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

Alzheimer Disease Clinical Trial

— Autonomy  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04619420
• Other study ID #: CR108832
• Secondary ID: 2020-000116-3063
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 6, 2021
• Est. completion date: December 30, 2032

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 523
• Est. completion date: December 30, 2032
• Est. primary completion date: February 27, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Cognitive Dysfunction
• Dementia

Intervention

Drug:
• JNJ-63733657
JNJ-63733657 low or high dose will be administered by IV infusion.
• Placebo
Placebo matching to JNJ-63733657 will be administered by IV infusion.

Locations

Country	Name	City	State
Australia	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
Belgium	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
Canada	Parkwood Institute	London	Ontario
Canada	McGill University	Montreal	Quebec
Canada	Kawartha Centre - Redefining Healthy Aging	Peterborough	Ontario
Canada	Toronto Memory Program (Neurology Research Inc.)	Toronto	Ontario
Canada	UHN-Toronto Western Hospital	Toronto	Ontario
France	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
Japan	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, Hyogo
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	Rakuwakai Otowa Hospital	Kyoto
Japan	Rakuwakai Otowa Rehabilitation Hospital	Kyoto-shi
Japan	Saiseikai Narashino Hospital	Narashino
Japan	National Center For Geriatrics And Gerontology	Obu-shi
Japan	Clinical Research Hospital Tokyo	Shinjuku-ku
Japan	Tokyo Medical University Hospital	Tokyo
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
Netherlands	BRC - Amsterdam	Amsterdam
Netherlands	BRC - Den Bosch	Den Bosch
Netherlands	QPS Netherlands	Leeuwarden
Netherlands	BRC - Zwolle	Zwolle
Spain	Centro At. Esp. Oroitu	Algorta - Getxo
Spain	Fund. Ace-Inst. Cat. Neuroc. Aplicades	Barcelona
Spain	Hosp. de La Santa Creu I Sant Pau	Barcelona
Spain	Hosp. Del Mar	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
Sweden	Karolinska Universitetssjukhuset	Stockholm
United Kingdom	Royal United Hospital	Bath
United Kingdom	Charing Cross Hospital	London
United States	Neurological Associates of Albany, PC	Albany	New York
United States	Emory Clinic	Atlanta	Georgia
United States	JEM Research LLC	Atlantis	Florida
United States	Memory Clinic Inc	Bennington	Vermont
United States	University of Alabama Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Anil Nair dba Alzheimer's Disease Center	Braintree	Massachusetts
United States	University of Virginia	Charlottesville	Virginia
United States	Great Lakes Clinical Trials	Chicago	Illinois
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	Sandhill Research	Decatur	Georgia
United States	Brain Matters Research	Delray Beach	Florida
United States	Velocity Clinical Research	East Syracuse	New York
United States	Alexian Brothers Medical Center - Neuroscience Research Institute	Elk Grove Village	Illinois
United States	Neuropsychiatric Research Center of SWFL	Fort Myers	Florida
United States	Hattiesburg Clinic	Hattiesburg	Mississippi
United States	The University of Texas Health Science Center at Houston	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Irvine Clinical Research	Irvine	California
United States	Clinical NeuroScience Solutions Inc	Jacksonville	Florida
United States	Alphab Global Research	Jupiter	Florida
United States	University of California San Diego Medical Center	La Jolla	California
United States	University of California - Los Angeles	Los Angeles	California
United States	ClinCloud Clinical Research	Maitland	Florida
United States	K2 Medical Research	Maitland	Florida
United States	Merritt Island Medical Research, LLC	Merritt Island	Florida
United States	Miami Jewish Health System	Miami	Florida
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	NeuroCognitive Institute	Mount Arlington	New Jersey
United States	Aqualane Clinical Research	Naples	Florida
United States	Yale University School Of Medicine	New Haven	Connecticut
United States	New York University Medical Center	New York	New York
United States	Renstar Medical Research	Ocala	Florida
United States	Sensible Healthcare	Ocoee	Florida
United States	Stanford University Medical Center	Palo Alto	California
United States	Dignity Health	Phoenix	Arizona
United States	Keystone Clinical Studies LLC	Plymouth Meeting	Pennsylvania
United States	Princeton Medical Institute	Princeton	New Jersey
United States	Brown University School of Medicine	Providence	Rhode Island
United States	Washington University School Of Medicine	Saint Louis	Missouri
United States	Pacific Research Network Prn	San Diego	California
United States	Syrentis Clinical Research	Santa Ana	California
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	Advanced Memory Research Institute of NJ	Toms River	New Jersey
United States	ClinCloud Clinical Research	Viera	Florida
United States	Georgetown University Hospital	Washington	District of Columbia
United States	Alzheimers Research and Treatment Center	Wellington	Florida
United States	Palm Beach Neurology and Premier Research Institute	West Palm Beach	Florida
United States	Wake Forest Health Sciences	Winston-Salem	North Carolina
United States	Conquest Research	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Japan,  Netherlands,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Integrated Alzheimer's Disease Rating Scale (iADRS) Total Score at 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).	Week 104
Secondary	Change From Baseline in Alzheimer's Disease Assessment Scale Cognitive subscale 13-item version (ADAS-Cog 13) Total Score at 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.	Week 104
Secondary	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	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.	Week 104
Secondary	Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Scale Index Score at 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.	Baseline, Week 88
Secondary	Change From Baseline in RBANS Indices at 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.	Baseline, Week 88
Secondary	Change From Baseline in Clinical Dementia Rating- Sum of Boxes (CDR-SB) at 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.	Baseline, Week 104
Secondary	Change from Baseline in Neuropsychiatric Inventory (NPI) at 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).	Baseline, Week 104
Secondary	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	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).	From Baseline through Week 104
Secondary	Change From Baseline in Brain tau Burden as Measured by tau PET at Week 104	Change from baseline in brain tau burden, as measured by tau positron emission tomography (PET) will be assessed.	Baseline, Week 104
Secondary	Change From Baseline in Cerebrospinal Fluid (CSF) concentrations of Total, Free, and Bound p217+tau Fragments at Week 104	Change from baseline in CSF concentrations of total, free, and bound p217+tau (phosphorylated tau) fragments will be assessed.	Baseline, Week 104
Secondary	CSF Concentrations of JNJ-63733657	CSF concentrations of JNJ-63733657 will be assessed.	At Weeks 52, 104, 208 (End of Treatment)
Secondary	Serum Concentrations of JNJ-63733657	Serum concentrations of JNJ-63733657 will be assessed.	At Weeks 4, 8, 12, 16, 20, 24, 36, 52, 76, 104, 128, 156, 180, 208, 232 (End of treatment)
Secondary	Anti-Drug Antibody to JNJ-63733657	Anti-drug antibody to JNJ-63733657 will be assessed.	Up to 245 Weeks (90 days [+-7 days] after last dose of study intervention)
Secondary	Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability	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.	Up to 245 Weeks
Secondary	Number of Participants with Treatment-Emergent Adverse Event of Special Interest (AESI)	Number of participants with a treatment-emergent AESI will be reported.	Up to 245 Weeks
Secondary	Number of Participants with Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability	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.	Up to 245 Weeks
Secondary	Number of Participants with Electrocardiogram (ECG) Abnormalities	Number of participants with ECG abnormalities will be reported.	Up to 245 Weeks
Secondary	Number of Participants with Clinical Laboratory Abnormalities	Number of participants with clinical laboratory (hematology, clinical chemistry, and urinalysis) abnormalities will be assessed.	Up to 245 Weeks
Secondary	Number of Participants with Physical and Neurological Examination Abnormalities	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.	Up to 245 Weeks
Secondary	Percentage of Participants with Vital Sign Abnormalities	Percentage of participants with vital sign abnormalities (temperature, pulse rate, systolic blood pressure [BP], diastolic BP) will be reported.	Up to 245 Weeks
Secondary	Changes From Baseline in Brain Magnetic Resonance Imaging (MRI) Safety Findings	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.	Baseline and Up to 4.5 years (End of treatment)
Secondary	Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) score	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).	Baseline and Up to 245 Weeks