The purpose of this study is to assess whether JNJ-64042056 affects the spread and build up of tau (a protein in brain) when compared with placebo, using brain scan (tau PET) to determine results from specific areas of the brain.

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

Alzheimer Disease

Neurodegenerative disorders

Brain and Nervous System Conditions

Placebo

JNJ-64042056

A Multicenter, Randomized, Placebo-Controlled, Double-Blind, Parallel-Group Study, to Assess Efficacy, Safety and Immunogenicity of JNJ-64042056, a Phosphorylated Tau Targeted Active Immunotherapy, in Participants With Preclinical Alzheimer's Disease

Change from baseline in brain tau burden, as measured by tau PET (including but not limited to Braak I-VI ROIs, tau naive composite ROI, Connection Rank ROI, and New Tau Composite ROI Volume) will be reported.

Levels of IgG titers against ePHF, p-tau peptide and tau peptide in serum will be measured.

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.

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.

Participants with vital signs abnormalities including temperature and blood pressure (systolic and diastolic) (supine) will be summarized over time.

Participants with clinical laboratory abnormalities values (chemistry, hematology, urinalysis and coagulation) will be reported.

Change from baseline in ECG values will be reported.

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 brain MRI safety findings will be reported.

Participants will receive intramuscular (IM) injection of JNJ-64042056 from Week 0 up to a maximum of Week 76.

Participants will receive IM injection of placebo from Week 0 up to a maximum of Week 76.

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.

Xenoscience Inc.

Irvine Clinical Research

Artemis Institute for Clinical Research

Yale University School Of Medicine

JEM Research LLC

Excel Medical Clinical Trials, LLC

K2 Medical Research Winter Garden

Clinical NeuroScience Solutions Inc

K2 Medical Research

Merritt Island Medical Research, LLC

Headlands Research Orlando

Alzheimers Research and Treatment Center

Charter Research

Palm Beach Neurology and Premier Research Institute

Great Lakes Clinical Trials

Quest Research Institute

Hattiesburg Clinic

The Cognitive and Research Center of New Jersey LLC

Neurological Associates of Albany, PC

Velocity Clinical Research

The Medical Research Network, LLC

AMC Research, LLC

Valley Medical Research

Keystone Clinical Studies LLC

Butler Hospital

Clinical Trials of Texas Inc

Memory Clinic Inc

University of Virginia

Neuro Trials Victoria

The Prince Charles Hospital

St Vincent's Centre for Applied Medical Research

Austin Health Heidelberg Repatriation Hospital

Southern Neurology

KaRa Institute of Neurological Diseases

Australian Alzheimer's Research Foundation Incorporated

Hopital Roger Salengro - CHU Lille

Hopital Nord Laennec CHU NANTES

Hopital Lariboisiere-Fernand Widal

CHU Toulouse - Hôpital La Grave

CHRU Tours Hopital Bretonneau

Universitaetsklinikum der RWTH Aachen

Universitaetsklinikum Koeln

Universitaetsklinikum des Saarlandes

Universitatsklinikum Munster

Enomoto Internal Medicine Clinic

Tokyo Asbo Clinic

Hatsuta Neurology Clinic

Kobe City Medical Center General Hospital

Kusunoki Clinic

Musashimurayama Hospital

Saiseikai Narashino Hospital

ToCROM Clinic

Higashi-Shinjuku Clinic

Medical corporation Shinanokai Samoncho Clinic

OCROM Clinic

Nagomi Clinic

Jinsenkai MI Clinic

Barcelona Beta Brain Research Center

Fund. Ace-Inst. Cat. Neuroc. Aplicades

Hosp Clinic de Barcelona

Centro At. Esp. Oroitu

Hosp. Univ. Santa Maria

Hosp. Clinico San Carlos

Clinica Univ. de Navarra

Hosp. Quiron Madrid Pozuelo

Idc Salud Hosp. Gral. de Catalunya

Hosp. Mutua Terrassa

Hosp. Viamed Montecanal

Skanes universitetssjukhus

Karolinska Universitetssjukhuset Huddinge

Royal United Hospital

Re-Cognition Health

Scottish Brain Sciences

Kings College Hospital

University of Oxford

Moorgreen Hospital Memory Assessment And Research Centre

Southampton General Hospital

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.

Change from baseline in brain tau burden as measured by tau positron emission tomography
(PET) at Weeks 102, 154 and 206 will be reported.

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) 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.

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 SUVR biomarkers will be reported.

Change from baseline in p217+tau will be reported.

Change from baseline in PACC-5 total score will be reported.

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.

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.

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.

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.

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

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 ePHF, p-tau peptide and tau peptide in serum will be
measured.

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.

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 including temperature and blood pressure (systolic
and diastolic) (supine) will be summarized over time.

Change from baseline in clinical laboratory values (chemistry, hematology, urinalysis)
will be reported.

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).

Participants will receive intramuscular (IM) injection of JNJ-64042056 from Week 0 until
Week 180.

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

Trials at a glance

Trials at a glance

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

Outcome measures

Primary outcome measures

Secondary outcome measures