A Study of JNJ-64042056 in Participants With Preclinical Alzheimer's Disease

Phase 2

Recruiting

• Conditions: Preclinical Alzheimer's Disease
• Interventions: Drug: JNJ-64042056; Drug: Placebo

• Registration Number: NCT06544616
• Lead Sponsor: Janssen Pharmaceutica N.V., Belgium

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-07-22
• Study First Submitted: 2024-08-06
• Study First Submitted QC: 2024-08-06
• Study First Posted: 2024-08-09
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-09
• Last Update Posted: 2025-01-10
• Primary Completion: 2031-07-17
• Study Completion: 2033-05-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 498

Inclusion Criteria

• Elevated brain tau pathology defined as Braak 3 region of interest standardized uptake value ratio (ROI SUVR) greater than (>) 1.1 on a screening tau PET scan, reviewed centrally by a qualified reader
• 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)
• 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

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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 in the opinion of the investigator it does not require treatment
• History of or current neurological disease other than preclinical AD that may make interpretation of possible new neurological signs or symptoms difficult

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A: JNJ-64042056	JNJ-64042056	Participants will receive intramuscular (IM) injection of JNJ-64042056 from Week 0 until Week 180.
Arm B: Placebo	Placebo	Participants will receive IM injection of placebo from Week 0 until Week 180.

Primary Outcome Measures

Name	Time	Method
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 score reflects an averaged z-score, with higher scores indicating better cognitive performance.

Secondary Outcome Measures

Name	Time	Method
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) in the Tau naive composite region of interest (ROI) 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. The score reflects an averaged z-score, with 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 (tau Naive Composite ROI and Other ROIs)	Baseline up to Week 206	Change from baseline in Tau PET SUVR in the tau naive composite ROI and other ROIs 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 206	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.

Trial Locations

Locations (53)

Karolinska Universitetssjukhuset, Huddinge; 🇸🇪 Stockholm, Sweden

University of Oxford; 🇬🇧 Oxford, United Kingdom

Moorgreen Hospital Memory Assessment And Research Centre; 🇬🇧 Southampton, United Kingdom

Xenoscience Inc.; 🇺🇸 Phoenix, Arizona, United States

Irvine Clinical Research; 🇺🇸 Irvine, California, United States

Artemis Institute for Clinical Research; 🇺🇸 San Diego, California, United States

JEM Research LLC; 🇺🇸 Atlantis, Florida, United States

Excel Medical Clinical Trials, LLC; 🇺🇸 Boca Raton, Florida, United States

K2 Medical Research Winter Garden; 🇺🇸 Clermont, Florida, United States

Clinical NeuroScience Solutions Inc; 🇺🇸 Jacksonville, Florida, United States

K2 Medical Research; 🇺🇸 Tampa, Florida, United States

Merritt Island Medical Research, LLC; 🇺🇸 Merritt Island, Florida, United States

Headlands Research Orlando; 🇺🇸 Orlando, Florida, United States

Alzheimers Research and Treatment Center; 🇺🇸 Wellington, Florida, United States

Charter Research; 🇺🇸 The Villages, Florida, United States

Palm Beach Neurology and Premier Research Institute; 🇺🇸 West Palm Beach, Florida, United States

Great Lakes Clinical Trials; 🇺🇸 Gurnee, Illinois, United States

Quest Research Institute; 🇺🇸 Farmington Hills, Michigan, United States

Hattiesburg Clinic; 🇺🇸 Hattiesburg, Mississippi, United States

The Cognitive and Research Center of New Jersey LLC; 🇺🇸 Springfield, New Jersey, United States

Neurological Associates of Albany, PC; 🇺🇸 Albany, New York, United States

Velocity Clinical Research; 🇺🇸 East Syracuse, New York, United States

The Medical Research Network, LLC; 🇺🇸 New York, New York, United States

AMC Research, LLC; 🇺🇸 Matthews, North Carolina, United States

Valley Medical Research; 🇺🇸 Centerville, Ohio, United States

Keystone Clinical Studies LLC; 🇺🇸 Plymouth Meeting, Pennsylvania, United States

Butler Hospital; 🇺🇸 Providence, Rhode Island, United States

Clinical Trials of Texas Inc; 🇺🇸 San Antonio, Texas, United States

Memory Clinic Inc; 🇺🇸 Bennington, Vermont, United States

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States

Neuro Trials Victoria; 🇦🇺 Carlton, Australia

The Prince Charles Hospital; 🇦🇺 Chermside, Australia

St Vincent's Centre for Applied Medical Research; 🇦🇺 Darlinghurst, Australia

Austin Health Heidelberg Repatriation Hospital; 🇦🇺 Ivanhoe, Australia

Southern Neurology; 🇦🇺 Kogarah, Australia

KaRa Institute of Neurological Diseases; 🇦🇺 Macquarie Park, Australia

Australian Alzheimer's Research Foundation Incorporated; 🇦🇺 Nedlands, Australia

Enomoto Internal Medicine Clinic; 🇯🇵 Chofu-shi, Japan

Tokyo Asbo Clinic; 🇯🇵 Chuo-ku, Japan

Hatsuta Neurology Clinic; 🇯🇵 Hirakata-shi, Japan

Kobe City Medical Center General Hospital; 🇯🇵 Kobe City, Japan

Kusunoki Clinic; 🇯🇵 Kobe, Japan

Musashimurayama Hospital; 🇯🇵 Musashimurayama, Japan

Saiseikai Narashino Hospital; 🇯🇵 Narashino-shi, Japan

ToCROM Clinic; 🇯🇵 Shinjuku ku, Japan

Higashi-Shinjuku Clinic; 🇯🇵 Shinjuku-ku, Japan

Medical corporation Shinanokai Samoncho Clinic; 🇯🇵 Shinjyuku Ku, Japan

OCROM Clinic; 🇯🇵 Suita shi, Japan

Jinsenkai MI Clinic; 🇯🇵 Toyonaka-shi, Japan

Nagomi Clinic; 🇯🇵 Toyonaka-shi, Japan

Royal United Hospital; 🇬🇧 Bath, United Kingdom

Re-Cognition Health; 🇬🇧 Winchester, United Kingdom

Gyleview House; 🇬🇧 Edinburgh, United Kingdom