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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04619420
Recruitment Status : Active, not recruiting
First Posted : November 6, 2020
Last Update Posted : June 20, 2024
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Cognitive Dysfunction Dementia Drug: JNJ-63733657 Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 523 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : January 6, 2021
Estimated Primary Completion Date : February 27, 2026
Estimated Study Completion Date : December 30, 2032

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: JNJ-63733657 Low-dose
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.
Drug: JNJ-63733657
JNJ-63733657 low or high dose will be administered by IV infusion.

Experimental: JNJ-63733657 High-dose
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.
Drug: JNJ-63733657
JNJ-63733657 low or high dose will be administered by IV infusion.

Placebo Comparator: 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.
Drug: Placebo
Placebo matching to JNJ-63733657 will be administered by IV infusion.




Primary Outcome Measures :
  1. Change From Baseline in Integrated Alzheimer's Disease Rating Scale (iADRS) Total Score at Week 104 [ Time Frame: 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 :
  1. Change From Baseline in Alzheimer's Disease Assessment Scale Cognitive subscale 13-item version (ADAS-Cog 13) Total Score at Week 104 [ Time Frame: 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.

  2. 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 [ Time Frame: 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.

  3. Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Scale Index Score at Week 88 [ Time Frame: 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.

  4. Change From Baseline in RBANS Indices at Week 88 [ Time Frame: 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.

  5. Change From Baseline in Clinical Dementia Rating- Sum of Boxes (CDR-SB) at Week 104 [ Time Frame: 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.

  6. Change from Baseline in Neuropsychiatric Inventory (NPI) at Week 104 [ Time Frame: 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).

  7. 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 [ Time Frame: 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).

  8. Change From Baseline in Brain tau Burden as Measured by tau PET at Week 104 [ Time Frame: Baseline, Week 104 ]
    Change from baseline in brain tau burden, as measured by tau positron emission tomography (PET) will be assessed.

  9. Change From Baseline in Cerebrospinal Fluid (CSF) concentrations of Total, Free, and Bound p217+tau Fragments at Week 104 [ Time Frame: Baseline, Week 104 ]
    Change from baseline in CSF concentrations of total, free, and bound p217+tau (phosphorylated tau) fragments will be assessed.

  10. CSF Concentrations of JNJ-63733657 [ Time Frame: At Weeks 52, 104, 208 (End of Treatment) ]
    CSF concentrations of JNJ-63733657 will be assessed.

  11. 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.

  12. 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.

  13. 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.

  14. Number of Participants with Treatment-Emergent Adverse Event of Special Interest (AESI) [ Time Frame: Up to 245 Weeks ]
    Number of participants with a treatment-emergent AESI will be reported.

  15. 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.

  16. Number of Participants with Electrocardiogram (ECG) Abnormalities [ Time Frame: Up to 245 Weeks ]
    Number of participants with ECG abnormalities will be reported.

  17. Number of Participants with Clinical Laboratory Abnormalities [ Time Frame: Up to 245 Weeks ]
    Number of participants with clinical laboratory (hematology, clinical chemistry, and urinalysis) abnormalities will be assessed.

  18. 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.

  19. 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.

  20. 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.

  21. 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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   55 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04619420


Locations
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Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT04619420    
Other Study ID Numbers: CR108832
2020-000116-30 ( EudraCT Number )
63733657ALZ2002 ( Other Identifier: Janssen Research & Development, LLC )
2022-501188-42-00 ( Registry Identifier: EUCT number )
First Posted: November 6, 2020    Key Record Dates
Last Update Posted: June 20, 2024
Last Verified: June 2024
Individual Participant Data (IPD) Sharing Statement:
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

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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
Additional relevant MeSH terms:
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Alzheimer Disease
Cognitive Dysfunction
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cognition Disorders