Preclinical Alzheimer's Disease
Conditions
Brief summary
The purpose of this study is to assess the effect of JNJ-64042056 on cognitive decline, as measured by Preclinical Alzheimer's disease Cognitive Composite 5 (PACC-5) compared with placebo.
Interventions
DRUGJNJ-64042056
JNJ-64042056 will be administered intramuscularly.
DRUGPlacebo
Placebo will be administered intramuscularly.
Sponsors
Janssen Pharmaceutica N.V., Belgium
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
55 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Elevated brain tau pathology defined as Braak 3 region of interest standardized uptake value ratio (ROI SUVR) greater than (\>) 1.1 (or equivalent based on emerging data) on a screening tau PET scan, reviewed centrally by a qualified reader to enrich for probability of disease progression during the study * Clinical Dementia Rating (CDR) global score of 0 at screening and baseline * Mini Mental State Examination (MMSE) greater than or equal to (\>=) 27 (with educational adjustment) at screening * Able to read and write and with a minimum 5 years of formal education as reported by participant and study partner at screening * A participant must be of non-childbearing potential
Exclusion criteria
* History consistent with or known autosomal dominant AD (mutation identified in the family and/or participant) * Fulfills diagnostic criteria for Alzheimer's Dementia or non-Alzheimer's Dementia, including, but not limited to Frontotemporal Dementia (FTD), Diffuse Lewy Body Dementia (DLBD), Vascular Dementia (VAD), alcoholic dementia, Parkinson's dementia, Korsakov, Creutzfeldt-Jakob or other prion diseases, Posterior Cortical Atrophy * Diagnosis of Mild Cognitive Impairment (MCI) * Vitamin B12 or folate levels below the central laboratory lower limit of normal, unless the investigator determines that supplementation is not required after randomization * History of or current neurological disease other than preclinical AD that may make interpretation of possible new neurological signs or symptoms difficult
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Preclinical Alzheimer's Disease Cognitive Composite 5 (PACC-5) Total Scores up to Week 206 | Baseline up to Week 206 | Cognition will be measured using the PACC-5 scale, which includes 5 components: free/cued selective reminding test, delayed paragraph recall (logical memory test), digit-symbol substitution test, mini mental state examination, and the category fluency test (CFT). PACC-5 is a composite score which provides unique information about early cognitive decline not currently captured by the episodic memory, executive function, and global cognition components. The total score is a sum of z-score, with higher scores indicating better cognitive performance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Brain tau Burden as Measured by tau PET | Baseline and Weeks 102, 154 and 206 | Change from baseline in brain tau burden as measured by tau positron emission tomography (PET) at Weeks 102, 154 and 206 will be reported. |
| Change From Baseline in PACC-5 Individual Domain Scores | Baseline up to Week 206 | Cognition will be measured using the PACC-5 scale, which includes 5 components: free/cued selective reminding test, delayed paragraph recall (logical memory test), digit-symbol substitution test, mini mental state examination, and the category fluency test (CFT). PACC-5 is a composite score which provides unique information about early cognitive decline not currently captured by the episodic memory, executive function, and global cognition components. Each of the individual scales that are used to form PACC-5 composite score will be analyzed. Higher scores indicating better cognitive performance. |
| Time to Event of Clinical Progression as Measured by Clinical Dementia Rating-Global Score (CDR-GS) | Baseline up to Week 206 | Time to event of clinical progression as measured by clinical dementia rating-global score (CDR-GS) will be reported. The CDR assesses 3 domains of cognition (memory, orientation, judgment/problem solving) and 3 domains of function (community affairs, home/hobbies, personal care) using semi-structured interviews of both the study participant and the study partner carried out by a trained rater. Each domain is rated on a 5-point scale of functioning as follows: (0) no impairment; (0.5) questionable impairment; (1) mild impairment; (2) moderate impairment; and (3) severe impairment (Personal care is scored on a 4-point scale without a 0.5 rating available). CDR Global score ranging from 0 to 3, with 0 indicating no signs of clinically apparent cognitive impairment or dementia and 3 indicating severe dementia. |
| Change From Baseline in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Scores | Baseline up to Week 206 | CDR assesses 3 domains of cognition (memory, orientation, judgment/problem solving) and 3 domains of function (community affairs, home/hobbies, personal care) using semi-structured interviews of both the study participant and the study partner carried out by a trained rater. Each domain is rated on a 5-point scale of functioning as follows: (0) no impairment; (0.5) questionable impairment; (1) mild impairment; (2) moderate impairment; and (3) severe impairment (Personal care is scored on a 4-point scale without a 0.5 rating available). Scores of the 6 domains (ranging from 0 to 3) summed to obtain the CDR. Sum of Boxes CDR-SB score with scores ranging from 0 to 18 where higher scores indicates greater impairment. |
| Change from Baseline in Tau PET Standardized Uptake Value Ratio (SUVR) Biomarkers | Baseline up to Week 206 | Change from baseline in Tau PET SUVR biomarkers will be reported. |
| Change From Baseline in p217+tau | Baseline up to Week 206 | Change from baseline in p217+tau will be reported. |
| Change From Baseline in PACC-5 Total Score | Baseline up to Week 180 | Change from baseline in PACC-5 total score will be reported. |
| Change From Baseline in Brain Tau Burden as Measured by Tau PET in Other ROI | Baseline up to Week 206 | Change from baseline in brain tau burden, as measured by tau PET (including but not limited to Braak I-VI ROIs, Connection Rank ROI, and New Tau Composite ROI Volume) will be reported. |
| Change From Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living -Prevention Instrument (ADCS-ADL-PI) | Baseline up to Week 206 | The ADCS-ADL-PI is a functional measure composed of 18 items that include 15 activities of daily living rated on a 4-point scale and 3 high-level function items. Study participants and their study partners independently rate the participant's level of ability. Study partners are additionally asked to evaluate whether activities were completed less often, required more time to complete, and if any errors were made performing the task. High-level function items are rated as "yes" or "no". Total scores range from 0 to 45 with higher scores indicating less impairment. |
| Change From Baseline in Mild Behavioral Impairment Checklist (MBI-C) Score | Baseline up to Week 206 | MBI-C is a 2-page questionnaire consisting of 34 items, in 5 domains. The apathy domain consists of 6 questions including assessments of cognitive, behavioral and emotional apathy. The affect domain contains 6 items, including 4 for depressive features of low mood, anhedonia, hopelessness, and guilt, and 1 question each for worry and panic. The impulse dyscontrol domain is the largest, with 12 questions describing agitation, aggression, impulsivity, recklessness, and abnormal reward and reinforcement. The social appropriateness domain consists of 5 questions assessing sensitivity, empathy, and tact. Finally, the abnormal thought and perception domain consists of 5 questions assessing suspiciousness, grandiosity, and auditory and visual hallucinations. |
| Change From Baseline in the Quality of Life- Alzheimer's Disease (QoL-AD) | Baseline up to Week 206 | QoL-AD is a 13-item scale with four possible scores for each question (score 1: poor and score 4: excellent). It evaluates the caregiver's own perceived quality of life. Total score ranges from 13 to 52. Higher scores represent a better outcome. |
| Change From Baseline in European Quality of Life-5 Dimensions 5-Levels (EQ-5D-5L) Score | Baseline up to Week 206 | The EQ-5D-5L essentially consists of 2 elements: the European Quality of Life-5 Dimensions (EQ-5D) descriptive system and the European Quality visual analogue scale (EQ VAS). The EQ-5D descriptive system comprises the following 5 dimensions: mobility, selfcare, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and unable to/extreme problems. The digits for the 5 dimensions can be combined in a 5-digit number describing the respondent's health state which can be converted into a single summary index (EQ-5D index) by applying a formula that attaches values to each of the levels in each dimension. The EQ VAS records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labeled Best imaginable health state and Worst imaginable health state. The EQ VAS can be used as a quantitative measure of health outcome as judged by the individual respondents |
| Change From Baseline in Resource Utilization in Dementia-Lite (RUD-Lite) Score | Baseline up to Week 206 | RUD-Lite assesses the healthcare resource utilization of participants and their study partners and determines the level of formal and informal care attributable to Alzheimer's disease (AD). It assesses time spent in assisting participants with basics such as dressing, bathing and instrumental activities of daily living (ADLs) such as shopping and cooking. The RUD-Lite results can be used for calculating cost offsets and cost effectiveness modeling. |
| Levels of IgG Titers Against Enriched Paired Helical Filaments (ePHF), p-tau and tau in Serum | Up to Week 206 | Levels of IgG titers against ePHF, p-tau peptide and tau peptide in serum will be measured. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Up to Week 208 | An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the pharmaceutical or biological agent under study. TEAEs are defined as AEs with onset or worsening on or after date of first dose of study treatment. |
| Number of Participants With Reactogenicity | Up to Week 182 | Solicited AEs will be used to assess the reactogenicity of the active immunotherapy and are predefined local (at the injection site) and systemic events for which the participant is specifically questioned, and which are noted by participants in their participant diary. |
| Change from Baseline in Vital Signs | Baseline up to Week 180 | Change from baseline in vital signs including temperature and blood pressure (systolic and diastolic) (supine) will be summarized over time. |
| Change From Baseline in Clinical Laboratory Values | Baseline up to Week 206 | Change from baseline in clinical laboratory values (chemistry, hematology, urinalysis) will be reported. |
| Change from Baseline in Electrocardiogram (ECG) Values | Baseline up to Week 206 | Change from baseline in ECG values will be reported. |
| Change From Baseline in Columbia-Suicidality Severity Rating Scale (C-SSRS) | Baseline up to Week 206 | A frequency distribution of C-SSRS scores at each scheduled time point by treatment will be provided. Shifts from the baseline visit to the most severe/maximum score during the treatment period will be summarized by treatment. The maximum score assigned for each participant will also be summarized into 1 of 3 categories: no suicidal ideation or behavior (0), suicidal ideation (1 to 5), suicidal behavior (6 to 10). |
| Change From Baseline in Magnetic Resonance Imaging (MRI) Findings | Baseline up to Week 206 | Change from baseline in brain MRI safety findings will be reported. |
Countries
Australia, Belgium, France, Germany, Japan, Spain, Sweden, United Kingdom, United States
Contacts
STUDY_DIRECTORJanssen Pharmaceutica N.V., Belgium Clinical trial
Janssen Pharmaceutica N.V., Belgium
Outcome results
None listed