A Study of JNJ-63733657 in Participants With Early Alzheimer's Disease

Phase 2

Active, not recruiting

• Conditions: Alzheimer Disease; Cognitive Dysfunction; Dementia
• Interventions: Drug: JNJ-63733657; Drug: Placebo

• Registration Number: NCT04619420
• Lead Sponsor: Janssen Research & Development, LLC

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-11-05
• Study First Submitted QC: 2020-11-05
• Study First Posted: 2020-11-06
• Study Start: 2021-01-06
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-08
• Last Update Posted: 2025-01-09
• Primary Completion: 2026-02-27
• Study Completion: 2032-12-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 523

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
JNJ-63733657 High-dose	JNJ-63733657	Participants will receive single dose of JNJ-63733657 high-dose administered by IV infusion every 4 weeks during double-blind treatment period. Participants will have an option to continue with the LTE phase of the trial and will continue to receive the same treatment and dose during the LTE treatment period.
JNJ-63733657 Low-dose	JNJ-63733657	Participants will receive single dose of JNJ-63733657 low-dose administered by intravenous (IV) infusion every 4 weeks during the double-blind treatment period. Participants will have an option to continue with the long-term extension (LTE) phase of the trial and will continue to receive the same treatment and dose during the LTE treatment period.
Placebo	Placebo	Participants will receive single dose of matching placebo to JNJ-63733657 administered by IV infusion every 4 weeks during double-blind treatment period. Participants will have an option to continue with the LTE phase of the trial and will be re-randomized in a 1:1 ratio to receive either JNJ-63733657 low-dose or JNJ-63733657 high-dose during the LTE treatment period.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Integrated Alzheimer's Disease Rating Scale (iADRS) Total Score at Week 104	Week 104	The linear combination of the ADAS Cog13 and ADCS ADL MCI that serves as a composite of cognition and function (overall clinical status) of the participant and score range from 0 to 138 with lower scores indicating worse performance. The iADRS will be a combination of ADAS Cog13 (score 0 to 85, higher scores indicate worse cognitive performance) and ADCS-ADL MCI (yielding a score 0 to 53, lower scores indicate worse daily function).

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Alzheimer's Disease Assessment Scale Cognitive subscale 13-item version (ADAS-Cog 13) Total Score at Week 104	Week 104	ADAS-Cog11 consists of 11 tasks measuring the disturbances of memory, language, praxis, attention, and other cognitive abilities. The modified ADAS-Cog 13 item scale includes all original ADAS-Cog items with the addition of a number cancellation task and a delayed free recall task, for a maximum total score of 85 points, with higher scores indicative of worse cognitive performance. Thus, a negative change from baseline represents improvement in cognition. Items are recorded on an electronic device which will provide the ADAS-Cog 13 total score.
Change From Baseline in Clinical Dementia Rating- Sum of Boxes (CDR-SB) at Week 104	Baseline, Week 104	CDR is a global clinical staging instrument that includes 3 cognitive and 3 functional ratings, including: memory, orientation, judgment and problem solving, involvement in community affairs, home and hobbies, and personal care based on the CDR interview. The CDR is scored 2 ways yielding a global CDR score (CDR GS, derived from an algorithm including categorical scoring of 0, 0.5, 1, 2, and 3), as well as CDR-Sum of Boxes (CDR-SB, the continuous sum of 6 domains, up to a total score of 18, with higher scores representing worse disease state). The Sum of boxes and global score is calculated from the overall CDR.
Change From Baseline in Brain tau Burden as Measured by tau PET at Week 104	Baseline, Week 104	Change from baseline in brain tau burden, as measured by tau positron emission tomography (PET) will be assessed.
Change From Baseline in Cerebrospinal Fluid (CSF) concentrations of Total, Free, and Bound p217+tau Fragments at Week 104	Baseline, Week 104	Change from baseline in CSF concentrations of total, free, and bound p217+tau (phosphorylated tau) fragments will be assessed.
Serum Concentrations of JNJ-63733657	At Weeks 4, 8, 12, 16, 20, 24, 36, 52, 76, 104, 128, 156, 180, 208, 232 (End of treatment)	Serum concentrations of JNJ-63733657 will be assessed.
Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability	Up to 245 Weeks	An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to that medicinal product.
Number of Participants with Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability	Up to 245 Weeks	An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product.
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	From Baseline through Week 104	The CDR is a subjectively rated outcome measure that serves as a global clinical staging instrument that includes 3 cognitive and 3 functional ratings, including: 1) memory, 2) orientation, 3) judgment and problem solving, 4) involvement in community affairs, 5) home and hobbies, and 6) personal care based on the CDR interview. The CDR is scored 2 ways yielding a global CDR score (CDR GS, derived from an algorithm developed by the Knight Alzheimer Disease Research Center at Washington University School of Medicine in St. Louis, Missouri, US, and including categorical scoring of 0= cognitively unimpaired, 0.5= mild cognitive impairment, 1= mild dementia, 2= moderate dementia, and 3= severe dementia), as well as CDR-Sum of Boxes (CDR-SB, the continuous sum of 6 domains, up to a total score of 18, with higher scores representing worse disease state).
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	Week 104	ADCS-ADL MCI is a functional measure based on information provided by the study partner (informant) that describes the performance of participants in several ADLs. It assesses 18 instrumental activities of daily living (higher level daily functions) and one basic daily function (dressing). Total score ranges from 0 to 53 with higher scores indicating less impairment.
Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Scale Index Score at Week 88	Baseline, Week 88	The RBANS includes 12 subtests that are divided into 5 RBANS indices: 1-Immediate memory (List learning and story memory); 2-Visuospatial/constructional (figure copy and line orientation); 3-Language (picture naming and semantic fluency); 4-Attention (digit span and coding); 5-Delayed memory (list recall, list recognition, story memory, and figure recall) will be reported. Index scores are expressed as an age-adjusted standard score with a normal mean of 100 and an SD of 15. The sum of Index Scores is the sum of the 5 index scores, and the Sum of Index Scores is converted to an RBANS Total Scale Index Score via a mapping table. RBANS Total Scale Index Score is a norm-based t-score, based on a distribution with a mean of 100 and standard deviation (SD) of 15. Higher scores on each sub measure and index indicate better performance.
Change From Baseline in RBANS Indices at Week 88	Baseline, Week 88	Change from baseline in RBANS indices will be assessed. The RBANS includes 12 subtests that are divided into 5 RBANS indices: 1-Immediate memory (List learning and story memory); 2-Visuospatial/constructional (figure copy and line orientation); 3-Language (picture naming and semantic fluency); 4-Attention (digit span and coding); 5-Delayed memory (list recall, list recognition, story memory, and figure recall) will be reported.
Change from Baseline in Neuropsychiatric Inventory (NPI) at Week 104	Baseline, Week 104	The NPI is a measure of psychobehavioral disturbances, assessing the frequency and severity of disturbances in 12 domains. Frequency for each domain is rated on a 4 point scale (from 1=rarely to 4=very often) and severity on a 3 point scale (from 1=mild to 3=severe), with the score for each domain being the product of the frequency and severity scores, such that each domain is scored from 1 to 12. The NPI total score is the sum of the 12 domain scores, ranging from 0 (best) to 144 (worst).
CSF Concentrations of JNJ-63733657	At Weeks 52, 104, 208 (End of Treatment)	CSF concentrations of JNJ-63733657 will be assessed.
Anti-Drug Antibody to JNJ-63733657	Up to 245 Weeks (90 days [+-7 days] after last dose of study intervention)	Anti-drug antibody to JNJ-63733657 will be assessed.
Number of Participants with Treatment-Emergent Adverse Event of Special Interest (AESI)	Up to 245 Weeks	Number of participants with a treatment-emergent AESI will be reported.
Number of Participants with Electrocardiogram (ECG) Abnormalities	Up to 245 Weeks	Number of participants with ECG abnormalities will be reported.
Number of Participants with Clinical Laboratory Abnormalities	Up to 245 Weeks	Number of participants with clinical laboratory (hematology, clinical chemistry, and urinalysis) abnormalities will be assessed.
Number of Participants with Physical and Neurological Examination Abnormalities	Up to 245 Weeks	Number of participants with physical (body weight, height) and neurological (evaluation of mental status, cranial nerves, motor ability \[including strength, tone, and involuntary movements\], coordination \[including finger-to-nose, gait, and postural reflexes\], and sensation \[including proprioception, cold, light touch, and deep tendon reflexes\]) examination abnormalities will be reported.
Percentage of Participants with Vital Sign Abnormalities	Up to 245 Weeks	Percentage of participants with vital sign abnormalities (temperature, pulse rate, systolic blood pressure \[BP\], diastolic BP) will be reported.
Changes From Baseline in Brain Magnetic Resonance Imaging (MRI) Safety Findings	Baseline and Up to 4.5 years (End of treatment)	Changes from baseline in brain MRI safety findings (brain tumors, aneurysm or atrioventricular malformations, territorial stroke (excluding smaller watershed strokes), recent hemorrhage (parenchymal or subdural), or obstructive hydrocephalus) will be assessed.
Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) score	Baseline and Up to 245 Weeks	C-SSRS is semi structured clinician-administered questionnaire designed to solicit the occurrence, severity, and frequency of suicide-related ideation and behaviors . Total score ranges from 1 to 10, a score of 0 will be assigned (0="no event that can be assessed on the basis of C-SSRS"). Higher scores indicate greater severity. The maximum score assigned for each participant will also be summarized into one of three broad categories: no suicidal ideation or behavior (0), suicidal ideation (1 to 5), suicidal behavior (6 to 10).

Trial Locations

Locations (121)

University of Alabama Birmingham; 🇺🇸 Birmingham, Alabama, United States

Dignity Health; 🇺🇸 Phoenix, Arizona, United States

Irvine Clinical Research; 🇺🇸 Irvine, California, United States

University of California San Diego Medical Center; 🇺🇸 La Jolla, California, United States

University of California - Los Angeles; 🇺🇸 Los Angeles, California, United States

Stanford University Medical Center; 🇺🇸 Palo Alto, California, United States

Pacific Research Network Prn; 🇺🇸 San Diego, California, United States

Syrentis Clinical Research; 🇺🇸 Santa Ana, California, United States

Yale University School Of Medicine; 🇺🇸 New Haven, Connecticut, United States

Georgetown University Hospital; 🇺🇸 Washington, District of Columbia, United States

JEM Research LLC; 🇺🇸 Atlantis, Florida, United States

Brain Matters Research; 🇺🇸 Delray Beach, Florida, United States

Neuropsychiatric Research Center of SWFL; 🇺🇸 Fort Myers, Florida, United States

Clinical NeuroScience Solutions Inc; 🇺🇸 Jacksonville, Florida, United States

Alphab Global Research; 🇺🇸 Jupiter, Florida, United States

ClinCloud Clinical Research; 🇺🇸 Viera, Florida, United States

K2 Medical Research; 🇺🇸 Maitland, Florida, United States

Merritt Island Medical Research, LLC; 🇺🇸 Merritt Island, Florida, United States

University of Miami Miller School of Medicine; 🇺🇸 Miami, Florida, United States

Miami Jewish Health System; 🇺🇸 Miami, Florida, United States

Aqualane Clinical Research; 🇺🇸 Naples, Florida, United States

Renstar Medical Research; 🇺🇸 Ocala, Florida, United States

Sensible Healthcare; 🇺🇸 Ocoee, Florida, United States

Axiom Clinical Research of Florida; 🇺🇸 Tampa, Florida, United States

Stedman Clinical Trials; 🇺🇸 Tampa, Florida, United States

University of South Florida - Health Byrd Alzheimer Institute; 🇺🇸 Tampa, Florida, United States

Charter Research; 🇺🇸 The Villages, Florida, United States

Alzheimers Research and Treatment Center; 🇺🇸 Wellington, Florida, United States

Palm Beach Neurology and Premier Research Institute; 🇺🇸 West Palm Beach, Florida, United States

Conquest Research; 🇺🇸 Winter Park, Florida, United States

The Emory Clinic; 🇺🇸 Atlanta, Georgia, United States

Sandhill Research; 🇺🇸 Decatur, Georgia, United States

Great Lakes Clinical Trials; 🇺🇸 Chicago, Illinois, United States

Alexian Brothers Medical Center - Neuroscience Research Institute; 🇺🇸 Elk Grove Village, Illinois, United States

Indiana University; 🇺🇸 Indianapolis, Indiana, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Anil Nair dba Alzheimer's Disease Center; 🇺🇸 Braintree, Massachusetts, United States

Hattiesburg Clinic; 🇺🇸 Hattiesburg, Mississippi, United States

Washington University School Of Medicine; 🇺🇸 Saint Louis, Missouri, United States

NeuroCognitive Institute; 🇺🇸 Mount Arlington, New Jersey, United States

Princeton Medical Institute; 🇺🇸 Princeton, New Jersey, United States

Advanced Memory Research Institute of NJ; 🇺🇸 Toms River, New Jersey, United States

Neurological Associates of Albany, PC; 🇺🇸 Albany, New York, United States

Velocity Clinical Research; 🇺🇸 East Syracuse, New York, United States

New York University Medical Center; 🇺🇸 New York, New York, United States

Wake Forest Health Sciences; 🇺🇸 Winston-Salem, North Carolina, United States

Cleveland Clinic Lou Revo Center for Brain Health; 🇺🇸 Cleveland, Ohio, United States

Wexner Medical Center at the Ohio State University; 🇺🇸 Columbus, Ohio, United States

Keystone Clinical Studies LLC; 🇺🇸 Plymouth Meeting, Pennsylvania, United States

Brown University School of Medicine; 🇺🇸 Providence, Rhode Island, United States

The University of Texas Health Science Center at Houston; 🇺🇸 Houston, Texas, United States

Memory Clinic Inc; 🇺🇸 Bennington, Vermont, United States

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States

Royal Adelaide Hospital; 🇦🇺 Adelaide, Australia

Box Hill Hospital; 🇦🇺 Box Hill, Australia

Neuro Trials Victoria; 🇦🇺 Carlton, Australia

Austin Health; 🇦🇺 Ivanhoe, Australia

HammondCare Neurodegenerative Clinical Trials - VIC; 🇦🇺 Malvern, Australia

Australian Alzheimer's Research Foundation Incorporated; 🇦🇺 Nedlands, Australia

Royal Melbourne Hospital; 🇦🇺 Parkville, Australia

AZ St.-Jan Brugge-Oostende AV; 🇧🇪 Brugge, Belgium

UCL Hopital Saint-Luc; 🇧🇪 Brussels, Belgium

UZ Antwerpen; 🇧🇪 Edegem, Belgium

Universitair Ziekenhuis Gent; 🇧🇪 Gent, Belgium

Jessa Ziekenhuis; 🇧🇪 Hasselt, Belgium

UZ Brussel; 🇧🇪 Jette, Belgium

UZ Leuven; 🇧🇪 Leuven, Belgium

Algemeen Ziekenhuis Delta; 🇧🇪 Roeselare, Belgium

Parkwood Institute; 🇨🇦 London, Ontario, Canada

Kawartha Centre - Redefining Healthy Aging; 🇨🇦 Peterborough, Ontario, Canada

Toronto Memory Program (Neurology Research Inc.); 🇨🇦 Toronto, Ontario, Canada

UHN-Toronto Western Hospital; 🇨🇦 Toronto, Ontario, Canada

McGill University; 🇨🇦 Montreal, Quebec, Canada

Hopital Pellegrin CHU Bordeaux; 🇫🇷 Bordeaux, France

Hopital Roger Salengro - CHU Lille; 🇫🇷 Lille, France

CHU Nantes - Hopital Nord Laënnec; 🇫🇷 Nantes, France

Hopital Lariboisiere-Fernand Widal; 🇫🇷 Paris, France

Hopital Pitie Salpetriere; 🇫🇷 Paris, France

Chu Rennes Hopital Pontchaillou; 🇫🇷 Rennes, France

Hopital Charles Nicolle; 🇫🇷 Rouen, France

CHU Toulouse - Hôpital La Grave; 🇫🇷 Toulouse, France

Hôpital Bretonneau; 🇫🇷 Tours, France

Takeda General Hospital; 🇯🇵 Aizuwakamatsu, Japan

Inage Neurology and Memory Clinic; 🇯🇵 Chiba-shi, Japan

Kawashima Neurology Clinic; 🇯🇵 Fujisawa-shi, Japan

Fukuoka University Hospital; 🇯🇵 Fukuoka, Japan

Keikokai P-One Clinic; 🇯🇵 Hachioji, Japan

Himeji Central Hospital Clinic; 🇯🇵 Himeji-city, Japan

Shonan Kamakura General Hospital; 🇯🇵 Kamakura-shi, Japan

National Hospital Organization Hizen Psychiatric Center; 🇯🇵 Kanzaki-gun, Japan

Koukan Clinic; 🇯🇵 Kawasaki, Japan

Kobe City Medical Center General Hospital; 🇯🇵 Kobe-shi, Japan

Rijikai Medical Corporation Katayama Medical Clinic; 🇯🇵 Kurashiki-shi, Japan

Kurume University Hospital; 🇯🇵 Kurume, Japan

Tokyo Medical University Hospital; 🇯🇵 Tokyo, Japan

Rakuwakai Otowa Rehabilitation Hospital; 🇯🇵 Kyoto-shi, Japan

Rakuwakai Otowa Hospital; 🇯🇵 Kyoto, Japan

Saiseikai Narashino Hospital; 🇯🇵 Narashino, Japan

National Center For Geriatrics And Gerontology; 🇯🇵 Obu-shi, Japan

Clinical Research Hospital Tokyo; 🇯🇵 Shinjuku-ku, Japan

Tokyo Metropolitan Geriatric Hospital; 🇯🇵 Tokyo, Japan

Jinsenkai MI Clinic; 🇯🇵 Toyonaka-shi, Japan

Nagomi Clinic; 🇯🇵 Toyonaka-shi, Japan

Yokohama Brain and Spine Center; 🇯🇵 Yokohama-shi, Japan

BRC - Amsterdam; 🇳🇱 Amsterdam, Netherlands

BRC - Den Bosch; 🇳🇱 Den Bosch, Netherlands

QPS Netherlands; 🇳🇱 Leeuwarden, Netherlands

BRC Zwolle; 🇳🇱 Zwolle, Netherlands

Centro At. Esp. Oroitu; 🇪🇸 Algorta - Getxo, Spain

Hosp. Del Mar; 🇪🇸 Barcelona, Spain

Hosp. de La Santa Creu I Sant Pau; 🇪🇸 Barcelona, Spain

Fund. Ace-Inst. Cat. Neuroc. Aplicades; 🇪🇸 Barcelona, Spain

Idc Salud Hosp. Gral. de Catalunya; 🇪🇸 Barcelona, Spain

Hosp. Univ. Santa Maria; 🇪🇸 Lleida, Spain

Hosp. Clinico San Carlos; 🇪🇸 Madrid, Spain

Hosp. Mutua Terrassa; 🇪🇸 Terrassa, Spain

Hosp. Univ. I Politecni La Fe; 🇪🇸 Valencia, Spain

Karolinska Universitetssjukhuset; 🇸🇪 Stockholm, Sweden

Royal United Hospital; 🇬🇧 Bath, United Kingdom

Charing Cross Hospital; 🇬🇧 London, United Kingdom