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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06647498




Registration number
NCT06647498
Ethics application status
Date submitted
15/10/2024
Date registered
17/10/2024
Date last updated
1/04/2025

Titles & IDs
Public title
A Study of a Potential Disease Modifying Treatment in Individuals at Risk for or With a Type of Early Onset AD Caused by a Genetic Mutation
Scientific title
A Phase II/III Multicenter Randomized, Double-Blind, Placebo-Controlled, Two-Stage Adaptive Design, Platform Trial of Investigational Treatments for Primary Prevention of Disease Progression in Dominantly Inherited Alzheimer's Disease
Secondary ID [1] 0 0
5U01AG059798
Secondary ID [2] 0 0
DIAN-TU-002 (REM)
Universal Trial Number (UTN)
Trial acronym
DIAN-TU-002
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 - Remternetug
Treatment: Drugs - Matching Placebo (Remternetug)

Experimental: Stage 1: Remternetug - Active Remternetug- blinded

Placebo comparator: Stage 1: Matching placebo (Remternetug) - Matching placebo

Active comparator: Stage 2: Remternetug Open Label - Open label will start after last dose of Stage 1


Treatment: Drugs: Remternetug
Administered subcutaneously every 12 weeks

Treatment: Drugs: Matching Placebo (Remternetug)
Administered as subcutaneous injection of placebo every 12 weeks
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Stage 1: Change in amyloid load as measured by centiloid (CL) [11C]PiB-PET as biomarker endpoint for DIAN-TU-002 remternetug arm
Timepoint [1] 0 0
Baseline and Week 192
Secondary outcome [1] 0 0
Stage 2: Odds ratio between the drug-treated and control groups of being in the lower biomarker disease progression stage based on two-stage modeling of 6 biomarkers.
Timepoint [1] 0 0
Weeks 0, 48, 96, 144, and 192
Secondary outcome [2] 0 0
Stage 1: The proportion of participants who are amyloid positive (CL level = 16.3) at the end of Stage 1
Timepoint [2] 0 0
Baseline and Week 104
Secondary outcome [3] 0 0
Stage 1: Change in CSF pTau217/Tau217 ratio
Timepoint [3] 0 0
Baseline and Week 104
Secondary outcome [4] 0 0
Stage 1: Change in CSF pTau231/Tau231 ratio
Timepoint [4] 0 0
Baseline and week 104
Secondary outcome [5] 0 0
Stage 1: Change in CSF 3-repeat isoform of MTBR (MTBR-3R)
Timepoint [5] 0 0
Baseline and week 104
Secondary outcome [6] 0 0
Stage 2: Change in CSF pTau217/Tau217 ratio CSF pTau231/Tau231 ratio, and CSF MTBR-3R
Timepoint [6] 0 0
Weeks 0, 48, 96, 144, and 192
Secondary outcome [7] 0 0
Stage 2: Change in Cognitive Composite Score
Timepoint [7] 0 0
Weeks 0, 48, 96, 144, and 192

Eligibility
Key inclusion criteria
1. Provide written informed consent, signed, and dated by the participant and study partner, or by the participant's legally authorized representative if applicable, according to local regulations for the ICF and, if applicable, country specific ICFs.
2. Participant is at least 18 years old.
3. People of childbearing potential

1. Must have a negative serum pregnancy test at screening (V1)
2. Must agree not to try to become pregnant during the study until 5 half-lives after the last dose of any study drug.
3. Must agree not to breastfeed from the time of signed ICF until 5 half-lives after the last dose of any study drug.
4. If partner is not sterilized, must agree to use highly effective contraceptive measures from screening (V1) until 5 half lives after last dose of any study drug
4. Mutation Status:

1. Participant is a carrier of a mutation in an APP, PSEN1, or PSEN2 gene that is associated with DIAD or does not know their mutation status and there is a mutation in their family pedigree that puts them at a direct risk of inheriting the known mutation;
2. Participant is -25 to -11 years from predicted age of cognitive symptom onset based on their mutation type or family pedigree Note: If the at-risk parent is deemed a non-carrier through confirmed genetic testing at any time during the study, the participant will be withdrawn.
5. Cognitive status of participant is normal (CDR-SB 0).
6. Fluency in DIAN-TU trial approved language and evidence of adequate premorbid intellectual functioning. Participants must be fluent in languages for which cognitive and clinical measures have been translated and validated for use in the DIAN-TU. Fluency is generally defined as daily or frequent functional use of a language generally from birth or a young age. In cultures where multiple languages are spoken or for participants who are multilingual, determination as to whether a participant's level of fluency in languages for which clinical and cognitive measures are available meets qualification for the study should be made by the site PI.
7. Participant has adequate visual and auditory abilities to perform all aspects of the cognitive and clinical assessments.
8. Participant is receiving stable doses of medication(s) for the treatment of non-excluded medical condition(s) for at least 30 days prior to baseline visit (V2) except for medications taken for episodic conditions (e.g., migraine abortive therapy, antibiotics, and other medications for upper respiratory and gastrointestinal ailments).
9. Participant has a study partner who in the PI's judgment can provide accurate information as to the participant's cognitive and functional abilities, who agrees to provide information at the study visits that require study partner input for scale completion, and who signs the necessary ICF, if applicable.
10. The participant agrees not to donate blood or blood products for transfusion from the time of Screening (V1) for a study drug arm, for the duration of the study, and for 5 half lives after the final dose of study drug.
11. In the opinion of the PI, the participant will be compliant and have a high probability of completing the study.
12. The participant is able and willing to complete all study-related testing, evaluations, and procedures.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Significant neurologic disease (other than AD) or psychiatric disease that may currently or during the study affect cognition or the participant's ability to complete the study. This would include disorders such as: recent or severe head trauma causing cognitive change, seizure disorder, neurodegenerative disease other than DIAD, hydrocephalus, cerebral/spinal hematoma, inflammatory disease, CNS infection (e.g., encephalitis or meningitis), neoplasm, toxic exposure, metabolic disorder (including hypoxic or hypoglycemic episodes) or endocrine disorder; psychiatric disorders such as schizophrenia, schizoaffective disorder, bipolar disorder or major depression, or any other psychiatric condition/disorder which could significantly interfere with the participant's cooperative participation (e.g., prominent anxiety, agitation or behavioral problems). Disorders that are controlled medically or remote history of these disorders (e.g., history of febrile seizures in childhood) that are not likely to interfere with cognitive function and compliance with study procedures are not exclusionary.
2. At high risk for suicide, e.g., significant suicidal ideation or attempt within last 12 months, current major depression (as defined in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [DSM-V]), or increased suicide risk based on screening Columbia Suicide Severity Rating Scale (C-SSRS). Current stable mild depression or current use of antidepressant medications are not exclusionary.
3. History of clinically evident stroke or history of clinically important carotid or vertebrobasilar stenosis, plaque, or other prominent risk factor for stroke or cerebral hemorrhage (including atrial fibrillation and anticoagulation, documented transient ischemic attack [TIA] in the last 12 months) that may be interfering with cognition or is likely to impact with the participant's ability to complete the study. Low dose aspirin (= 325 mg daily) is not exclusionary.
4. Alcohol or substance use sufficient to meet DSM-V criteria currently or within the past year.
5. History of or Baseline (V2) visit brain MRI scan indicative of any other significant abnormality, definite microhemorrhages, evidence of a cerebral contusion, encephalomalacia, or aneurysms. Minor or clinically insignificant imaging findings are not exclusionary.
6. 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.
7. Cardiovascular complications such as uncontrolled hypertension, history of myocardial infarcts, heart failure, atrial fibrillation, long QT interval on ECG likely to interfere with participation in or analysis of the trial in the opinion of the investigator
8. Hepatic or renal abnormalities that in the opinion of the investigator would interfere with participation in or analysis of the trial.
9. History of Human Immunodeficiency Virus (HIV) infection, history of Hepatitis B infection within the past year, history of Hepatitis C infection which has not been adequately treated, history of spirochete infection (e.g., syphilis, Lyme) of the CNS or history of other infection with high risk for interfering with participation or interpretation of the study in the opinion of the investigator.
10. History of clinically significant multiple or severe drug allergies, significant atopy, or severe post-treatment hypersensitivity reactions (including but not limited to erythema multiforme major, linear IgA dermatosis, toxic epidermal necrolysis, and/or exfoliative dermatitis) or sensitivity to study-drug specific PET imaging agents with a high risk for interfering with participation or interpretation of the study in the opinion of the investigator.
11. Treatment with immunosuppressive medications (e.g., systemic corticosteroids) within 90 days prior to Baseline (V2) visit (topical and nasal corticosteroids and inhaled corticosteroids for asthma are permitted) or chemotherapeutic agents for malignancy within the last 3 years.
12. Current clinically significant abnormalities of thyroid function, or clinically significant deficiency in vitamin B12. Vitamin B12 less than the lower limits of normal with normal methylmalonic acid (MMA)/homocysteine is not deemed clinically significant, therefore not exclusionary.
13. Unstable or poorly controlled diabetes which the investigator believes may interfere with participation in or analysis of the study protocol. Participants may be rescreened after 3 months to allow optimization of diabetic control
14. Morbid obesity with significant comorbidities or that would preclude MRI imaging.
15. Current use of anticoagulants (e.g., warfarin, dabigatran, rivaroxaban, or apixaban). Daily use of low dose (< 325 mg) aspirin is not exclusionary.
16. Have been exposed to a monoclonal antibody targeting Aß peptide within the past 6 months or 5 half-lives from screening, whichever is longer.
17. Received any other investigational pharmacological treatment within 3 months of Screening or 5 half-lives, whichever is longer.

Note: Use of approved treatments for AD and other medications may be permitted in this study.
18. Lack of sufficient venous access.
19. Clinically relevant abnormalities in hematology, coagulation, or clinical chemistry.
20. History of cancer that the investigator believes has high risk of recurrence and impacting study participation or analysis.
21. Any other medical condition that could be expected to progress, recur, or change to such an extent that it could bias the assessment of the clinical or mental status of the participant to a significant degree or put the participant at special risk.
22. Currently, or within the last month prior to screening, participated in a clinical study, including a nonpharmacological study, without prior approval.
23. Participants with the "Dutch" APP E693Q mutation.
24. Unable to complete baseline visit (V2) procedures with appropriate cognitive and clinical scores for eligibility
25. A centrally read MRI demonstrating presence of ARIA-E, > 4 cerebral microhemorrhages, any superficial siderosis, any macrohemorrhage, or severe white matter disease at screening.
26. Exposure to lecanemab, donanemab, or other investigational amyloid lowering agents within the past 6 months or five half-lives from screening, whichever is longer.

Note: Use of approved treatments for AD and other medications may be permitted.
27. Investigator site personnel directly affiliated with this trial and/or their immediate families, defined as a spouse, parent, child, or sibling, whether biological or legally adopted
28. Lilly employees or employees of a third-party organization (TPO) involved in this study that requires exclusion of their employees or have study partners who are Lilly employees or are employees of TPOs involved in this study that require exclusion of their employees

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/11/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/08/2034
Actual
Sample size
Target
280
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Neuroscience Research Australia - Randwick
Recruitment hospital [2] 0 0
Mental Health Research Institute - Melbourne
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
3010 - Melbourne
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
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Rhode Island
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
Argentina
State/province [13] 0 0
Ciudad Autonoma de Buenos Aire
Country [14] 0 0
Canada
State/province [14] 0 0
British Columbia
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
Canada
State/province [17] 0 0
Québec
Country [18] 0 0
Colombia
State/province [18] 0 0
Medellín
Country [19] 0 0
France
State/province [19] 0 0
Haute Garonne
Country [20] 0 0
France
State/province [20] 0 0
Nord
Country [21] 0 0
France
State/province [21] 0 0
Paris
Country [22] 0 0
France
State/province [22] 0 0
Rhone
Country [23] 0 0
France
State/province [23] 0 0
Seine Maritime
Country [24] 0 0
Germany
State/province [24] 0 0
Baden Wuerttemberg
Country [25] 0 0
Germany
State/province [25] 0 0
Bayern
Country [26] 0 0
Ireland
State/province [26] 0 0
Dublin
Country [27] 0 0
Italy
State/province [27] 0 0
Brescia
Country [28] 0 0
Italy
State/province [28] 0 0
Firenze
Country [29] 0 0
Mexico
State/province [29] 0 0
Distrito Federal
Country [30] 0 0
Netherlands
State/province [30] 0 0
Amsterdam
Country [31] 0 0
Puerto Rico
State/province [31] 0 0
San Juan
Country [32] 0 0
Spain
State/province [32] 0 0
Barcelona
Country [33] 0 0
United Kingdom
State/province [33] 0 0
Greater London

Funding & Sponsors
Primary sponsor type
Other
Name
Washington University School of Medicine
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Alzheimer's Association
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Eli Lilly and Company
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
Other collaborator category [4] 0 0
Other
Name [4] 0 0
GHR Foundation
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Private Donors
Address [5] 0 0
Country [5] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Eric M McDade, DO
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
Jamie Bartzel
Address 0 0
Country 0 0
Phone 0 0
844-DIANEXR (342-6397)
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT06647498