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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06424236




Registration number
NCT06424236
Ethics application status
Date submitted
16/04/2024
Date registered
22/05/2024
Date last updated
22/05/2024

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
The Alzheimer's Association
Secondary ID [2] 0 0
DIAN-TU-001 (Gant OLE)
Universal Trial Number (UTN)
Trial acronym
DIAN-TU
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimers Disease 0 0
Dementia 0 0
Alzheimers Disease, Familial 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Gantenerumab

Experimental: Gantenerumab Open Label Extension - Gantenerumab: Subcutaneously every 4 weeks, at escalating doses


Treatment: Drugs: Gantenerumab
Open-label administered Subcutaneously every 4 weeks at escalating doses
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in amyloid load as measured by [11C]PiB-PET composite standardized uptake value ration (C-SUVR)
Timepoint [1] 0 0
Week 0 and Weeks 48, 104, and 156
Secondary outcome [1] 0 0
Annual Rate of change in Clinical Dementia Rating (CDR) Sum of Boxes
Timepoint [1] 0 0
Week 0 and Weeks 48, 104, and 156
Secondary outcome [2] 0 0
Annual Rate of change in Clinical Dementia Rating (CDR) Global
Timepoint [2] 0 0
Week 0 and Weeks 48, 104, and 156
Secondary outcome [3] 0 0
Annual Rate of change in Functional Assessment Scale (FAS)
Timepoint [3] 0 0
Week 0 and Weeks 48, 104, and 156
Secondary outcome [4] 0 0
Annual Rate of change in Mini-Mental State Examination (MMSE)
Timepoint [4] 0 0
Week 0 and Weeks 48, 104, and 156
Secondary outcome [5] 0 0
Annual Rate of change in Tau PET Binding Partial Volume Corrected Standardized Uptake Value Ratio (Tau PET SUVR)
Timepoint [5] 0 0
Week 0 and Weeks 48, 104, and 156
Secondary outcome [6] 0 0
Annual Rate of change in Cerebrospinal Fluid (CSF) phosphorylated Tau (pTau)-181
Timepoint [6] 0 0
Week 0 and Weeks 48, 104, and 156
Secondary outcome [7] 0 0
Annual Rate of change in Neurofilament Light chain (NfL) in CSF (CSF NfL)
Timepoint [7] 0 0
Week 0 and Weeks 48, 104, and 156
Secondary outcome [8] 0 0
Annual Rate of change in Cerebrospinal Fluid (CSF) Amyloid Beta1-42/40
Timepoint [8] 0 0
Week 0 and Weeks 48, 104, and 156
Secondary outcome [9] 0 0
Annual Rate of change in DIAN-TU Open Label Extension Cognitive Composite
Timepoint [9] 0 0
Week 0 and Weeks 48, 104, and 156

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2/Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/06/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
13/11/2023
Sample size
Target
Accrual to date
Final
73
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Neuroscience Research Australia - Randwick
Recruitment hospital [2] 0 0
Mental Health Research Institute - Melbourne
Recruitment hospital [3] 0 0
The McCuster Foundation of Alzheimer's Disease Research - Nedlands
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
3010 - Melbourne
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Rhode Island
Country [9] 0 0
United States of America
State/province [9] 0 0
Washington
Country [10] 0 0
Canada
State/province [10] 0 0
British Columbia
Country [11] 0 0
France
State/province [11] 0 0
Haute Garonne
Country [12] 0 0
France
State/province [12] 0 0
Nord
Country [13] 0 0
France
State/province [13] 0 0
Paris
Country [14] 0 0
France
State/province [14] 0 0
Rhone
Country [15] 0 0
France
State/province [15] 0 0
Seine Maritime
Country [16] 0 0
Ireland
State/province [16] 0 0
Dublin
Country [17] 0 0
Puerto Rico
State/province [17] 0 0
San Juan
Country [18] 0 0
Spain
State/province [18] 0 0
Barcelona
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Greater London

Funding & Sponsors
Primary sponsor type
Other
Name
Washington University School of Medicine
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Hoffmann-La Roche
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Alzheimer's Association
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Government body
Name [3] 0 0
National Institute on Aging (NIA)
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT06424236
Trial related presentations / publications
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Randall J Bateman, MD
Address 0 0
Washington University School of Medicine
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT06424236