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

JRCT ID: jRCT2031200295

Registered date:13/01/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Alzheimer disease, Cognitive Dysfunction, Dementia
• Date of first enrollment: 19/01/2021
• Target sample size: 523
• Countries of recruitment: Australia,Japan,Belgium,Japan,Canada,Japan,Spain,Japan,France,Japan,Netherland,Japan,United States of America,Japan,United Kingdom Of Great Britain,Japan,Sweden,Japan
• Study type: Interventional

Intervention(s)

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.
JNJ-63733657 High-dose: Participants will receive single dose of JNJ-63733657 high-dose administered by IV infusion every 4 weeks during doubleblind 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:
Participants will receive single dose of matching placebo to JNJ-63733657 administered by IV infusion every 4 weeks during double-blind treatment period.

Outcome(s)

Primary Outcome

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).

Secondary Outcome

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.

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.

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.

Key inclusion & exclusion criteria

• Age minimum: >= 55age old
• Age maximum: <= 80age old
• Gender: Both

Include 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

Exclude 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 Information

• Primary Sponsor: Nakano Masayoshi
• Secondary ID(s): NCT04619420