Clinical trial NCT04867616: A Study to Test the Efficacy, Safety, and Tolerability of Bepranemab (UCB0107) in Patients With Mild Cognitive Impairment or Mild Alzheimer's Disease (AD)
Official title: A Patient- and Investigator-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Bepranemab (UCB0107) in Study Participants With Prodromal to Mild Alzheimer's Disease (AD), Followed by an Open-Label Extension Period
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Alzheimer's Disease
Keywords: Alzheimer's Disease
Bepranemab
UCB0107
Phase 2
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2021-04-30
Enrollment: 466
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Upon completion of the 80-week Double-blind Treatment Period, study participants will be eligible to enter a 48-week Open-label Extension Period with planned treatments of bepranemab for 44 weeks, followed by a Safety Follow-up Visit 20 weeks after the last infusion of investigational medicinal product.
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to investigate the effect of bepranemab versus (vs) placebo on the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) up to Week 80 in study participants with prodromal or mild Alzheimer's Disease (AD).


Eligibility criteria: Inclusion Criteria:

* 50 to 80 years of age
* Diagnosis of prodromal/mild cognitive impairment (MCI) due to Alzheimer's Disease (AD) or mild AD according to National Institute of Aging-Alzheimer's Association (NIA-AA)
* A global Clinical Dementia Rating (CDR) score of 0.5 to 1.0 and CDR-Memory Box (CDRMB) score ≥0.5 at Screening and Baseline
* Score of ≤85 for the delayed recall domain of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) at Screening
* Mini-Mental State Examination (MMSE) score ≥20 at Screening
* Participant has an identified informant that has and will maintain sufficient contact (minimum of 5 hours per week) with the participant to be able to provide accurate information on the participant's cognitive, functional, and emotional states and of the participant's personal care
* At least 6 years of formal education after the age of 5 or work experience to exclude mental deficits other than prodromal or mild AD dementia
* Evidence of cerebral Aβ accumulation by either positive amyloid assessment by either positron emission tomography (PET) scan or cerebrospinal fluid pTau181/Aβ1-42 ratio assessment

Exclusion Criteria:

* Any evidence of a condition that may affect cognition other than AD
* Contraindications to PET imaging
* Inability to tolerate or contraindication to magnetic resonance imaging
* Any serious medical condition or abnormality that in the opinion of the investigator would preclude safe participation in and completion of the study or interfere with study assessments and/or study interpretation
* Alcohol or drug abuse within 2 years of screening
* Use of any experimental therapy within the past 6 months (or 5 half lives) prior to screening
* Previous treatment with medication intended to treat a neurodegenerative disorder (other than AD) within 1 year of screening
* Chronic daily treatment with atypical antipsychotics, opiates or opioids, benzodiazepines, barbiturates, hypnotics, or any medication with clinically significant centrally acting antihistamine or anticholinergic activitiy
* Received treatment with monoclonal antibodies (mAbs), cytokines, immunoglobulins, or other blood products within 3 months or 5 half-lives (whichever is longer) prior to first dosing

Primary outcomes:
measure: Change from Baseline to Week 80 in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) total score
timeFrame: From from Baseline to Week 80
Secondary outcomes:
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: From Baseline to the Safety Follow-Up (Week 152)
measure: Incidence of treatment-emergent serious adverse events (TESAEs)
timeFrame: From Baseline to the Safety Follow-Up (Week 152)
measure: Incidence of TEAEs leading to discontinuation or death
timeFrame: From Baseline to the Safety Follow-Up (Week 152)
measure: Incidence of Drug-related TEAEs
timeFrame: From Baseline to the Safety Follow-Up (Week 152)
measure: Change from Baseline in suicidal ideation and behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: From from Baseline to Week 80
measure: Change from Baseline to Week 56 and Week 80 on indices of tau burden in the brain as measured by [18F]Genentech tau probe 1 (GTP1) positron emission tomography (PET)
timeFrame: From from Baseline to Week 56 and Week 80
measure: Change from Baseline to Week 56 and Week 80 in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14)
timeFrame: From from Baseline to Week 56 and Week 80
measure: Change from Baseline to Week 56 and Week 80 in Amsterdam-Instrumental Activities of Daily Living (A-iADL)
timeFrame: From from Baseline to Week 56 and Week 80
measure: Change from Baseline to Week 56 and Week 80 in Mini-Mental State Examination (MMSE) total score
timeFrame: From from Baseline to Week 56 and Week 80
measure: Serum concentrations of bepranemab over the 80-week Double-blind Treatment Period
timeFrame: From from Baseline to Week 80
Other outcomes:
Locations:
city: Fresno
country: United States
facility: Ah0003 50428
state: California
city: Fullerton
country: United States
facility: Ah0003 50431
state: California
city: Irvine
country: United States
facility: Ah0003 50442
state: California
city: Long Beach
country: United States
facility: Ah0003 50458
state: California
city: Palo Alto
country: United States
facility: Ah0003 50450
state: California
city: Pasadena
country: United States
facility: Ah0003 50452
state: California
city: San Diego
country: United States
facility: Ah0003 50447
state: California
city: Santa Ana
country: United States
facility: Ah0003 50434
state: California
city: New Haven
country: United States
facility: Ah0003 50422
state: Connecticut
city: New Haven
country: United States
facility: Ah0003 50467
state: Connecticut
city: Stamford
country: United States
facility: Ah0003 50421
state: Connecticut
city: Atlantis
country: United States
facility: Ah0003 50465
state: Florida
city: Aventura
country: United States
facility: Ah0003 50449
state: Florida
city: Boca Raton
country: United States
facility: Ah0003 50435
state: Florida
city: Delray Beach
country: United States
facility: Ah0003 50430
state: Florida
city: Fort Myers
country: United States
facility: Ah0003 50429
state: Florida
city: Hialeah
country: United States
facility: Ah0003 50436
state: Florida
city: Maitland
country: United States
facility: Ah0003 50426
state: Florida
city: Miami
country: United States
facility: Ah0003 50427
state: Florida
city: Naples
country: United States
facility: Ah0003 50478
state: Florida
city: Ocoee
country: United States
facility: Ah0003 50464
state: Florida
city: Pensacola
country: United States
facility: Ah0003 50438
state: Florida
city: Pensacola
country: United States
facility: Ah0003 50623
state: Florida
city: Port Orange
country: United States
facility: Ah0003 50457
state: Florida
city: Tampa
country: United States
facility: Ah0003 50454
state: Florida
city: West Palm Beach
country: United States
facility: Ah0003 50444
state: Florida
city: West Palm Beach
country: United States
facility: Ah0003 50476
state: Florida
city: Westchester
country: United States
facility: Ah0003 50446
state: Florida
city: Decatur
country: United States
facility: Ah0003 50479
state: Georgia
city: Braintree
country: United States
facility: Ah0003 50445
state: Massachusetts
city: Newton
country: United States
facility: Ah0003 50453
state: Massachusetts
city: Saint Paul
country: United States
facility: Ah0003 50448
state: Minnesota
city: Neptune
country: United States
facility: Ah0003 50420
state: New Jersey
city: Cincinnati
country: United States
facility: Ah0003 50451
state: Ohio
city: East Providence
country: United States
facility: Ah0003 50423
state: Rhode Island
city: Cordova
country: United States
facility: Ah0003 50455
state: Tennessee
city: Houston
country: United States
facility: Ah0003 50380
state: Texas
city: Fairfax
country: United States
facility: Ah0003 50424
state: Virginia
city: Norfolk
country: United States
facility: Ah0003 50432
state: Virginia
city: Bellevue
country: United States
facility: Ah0003 50440
state: Washington
city: Brussels
country: Belgium
facility: Ah0003 40123
city: Brussels
country: Belgium
facility: Ah0003 40575
city: Kortrijk
country: Belgium
facility: Ah0003 40576
city: Leuven
country: Belgium
facility: Ah0003 40002
city: Kelowna
country: Canada
facility: Ah0003 50463
city: Ottawa
country: Canada
facility: Ah0003 50461
city: QC
country: Canada
facility: Ah0003 50520
city: Toronto
country: Canada
facility: Ah0003 50045
city: Toronto
country: Canada
facility: Ah0003 50291
city: Toronto
country: Canada
facility: Ah0003 50462
city: West Vancouver
country: Canada
facility: Ah0003 50522
city: Bordeaux
country: France
facility: Ah0003 40129
city: Bron Cedex
country: France
facility: Ah0003 40580
city: Marseille
country: France
facility: Ah0003 40493
city: Nantes
country: France
facility: Ah0003 40635
city: Paris
country: France
facility: Ah0003 40578
city: Rennes
country: France
facility: Ah0003 40201
city: Toulouse
country: France
facility: Ah0003 40581
city: Villeurbanne
country: France
facility: Ah0003 40579
city: Berlin
country: Germany
facility: Ah0003 40028
city: Munich
country: Germany
facility: Ah0003 40430
city: Monza
country: Italy
facility: Ah0003 40371
city: Parma
country: Italy
facility: Ah0003 40600
city: Pavia
country: Italy
facility: Ah0003 40597
city: Roma
country: Italy
facility: Ah0003 40438
city: Rome
country: Italy
facility: Ah0003 40596
city: Rome
country: Italy
facility: Ah0003 40598
city: Amsterdam
country: Netherlands
facility: Ah0003 40450
city: Den Bosch
country: Netherlands
facility: Ah0003 40449
city: Zwolle
country: Netherlands
facility: Ah0003 40601
city: Bialystok
country: Poland
facility: Ah0003 40603
city: Bydgoszcz
country: Poland
facility: Ah0003 40606
city: Katowice
country: Poland
facility: Ah0003 40605
city: Katowice
country: Poland
facility: Ah0003 40609
city: Katowice
country: Poland
facility: Ah0003 40774
city: Scinawa
country: Poland
facility: Ah0003 40638
city: Szczecin
country: Poland
facility: Ah0003 40608
city: Warsaw
country: Poland
facility: Ah0003 40604
city: Warsaw
country: Poland
facility: Ah0003 40607
city: Warszawa
country: Poland
facility: Ah0003 40602
city: Wroclaw
country: Poland
facility: Ah0003 40611
city: Barcelona
country: Spain
facility: Ah0003 40159
city: Barcelona
country: Spain
facility: Ah0003 40160
city: Barcelona
country: Spain
facility: Ah0003 40267
city: Barcelona
country: Spain
facility: Ah0003 40612
city: Cordoba
country: Spain
facility: Ah0003 40105
city: Donostia
country: Spain
facility: Ah0003 40614
city: Madrid
country: Spain
facility: Ah0003 40540
city: Madrid
country: Spain
facility: Ah0003 40615
city: Pamplona
country: Spain
facility: Ah0003 40352
city: Sant Cugat Del Valles
country: Spain
facility: Ah0003 40280
city: Sevilla
country: Spain
facility: Ah0003 40049
city: Terrassa
country: Spain
facility: Ah0003 40453
city: Valencia
country: Spain
facility: Ah0003 40230
city: Valencia
country: Spain
facility: Ah0003 40613
city: Zaragoza
country: Spain
facility: Ah0003 40616
city: Birmingham
country: United Kingdom
facility: Ah0003 40662
city: Bristol
country: United Kingdom
facility: Ah0003 40619
city: Guildford
country: United Kingdom
facility: Ah0003 40622
city: London
country: United Kingdom
facility: Ah0003 40618
city: London
country: United Kingdom
facility: Ah0003 40621
city: Plymouth
country: United Kingdom
facility: Ah0003 40623
city: Winchester
country: United Kingdom
facility: Ah0003 40691
Study officials:
affiliation: 001 844 599 2273 (UCB)
name: UCB Cares
role: STUDY_DIRECTOR
References: