A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset AD Caused by a Genetic Mutation

NCT05552157 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: DIAN-TU-002 (Master)5U01AG059798
• Study Type: interventional
• Target: 280
• Locations: 14 countries
• Sites: 35

Brief Summary

The purpose is to evaluate the biomarker effect, safety, and tolerability of investigational study drugs in participants who are known to have an Alzheimer's disease (AD)-causing mutation. Stage 1 will determine if treatment with the study drug prevents or slows the rate of amyloid beta (Aβ) pathological disease accumulation demonstrated by Aβ positron emission tomography (PET) imaging. Stage 2 will evaluate the effect of early Aβ plaque reduction/prevention on disease progression by assessing downstream non-Aβ biomarkers of AD (e.g., CSF total tau, p-tau, NfL) compared to an external control group from the DIAN-OBS natural history study and the DIAN-TU-001 placebo-treated participants.

Conditions

Alzheimers Disease; Dementia; Alzheimers Disease, Familial

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

Outcome Measures

Primary Outcomes (2)

• Stage 1: Evaluate the ability of study drug to prevent or slow the rate of Aβ accumulation compared with placebo in participants with mutations that cause DIAD

  Defined in each drug-specific appendix; will be an assessment of biomarkers of early-stage disease (e.g., amyloid PET, soluble amyloid, soluble phospho-tau) compared with baseline in each treatment group

  Baseline and Week 208

• Stage 2: Evaluate the effect of anti-amyloid treatment on downstream biomarkers of AD

  If applicable, will be defined in each drug-specific appendix, and will be an assessment of the change in progression of biomarkers representing tau, neurodegenerative, and inflammatory pathobiological events in the disease cascade for temporally different periods of the pre-symptomatic phases of the disease.

  Stage 2 Week 208

Study Arms (3)

Stage 1: Remternetug

EXPERIMENTAL

Active Remternetug- blinded

Drug: Remternetug (SC)

Stage 1: Matching Placebo (Remternetug)

PLACEBO COMPARATOR

Matching placebo

Drug: Matching Placebo (Remternetug)

Stage 2: Remternetug Open Label

ACTIVE COMPARATOR

Open label will start after last dose of Stage 1

Drug: Remternetug (SC)

Interventions

Remternetug (SC) DRUG

Administered subcutaneously every 12 weeks

Stage 1: Remternetug; Stage 2: Remternetug Open Label

Matching Placebo (Remternetug) DRUG

Administered as subcutaneous injection of placebo every 12 weeks

Stage 1: Matching Placebo (Remternetug)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 during the study until 5 half-lives after the last dose of any study drug.
• Must agree not to breastfeed from the time of signed ICF until 5 half-lives after the last dose of any study drug.
• If partner is not sterilized, must agree to use highly effective contraceptive measuresfrom screening (V1) until 5 half lives after last dose of any study drug
• 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.
• Participant has adequate visual and auditory abilities to perform all aspects of the cognitive and clinical assessments.
• 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).
• The 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.

You may not qualify if:

• Alcohol or substance use sufficient to meet DSM-V criteria currently or within the past year.
• 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 or 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.
• 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.
• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Alzheimer's Association: collaborator
• Eli Lilly and Company: collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (35)

University of Alabama in Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

University of California San Diego Medical Center

La Jolla, California, 92037, United States

RECRUITING

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

RECRUITING

Emory University

Atlanta, Georgia, 30329, United States

RECRUITING

Advocate Lutheran General Hospital

Park Ridge, Illinois, 60068, United States

RECRUITING

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

RECRUITING

Washington University in St. Louis

St Louis, Missouri, 63110, United States

RECRUITING

New York University Medical Center

New York, New York, 10016, United States

RECRUITING

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Butler Hospital

Providence, Rhode Island, 02096, United States

RECRUITING

Kerwin Research and Memory Center

Dallas, Texas, 75231, United States

RECRUITING

University of Washington

Seattle, Washington, 98195, United States

RECRUITING

Instituto de Investigaciones Neurologicas Raul Carrea, FLENI

Ciudad Autonoma de Buenos Aire, C1428AQK, Argentina

RECRUITING

Neuroscience Research Australia

Randwick, New South Wales, 2031, Australia

RECRUITING

Alzheimer's Research Australia

Melbourne, Victoria, 3010, Australia

NOT YET RECRUITING

UBC Hospital

Vancouver, British Columbia, V6T 2B5, Canada

RECRUITING

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

McGill Center for Studies in Aging

Verdun, Quebec, H4H 1R3, Canada

NOT YET RECRUITING

CHU de Quebec - Hôpital de l' Enfant Jésus

Québec, G1J 1Z4, Canada

RECRUITING

Grupo de Neurociencias Sede de la Universidad de Antioquia

Medellín, Colombia

RECRUITING

CHU de Toulouse - Hôpital Purpan

Toulouse, Haute Garonne, 31059, France

NOT YET RECRUITING

Hopital Roger Salengro - CHU Lille

Lille, Nord, 59037, France

NOT YET RECRUITING

Groupe Hospitalier Pitie-Salpetriere

Paris, Paris, 69677, France

NOT YET RECRUITING

Hopital Neurologique Pierre Wertheimer

Bron, Rhone, 69677, France

NOT YET RECRUITING

CHU de Rouen - Hôpital Charles Nicolle

Rouen, Seine Maritime, 76031, France

NOT YET RECRUITING

Universitaetsklinikum Tubingen

Tübingen, Baden-Wurttemberg, 72076, Germany

NOT YET RECRUITING

LMU-Campus Grosshadern

Munich, Bavaria, 81377, Germany

NOT YET RECRUITING

IRCCS Centro San Giovanni di Dio Fatebenefratelli

Brescia, 25125, Italy

NOT YET RECRUITING

Azienda Ospedaliera Universitaria Careggi

Florence, 50134, Italy

NOT YET RECRUITING

Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez

Mexico City, Mexico City, 14269, Mexico

NOT YET RECRUITING

Brain Research Center

Amsterdam, 1081 GM, Netherlands

NOT YET RECRUITING

New Zealand Brain Research Institute

Christchurch, 8011, New Zealand

NOT YET RECRUITING

University of Puerto Rico, School of Medicine

San Juan, 00936, Puerto Rico

RECRUITING

Hospital Clínic I Provincial de Barcelona

Barcelona, 8036, Spain

NOT YET RECRUITING

The National Hospital for Neurology and Neurosurgery

London, Greater London, WC1B 3BG, United Kingdom

RECRUITING

Related Publications (13)

• 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.

  PMID: 30217935 BACKGROUND

• 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.

  PMID: 24016464 BACKGROUND

• 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.

  PMID: 22784036 BACKGROUND

• 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.

  PMID: 30006100 BACKGROUND

• 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.

  PMID: 23217740 BACKGROUND

• 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.

  PMID: 25012224 BACKGROUND

• 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.

  PMID: 29435570 BACKGROUND

• 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.

  PMID: 29761523 BACKGROUND

• 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.

  PMID: 27157073 BACKGROUND

• 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.

  PMID: 26203303 BACKGROUND

• 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.

  PMID: 28703214 BACKGROUND

• 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.

  PMID: 24928124 BACKGROUND

• 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.

  PMID: 29250611 BACKGROUND

Related Links

• Expanded registry

MeSH Terms

Conditions

Alzheimer Disease; Dementia

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Eric M McDade, DO

  Washington University School of Medicine

  STUDY DIRECTOR

Central Study Contacts

Jamie Bartzel

CONTACT

844-DIANEXR (342-6397); dianexr@wustl.edu

Ellen Ziegemeier

CONTACT

844-DIANEXR (342-6397); dianexr@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Stage 1: Interventional/matching placebo; Stage 2: Open Label Potential for future interventions to be added

Study Record Dates

• First Submitted: September 19, 2022
• First Posted: September 23, 2022
• Study Start: November 22, 2024
• Primary Completion (Estimated): March 30, 2034
• Study Completion (Estimated): August 30, 2034
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

AR (1); PR (1); NZ (1); CO (1); ME (1); ES (1); DE (2); FR (5); IT (2); CA (4); AU (2); GB (1); NL (1); US (12)