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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Janssen Research & Development, LLC
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01978548
First received: October 31, 2013
Last updated: September 9, 2014
Last verified: September 2014
  Purpose

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).


Condition Intervention Phase
Alzheimer Disease
Drug: JNJ-54861911 10 mg
Drug: JNJ-54861911 50 mg
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Levels of amyloid beta 1-40 in cerebrospinal (CSF) after treatment at the intended target dose range [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]
  • Levels of amyloid beta 1-40 in plasma after treatment at the intended target dose range [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]
  • Maximum observed plasma concentration (Cmax) of JNJ-54861911 [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]
    Cmax is the observed maximum plasma concentration of study drug, taken directly from the plasma concentration-time profile

  • Time to reach maximum observed plasma concentration of JNJ-54861911 [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]
    Time when Cmax is observed, taken directly from the plasma concentration-time profile

  • Area under the plasma concentration time curve (AUC) from 0 to t hours of JNJ-54861911 [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]
    Area under the plasma concentration-time curve from 0 to t hours post dosing (time t is the dosing interval)

  • Half-life of JNJ-54861911 [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]
    Elimination half-life associated with the terminal slope of the semi-logarithmic drug concentration-time curve, calculated as 0.693/terminal slope

  • Cerebrospinal fluid exposure of JNJ-54861911 [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 48
Study Start Date: December 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   50 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01978548

Contacts
Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions: JNJ.CT@sylogent.com

Locations
Belgium
Completed
Antwerp, Belgium
Recruiting
Gent, Belgium
Recruiting
Hoboken, Belgium
Netherlands
Recruiting
Amsterdam, Netherlands
Spain
Recruiting
Barcelona, Spain
Not yet recruiting
Barcelona, Spain
Recruiting
Madrid, Spain
Recruiting
Madrid N/A, Spain
Recruiting
Terrassa, Spain
Not yet recruiting
Valencia, Spain
Sweden
Recruiting
Mölndal, Sweden
Recruiting
Stockholm, Sweden
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

Additional Information:
No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01978548     History of Changes
Other Study ID Numbers: CR103012, 54861911ALZ1005, 2013-003036-69
Study First Received: October 31, 2013
Last Updated: September 9, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Netherlands: Centrale Commissie Mensgebonden Onderzoek (CCMO)
Sweden: Medical Products Agency/Lakemedelsverket
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Spain: Spanish Agency of Medicines

Keywords provided by Janssen Research & Development, LLC:
Alzheimer Disease
Prodromal Alzheimer Disease
Safety
Tolerability
Pharmacokinetic
Proof of Mechanism
JNJ-54861911

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on September 16, 2014