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

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ClinicalTrials.gov Identifier: NCT04619420
Recruitment Status : Recruiting
First Posted : November 6, 2020
Last Update Posted : July 23, 2021
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE November 5, 2020
First Posted Date  ICMJE November 6, 2020
Last Update Posted Date July 23, 2021
Actual Study Start Date  ICMJE January 4, 2021
Estimated Primary Completion Date March 7, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 5, 2020)
Change From Baseline in Alzheimer's Disease Assessment Scale Cognitive subscale 13-item version (ADAS-Cog 13) Total Score [ Time Frame: Baseline and up to 4.5 years (End of treatment) ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 5, 2020)
  • Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Scale Index Score [ Time Frame: Baseline and up to 4.5 years (End of treatment) ]
    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 [ Time Frame: Baseline and up to 4.5 years (End of treatment) ]
    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 Clinical Dementia Rating- Sum of Boxes (CDR-SB) [ Time Frame: Baseline and up to 4.5 years (End of treatment) ]
    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 Alzheimer's Disease Cooperative Study Activities of Daily Living for Mild Cognitive Impairment (ADCS-ADL MCI) [ Time Frame: Baseline and up to 4.5 years (End of treatment) ]
    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 17 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 Integrated Alzheimer's Disease Rating Scale (iADRS) [ Time Frame: Baseline and up to 4.5 years (End of treatment) ]
    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 134 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 (score 0 to 53, lower scores indicate worse daily function).
  • Change from Baseline in Neuropsychiatric Inventory (NPI) [ Time Frame: Baseline and up to 4.5 years (End of treatment) ]
    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).
  • Percentage of Participants Progressing From Clinical Dementia Rating- Global Score (CDR-GS) 0.5 to 1 or Higher [ Time Frame: Baseline and up to 4.5 years (End of treatment) ]
    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 Brain tau Burden as Measured by tau PET [ Time Frame: Baseline and up to 4.5 years (End of treatment) ]
    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 [ Time Frame: Baseline and up to 4.5 years (End of treatment) ]
    Change from baseline in CSF concentrations of total, free, and bound p217+tau (phosphorylated tau) fragments will be assessed.
  • CSF Concentrations of JNJ-63733657 [ Time Frame: At Weeks 52, 104, 208 (End of Treatment) ]
    CSF concentrations of JNJ-63733657 will be assessed.
  • Serum Concentrations of JNJ-63733657 [ Time Frame: 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.
  • Anti-Drug Antibody to JNJ-63733657 [ Time Frame: 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 Adverse Events (AEs) as a Measure of Safety and Tolerability [ Time Frame: 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 [ Time Frame: 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.
  • Number of Participants with Electrocardiogram (ECG) Abnormalities [ Time Frame: Up to 245 Weeks ]
    Number of participants with ECG abnormalities will be reported.
  • Number of Participants with Clinical Laboratory Abnormalities [ Time Frame: Baseline and 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of JNJ-63733657 in Participants With Early Alzheimer's Disease
Official Title  ICMJE A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Assess the Efficacy and Safety of JNJ-63733657, an Anti-tau Monoclonal Antibody, in Participants With Early Alzheimer's Disease
Brief Summary The primary purpose of this study is to evaluate the effect of JNJ-63733657 versus placebo on cognitive decline using the Alzheimer's Disease Assessment Scale Cognitive subscale 13-item version (ADAS-Cog13).
Detailed Description Alzheimer's disease (AD) is a fatal neurodegenerative disease that is manifested by progressive cognitive deficits including memory loss followed by loss of independent function as well as neuropsychiatric symptoms such as apathy, depression, anxiety, agitation and psychosis. JNJ-63733657 is a humanized monoclonal anti-tau antibody which binds to phosphorylated tau (P-tau). The study will evaluate whether JNJ-63733657 can slow cognitive decline in participants with Early AD with evidence of elevated brain tau (T+) and assess its safety and tolerability. The study consists of: screening period (13 weeks), double-blind treatment period (up to 232 weeks), and a follow-up period (13 weeks). Safety and tolerability assessments will include adverse events (AEs), vital signs, electrocardiogram (ECG), early discontinuations, physical and neurological examinations, safety laboratory evaluations, suicidality risks (Columbia Suicide Severity Rating Scale [CSSRS]) and brain MRI will be performed during the study. The maximum treatment duration is up to 232 weeks (4.5 years).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Alzheimer Disease
  • Cognitive Dysfunction
  • Dementia
Intervention  ICMJE
  • Drug: JNJ-63733657
    JNJ-63733657 low or high dose will be administered by IV infusion.
  • Drug: Placebo
    Placebo matching to JNJ-63733657 will be administered by IV infusion.
Study Arms  ICMJE
  • Experimental: JNJ-63733657
    Participants will receive single dose of JNJ-63733657 low dose or high dose administered by intravenous (IV) infusion every 4 weeks.
    Intervention: Drug: JNJ-63733657
  • Placebo Comparator: Placebo
    Participants will receive single dose of matching placebo to JNJ-63733657 administered by IV infusion every 4 weeks.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 5, 2020)
420
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 7, 2025
Estimated Primary Completion Date March 7, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • 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 during the study and up to 16 weeks after the last dose of study intervention

Exclusion Criteria:

  • Participants with CDR GS >=1 during screening or at predose baseline 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 (eg, MCI/dementia due to frontotemporal lobar degeneration, diffuse lewy body disease, 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 >=11
  • Rosen Modified 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 55 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   France,   Japan,   Netherlands,   Spain,   Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04619420
Other Study ID Numbers  ICMJE CR108832
2020-000116-30 ( EudraCT Number )
63733657ALZ2002 ( Other Identifier: Janssen Research & Development, LLC )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
URL: https://www.janssen.com/clinical-trials/transparency
Responsible Party Janssen Research & Development, LLC
Study Sponsor  ICMJE Janssen Research & Development, LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
PRS Account Janssen Research & Development, LLC
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP