Dementia Clinical Trial
— DIAN-TUOfficial 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
Verified date | May 2024 |
Source | Washington University School of Medicine |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The purpose of this study is 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 slows the rate of progression of cognitive/clinical impairment or improves disease-related biomarkers.
Status | Terminated |
Enrollment | 73 |
Est. completion date | November 13, 2023 |
Est. primary completion date | August 12, 2023 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 80 Years |
Eligibility | Inclusion Criteria: - Between 18-80 years of age - Individuals who know they have an Alzheimer's disease-causing mutation - Individuals who have participated in the double-blind period - In the opinion of the investigator and sponsor, treatment is not contraindicated for safety - Capable of receiving drug and appropriate clinical safety assessment - 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. |
Country | Name | City | State |
---|---|---|---|
Australia | Mental Health Research Institute | Melbourne | Victoria |
Australia | The McCuster Foundation of Alzheimer's Disease Research | Nedlands | Western Australia |
Australia | Neuroscience Research Australia | Randwick | New South Wales |
Canada | UBC Hospital | Vancouver | British Columbia |
France | Hopital Neurologique Pierre Wertheimer | Bron cedex | Rhone |
France | Hopital Roger Salengro - CHU Lille | Lille | Nord |
France | Groupe Hospitalier Pitie-Salpetriere | Paris cedex 13 | Paris |
France | CHU de Rouen - Hôpital Charles Nicolle | Rouen | Seine Maritime |
France | CHU de Toulouse - Hôpital Purpan | Toulouse | Haute Garonne |
Ireland | St Vincent's University Hospital | Dublin | |
Puerto Rico | University of Puerto Rico, School of Medicine | San Juan | |
Spain | Hospital Clínic I Provincial de Barcelona | Barcelona | |
United Kingdom | The National Hospital for Neurology and Neurosurgery | London | Greater London |
United States | Emory University | Atlanta | Georgia |
United States | University of Alabama in Birmingham | Birmingham | Alabama |
United States | Indiana University School of Medicine | Indianapolis | Indiana |
United States | University of California San Diego Medical Center | La Jolla | California |
United States | Yale University School of Medicine | New Haven | Connecticut |
United States | University of Pittsburgh | Pittsburgh | Pennsylvania |
United States | Butler Hospital | Providence | Rhode Island |
United States | Washington University in St. Louis | Saint Louis | Missouri |
United States | University of Washington | Seattle | Washington |
Lead Sponsor | Collaborator |
---|---|
Washington University School of Medicine | Alzheimer's Association, Hoffmann-La Roche, National Institute on Aging (NIA) |
United States, Australia, Canada, France, Ireland, Puerto Rico, Spain, United Kingdom,
Bateman RJ, Benzinger TL, Berry S, Clifford DB, Duggan C, Fagan AM, Fanning K, Farlow MR, Hassenstab J, McDade EM, Mills S, Paumier K, Quintana M, Salloway SP, Santacruz A, Schneider LS, Wang G, Xiong C; DIAN-TU Pharma Consortium for the Dominantly Inherited Alzheimer Network. The DIAN-TU Next Generation Alzheimer's prevention trial: Adaptive design and disease progression model. Alzheimers Dement. 2017 Jan;13(1):8-19. doi: 10.1016/j.jalz.2016.07.005. Epub 2016 Aug 29. — View Citation
Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, Marcus DS, Cairns NJ, Xie X, Blazey TM, Holtzman DM, Santacruz A, Buckles V, Oliver A, Moulder K, Aisen PS, Ghetti B, Klunk WE, McDade E, Martins RN, Masters CL, Mayeux R, Ringman JM, Rossor MN, Schofield PR, Sperling RA, Salloway S, Morris JC; Dominantly Inherited Alzheimer Network. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med. 2012 Aug 30;367(9):795-804. doi: 10.1056/NEJMoa1202753. Epub 2012 Jul 11. Erratum In: N Engl J Med. 2012 Aug 23;367(8):780. — View Citation
Farlow M, Arnold SE, van Dyck CH, Aisen PS, Snider BJ, Porsteinsson AP, Friedrich S, Dean RA, Gonzales C, Sethuraman G, DeMattos RB, Mohs R, Paul SM, Siemers ER. Safety and biomarker effects of solanezumab in patients with Alzheimer's disease. Alzheimers Dement. 2012 Jul;8(4):261-71. doi: 10.1016/j.jalz.2011.09.224. Epub 2012 Jun 5. — View Citation
Grill JD, Bateman RJ, Buckles V, Oliver A, Morris JC, Masters CL, Klunk WE, Ringman JM; Dominantly Inherited Alzheimer's Network. A survey of attitudes toward clinical trials and genetic disclosure in autosomal dominant Alzheimer's disease. Alzheimers Res Ther. 2015 Jul 22;7(1):50. doi: 10.1186/s13195-015-0135-0. eCollection 2015. — View Citation
McDade E, Bateman RJ. Stop Alzheimer's before it starts. Nature. 2017 Jul 12;547(7662):153-155. doi: 10.1038/547153a. No abstract available. — View Citation
McDade E, Wang G, Gordon BA, Hassenstab J, Benzinger TLS, Buckles V, Fagan AM, Holtzman DM, Cairns NJ, Goate AM, Marcus DS, Morris JC, Paumier K, Xiong C, Allegri R, Berman SB, Klunk W, Noble J, Ringman J, Ghetti B, Farlow M, Sperling RA, Chhatwal J, Salloway S, Graff-Radford NR, Schofield PR, Masters C, Rossor MN, Fox NC, Levin J, Jucker M, Bateman RJ; Dominantly Inherited Alzheimer Network. Longitudinal cognitive and biomarker changes in dominantly inherited Alzheimer disease. Neurology. 2018 Oct 2;91(14):e1295-e1306. doi: 10.1212/WNL.0000000000006277. Epub 2018 Sep 14. — View Citation
Mills SM, Mallmann J, Santacruz AM, Fuqua A, Carril M, Aisen PS, Althage MC, Belyew S, Benzinger TL, Brooks WS, Buckles VD, Cairns NJ, Clifford D, Danek A, Fagan AM, Farlow M, Fox N, Ghetti B, Goate AM, Heinrichs D, Hornbeck R, Jack C, Jucker M, Klunk WE, Marcus DS, Martins RN, Masters CM, Mayeux R, McDade E, Morris JC, Oliver A, Ringman JM, Rossor MN, Salloway S, Schofield PR, Snider J, Snyder P, Sperling RA, Stewart C, Thomas RG, Xiong C, Bateman RJ. Preclinical trials in autosomal dominant AD: implementation of the DIAN-TU trial. Rev Neurol (Paris). 2013 Oct;169(10):737-43. doi: 10.1016/j.neurol.2013.07.017. Epub 2013 Sep 6. — View Citation
Ryman DC, Acosta-Baena N, Aisen PS, Bird T, Danek A, Fox NC, Goate A, Frommelt P, Ghetti B, Langbaum JB, Lopera F, Martins R, Masters CL, Mayeux RP, McDade E, Moreno S, Reiman EM, Ringman JM, Salloway S, Schofield PR, Sperling R, Tariot PN, Xiong C, Morris JC, Bateman RJ; Dominantly Inherited Alzheimer Network. Symptom onset in autosomal dominant Alzheimer disease: a systematic review and meta-analysis. Neurology. 2014 Jul 15;83(3):253-60. doi: 10.1212/WNL.0000000000000596. Epub 2014 Jun 13. — View Citation
Wang G, Berry S, Xiong C, Hassenstab J, Quintana M, McDade EM, Delmar P, Vestrucci M, Sethuraman G, Bateman RJ; Dominantly Inherited Alzheimer Network Trials Unit. A novel cognitive disease progression model for clinical trials in autosomal-dominant Alzheimer's disease. Stat Med. 2018 Sep 20;37(21):3047-3055. doi: 10.1002/sim.7811. Epub 2018 May 14. — View Citation
Weng H, Bateman R, Morris JC, Xiong C. Validity and power of minimization algorithm in longitudinal analysis of clinical trials. Biostat Epidemiol. 2017;1(1):59-77. doi: 10.1080/24709360.2017.1331822. Epub 2017 Jun 13. — View Citation
Weninger S, Carrillo MC, Dunn B, Aisen PS, Bateman RJ, Kotz JD, Langbaum JB, Mills SL, Reiman EM, Sperling R, Santacruz AM, Tariot PN, Welsh-Bohmer KA. Collaboration for Alzheimer's Prevention: Principles to guide data and sample sharing in preclinical Alzheimer's disease trials. Alzheimers Dement. 2016 May;12(5):631-2. doi: 10.1016/j.jalz.2016.04.001. No abstract available. — View Citation
* Note: There are 11 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Change in amyloid load as measured by [11C]PiB-PET composite standardized uptake value ration (C-SUVR) | The composite PiB partial volume corrected standardized uptake value ratio is used as the biomarker endpoint for amyloid deposition. Corresponding analyses based on conversion of SUVR to centiloid will be performed by Washington University. | Week 0 and Weeks 48, 104, and 156 | |
Secondary | Annual Rate of change in Clinical Dementia Rating (CDR) Sum of Boxes | Evaluate the efficacy of gantenerumab in reducing disease progression as assessed in the CDR Sum of Boxes. Minimum score 0; maximum score 18. Higher score indicates worse performance. | Week 0 and Weeks 48, 104, and 156 | |
Secondary | Annual Rate of change in Clinical Dementia Rating (CDR) Global | Evaluate the efficacy of gantenerumab in reducing disease progression as assessed in the CDR Global. Minimum score 0; maximum score 3. Higher score indicates worse performance. | Week 0 and Weeks 48, 104, and 156 | |
Secondary | Annual Rate of change in Functional Assessment Scale (FAS) | Evaluate the efficacy of gantenerumab in reducing disease progression as assessed in the Functional Assessment Scale (FAS). Higher score indicates worse performance. | Week 0 and Weeks 48, 104, and 156 | |
Secondary | Annual Rate of change in Mini-Mental State Examination (MMSE) | Evaluate the efficacy of gantenerumab in reducing disease progression as assessed in the Mini-Mental State Examination (MMSE). Minimum score 0; maximum score 30. Lower score indicates worse performance. | Week 0 and Weeks 48, 104, and 156 | |
Secondary | Annual Rate of change in Tau PET Binding Partial Volume Corrected Standardized Uptake Value Ratio (Tau PET SUVR) | Evaluate the efficacy of gantenerumab in reducing disease progression as assessed in the Tau PET Binding Partial Volume Corrected Standardized Uptake Value Ratio (Tau PET SUVR) | Week 0 and Weeks 48, 104, and 156 | |
Secondary | Annual Rate of change in Cerebrospinal Fluid (CSF) phosphorylated Tau (pTau)-181 | Evaluate the efficacy of gantenerumab in reducing disease progression as assessed in the Cerebrospinal Fluid (CSF) phosphorylated Tau (pTau)-181 | Week 0 and Weeks 48, 104, and 156 | |
Secondary | Annual Rate of change in Neurofilament Light chain (NfL) in CSF (CSF NfL) | Evaluate the efficacy of gantenerumab in reducing disease progression as assessed in the Neurofilament Light chain (NfL) in CSF (CSF NfL) | Week 0 and Weeks 48, 104, and 156 | |
Secondary | Annual Rate of change in Cerebrospinal Fluid (CSF) Amyloid Beta1-42/40 | Evaluate the efficacy of gantenerumab in reducing disease progression as assessed in CSF Amyloid Beta1-42/40 | Week 0 and Weeks 48, 104, and 156 | |
Secondary | Annual Rate of change in DIAN-TU Open Label Extension Cognitive Composite | Evaluate the efficacy of gantenerumab in reducing disease progression as assessed in the DIAN-TU OLE Cognitive Composite. The Cognitive Composite is calculated using the WMS-R Digit Span Backward Recall (Minimum score 0; Maximum score 7. Lower indicates worse performance.), the Category Fluency (Animals) value (Minimum score 0; Maximum score Unlimited. Lower score indicates worse performance.), the Wechsler Adult Intelligence Scale Digit Symbol Substitution test (Minimum score 0; Maximum score 93. Lower score indicates worse performance.) , and the Mini Mental State Examination (Minimum score 0; Maximum score 30. Lower score indicates worse performance). | Week 0 and Weeks 48, 104, and 156 |
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