Clinical trial NCT04619420: A Study of JNJ-63733657 in Participants With Early Alzheimer's Disease
Official title: A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study With a Long-Term Extension Treatment Period to Assess the Efficacy and Safety of JNJ-63733657, an Anti-tau Monoclonal Antibody, in Participants With Early Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Alzheimer Disease
Cognitive Dysfunction
Dementia
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2020-11-06
Enrollment: 523
Sex: ALL
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: There will be 3 treatment arms for the Double-Blind treatment period, whereas there will be only 2 treatment arms for the Long-Term extension treatment period.
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to evaluate the effect of JNJ-63733657 versus placebo on clinical decline as measured by the Integrated Alzheimer's Disease Rating Scale (iADRS), a composite of cognition and function.


Eligibility criteria: Inclusion Criteria:

* Early Alzheimer's disease (AD): Gradual and progressive subjective decline in the participant's cognition over at least the past 6 months, as reported by the participant and informant (study partner) and Clinical Dementia Rating-Global Score (CDR-GS) of 0.5 and memory box score greater than or equal to (\>=) 0.5 at screening
* Participants must have positive tau PET results
* Able to read and write and with a minimum 5 years of formal education as reported by participant and study partner at screening
* Have a designated study partner who has adequate literacy to participate and be judged to have high likelihood of completing the study with the participant
* Male participants must agree not to donate sperm for the purpose of reproduction during the study and up to 16 weeks after receiving the last dose of study intervention

Exclusion Criteria:

* Participants with CDR GS \>=2 at predose baseline Clinical Dementia Rating (CDR) administration
* Participants who fulfill diagnostic criteria for Mild Cognitive Impairment (MCI) or dementia/mild or major neurocognitive disorder suspected to be due to any etiology other than AD (example, Parkinson's disease, cerebrovascular disease, normal pressure hydrocephalus, head injury, drug or alcohol abuse/dependence, anoxic brain injury, (Et cetera\[etc\])
* Geriatric Depression Scale (GDS) 30 score greater than (\>) 12
* Hachinski Ischemic Scale (HIS) \>4
* Has received medications that affect the central nervous system (CNS), except treatments for AD, for less than 2 months; that is, doses of chronic medications that effect the CNS should be stable for at least 2 months before the start of screening. If a participant has recently stopped a chronic medication that effects the CNS, he or she must have discontinued treatment at least 2 months before the start of screening. Chronic use of benzodiazepines is not permitted

Primary outcomes:
measure: Change From Baseline in Integrated Alzheimer's Disease Rating Scale (iADRS) Total Score at Week 104
timeFrame: Week 104
Secondary outcomes:
measure: Change From Baseline in Alzheimer's Disease Assessment Scale Cognitive subscale 13-item version (ADAS-Cog 13) Total Score at Week 104
timeFrame: Week 104
measure: Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living for Mild Cognitive Impairment (ADCS-ADL MCI) Total Score at Week 104
timeFrame: Week 104
measure: Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Scale Index Score at Week 88
timeFrame: Baseline, Week 88
measure: Change From Baseline in RBANS Indices at Week 88
timeFrame: Baseline, Week 88
measure: Change From Baseline in Clinical Dementia Rating- Sum of Boxes (CDR-SB) at Week 104
timeFrame: Baseline, Week 104
measure: Change from Baseline in Neuropsychiatric Inventory (NPI) at Week 104
timeFrame: Baseline, Week 104
measure: Percentage of Participants Progressing From Clinical Dementia Rating- Global Score (CDR-GS) 0 to 0.5 or Higher, 0.5 to 1 or Higher, 1 to 2 or Higher, from Baseline to Post-baseline through Week 104
timeFrame: From Baseline through Week 104
measure: Change From Baseline in Brain tau Burden as Measured by tau PET at Week 104
timeFrame: Baseline, Week 104
measure: Change From Baseline in Cerebrospinal Fluid (CSF) concentrations of Total, Free, and Bound p217+tau Fragments at Week 104
timeFrame: Baseline, Week 104
measure: CSF Concentrations of JNJ-63733657
timeFrame: At Weeks 52, 104, 208 (End of Treatment)
measure: Serum Concentrations of JNJ-63733657
timeFrame: At Weeks 4, 8, 12, 16, 20, 24, 36, 52, 76, 104, 128, 156, 180, 208, 232 (End of treatment)
measure: Anti-Drug Antibody to JNJ-63733657
timeFrame: Up to 245 Weeks (90 days [+-7 days] after last dose of study intervention)
measure: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
timeFrame: Up to 245 Weeks
measure: Number of Participants with Treatment-Emergent Adverse Event of Special Interest (AESI)
timeFrame: Up to 245 Weeks
measure: Number of Participants with Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability
timeFrame: Up to 245 Weeks
measure: Number of Participants with Electrocardiogram (ECG) Abnormalities
timeFrame: Up to 245 Weeks
measure: Number of Participants with Clinical Laboratory Abnormalities
timeFrame: Up to 245 Weeks
measure: Number of Participants with Physical and Neurological Examination Abnormalities
timeFrame: Up to 245 Weeks
measure: Percentage of Participants with Vital Sign Abnormalities
timeFrame: Up to 245 Weeks
measure: Changes From Baseline in Brain Magnetic Resonance Imaging (MRI) Safety Findings
timeFrame: Baseline and Up to 4.5 years (End of treatment)
measure: Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) score
timeFrame: Baseline and Up to 245 Weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Dignity Health
state: Arizona
city: Irvine
country: United States
facility: Irvine Clinical Research
state: California
city: La Jolla
country: United States
facility: University of California San Diego Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California - Los Angeles
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: San Diego
country: United States
facility: Pacific Research Network Prn
state: California
city: Santa Ana
country: United States
facility: Syrentis Clinical Research
state: California
city: New Haven
country: United States
facility: Yale University School Of Medicine
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Atlantis
country: United States
facility: JEM Research LLC
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 SWFL
state: Florida
city: Jacksonville
country: United States
facility: Clinical NeuroScience Solutions Inc
state: Florida
city: Jupiter
country: United States
facility: Alphab Global Research
state: Florida
city: Maitland
country: United States
facility: K2 Medical Research
state: Florida
city: Maitland
country: United States
facility: Tandem Intermediate LLC
state: Florida
city: Merritt Island
country: United States
facility: Merritt Island Medical Research, LLC
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Miami
country: United States
facility: Miami Jewish Health System
state: Florida
city: Naples
country: United States
facility: Aqualane Clinical Research
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Ocoee
country: United States
facility: Sensible Healthcare
state: Florida
city: Tampa
country: United States
facility: Axiom Clinical Research of Florida
state: Florida
city: Tampa
country: United States
facility: Stedman Clinical Trials
state: Florida
city: Tampa
country: United States
facility: University of South Florida - Health Byrd Alzheimer Institute
state: Florida
city: The Villages
country: United States
facility: Charter Research
state: Florida
city: Viera
country: United States
facility: ClinCloud Clinical Research
state: Florida
city: Wellington
country: United States
facility: Alzheimers Research and Treatment Center
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Neurology and Premier Research Institute
state: Florida
city: Winter Park
country: United States
facility: Conquest Research
state: Florida
city: Atlanta
country: United States
facility: The Emory Clinic
state: Georgia
city: Decatur
country: United States
facility: Sandhill Research
state: Georgia
city: Chicago
country: United States
facility: Great Lakes Clinical Trials
state: Illinois
city: Elk Grove Village
country: United States
facility: Alexian Brothers Medical Center - Neuroscience Research Institute
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Braintree
country: United States
facility: Anil Nair dba Alzheimer's Disease Center
state: Massachusetts
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University School Of Medicine
state: Missouri
city: Mount Arlington
country: United States
facility: NeuroCognitive Institute
state: New Jersey
city: Princeton
country: United States
facility: Princeton Medical Institute
state: New Jersey
city: Toms River
country: United States
facility: Advanced Memory Research Institute of NJ
state: New Jersey
city: Albany
country: United States
facility: Neurological Associates of Albany, PC
state: New York
city: East Syracuse
country: United States
facility: Velocity Clinical Research
state: New York
city: New York
country: United States
facility: New York University Medical Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Health Sciences
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Lou Revo Center for Brain Health
state: Ohio
city: Columbus
country: United States
facility: Wexner Medical Center at the Ohio State University
state: Ohio
city: Plymouth Meeting
country: United States
facility: Keystone Clinical Studies LLC
state: Pennsylvania
city: Providence
country: United States
facility: Brown University School of Medicine
state: Rhode Island
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Bennington
country: United States
facility: Memory Clinic Inc
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Box Hill
country: Australia
facility: Box Hill Hospital
city: Carlton
country: Australia
facility: Neuro Trials Victoria
city: Ivanhoe
country: Australia
facility: Austin Health
city: Malvern
country: Australia
facility: HammondCare Neurodegenerative Clinical Trials - VIC
city: Nedlands
country: Australia
facility: Australian Alzheimer's Research Foundation Incorporated
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
city: Brugge
country: Belgium
facility: AZ St.-Jan Brugge-Oostende AV
city: Brussels
country: Belgium
facility: UCL Hopital Saint-Luc
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis
city: Jette
country: Belgium
facility: UZ Brussel
city: Leuven
country: Belgium
facility: UZ Leuven
city: Roeselare
country: Belgium
facility: Algemeen Ziekenhuis Delta
city: London
country: Canada
facility: Parkwood Institute
state: Ontario
city: Peterborough
country: Canada
facility: Kawartha Centre - Redefining Healthy Aging
state: Ontario
city: Toronto
country: Canada
facility: Toronto Memory Program (Neurology Research Inc.)
state: Ontario
city: Toronto
country: Canada
facility: UHN-Toronto Western Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University
state: Quebec
city: Bordeaux
country: France
facility: Hopital Pellegrin CHU Bordeaux
city: Lille
country: France
facility: Hopital Roger Salengro - CHU Lille
city: Nantes
country: France
facility: CHU Nantes - Hopital Nord Laënnec
city: Paris
country: France
facility: Hopital Lariboisiere-Fernand Widal
city: Paris
country: France
facility: Hopital Pitie Salpetriere
city: Rennes
country: France
facility: Chu Rennes Hopital Pontchaillou
city: Rouen
country: France
facility: Hopital Charles Nicolle
city: Toulouse
country: France
facility: CHU Toulouse - Hôpital La Grave
city: Tours
country: France
facility: Hôpital Bretonneau
city: Aizuwakamatsu
country: Japan
facility: Takeda General Hospital
city: Chiba-shi
country: Japan
facility: Inage Neurology and Memory Clinic
city: Fujisawa-shi
country: Japan
facility: Kawashima Neurology Clinic
city: Fukuoka
country: Japan
facility: Fukuoka University Hospital
city: Hachioji
country: Japan
facility: Keikokai P-One Clinic
city: Himeji-city
country: Japan
facility: Himeji Central Hospital Clinic
city: Kamakura-shi
country: Japan
facility: Shonan Kamakura General Hospital
city: Kanzaki-gun
country: Japan
facility: National Hospital Organization Hizen Psychiatric Center
city: Kawasaki
country: Japan
facility: Koukan Clinic
city: Kobe-shi
country: Japan
facility: Kobe City Medical Center General Hospital
city: Kurashiki-shi
country: Japan
facility: Rijikai Medical Corporation Katayama Medical Clinic
city: Kurume
country: Japan
facility: Kurume University Hospital
city: Kyoto-shi
country: Japan
facility: Rakuwakai Otowa Rehabilitation Hospital
city: Kyoto
country: Japan
facility: Rakuwakai Otowa Hospital
city: Narashino
country: Japan
facility: Saiseikai Narashino Hospital
city: Obu-shi
country: Japan
facility: National Center For Geriatrics And Gerontology
city: Shinjuku-ku
country: Japan
facility: Clinical Research Hospital Tokyo
city: Tokyo
country: Japan
facility: Tokyo Medical University Hospital
city: Tokyo
country: Japan
facility: Tokyo Metropolitan Geriatric Hospital
city: Toyonaka-shi
country: Japan
facility: Nagomi Clinic
city: Toyonaka-shi
country: Japan
facility: Jinsenkai MI Clinic
city: Yokohama-shi
country: Japan
facility: Yokohama Brain and Spine Center
city: Amsterdam
country: Netherlands
facility: BRC - Amsterdam
city: Den Bosch
country: Netherlands
facility: BRC - Den Bosch
city: Leeuwarden
country: Netherlands
facility: QPS Netherlands
city: Zwolle
country: Netherlands
facility: BRC Zwolle
city: Algorta - Getxo
country: Spain
facility: Centro At. Esp. Oroitu
city: Barcelona
country: Spain
facility: Hosp. Del Mar
city: Barcelona
country: Spain
facility: Hosp. de La Santa Creu I Sant Pau
city: Barcelona
country: Spain
facility: Fund. Ace-Inst. Cat. Neuroc. Aplicades
city: Barcelona
country: Spain
facility: Idc Salud Hosp. Gral. de Catalunya
city: Lleida
country: Spain
facility: Hosp. Univ. Santa Maria
city: Madrid
country: Spain
facility: Hosp. Clinico San Carlos
city: Terrassa
country: Spain
facility: Hosp. Mutua Terrassa
city: Valencia
country: Spain
facility: Hosp. Univ. I Politecni La Fe
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset
city: Bath
country: United Kingdom
facility: Royal United Hospital
city: London
country: United Kingdom
facility: Charing Cross Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: