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Trial record 2 of 2 for:    DIAN-TU-001

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04623242
Recruitment Status : Completed
First Posted : November 10, 2020
Last Update Posted : November 23, 2020
Sponsor:
Collaborators:
Eli Lilly and Company
Hoffmann-La Roche
Alzheimer's Association
National Institute on Aging (NIA)
Avid Radiopharmaceuticals
Accelerating Medicines Partnership (AMP)
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:

The purpose of this study is to assess the safety, tolerability, biomarker and cognitive efficacy of investigational products in subjects who are known to have an Alzheimer's disease-causing mutation by determining if treatment with the study drug slows the rate of progression of cognitive impairment and improves disease-related biomarkers.

This is an analysis study for an MPRP: DIAN-TU-001 Master NCT01760005


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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 194 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 Randomized, Double-Blind, Placebo-Controlled, Cognitive Endpoint, Multi-Center Study of Potential Disease Modifying Therapies in Individuals at Risk for and With Dominantly Inherited Alzheimer's Disease
Actual Study Start Date : December 2012
Actual Primary Completion Date : November 22, 2019
Actual Study Completion Date : March 6, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Gantenerumab Drug: Gantenerumab
Subcutaneously every 4 weeks at escalating doses
Other Name: RO4909832

Experimental: Solanezumab Drug: Solanezumab
Intravenous infusion every 4 weeks at escalating doses
Other Name: LY2062430

Placebo Comparator: Matching placebo (Gantenerumab) Drug: Matching Placebo (Gantenerumab)
Subcutaneous injection of placebo every 4 weeks

Placebo Comparator: Matching Placebo (Solanezumab) Drug: Matching Placebo (Solanezumab)
Intravenous infusion of placebo every 4 weeks




Primary Outcome Measures :
  1. Assess cognitive efficacy in individuals with mutations causing dominantly inherited AD as measured by the DIAN-Multivariate Cognitive Endpoint (DIAN-MCE) [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
    The DIAN-Multivariate Cognitive Endpoint (DIAN-MCE) consists of 4 cognitive measures: Wechsler Memory Scale-Revised Logical Memory Delayed Recall Test, Wechsler Adult Intelligence Sale Digit Symbol Substitution Test (WAIS), International Shopping List Task (ISLT), Mini-Mental State Examination (MMSE)


Secondary Outcome Measures :
  1. Gantenerumab: Rate of change over time- Clinical Dementia Rating Sum of Boxes (CDR-SB) [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
  2. Gantenerumab: Rate of change over time- Functional Assessment Scale (FAS) [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
  3. Solanezumab: Clinical Measures- Clinical Dementia Rating (CDR) [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
  4. Solanezumab: Clinical Measures- CDR sum of boxes (CDR-SB) [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
  5. Solanezumab: Clinical Measures- Geriatric Depression Scale (GDS) [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
  6. Solanezumab: Clinical Measures- Neuropsychiatric Inventory Questionnaire (NPI-Q) [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
  7. Solanezumab: Clinical Measures- Functional Assessment Scale (FAS) [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
  8. Solanezumab: Clinical Measures- Mini-Mental Status State Examination (MMSE) [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
  9. Solanezumab: Cognitive Measures- 30-min Delayed Recall [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
  10. Solanezumab: Cognitive Measures- 30-min Delayed/Reversed Recall [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
  11. Solanezumab: Cognitive Measures- Trailmaking Test parts A & B [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
  12. Solanezumab: Cognitive Measures- WMS-R Digit Span [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
  13. Solanezumab: Cognitive Measures- WAIS-R Digit-Symbol Substitution Test [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
  14. Solanezumab: Cognitive Measures- Raven's Progressive Matrices (Set A) [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
  15. Solanezumab: Cognitive Measures- Category Fluency (Animals & Vegetables) [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
  16. Solanezumab: Cognitive Measures- WMS-R Logical Memory (Immediate & Delayed Recall) [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
  17. Solanezumab: Cognitive Measures- Composite including: Alternative multivariate composite: (1) Digit Span backwards; (2) Logical Memory (Immediate); (3) Trailmaking B; (4) Category Fluency (Animals) [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
  18. Solanezumab: Imaging Measures- Brain amyloid load as measured by [11C]PiB-PET [ Time Frame: Baseline and Weeks 52, 104 and 208 ]
  19. Solanezumab: Imaging Measures- Brain amyloid load as measured by florbetapir PET [ Time Frame: Baseline and Weeks 52, 104 and 208 ]
  20. Solanezumab: Imaging Measures- Brain glucose metabolism as measured by fluorodeoxyglucose (FDG)-PET [ Time Frame: Baseline and Weeks 52, 104 and 208 ]
  21. Solanezumab: Imaging Measures- Brain atrophy as measured by cortical thickness of regions of interest [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
  22. Solanezumab: Imaging Measures- Brain atrophy as measured by whole brain volume [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
  23. Solanezumab: Imaging Measures- Brain atrophy as measured by ventricular volume (volumetric MRI) [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
  24. Solanezumab: Imaging Measures- Brain tau load as measured by flortaucipir PET [ Time Frame: Baseline and Weeks 52, 104 and 208 ]
  25. Solanezumab: Fluid Biomarker Measures- CSF Aβ 40 and 42, free and total [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
  26. Solanezumab: Fluid Biomarker Measures- CSF Tau and pTau [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
  27. Solanezumab: Fluid Biomarker Measures- CSF Neurofilament light chain (NfL) [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
  28. Solanezumab: Fluid Biomarker Measures- Plasma Neurofilament light chain (NfL) [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
  29. Solanezumab: Fluid Biomarker Measures- Plasma Aβ 40 and 42, total [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
  30. Solanezumab: Fluid Biomarker Measures- Plasma Anti-drug antibodies (ADA) [ Time Frame: Baseline and Weeks 52, 104, 156, 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:   Yes
Criteria

Inclusion Criteria:

  • Between 18-80 years of age
  • Individuals who know they have an Alzheimer's disease-causing mutation or are unaware of their genetic status and have dominantly inherited Alzheimer's disease (DIAD) mutation in their family.
  • Are within -15 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, subject 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.

Exclusion Criteria:

  • History or presence of brain MRI scans indicative of any other significant abnormality
  • Alcohol or drug dependence 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): NCT04623242


Locations
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United States, Alabama
University of Alabama in Birmingham
Birmingham, Alabama, United States, 35294
United States, California
University of California San Diego Medical Center
La Jolla, California, United States, 92037
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06510
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30329
United States, Indiana
Indiana University School of Medicine
Indianapolis, Indiana, United States, 46202
United States, Missouri
Washington University in St. Louis
Saint Louis, Missouri, United States, 63110
United States, New York
Columbia University
New York, New York, United States, 10032
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Rhode Island
Butler Hospital
Providence, Rhode Island, United States, 02096
United States, Washington
University of Washington
Seattle, Washington, United States, 98195
Australia, New South Wales
Neuroscience Research Australia
Randwick, New South Wales, Australia, 2031
Australia, Victoria
Mental Health Research Institute
Melbourne, Victoria, Australia, 3010
Australia, Western Australia
The McCuster Foundation of Alzheimer's Disease Research
Nedlands, Western Australia, Australia, 6009
Canada, British Columbia
UBC Hospital
Vancouver, British Columbia, Canada, V6T 2B5
Canada, Ontario
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
McGill Center for Studies in Aging
Verdun, Quebec, Canada, H4H 1R3
France
CHU de Toulouse - Hôpital Purpan
Toulouse, Haute Garonne, France, 31059
Hopital Roger Salengro - CHU Lille
Lille, Nord, France, 59037
Groupe Hospitalier Pitie-Salpetriere
Paris cedex 13, Paris, France, 69677
Hopital Neurologique Pierre Wertheimer
Bron cedex, Rhone, France, 69677
CHU de Rouen - Hôpital Charles Nicolle
Rouen, Seine Maritime, France, 76031
Ireland
St Vincent's University Hospital
Dublin, Ireland, DUBLIN 4
Puerto Rico
University of Puerto Rico, School of Medicine
San Juan, Puerto Rico, 00936
Spain
Hospital Clínic I Provincial de Barcelona
Barcelona, Spain, 8036
United Kingdom
The National Hospital for Neurology and Neurosurgery
London, Greater London, United Kingdom, WC1B 3BG
Sponsors and Collaborators
Washington University School of Medicine
Eli Lilly and Company
Hoffmann-La Roche
Alzheimer's Association
National Institute on Aging (NIA)
Avid Radiopharmaceuticals
Accelerating Medicines Partnership (AMP)
Investigators
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Study Director: Randall J Bateman, MD Washington University School of Medicine
Additional Information:
Publications:

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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT04623242    
Other Study ID Numbers: DIAN-TU-001 (gant-sola)
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 )
First Posted: November 10, 2020    Key Record Dates
Last Update Posted: November 23, 2020
Last Verified: November 2020
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].
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
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
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs