A Study to Evaluate the Effects of JNJ-54861911 on Amyloid Beta Processing in Cerebrospinal Fluid and Plasma in Patients With Prodromal Alzheimer's Disease

June 24, 2015 updated by: Janssen Research & Development, LLC

A Double-blind, Placebo-Controlled, Randomized, 4-Week, Multiple-Dose, Proof-of-Mechanism Study in Subjects With Prodromal Alzheimer's Disease Investigating the Effects of JNJ-54861911 on Aβ Processing in CSF and Plasma

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of JNJ-54861911 in patients with prodromal Alzheimer's disease (pAD).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This will be a multicenter, double-blind (neither investigator nor patient knows which treatment the patient receives), placebo-controlled (placebo is an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial), randomized (patients are assigned different treatments based on chance), multiple-dose, proof-of-mechanism (POM) study in pAD. Approximately 24 outpatients (n=8/treatment group) diagnosed with pAD, according to the inclusion and exclusion criteria, will participate in this 4-week treatment study. For all enrolled patients, this study will consist of an 8-week eligibility screening period, a 4-week double-blind treatment period, and a follow-up examination (7-14 days after the last dose). Patients will be assigned randomly to 1 of 3 treatment groups: placebo, JNJ-54861911 10 mg once daily, or JNJ-54861911 50 mg once daily. Safety assessments will be performed throughout the study. The maximal study duration for a patient will be 14 weeks.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
45

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Antwerp, Belgium
      • Gent, Belgium
      • Hoboken, Belgium
  • Netherlands
      • Amsterdam, Netherlands
  • Spain
      • Barcelona, Spain
      • Madrid, Spain
      • Madrid N/A, Spain
      • Terrassa, Spain
      • Valencia, Spain
  • Sweden
      • Mölndal, Sweden
      • Stockholm, Sweden

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

50 years to 90 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients must have had sufficient education or work experience to exclude mental retardation
  • Patients must have an abnormal cognitive performance consistent with mild cognitive impairment based on the computerized neuropsychological test battery (CANTAB Elect) that can effectively screen patients and identify cognitive deficits consistent with mild cognitive impairment
  • Patients must have evidence of amyloid deposition by means of either 1) low cerebrospinal fluid amyloid beta 1-42 (CSF amyloid beta 1-42) levels and elevated CSF p-Tau and/or total tau levels at screening (cut off values for CSF amyloid beta 1-42 and CSF p-tau and/or total tau will be based on the values established by the Clinical Neurochemistry Lab, Sahlgrenska University Hospital, Mölndal, Sweden and specified in a separate lab manual) or 2) a positive 18F-flutematol amyloid positron emission tomography (PET) amyloid scan at screening (optional depending on the site's PET capability) or both
  • Patients must have a body mass index (BMI=weight/height²) between 18 and 35 kg/m2, inclusive, at screening
  • Women must be postmenopausal, permanently sterilized or otherwise be incapable of pregnancy
  • Must adhere to required contraception during and for 3 months after study
  • Patients must be otherwise healthy for their age group or medically stable with or without medication
  • Patients must be able to be compliant with self-administration of medication
  • Patients must be able to swallow drug as a whole

Exclusion Criteria:

  • Patient has evidence of brain disease, other than Alzheimer's Disease (AD), or any other abnormality (e.g. folic acid/Vitamin B12 deficiency) that could explain the cognitive deficit (including, but not limited to vascular encephalopathy or strokes, as imaged by cerebral MRI and Major Depression, as defined by DSM-IV criteria)
  • Patient has been diagnosed with dementia due to AD, due to other diseases, or with AD and contribution of other disorders (mixed dementia)
  • Patient has evidence of familial autosomal dominant AD
  • Patient has a history of substance or alcohol abuse
  • Relevant history of lower back pain or scoliosis and/or major (lumbar) back surgery
  • Patient is allergic to local anesthetics and/or iodine or chlorhexidine
  • Patient has taken aspirin (even low dose) within 5 days prior to lumbar puncture (screening or Day 1)
  • Patient has taken Low Molecular Weight Heparin (LMWH) within 12 hours prior to lumbar puncture (screening or Day 1)
  • Patient has taken any anticoagulant treatment (e.g. warfarin; besides LMWH described above) within 1 week prior to lumbar puncture (screening or Day 1)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: JNJ-54861911 10 mg
From Day 1 to Day 28 inclusive, patients will self-administer once daily study drug (JNJ-54861911 or placebo) with a glass of non-carbonated water (approximately 200 mL).
Drug: JNJ-54861911 10 mg
JNJ-54861911 10 mg will be administered as two 5 mg oral tablets once daily.
EXPERIMENTAL: JNJ-54861911 50 mg
Drug: JNJ-54861911 50 mg
JNJ-54861911 50 mg will be administered as two 25 mg oral tablets once daily.
PLACEBO_COMPARATOR: Placebo
Patients will receive matching placebo.
Drug: Placebo
Matching placebo will be administered as 2 oral tablets once daily.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Levels of amyloid beta 1-40 in cerebrospinal (CSF) after treatment at the intended target dose range
Time Frame: Up to 4 weeks
Up to 4 weeks
Levels of amyloid beta 1-40 in plasma after treatment at the intended target dose range
Time Frame: Up to 4 weeks
Up to 4 weeks
Maximum observed plasma concentration (Cmax) of JNJ-54861911
Time Frame: Up to 4 weeks
Cmax is the observed maximum plasma concentration of study drug, taken directly from the plasma concentration-time profile
Up to 4 weeks
Time to reach maximum observed plasma concentration of JNJ-54861911
Time Frame: Up to 4 weeks
Time when Cmax is observed, taken directly from the plasma concentration-time profile
Up to 4 weeks
Area under the plasma concentration time curve (AUC) from 0 to t hours of JNJ-54861911
Time Frame: Up to 4 weeks
Area under the plasma concentration-time curve from 0 to t hours post dosing (time t is the dosing interval)
Up to 4 weeks
Half-life of JNJ-54861911
Time Frame: Up to 4 weeks
Elimination half-life associated with the terminal slope of the semi-logarithmic drug concentration-time curve, calculated as 0.693/terminal slope
Up to 4 weeks
Cerebrospinal fluid exposure of JNJ-54861911
Time Frame: Up to 4 weeks
Up to 4 weeks
The number of volunteers who experience adverse events as a measure of safety and tolerability of JNJ-54861911 after multiple-dose administration in the anticipated target dose range
Time Frame: Up to 4 weeks
Up to 4 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Levels of amyloid beta fragments (amyloid beta 1-37, 1-38, and 1-42) in cerebrospinal fluid after treatment at the intended target dose range
Time Frame: Up to 4 weeks
Up to 4 weeks
Levels of amyloid beta fragments (amyloid beta 1-37, 1-38, and 1-42) in plasma after treatment at the intended target dose range
Time Frame: Up to 4 weeks
Up to 4 weeks
Levels of amyloid precursor protein (APP) fragments (soluble amyloid precursor protein α [sAPPalpha], sAPPbeta, totalAPP) in CSF after treatment at the intended target dose range
Time Frame: Up to 4 weeks
Up to 4 weeks
Compare the relationship of amyloid beta 1-40 levels in plasma and cerebrospinal fluid after treatment at the intended target dose range
Time Frame: Up to 4 weeks
Up to 4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Janssen Research & Development, LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2013

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2015

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 31, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 31, 2013

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 7, 2013

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 25, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 24, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CR103012
  • 54861911ALZ1005 (OTHER: Janssen Research & Development, LLC)
  • 2013-003036-69 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings