Alzheimer Disease, Cognitive Dysfunction, Dementia
Conditions
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.
Interventions
DRUGJNJ-63733657
JNJ-63733657 low or high dose will be administered by IV infusion.
DRUGPlacebo
Placebo matching to JNJ-63733657 will be administered by IV infusion.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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.
Eligibility
Sex/Gender
ALL
Age
55 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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 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). |
| 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 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. |
| CSF Concentrations of JNJ-63733657 | At Weeks 52, 104, 208 (End of Treatment) | CSF concentrations of JNJ-63733657 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. |
| 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 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 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 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. |
| 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). |
Countries
Australia, Belgium, Canada, France, Japan, Netherlands, Spain, Sweden, United Kingdom, United States
Contacts
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Outcome results
None listed