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Looking for participantsPhase2/Phase3

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

Sponsor: Washington University School of Medicine

NCT ID: NCT06647498

View on ClinicalTrials.gov ↗

At a glance

What the study gets you
Access to the study treatment being tested
Type of study
Interventional (receives a drug or procedure)
Time in hospital
In-person visits at study sites — visit count not specified by the sponsor
Drug or intervention
Remternetug (drug), Matching Placebo (Remternetug) (drug)
How long the study runs
Study runs about 117 months (dates as stated)
About the drug or intervention
Remternetug — drug: Administered subcutaneously every 12 weeks · Matching Placebo (Remternetug) — drug: Administered as subcutaneous injection of placebo every 12 weeks
Patient visit burden
Not specified by the sponsor

In plain English

This study looks at a potential disease-modifying treatment for people at risk of, or with, an early-onset form of Alzheimer's disease caused by an inherited genetic change (known as dominantly inherited Alzheimer's disease). It is for people who carry or may have inherited a change in the APP, PSEN1, or PSEN2 gene. The study is sponsored by Washington University School of Medicine.

Who can take part

  • You are at least 18 years old and can give written informed consent (you and a study partner, or a legal representative if needed)
  • You carry a change (mutation) in the APP, PSEN1, or PSEN2 gene linked to this inherited type of Alzheimer's, or you don't know your status but the change runs in your family and you are directly at risk of having it
  • You are estimated to be 11 to 25 years before the age at which your thinking and memory symptoms are predicted to start
  • Your thinking and memory are currently normal (a score of 0 on a test called the CDR-SB)
  • You speak a language fluently that the study's memory and thinking tests are available in
  • Your sight and hearing are good enough to do all the tests
  • Any regular medicines you take for other health conditions have been on a stable dose for at least 30 days before the baseline visit
  • You have a study partner (such as a family member or friend) who knows you well, agrees to attend visits and answer questions about your memory and daily abilities, and signs the consent form if needed
  • You agree not to donate blood from screening, during the study, and for 5 half-lives after the final dose of study drug
  • You are willing and likely to complete all study tests, checks and procedures
  • If you could become pregnant: a negative pregnancy test at screening, agreement not to try to become pregnant or breastfeed until 20 weeks after the last dose, and use of a highly effective contraceptive (for example an IUD, implant, or sterilised partner) unless your partner is sterilised

Who may not be able to

  • Significant brain (other than Alzheimer's) or mental health conditions that could affect your memory or ability to take part, such as severe head injury, seizures, other degenerative brain diseases, schizophrenia, bipolar disorder, or major depression
  • High risk of suicide, for example serious suicidal thoughts or an attempt in the last 12 months, or a high score on a suicide-risk screening questionnaire (stable mild depression or antidepressant use is allowed)
  • History of stroke, major narrowing of neck or brain arteries, or other strong risk factors for stroke or bleeding in the brain (including atrial fibrillation, blood thinners, or a TIA (transient ischaemic attack, sometimes called a mini-stroke) in the last 12 months)
  • Alcohol or drug use problems, currently or within the past year
  • A brain scan showing certain abnormalities, such as microbleeds, bruising, scarring, or aneurysms (minor findings are allowed)
  • Certain implanted metal devices (such as some pacemakers, aneurysm clips, artificial heart valves, or ear implants) or metal in the eyes, skin or body that would make MRI (magnetic resonance imaging) scans unsafe
  • Heart problems such as uncontrolled high blood pressure, past heart attack, heart failure, atrial fibrillation, or a long QT interval on a heart trace (ECG) that could interfere with the study
  • Liver or kidney problems that could interfere with the study
  • HIV infection, Hepatitis B in the past year, untreated Hepatitis C, or past syphilis or Lyme infection affecting the brain or spinal cord
  • Severe or multiple drug allergies, or serious skin reactions after treatment, or sensitivity to the PET (positron emission tomography) scanning substances used in this study
  • Taking medicines that suppress the immune system (for example steroid tablets) in the past 90 days (inhaled, nasal, or skin steroids are allowed), or chemotherapy in the past 3 years
  • Thyroid problems or low vitamin B12 that are clinically significant
  • Unstable or poorly controlled diabetes (you may be able to be re-screened after 3 months)
  • Severe obesity with significant other health problems, or that would prevent MRI scanning
  • Taking blood-thinning medicines such as warfarin, dabigatran, rivaroxaban, or apixaban (daily low-dose aspirin under 325 mg is allowed)
  • Having had a monoclonal antibody treatment targeting amyloid (a protein linked to Alzheimer's) in the past 6 months or 5 half-lives, whichever is longer
  • Having had another experimental drug treatment in the past 3 months or 5 half-lives, whichever is longer (approved Alzheimer's medicines may be allowed)
  • Poor veins that make blood tests difficult
  • Abnormal blood test results that matter clinically
  • A history of cancer with a high risk of coming back and affecting the study
  • Any other condition that could affect your mental or physical status enough to bias the study or put you at extra risk
  • Taking part in another clinical study now or in the past month without prior approval
  • Having the 'Dutch' APP E693Q mutation
  • A screening brain scan showing ARIA-E (brain swelling or fluid changes), more than 4 microbleeds, any superficial siderosis (iron deposits on the brain surface), any larger bleed, or severe white matter disease
  • Exposure to lecanemab, donanemab, or other experimental amyloid-lowering treatments in the past 6 months or 5 half-lives, whichever is longer
  • Being study staff on this trial or their close family, or being an employee of the sponsor (Lilly) or a third-party organisation involved in the study, or having a study partner who is

What taking part involves

  • • Not stated — ask the trial team (the study tests a potential disease-modifying treatment for a genetically caused early-onset type of Alzheimer's disease, but details of the treatment itself, such as what form it takes, are not stated)

Time commitment: Not stated — ask the trial team (the study involves screening and baseline visits, memory and thinking tests, MRI and PET scans, blood tests, and a study partner attending visits, but the total number of visits and study length are not stated).

Plain-English summary (AI-generated) from registry data. Not eligibility advice — only the trial team can confirm whether you can take part. Use the eligibility checker to see how your health profile matches this trial.

Type of study
Testing a treatment
Ages
18 Years and over
Who
All
Number of participants
280
Started
2024-11-22
Last checked
2026-07

Plain English Summary

What is this study?

  • • Testing a new treatment for alzheimers disease
  • • Phase2/Phase3 - 280 participants
  • • 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

Who can take part?

  • • Ages 18 Years and over
  • • Diagnosed with alzheimers disease

Where?

  • • London - The National Hospital for Neurology and Neurosurgery

This is a simplified summary. Always discuss with your doctor before making any decisions.

About This Trial

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.

More detail

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)

Alzheimers DiseaseDementiaAlzheimers Disease, Familial

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What we know so far

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Preliminary match based on your answers. Full eligibility requires on-site assessment including medical history, physical exam, and lab tests. This does not guarantee enrolment.

Eligibility at a Glance

Key info

  • Age: 18 Years and over
  • Who can join: All genders

Biomarkers mentioned

have a negative

Treatment history

Treatments you must have had:

  • ✓ a negative serum pregnancy test at screening (V1)
  • ✓ study partner input for scale completion, and who signs the necessary ICF, if applicable

Treatments you must NOT have had:

  • ✗ approval

What the study is looking for

  • ✓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...
  • ✓Must agree not to breastfeed from the time of signed ICF until twenty (20) weeks after the last dose of any the study treatment.

Who cannot take part

  • ✗Alcohol or substance use sufficient to meet DSM-V criteria currently or within the past year.
  • ✗liver or kidney abnormalities that in the opinion of the investigator would interfere with participation in or...
  • ✗Morbid obesity with significant other health conditions or that would preclude MRI imaging.
  • ✗Current use of anticoagulants (e.g., warfarin, dabigatran, rivaroxaban, or apixaban). Daily use of low dose (\< 325...
  • ✗Have been exposed to a monoclonal antibody targeting Aβ peptide within the past 6 months or 5 half-lives from...
See the full criteria
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 from the time of signed ICF until twenty (20) weeks after the last dose of any study drug. 3. Must agree not to breastfeed from the time of signed ICF until twenty (20) weeks after the last dose of any study drug. 4. 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. i. 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) 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. Adequate visual and auditory abilities to perform all aspects of the cognitive and clinical assessments. 8. 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). 9. 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. 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. Willing to complete all study-related testing, evaluations, and procedures. 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. 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 Aβ 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. 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

Where Is This Study? (1 UK site)

The National Hospital for Neurology and Neurosurgery

London WC1B 3BG, United Kingdom

Recruiting
Site contact (verified)
Catherine MummeryPrincipal Investigator

How to Get in Touch

Jamie Bartzel

Sponsor contact

CONTACT

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

Ellen Ziegemeier

Sponsor contact

CONTACT

844-DIANEXR (342-6397) dianexr@wustl.edu
Data sourced from ClinicalTrials.gov · Last verified: 2026-07