Ignite Creation Date:
2024-10-26 @ 3:43 PM
Last Modification Date:
2024-10-26 @ 3:43 PM
Study NCT ID:
NCT06647498
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-10-15
Brief 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
Sponsor:
None
Organization:
None
Study Overview
Official Title:
A Phase IIIII Multicenter Randomized Double-Blind Placebo-Controlled Two-Stage Adaptive Design Platform Trial of Investigational Treatments for Primary Prevention of Disease Progression in Dominantly Inherited Alzheimers Disease
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DIAN-TU-002
Brief 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 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 Alzheimers 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
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 Alzheimers 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
Detailed Description:
Alzheimers 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 Alzheimers 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 eg 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
The ability to identify individuals destined to develop Alzheimers 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 eg 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None