A Study of JNJ-64042056 in Participants With Preclinical Alzheimer's Disease
NCT Number: NCT06544616
Acronym: Reτain
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Preclinical Alzheimer's Disease
Interventions: DRUG: JNJ-64042056|DRUG: Placebo
Sponsor: Janssen Pharmaceutica N.V., Belgium
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 498
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: DOUBLE (PARTICIPANT, INVESTIGATOR)|Primary Purpose: TREATMENT
Start Date: 2024-07-22
Completion Date: 2033-05-31
Locations: Xenoscience Inc., Phoenix, Arizona, 85004, United States|Irvine Clinical Research, Irvine, California, 92614, United States|Artemis Institute for Clinical Research, Riverside, California, 92503, United States|Artemis Institute for Clinical Research, San Diego, California, 92103, United States|JEM Research LLC, Atlantis, Florida, 33462, United States|Excel Medical Clinical Trials, LLC, Boca Raton, Florida, 33434, United States|K2 Medical Research Winter Garden, Clermont, Florida, 34711, United States|K2 Medical Research, Maitland, Florida, 32751, United States|Merritt Island Medical Research, LLC, Merritt Island, Florida, 32952, United States|Headlands Research Orlando, Orlando, Florida, 32819, United States|Alzheimers Research and Treatment Center, Stuart, Florida, 34997, United States|K2 Medical Research, Tampa, Florida, 33607, United States|Charter Research, The Villages, Florida, 32159, United States|K2 Medical Research, The Villages, Florida, 32159, United States|Alzheimers Research and Treatment Center, Wellington, Florida, 33414, United States|Palm Beach Neurology and Premier Research Institute, West Palm Beach, Florida, 33407, United States|Great Lakes Clinical Trials, Chicago, Illinois, 60640, United States|Great Lakes Clinical Trials, Gurnee, Illinois, 60031, United States|Quest Research Institute, Farmington Hills, Michigan, 48334, United States|Hattiesburg Clinic, Hattiesburg, Mississippi, 39401, United States|Neurological Associates of Albany, PC, Albany, New York, 12208, United States|Velocity Clinical Research, East Syracuse, New York, 13057, United States|AMC Research, LLC, Matthews, North Carolina, 28105, United States|Valley Medical Research, Centerville, Ohio, 45459-2785, United States|Keystone Clinical Studies LLC, Plymouth Meeting, Pennsylvania, 19462, United States|Neuro Trials Victoria, Carlton, 3053, Australia|St Vincent's Centre for Applied Medical Research, Darlinghurst, 2010, Australia|Southern Neurology, Kogarah, 2217, Australia|KaRa Institute of Neurological Diseases, Macquarie Park, 2113, Australia|Australian Alzheimer's Research Foundation Incorporated, Nedlands, 6009, Australia|Enomoto Internal Medicine Clinic, Chofu-shi, 1820036, Japan|Tokyo Asbo Clinic, Chuo-ku, 104-0031, Japan|Hatsuta Neurology Clinic, Hirakata-shi, 573-1121, Japan|Kusunoki Clinic, Kobe, 650-0044, Japan|Saiseikai Narashino Hospital, Narashino-shi, 275-8580, Japan|Medical Corporation Heishinkai ToCROM Clinic, Shinjuku-ku, 160-0008, Japan|Higashi-Shinjuku Clinic, Shinjuku-ku, 169-0072, Japan|Medical corporation Shinanokai Samoncho Clinic, Shinjyuku Ku, 160 0017, Japan|Heishinkai OCROM Clinic, Suita-shi, 565-0853, Japan|Jinsenkai MI Clinic, Toyonaka-shi, 560-0004, Japan|Nagomi Clinic, Toyonaka-shi, 560-0004, Japan|Gyleview House, Edinburgh, EH12 9DQ, United Kingdom|Cognition Health Ltd, London, W1G 9JF, United Kingdom

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.

Primary Outcome Measures: Change From Baseline in Preclinical Alzheimer's Disease Cognitive Composite 5 (PACC-5) Total Scores 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 score reflects an averaged z-score, with higher scores indicating better cognitive performance., Baseline up to Week 206
Secondary Outcome Measures: Change From Baseline in Brain tau Burden as Measured by tau PET, Change from baseline in brain tau burden as measured by tau positron emission tomography (PET) in the Tau naive composite region of interest (ROI) at Weeks 102, 154 and 206 will be reported., Baseline and Weeks 102, 154 and 206|Change From Baseline in PACC-5 Individual Domain Scores, 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 score reflects an averaged z-score, with higher scores indicating better cognitive performance., Baseline up to Week 206|Time to Event of Clinical Progression as Measured by Clinical Dementia Rating-Global Score (CDR-GS), 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., Baseline up to Week 206|Change From Baseline in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Scores, 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., Baseline up to Week 206|Change from Baseline in Tau PET Standardized Uptake Value Ratio (SUVR) Biomarkers (tau Naive Composite ROI and Other ROIs), Change from baseline in Tau PET SUVR in the tau naive composite ROI and other ROIs will be reported., Baseline up to Week 206|Change From Baseline in p217+tau, Change from baseline in p217+tau will be reported., Baseline up to Week 206|Change From Baseline in PACC-5 Total Score, Change from baseline in PACC-5 total score will be reported., Baseline up to Week 180|Change From Baseline in Brain Tau Burden as Measured by Tau PET in Other ROI, 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., Baseline up to Week 206|Change From Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living -Prevention Instrument (ADCS-ADL-PI), 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., Baseline up to Week 206|Change From Baseline in Mild Behavioral Impairment Checklist (MBI-C) Score, 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., Baseline up to Week 206|Change From Baseline in the Quality of Life- Alzheimer's Disease (QoL-AD), 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., Baseline up to Week 206|Change From Baseline in European Quality of Life-5 Dimensions 5-Levels (EQ-5D-5L) Score, 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, Baseline up to Week 206|Change From Baseline in Resource Utilization in Dementia-Lite (RUD-Lite) Score, 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., Baseline up to Week 206|Levels of IgG Titers Against Enriched Paired Helical Filaments (ePHF), p-tau and tau in Serum, Levels of IgG titers against ePHF, p-tau peptide and tau peptide in serum will be measured., Up to Week 206|Number of Participants With Treatment Emergent Adverse Events (TEAEs), 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., Up to Week 208|Number of Participants With Reactogenicity, 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., Up to Week 182|Change from Baseline in Vital Signs, Change from baseline in vital signs including temperature and blood pressure (systolic and diastolic) (supine) will be summarized over time., Baseline up to Week 206|Change From Baseline in Clinical Laboratory Values, Change from baseline in clinical laboratory values (chemistry, hematology, urinalysis) will be reported., Baseline up to Week 206|Change from Baseline in Electrocardiogram (ECG) Values, Change from baseline in ECG values will be reported., Baseline up to Week 206|Change From Baseline in Columbia-Suicidality Severity Rating Scale (C-SSRS), 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)., Baseline up to Week 206|Change From Baseline in Magnetic Resonance Imaging (MRI) Findings, Change from baseline in brain MRI safety findings will be reported., Baseline up to Week 206