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

Status: Recruiting
Location: See all (35) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 2/Phase 3
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: t
View:

• 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.

⁃ 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.

⁃ In the opinion of the PI, the participant will be compliant and have a high probability of completing the study.

⁃ The participant is able and willing to complete all study-related testing, evaluations, and procedures.

Locations
United States
Alabama
University of Alabama in Birmingham
RECRUITING
Birmingham
California
University of California San Diego Medical Center
RECRUITING
La Jolla
Connecticut
Yale University School of Medicine
RECRUITING
New Haven
Georgia
Emory University
NOT_YET_RECRUITING
Atlanta
Illinois
Advocate Lutheran General Hospital
RECRUITING
Park Ridge
Indiana
Indiana University School of Medicine
RECRUITING
Indianapolis
Missouri
Washington University in St. Louis
RECRUITING
St Louis
New York
New York University Medical Center
RECRUITING
New York
Pennsylvania
University of Pittsburgh
RECRUITING
Pittsburgh
Rhode Island
Butler Hospital
RECRUITING
Providence
Texas
Kerwin Research and Memory Center
RECRUITING
Dallas
Washington
University of Washington
RECRUITING
Seattle
Other Locations
Argentina
Instituto de Investigaciones Neurologicas Raul Carrea, FLENI
NOT_YET_RECRUITING
Ciudad Autonoma De Buenos Aire
Australia
Mental Health Research Institute
NOT_YET_RECRUITING
Melbourne
Neuroscience Research Australia
NOT_YET_RECRUITING
Randwick
Canada
CHU de Quebec - Hôpital de l' Enfant Jésus
NOT_YET_RECRUITING
Québec
Sunnybrook Health Sciences Centre
RECRUITING
Toronto
UBC Hospital
NOT_YET_RECRUITING
Vancouver
McGill Center for Studies in Aging
NOT_YET_RECRUITING
Verdun
Colombia
Grupo de Neurociencias Sede de la Universidad de Antioquia
NOT_YET_RECRUITING
Medellín
France
Hopital Neurologique Pierre Wertheimer
NOT_YET_RECRUITING
Bron
Hopital Roger Salengro - CHU Lille
NOT_YET_RECRUITING
Lille
Groupe Hospitalier Pitie-Salpetriere
NOT_YET_RECRUITING
Paris
CHU de Rouen - Hôpital Charles Nicolle
NOT_YET_RECRUITING
Rouen
CHU de Toulouse - Hôpital Purpan
NOT_YET_RECRUITING
Toulouse
Germany
LMU-Campus Grosshadern
NOT_YET_RECRUITING
Munich
Universitaetsklinikum Tubingen
NOT_YET_RECRUITING
Tübingen
Italy
IRCCS Centro San Giovanni di Dio Fatebenefratelli
NOT_YET_RECRUITING
Brescia
Azienda Ospedaliera Universitaria Careggi
NOT_YET_RECRUITING
Florence
Mexico
Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez
NOT_YET_RECRUITING
Mexico City
Netherlands
Brain Research Center
NOT_YET_RECRUITING
Amsterdam
New Zealand
New Zealand Brain Research Institute
NOT_YET_RECRUITING
Christchurch
Puerto Rico
University of Puerto Rico, School of Medicine
RECRUITING
San Juan
Spain
Hospital Clínic I Provincial de Barcelona
NOT_YET_RECRUITING
Barcelona
United Kingdom
The National Hospital for Neurology and Neurosurgery
NOT_YET_RECRUITING
London
Contact Information
Primary
Jamie Bartzel
dianexr@wustl.edu
844-DIANEXR (342-6397)
Backup
Ellen Ziegemeier
dianexr@wustl.edu
844-DIANEXR (342-6397)
Time Frame
Start Date: 2024-11-22
Estimated Completion Date: 2030-06-30
Participants
Target number of participants: 280
Treatments
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
Related Therapeutic Areas
Sponsors
Leads: Washington University School of Medicine
Collaborators: Alzheimer's Association, Eli Lilly and Company, National Institute on Aging (NIA)

This content was sourced from clinicaltrials.gov