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Alzheimers DiseasePhase 2/3DIAN-TU-002NCT06647498

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

A Phase 2/3 study testing Remternetug in people with Alzheimers Disease and Dementia, run by Washington University School of Medicine at 37 sites in 15 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

The purpose of this research study is to test the study drug, referred to as remternetug, to determine its effectiveness for the study treatment of asymptomatic (at risk) Alzheimer disease in individuals with AD-causing mutations. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
What is being tested?
Remternetug
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
280 participants
Where
37 sitesin 15 countries
Study dates
22 Nov 2024to Aug 2034
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.
  • Participant is at least 18 years old.
  • People of childbearing potential
  • Must have a negative serum pregnancy test at screening (V1)
  • Must agree not to try to become pregnant from the time of signed ICF until twenty (20) weeks after the last dose of any study drug.
  • Must agree not to breastfeed from the time of signed ICF until twenty (20) weeks after the last dose of any study drug.
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  • If partner is not sterilized, must agree to use highly effective contraceptive measures, methods that can achieve a failure rate of less than 1% per year when used consistently and correctly from screening (V1) until twenty (20) weeks after last dose of any study drug.
  • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal ii. progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable iii. intra-uterine device (IUD) iv. intrauterine hormone-releasing systems (IUS) v. bilateral tubal occlusion vi. vasectomized partner (only when this is the only partner) vii. true sexual abstinence when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods], declaration of abstinence for the duration of exposure to IMP, and withdrawal are not acceptable methods of contraception)
  • Mutation Status:
  • 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;
  • 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.
  • Cognitive status of participant is normal (CDR-SB 0).
  • 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.
  • Adequate visual and auditory abilities to perform all aspects of the cognitive and clinical assessments.
  • 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) with the exceptions of medications taken for episodic conditions (e.g., migraine abortive therapy, antibiotics, and other medications for upper respiratory and gastrointestinal ailments).
  • 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.
  • 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.
  • In the opinion of the PI, the participant will be compliant and have a high probability of completing the study.
  • Willing to complete all study-related testing, evaluations, and procedures.

Who cannot join

  • 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.
  • 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.
  • 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.
  • Alcohol or substance use sufficient to meet DSM-V criteria currently or within the past year.
  • 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.
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  • 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.
  • 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
  • Hepatic or renal abnormalities that in the opinion of the investigator would interfere with participation in or analysis of the trial.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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
  • Morbid obesity with significant comorbidities or that would preclude MRI imaging.
  • Current use of anticoagulants (e.g., warfarin, dabigatran, rivaroxaban, or apixaban). Daily use of low dose (< 325 mg) aspirin is not exclusionary.
  • Have been exposed to a monoclonal antibody targeting Aβ peptide within the past 6 months or 5 half-lives from screening, whichever is longer.
  • 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.
  • Lack of sufficient venous access.
  • Clinically relevant abnormalities in hematology, coagulation, or clinical chemistry.
  • History of cancer that the investigator believes has high risk of recurrence and impacting study participation or analysis.
  • 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.
  • Currently, or within the last month prior to screening, participated in a clinical study, including a nonpharmacological study, without prior approval.
  • Participants with the "Dutch" APP E693Q mutation.
  • Unable to complete baseline visit (V2) procedures with appropriate cognitive and clinical scores for eligibility
  • A centrally read MRI demonstrating presence of ARIA-E, > 4 cerebral microhemorrhages, any superficial siderosis, any macrohemorrhage, or severe white matter disease at screening.
  • Exposure to lecanemab, donanemab, or other investigational amyloid lowering agents within the past 6 months or five half-lives from screening, whichever is longer.
  • 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
  • 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

Trial locations and contacts

37 sites in 15 countries. Contact the study team or a site near you to ask about taking part.

Jamie Bartzel contact

844-DIANEXR (342-6397)

dianexr@wustl.edu

Ellen Ziegemeier contact

844-DIANEXR (342-6397)

dianexr@wustl.edu

37 sites in 15 countries

United States13 sites, 13 recruiting

  • Emory University

    Atlanta, Georgia, 30329

    James Lah

    Recruiting

  • University of Alabama in Birmingham

    Birmingham, Alabama, 35294

    Erik Roberson

    Recruiting

  • Kerwin Research and Memory Center

    Dallas, Texas, 75231

    Alka Khera, MD

    Recruiting

  • Indiana University School of Medicine

    Indianapolis, Indiana, 46202

    Jared Brosch

    Recruiting

  • University of California San Diego Medical Center

    La Jolla, California, 92037

    Doug Galasko

    Recruiting

  • University of Southern Califonria

    Los Angeles, California, 90089

    John Ringman, M.D.

    Not yet recruiting

  • Yale University School of Medicine

    New Haven, Connecticut, 06510

    Christopher Van Dyck

    Recruiting

  • New York University Medical Center

    New York, New York, 10016

    Thomas Wisniewski, MD

    Recruiting

  • Advocate Lutheran General Hospital

    Park Ridge, Illinois, 60068

    Darren Gitelman

    Recruiting

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

    Sarah Berman

    Recruiting

  • Butler Hospital

    Providence, Rhode Island, 02096

    Edward Denmead Huey

    Recruiting

  • University of Washington

    Seattle, Washington, 98195

    Suman Jayadev

    Recruiting

  • Washington University in St. Louis

    St Louis, Missouri, 63110

    Barbara Snider

    Recruiting

Other trials in United States

France5 sites, 5 recruiting

  • Hopital Neurologique Pierre Wertheimer

    Bron, Rhone, 69677

    Maité Formaglio

    Not yet recruiting

  • Hopital Roger Salengro - CHU Lille

    Lille, Nord, 59037

    Adeline Rollin-Sillaire

    Not yet recruiting

  • Groupe Hospitalier Pitie-Salpetriere

    Paris, Paris, 69677

    Nicolas Villian

    Not yet recruiting

  • CHU de Rouen - Hôpital Charles Nicolle

    Rouen, Seine Maritime, 76031

    David Wallon

    Not yet recruiting

  • CHU de Toulouse - Hôpital Purpan

    Toulouse, Haute Garonne, 31059

    Jérémie Pariente

    Not yet recruiting

Other trials in France

Canada4 sites, 4 recruiting

  • CHU de Quebec - Hôpital de l' Enfant Jésus

    Québec, G1J 1Z4

    Robert LaForce

    Recruiting

  • Sunnybrook Health Sciences Centre

    Toronto, Ontario, M4N 3M5

    Mario Masellis

    Recruiting

  • UBC Hospital

    Vancouver, British Columbia, V6T 2B5

    Robin Hsiung

    Recruiting

  • McGill Center for Studies in Aging

    Verdun, Quebec, H4H 1R3

    Paola Vitali

    Recruiting

Other trials in Canada

Australia2 sites, 2 recruiting

  • Alzheimer's Research Australia

    Melbourne, Victoria, 3010

    Colin Masters

    Recruiting

  • Neuroscience Research Australia

    Randwick, New South Wales, 2031

    Emma Devenney

    Recruiting

Other trials in Australia

Germany2 sites, 2 recruiting

  • LMU-Campus Grosshadern

    Munich, Bavaria, 81377

    Johannes Levin, M.D,

    Not yet recruiting

  • Universitaetsklinikum Tubingen

    Tübingen, Baden-Wurttemberg, 72076

    Cristoph Laske, M.D.

    Recruiting

Other trials in Germany

Italy2 sites, 2 recruiting

  • IRCCS Centro San Giovanni di Dio Fatebenefratelli

    Brescia, 25125

    Barbara Borroni

    Not yet recruiting

  • Azienda Ospedaliera Universitaria Careggi

    Florence, 50134

    Valentina Bessi, M.D.

    Not yet recruiting

Other trials in Italy

Argentina1 site, 1 recruiting

  • Instituto de Investigaciones Neurologicas Raul Carrea, FLENI

    Ciudad Autonoma de Buenos Aire, C1428AQK

    Ricardo Allegri

    Recruiting

Other trials in Argentina

Colombia1 site, 1 recruiting

  • Grupo de Neurociencias Sede de la Universidad de Antioquia

    Medellín

    David Fernando Aguillon Nino, M.D.

    Recruiting

Other trials in Colombia

Mexico1 site, 1 recruiting

  • Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez

    Mexico City, Mexico City, 14269

    Ana Luisa Sosa Ortiz, M.D.

    Not yet recruiting

Other trials in Mexico

Netherlands1 site, 1 recruiting

  • Brain Research Center

    Amsterdam, 1081 GM

    Jort Vijverberg, MD

    Not yet recruiting

Other trials in Netherlands

New Zealand1 site, 1 recruiting

  • New Zealand Brain Research Institute

    Christchurch, 8011

    Campbell Le Heron, M.D.

    Not yet recruiting

Other trials in New Zealand

Puerto Rico1 site, 1 recruiting

  • University of Puerto Rico, School of Medicine

    San Juan, 00936

    Ivonne Jimenez-Velazquez

    Recruiting

Other trials in Puerto Rico

South Korea1 site, 1 recruiting

  • Asan Medical Center

    Seoul

    Jae Sung Lim

    Not yet recruiting

Other trials in South Korea

Spain1 site, 1 recruiting

  • Hospital Clínic I Provincial de Barcelona

    Barcelona, 8036

    Raquel Sanchez Valle

    Recruiting

Other trials in Spain

United Kingdom1 site, 1 recruiting

  • The National Hospital for Neurology and Neurosurgery

    London, Greater London, WC1B 3BG

    Catherine Mummery

    Recruiting

Other trials in United Kingdom

About this study

Official 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

The purpose of this research study is to test the study drug, referred to as remternetug, to determine its effectiveness for the study treatment of asymptomatic (at risk) Alzheimer disease in individuals with AD-causing mutations. This study will also investigate the effects of remternetug on biomarkers (measures of the disease including brain scans, blood and spinal fluid tests), examine safety data to identify any potential benefits or risks, and examine how well participants can tolerate remternetug.

Stage 1 will determine if treatment with the study drug prevents or reverses amyloid beta (Aβ) accumulation compared with placebo in participants with dominantly inherited Alzheimer's disease (DIAD).

Stage 2 will evaluate the effect of early anti-amyloid treatment on downstream biomarkers of AD in treated participants compared to external control groups.

Read the detailed description

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by progressive decline in cognitive function and the ability to perform activities of daily living. The amyloid hypothesis of AD postulates that the accumulation of amyloid beta (Aβ) is an early and necessary event in the pathogenesis of AD. This hypothesis suggests that interventions that slow the accumulation of Aβ plaque in the brain or increase clearance of Aβ may be able to slow the progression of the AD clinical syndrome. AD occurs on a continuum from asymptomatic (preclinical) to mild cognitive impairment (MCI), and then to dementia in mild, moderate, and severe stages. Evidence from both genetic at-risk and age at-risk cohorts, such as in dominantly inherited AD (DIAD) suggests that the pathophysiological process of AD begins well more than a decade before the clinical stage now recognized as AD dementia, and that neurodegeneration is already apparent on MRI by the stage of mild cognitive impairment. Recent clinical trial data suggest that treating AD during the earlier stages could have the greatest potential benefit on the disease by slowing progression

The ability to identify individuals destined to develop Alzheimer's disease (AD) with a high degree of confidence provides a unique opportunity to assess the efficacy of therapies at asymptomatic and very early stages of dementia. Families with known disease-causing mutations are extremely rare and are geographically dispersed throughout the world.

Participants in this study will not yet have developed any clinical symptoms of AD; they will be "asymptomatic" carriers of mutations that cause DIAD and would be expected to perform normally on standard cognitive and functional testing. Further, most mutation carriers will have levels of AD-associated amyloid beta (Aβ) and non-Aβ biomarkers that are the same as non-carriers.

Amyloid beta is a protein that accumulates in the brain of people with AD. Although we do not understand exactly what causes AD, the abnormal accumulation of amyloid beta protein in the brain is thought to play an important role in the symptoms of AD. Recent research studies indicate that amyloid beta may start building up in the brain 15 years or more before the onset of memory loss.

Imaging and fluid biomarkers will be used to demonstrate that the treatment compounds have engaged their therapeutic targets. A set of cognitive measures designed to assess the very earliest and most subtle cognitive changes will be collected. The overall objectives of this study are to evaluate the biomarker effect, safety, and tolerability of investigational study drugs in participants who are known to have an AD-causing mutation.

The primary objective of Stage 1 is to determine if treatment with the study drug prevents or slows the rate of Aβ pathological disease accumulation demonstrated by Aβ PiB positron emission tomography (PET) imaging.

The primary objective of Stage 2 is to evaluate the effect of early anti-amyloid treatment on disease progression by assessing downstream non-Aβ biomarkers of AD (e.g., CSF total tau, NfL, MRI volume) compared to a control group from the DIAN Obs natural history study and the DIAN-TU-001 placebo-treated participants.

Remternetug is a monoclonal antibody. The mechanism of action of remternetug is to target and remove aggregated amyloid plaque, a key pathological hallmark of AD, via microglial-mediated clearance. Remternetug has demonstrated the ability to reduce brain amyloid plaque.

The remternetug arm is part of Master Protocol DIAN-TU-002 (NCT05552157)

Being tested
Remternetug, Matching Placebo (Remternetug)
Keywords
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
Medical subject headings
Alzheimer Disease, Dementia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RemternetugDrug

    Also called LY3372993

    Administered subcutaneously every 12 weeks

  • Matching Placebo (Remternetug)Drug

    Administered as subcutaneous injection of placebo every 12 weeks

Study groups in NCT06647498
Study groupRoleWhat they receive
Stage 1: RemternetugExperimentalActive Remternetug- blinded
Receives: Drug: Remternetug
Stage 1: Matching placebo (Remternetug)Placebo comparatorMatching placebo
Receives: Drug: Matching Placebo (Remternetug)
Stage 2: Remternetug Open LabelActive comparatorOpen label will start after last dose of Stage 1
Receives: Drug: Remternetug

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Stage 1: Change in amyloid load as measured by centiloid (CL) [11C]PiB-PET as biomarker endpoint for DIAN-TU-002 remternetug arm

    CL calculated using [11C] PiB PET non-partial volume corrected (regional spread function) standardized uptake value ratio cortical composite (PiB PET SUVR) is the primary outcome and change from baseline at 2 years is the primary endpoint.

    Measured: Baseline and Week 192

Secondary outcomes (7)

  1. 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.

    The key secondary efficacy endpoint for Stage 2 is the odds ratio between the treated group and the external control group (DIAN Obs and DIAN-TU-001 placebo) of being in the lower biomarker disease progression stage based on two-stage modeling of 6 biomarkers (CSF tau phosphorylated tau at residue 153 (pTau153)/Tau153 ratio, CSF pTau205/Tau205 ratio, CSF microtubule binding region of tau 243 amino acids long (MTBR-tau243), MRI hippocampal volume, CSF neurofilament light chain (NfL), and MRI precuneus thickness).

    Measured: Weeks 0, 48, 96, 144, and 192

  2. Stage 1: The proportion of participants who are amyloid positive (CL level ≥ 16.3) at the end of Stage 1

    For participants in the active treatment group, the amyloid positivity status is defined using the last available PiB-PET CL value during Stage 1: amyloid positive if CL>=16.3 and amyloid negative if CL<16.3. For participants in the placebo group, the amyloid positivity status: (i) is either defined using the last available PiB-PET CL value during Stage 1 (amyloid positive if CL>=16.3 and amyloid negative if CL<16.3)

    Measured: Baseline and Week 104

  3. Stage 1: Change in CSF pTau217/Tau217 ratio

    Measured: Baseline and Week 104

  4. Stage 1: Change in CSF pTau231/Tau231 ratio

    Measured: Baseline and week 104

  5. Stage 1: Change in CSF 3-repeat isoform of MTBR (MTBR-3R)

    Measured: Baseline and week 104

  6. Stage 2: Change in CSF pTau217/Tau217 ratio CSF pTau231/Tau231 ratio, and CSF MTBR-3R

    Measured: Weeks 0, 48, 96, 144, and 192

  7. Stage 2: Change in Cognitive Composite Score

    A cognitive composite derived as an average of these four tests: Memory Complaint Questionnaire (MAC-Q), Category Fluency (Animals), Buschke and Grober Free and Cued Selective Reminding Test - Immediate Recall (FCSRT-IR), Wechsler Adult Intelligence Scale - Revised (WAIS-R) Digit Symbol Substitution Test, and Mini-Mental State Examination (MMSE). Each of the four tests will be converted to a z-score using the mean (SD) of the baseline score in Stage 1 of both the treatment arm and the placebo arm, and then equally weighted to obtain the composite.

    Measured: Weeks 0, 48, 96, 144, and 192

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Oct 2024
  2. Study start22 Nov 2024
  3. Primary completionMar 2034 (estimated)
  4. Study completionAug 2034 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Stage 1: Interventional/matching placebo; Stage 2: Open Label
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
280 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06647498
Sponsor's protocol ID
DIAN-TU-002 (REM)
Other IDs
5U01AG059798
Acronym
DIAN-TU-002
Status last verified
Jul 2026
First submitted
15 Oct 2024
Last updated
27 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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 \[CAP REF\].

Publications

  • McDade E, Bateman RJ. Tau Positron Emission Tomography in Autosomal Dominant Alzheimer Disease: Small Windows, Big Picture. JAMA Neurol. 2018 May 1;75(5):536-538. doi: 10.1001/jamaneurol.2017.4026. No abstract available.

    PubMed 29435570

  • Fagan AM, Xiong C, Jasielec MS, Bateman RJ, Goate AM, Benzinger TL, Ghetti B, Martins RN, Masters CL, Mayeux R, Ringman JM, Rossor MN, Salloway S, Schofield PR, Sperling RA, Marcus D, Cairns NJ, Buckles VD, Ladenson JH, Morris JC, Holtzman DM; Dominantly Inherited Alzheimer Network. Longitudinal change in CSF biomarkers in autosomal-dominant Alzheimer's disease. Sci Transl Med. 2014 Mar 5;6(226):226ra30. doi: 10.1126/scitranslmed.3007901.

    PubMed 24598588

  • Fagan AM, Roe CM, Xiong C, Mintun MA, Morris JC, Holtzman DM. Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults. Arch Neurol. 2007 Mar;64(3):343-9. doi: 10.1001/archneur.64.3.noc60123. Epub 2007 Jan 8.

    PubMed 17210801

  • Demattos RB, Lu J, Tang Y, Racke MM, Delong CA, Tzaferis JA, Hole JT, Forster BM, McDonnell PC, Liu F, Kinley RD, Jordan WH, Hutton ML. A plaque-specific antibody clears existing beta-amyloid plaques in Alzheimer's disease mice. Neuron. 2012 Dec 6;76(5):908-20. doi: 10.1016/j.neuron.2012.10.029.

    PubMed 23217740

  • Young AL, Oxtoby NP, Daga P, Cash DM, Fox NC, Ourselin S, Schott JM, Alexander DC; Alzheimer's Disease Neuroimaging Initiative. A data-driven model of biomarker changes in sporadic Alzheimer's disease. Brain. 2014 Sep;137(Pt 9):2564-77. doi: 10.1093/brain/awu176. Epub 2014 Jul 9.

    PubMed 25012224

  • Sims JR, Zimmer JA, Evans CD, Lu M, Ardayfio P, Sparks J, Wessels AM, Shcherbinin S, Wang H, Monkul Nery ES, Collins EC, Solomon P, Salloway S, Apostolova LG, Hansson O, Ritchie C, Brooks DA, Mintun M, Skovronsky DM; TRAILBLAZER-ALZ 2 Investigators. Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA. 2023 Aug 8;330(6):512-527. doi: 10.1001/jama.2023.13239.

    PubMed 37459141

  • Oxtoby NP, Young AL, Cash DM, Benzinger TLS, Fagan AM, Morris JC, Bateman RJ, Fox NC, Schott JM, Alexander DC. Data-driven models of dominantly-inherited Alzheimer's disease progression. Brain. 2018 May 1;141(5):1529-1544. doi: 10.1093/brain/awy050.

    PubMed 29579160

  • Navitsky M, Joshi AD, Kennedy I, Klunk WE, Rowe CC, Wong DF, Pontecorvo MJ, Mintun MA, Devous MD Sr. Standardization of amyloid quantitation with florbetapir standardized uptake value ratios to the Centiloid scale. Alzheimers Dement. 2018 Dec;14(12):1565-1571. doi: 10.1016/j.jalz.2018.06.1353. Epub 2018 Jul 11.

    PubMed 30006100

  • Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science. 2002 Jul 19;297(5580):353-6. doi: 10.1126/science.1072994.

    PubMed 12130773

  • 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.

    PubMed 22784036

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Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Remternetug in people with Alzheimers Disease and Dementia, run by Washington University School of Medicine at 37 sites in 15 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 27 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 37 sites in United States, France, Canada, Australia, Germany and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Jamie Bartzel (844-DIANEXR (342-6397), dianexr@wustl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Stage 1: Change in amyloid load as measured by centiloid (CL) [11C]PiB-PET as biomarker endpoint for DIAN-TU-002 remternetug arm (time frame: Baseline and Week 192). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06647498, which also lists 16 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2026.

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