability to complete the study.
  • At high risk for suicide, e.g., significant suicidal ideation or attempt within last 12 months. Current stable mild depression or current use of antidepressant medications is not exclusionary.
  • History or presence of brain MRI scans indicative of any other significant abnormality
  • Substance or alcohol use disorder currently or within the past 1 year
  • Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, or foreign metal objects in the eyes, skin or body which would preclude MRI scan.
  • History or presence of clinically significant cardiovascular disease, hepatic/renal disorders, infectious disease or immune disorder, or metabolic/endocrine disorders
  • Anticoagulants except low dose (≤ 325 mg) aspirin.
  • Have been exposed to a monoclonal antibody targeting beta amyloid peptide within the past six months.
  • History of cancer within the last 5 years, except basal cell carcinoma, non-squamous skin carcinoma, prostate cancer or carcinoma in situ with no significant progression over the past 2 years.
  • Positive urine or serum pregnancy test or plans or desires to become pregnant during the course of the trial.
  • Subjects unable to complete all study related testing, including implanted metal that cannot be removed for MRI scanning, required anticoagulation and pregnancy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05269394


Contacts
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Contact: Ellen Ziegemeier, MA 844-DIANEXR (342-6397) dianexr@wustl.edu
Contact: Jennifer Petranek 844-DIANEXR (342-6397) dianexr@wustl.edu

Locations
Show Show 40 study locations
Sponsors and Collaborators
Washington University School of Medicine
Alzheimer's Association
National Institute on Aging (NIA)
Accelerating Medicines Partnership (AMP)
Eisai Inc.
Investigators
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Study Director: Randall J Bateman, MD Washington University School of Medicine
Additional Information:
Publications:
Salloway S, Farlow M, McDade E, Clifford DB, Wang G, Llibre-Guerra JJ, Hitchcock JM, Mills SL, Santacruz AM, Aschenbrenner AJ, Hassenstab J, Benzinger TLS, Gordon BA, Fagan AM, Coalier KA, Cruchaga C, Goate AA, Perrin RJ, Xiong C, Li Y, Morris JC, Snider BJ, Mummery C, Surti GM, Hannequin D, Wallon D, Berman SB, Lah JJ, Jimenez-Velazquez IZ, Roberson ED, van Dyck CH, Honig LS, Sánchez-Valle R, Brooks WS, Gauthier S, Galasko DR, Masters CL, Brosch JR, Hsiung GR, Jayadev S, Formaglio M, Masellis M, Clarnette R, Pariente J, Dubois B, Pasquier F, Jack CR Jr, Koeppe R, Snyder PJ, Aisen PS, Thomas RG, Berry SM, Wendelberger BA, Andersen SW, Holdridge KC, Mintun MA, Yaari R, Sims JR, Baudler M, Delmar P, Doody RS, Fontoura P, Giacobino C, Kerchner GA, Bateman RJ; Dominantly Inherited Alzheimer Network-Trials Unit. A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer's disease. Nat Med. 2021 Jul;27(7):1187-1196. doi: 10.1038/s41591-021-01369-8. Epub 2021 Jun 21.

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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT05269394    
Other Study ID Numbers: DIAN-TU-001 (E2814)
The Alzheimer's Association ( Other Grant/Funding Number: DIAN TTU-12-243040 )
U01AG042791 ( U.S. NIH Grant/Contract )
2013-000307-17 ( EudraCT Number )
R01AG046179 ( U.S. NIH Grant/Contract )
REec-2014-0817 ( Registry Identifier: Spanish Clinical Studies Registry )
The Alzheimer's Association ( Other Grant/Funding Number: DIAN-TU Tau-15-347219 )
GHR Foundation ( Other Grant/Funding Number: File 4401 )
Alzheimer's Association ( Other Identifier: HDE 18S84914 )
The Alzheimer's Association ( Other Grant/Funding Number: DIAN-TU NG-16-434362 )
R56AG053267 ( U.S. NIH Grant/Contract )
U01AG059798 ( U.S. NIH Grant/Contract )
R01AG053267 ( U.S. NIH Grant/Contract )
R01AG068319 ( U.S. NIH Grant/Contract )
The Alzheimer's Association ( Other Grant/Funding Number: DIAN-TU Tau-21822987 )
The Alzheimer's Association ( Other Identifier: DIAN-TU OLE-21725093 )
First Posted: March 8, 2022    Key Record Dates
Last Update Posted: March 8, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Access to DIAN-TU trial data will follow the DIAN-TU data access policy, which complies with the guidelines established by the Collaboration for Alzheimer's Prevention [CAP REF].

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Washington University School of Medicine:
Alzheimer's
Alzheimer's Disease
Dementia
Mutation
Genetic Mutation
Dominantly Inherited Alzheimer's Disease
Dominantly Inherited Alzheimer Network
Autosomal Dominant Alzheimer's Disease
Early Onset Alzheimer's Disease
DIAN
DIAN-TU
DIAN TU
DIAD
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders