Clinical trial NCT05291234: A Study to Assess Safety of ABBV-916 and How Intravenous ABBV-916 Moves Through Body and Affects Brain Amyloid Plaque Clearance in Adult Participants (Aged 50-90 Years) With Early Alzheimer's Disease
Official title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of ABBV-916 in Subjects With Early Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Alzheimer's Disease (AD)
Keywords: Alzheimer's Disease (AD)
Early Alzheimer's Disease
ABBV-916
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2022-03-22
Enrollment: 106
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Alzheimer's disease (AD) is a progressive, irreversible neurological disorder and is the most common cause of dementia in the elderly population. Clinical symptoms of the disease may begin with occasional forgetfulness such as misplacement of items, forgetting important dates or events, and may progress to noticeable memory loss, increased confusion and agitation, and eventually, loss of independence and non-responsiveness. This study will assess how safe and effective ABBV-916 is in treating early AD. Adverse events, change in disease activity, and how ABBV-916 moves through body of participants will be assessed.

ABBV-916 is an investigational drug being developed for the treatment of early AD. This study is conducted in 2 stages. Stage A is a multiple ascending dose study. There is a 1 in 4 chance that participants are assigned to receive placebo. Stage B is a proof-of-concept study. In Stage B, there is a 1 in 5 chance that participants will be assigned to receive placebo. The first 6 months of this study are "double-blind," which means that neither the trial participant nor the study doctors know which treatments will be given. This will be followed by a 2-year extension period in which all participants will receive ABBV-916. Approximately 195 participants aged 50-90 years will be enrolled in about 90 sites across the world.

Participants will receive intravenous (IV) doses of ABBV-916 or placebo once every 4 weeks (Q4W) for 24 weeks and will be followed for an additional 16 weeks. Participants will have the option of participating in a 2-year, open-label, Extension Period receiving IV ABBV-916.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, magnetic resonance imaging (MRI), blood tests, checking for side effects and completing questionnaires.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of Stage 3 or Stage 4 Alzheimer's disease (AD) based on the 2018 National Institute on Aging (NIA)-Alzheimer's Association (AA) Research Framework Criteria.

  * Mini-Mental State Examination (MMSE) score of 20 to 28, inclusive, at Screening.
  * Blood-based biomarker results with a value consistent with amyloid positron emission tomography (PET) positivity. The biomarker will be chosen by the sponsor and described in the Laboratory Manual. Biomarker results will not be required for eligibility if the participant has a positive Amyloid PET scan meeting the central reader criteria.
* Amyloid PET scan results consistent with amyloid pathology.
* Stage B: Participants must have a study partner who spends a minimum average of 10 hours per week with the participant.

Exclusion Criteria:

* Significant pathological findings on brain MRI at screening including, but not limited to, evidence of vasogenic edema, 4 or more microhemorrhages, any macrohemorrhages, any superficial siderosis, or severe white matter disease.
* Any anticoagulants or have a bleeding disorder that is not adequately controlled.

Primary outcomes:
measure: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: Up to approximately 160 weeks
measure: Stage A: Maximum Observed Serum Concentration (Cmax) for Multiple Ascending Dose of ABBV-916
timeFrame: Up to approximately 24 weeks
measure: Stage A: Time to Cmax (Tmax) for Multiple Ascending Dose of ABBV-916
timeFrame: Up to approximately 24 weeks
measure: Stage A: Apparent Terminal Phase Elimination Rate Constant (β) of ABBV-916
timeFrame: Up to approximately 24 weeks
measure: Stage A: Terminal Phase Elimination Half-Life (t1/2) of ABBV-916
timeFrame: Up to approximately 24 weeks
measure: Stage A: Trough Serum Concentration (Ctrough) of ABBV-916 at the End of a Dosing Interval
timeFrame: Up to approximately 24 weeks
measure: Stage A: Area Under the Concentration-Time Curve (AUC) of ABBV-916
timeFrame: Up to approximately 24 weeks
measure: Stage A: Cerebrospinal Fluid (CSF) Concentration as a Measure of ABBV-916 Crossing the Blood Brain Barrier
timeFrame: Up to approximately 24 weeks
measure: Stage A: Percentage of Participants With Antidrug Antibodies (ADA) as a Measure of Immunogenicity Following Multiple Ascending Dose of ABBV-916
timeFrame: Up to approximately 24 weeks
measure: Stage B: Change in Brain Amyloid Plaque Deposition (Amyloid Centiloid Value)
timeFrame: Baseline (Week 0) through Week 24
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Tucson Neuroscience Research /ID# 244957
state: Arizona
city: Irvine
country: United States
facility: Irvine Clinical Research /ID# 239469
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research - San Diego /ID# 244508
state: California
city: San Diego
country: United States
facility: Pacific Research Network, Inc. /ID# 244083
state: California
city: Santa Ana
country: United States
facility: Syrentis Clinical Research /ID# 239682
state: California
city: Aventura
country: United States
facility: Aventura Neurological Associates /ID# 243892
state: Florida
city: Lady Lake
country: United States
facility: Charter Research - Lady Lake /ID# 244657
state: Florida
city: Lake Worth
country: United States
facility: JEM Research Institute /ID# 239122
state: Florida
city: Maitland
country: United States
facility: ClinCloud - Maitland /ID# 244507
state: Florida
city: Melbourne
country: United States
facility: ClinCloud LLC - Viera/Melbourne /ID# 240635
state: Florida
city: Merritt Island
country: United States
facility: Merritt Island Medical Research /ID# 239495
state: Florida
city: Miami
country: United States
facility: Optimus U /ID# 245868
state: Florida
city: Miami
country: United States
facility: Finlay Medical Research /ID# 245996
state: Florida
city: Miami
country: United States
facility: Allied Biomedical Res Inst Inc /ID# 244823
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research /ID# 240153
state: Florida
city: Ocoee
country: United States
facility: K2 Medical Research - Ocoee /ID# 246849
state: Florida
city: Orlando
country: United States
facility: K2 Medical Research - Orlando - South Orlando Avenue /ID# 243919
state: Florida
city: Orlando
country: United States
facility: Charter Research - Winter Park /ID# 244778
state: Florida
city: Orlando
country: United States
facility: Headlands Research - Orlando /ID# 239119
state: Florida
city: Ormond Beach
country: United States
facility: Neurology Associates Ormond Beach /ID# 245527
state: Florida
city: Palmetto Bay
country: United States
facility: IMIC Inc. Medical Research /ID# 245900
state: Florida
city: Stuart
country: United States
facility: Alzheimer's Research and Treatment Center - Stuart /ID# 245477
state: Florida
city: Wellington
country: United States
facility: Alzheimer's Research and Treatment Center - Wellington /ID# 245201
state: Florida
city: West Palm Beach
country: United States
facility: Premiere Research Institute - Palm Beach /ID# 240108
state: Florida
city: Winter Park
country: United States
facility: Clinical Site Partners (CSP) - Orlando /ID# 245127
state: Florida
city: Winter Park
country: United States
facility: Conquest Research /ID# 243916
state: Florida
city: Columbus
country: United States
facility: Columbus Memory Center /ID# 245054
state: Georgia
city: Farmington Hills
country: United States
facility: QUEST Research Institute /ID# 239459
state: Michigan
city: Toms River
country: United States
facility: Advanced Memory Research Institute of NJ /ID# 239533
state: New Jersey
city: Plymouth Meeting
country: United States
facility: Keystone Clinical Studies LLC /ID# 239973
state: Pennsylvania
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc /ID# 244917
state: Texas
city: Fairfax
country: United States
facility: Re:Cognition Health - Fairfax VA /ID# 239501
state: Virginia
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: