Clinical trial NCT05738486: A Study of Different Donanemab (LY3002813) Dosing Regimens in Adults With Early Alzheimer's Disease (TRAILBLAZER-ALZ 6)
Official title: Investigating the Effect of Different Donanemab Dosing Regimens on ARIA-E and Amyloid Lowering in Adults With Early Symptomatic Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Alzheimer's Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2023-02-22
Enrollment: 1100
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 3b
Primary purpose: TREATMENT

Brief summary: This study will investigate different donanemab dosing regimens and their effect on the frequency and severity of ARIA-E in adults with early symptomatic Alzheimer's disease (AD) and explore participant characteristics that might predict risk of ARIA.

Approximately 300 additional participants will be enrolled per addendum.

The study will last approximately 91 weeks and include up to 26 visits in the main study.


Eligibility criteria: Inclusion Criteria:

* Gradual and progressive change in memory function reported by the participant or informant for ≥6 months.
* A mini mental state examination (MMSE) score of 20 to 28 (inclusive) at screening.
* Have an amyloid PET scan result from central read, consistent with the presence of amyloid pathology.

Exclusion Criteria:

* Have significant neurological disease affecting the central nervous system other than AD, that may affect cognition or ability to complete the study, including but not limited to, other dementias, serious infection of the brain, Parkinson's disease, multiple concussions, or epilepsy or recurrent seizures, except febrile childhood seizures.
* Has current serious or unstable illnesses including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic (other than AD), psychiatric, immunologic, or hematologic disease and other conditions that, in the investigator's opinion, could interfere with the analyses in this study.
* A life expectancy of \<24 months.
* Contraindication to MRI or PET scans
* Have had prior treatment with a passive anti-amyloid immunotherapy.
* Have a presence or history of malignant neoplasms within the past 5 years prior to Visit 1.

Exceptions:

* non-metastatic basal- or squamous-cell skin cancer
* Stage 0 non-invasive carcinoma of the cervix
* Stage 0 non-invasive prostate cancer, or
* other cancers with low risk of recurrence or spread

Primary outcomes:
measure: Percentage of Participants with Any Occurrence of Amyloid-Related Imaging Abnormality-Edema/Effusion (ARIA-E)
timeFrame: 24 Weeks
Secondary outcomes:
measure: Percentage of Participants with Any Occurrence of ARIA-E
timeFrame: 52 Weeks
measure: Change from Baseline in Brain Amyloid Plaque Deposition As Measured By Amyloid Positron Emission Tomography (PET) Scan
timeFrame: Baseline, 76 Weeks
measure: Percentage of Participants with Any Occurrence of Amyloid-Related Imaging Abnormality-Hemorrhage/Hemosiderin Deposits (ARIA-H)
timeFrame: 24 Weeks
measure: Percentage of Participants with ARIA-H
timeFrame: 52 Weeks
measure: Percentage of Participants with Maximum Severity of ARIA-E or ARIA-H
timeFrame: 52 Weeks
measure: Pharmacokinetics (PK): Average Serum Concentration of Donanemab
timeFrame: Baseline to 52 Weeks
measure: Number of Participants with Anti-Drug Antibodies (ADAs) Against Donanemab, including Treatment Emergent ADAs and Neutralizing Antibodies
timeFrame: Baseline to End of Follow-Up (91 Weeks)
Other outcomes:
Locations:
city: Chandler
country: United States
facility: MD First Research - Chandler
state: Arizona
city: Irvine
country: United States
facility: Irvine Clinical Research
state: California
city: Long Beach
country: United States
facility: Healthy Brain Clinic
state: California
city: Sherman Oaks
country: United States
facility: California Neuroscience Research Medical Group, Inc.
state: California
city: Atlantis
country: United States
facility: JEM Research Institute
state: Florida
city: Aventura
country: United States
facility: VIN-Julie Schwartzbard
state: Florida
city: Boca Raton
country: United States
facility: Excel Medical Clinical Trials
state: Florida
city: Clermont
country: United States
facility: K2 Medical Research
state: Florida
city: Delray Beach
country: United States
facility: Brain Matters Research
state: Florida
city: Fort Myers
country: United States
facility: Neuropsychiatric Research Center of Southwest Florida
state: Florida
city: Greenacres City
country: United States
facility: Finlay Medical Research
state: Florida
city: Hollywood
country: United States
facility: Infinity Clinical Research, LLC
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Maitland
country: United States
facility: ClinCloud - Maitland
state: Florida
city: Maitland
country: United States
facility: K2 Medical Research
state: Florida
city: Melbourne
country: United States
facility: ClinCloud - Viera
state: Florida
city: New Port Richey
country: United States
facility: Suncoast Clinical Research, Inc.
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Orlando
country: United States
facility: Charter Research - Winter Park
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Stuart
country: United States
facility: Alzheimer's Research and Treatment Center
state: Florida
city: Tampa
country: United States
facility: K2 Medical Research - Tampa
state: Florida
city: The Villages
country: United States
facility: K2 Summit Research
state: Florida
city: The Villages
country: United States
facility: Charter Research - Lady Lake
state: Florida
city: Wellington
country: United States
facility: Alzheimer's Research and Treatment Center
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Neurology
state: Florida
city: Winter Park
country: United States
facility: Conquest Research
state: Florida
city: Columbus
country: United States
facility: Columbus Memory Center, LLC
state: Georgia
city: Decatur
country: United States
facility: CenExel iResearch, LLC
state: Georgia
city: Gainesville
country: United States
facility: Center for Advanced Research & Education
state: Georgia
city: Savannah
country: United States
facility: CenExel iResearch, LLC
state: Georgia
city: Waltham
country: United States
facility: MedVadis Research Corporation
state: Massachusetts
city: Watertown
country: United States
facility: Adams Clinical
state: Massachusetts
city: Farmington Hills
country: United States
facility: QUEST Research Institute
state: Michigan
city: Springfield
country: United States
facility: The Cognitive and Research Center of New Jersey
state: New Jersey
city: Providence
country: United States
facility: Butler Hospital
state: Rhode Island
city: Cordova
country: United States
facility: Neurology Clinic, P.C.
state: Tennessee
city: Beaumont
country: United States
facility: Gadolin Research
state: Texas
city: Dallas
country: United States
facility: Kerwin Medical Center
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Fairfax
country: United States
facility: Re:Cognition Health
state: Virginia
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Tacoma
country: United States
facility: Universal Research Group
state: Washington
city: Bristol
country: United Kingdom
facility: Re:Cognition Health - Bristol
state: Bristol, City Of
city: Winchester
country: United Kingdom
facility: Re:Cognition Health - Winchester
state: Hampshire
city: London
country: United Kingdom
facility: Re:Cognition Health - London
state: London, City Of
city: Guildford
country: United Kingdom
facility: Re:Cognition Health Guildford
state: Reading
city: Birmingham
country: United Kingdom
facility: Re:Cognition Health - Birmingham
city: Plymouth
country: United Kingdom
facility: Re:Cognition Health - Plymouth
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: