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

NCT01978548 | Completed Phase 1 DMC

• 3 other identifiers: CR10301254861911ALZ10052013-003036-69
• Study Type: interventional
• Target: 45
• Locations: 4 countries
• Sites: 10

Brief Summary

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).

Conditions

Alzheimer Disease

Keywords

Alzheimer Disease; Prodromal Alzheimer Disease; Safety; Tolerability; Pharmacokinetic; Proof of Mechanism; JNJ-54861911

Outcome Measures

Primary Outcomes (8)

• Levels of amyloid beta 1-40 in cerebrospinal (CSF) after treatment at the intended target dose range

  Up to 4 weeks

• Levels of amyloid beta 1-40 in plasma after treatment at the intended target dose range

  Up to 4 weeks

• Maximum observed plasma concentration (Cmax) of JNJ-54861911

  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 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

  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

  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

  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

  Up to 4 weeks

Secondary Outcomes (4)

• 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

  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

  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

  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

  Up to 4 weeks

Study Arms (3)

JNJ-54861911 10 mg

EXPERIMENTAL

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 50 mg

EXPERIMENTAL

Drug: JNJ-54861911 50 mg

Placebo

PLACEBO COMPARATOR

Patients will receive matching placebo.

Drug: Placebo

Interventions

JNJ-54861911 10 mg DRUG

JNJ-54861911 10 mg will be administered as two 5 mg oral tablets once daily.

JNJ-54861911 10 mg

JNJ-54861911 50 mg DRUG

JNJ-54861911 50 mg will be administered as two 25 mg oral tablets once daily.

JNJ-54861911 50 mg

Placebo DRUG

Matching placebo will be administered as 2 oral tablets once daily.

Placebo

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (10)

Unknown Facility

Antwerp, Belgium

Location

Unknown Facility

Ghent, Belgium

Location

Unknown Facility

Hoboken, Belgium

Location

Unknown Facility

Amsterdam, Netherlands

Location

Unknown Facility

Barcelona, Spain

Location

Unknown Facility

Madrid, Spain

Location

Unknown Facility

Terrassa, Spain

Location

Unknown Facility

Valencia, Spain

Location

Unknown Facility

Mölndal, Sweden

Location

Unknown Facility

Stockholm, Sweden

Location

Related Publications (1)

• Timmers M, Streffer JR, Russu A, Tominaga Y, Shimizu H, Shiraishi A, Tatikola K, Smekens P, Borjesson-Hanson A, Andreasen N, Matias-Guiu J, Baquero M, Boada M, Tesseur I, Tritsmans L, Van Nueten L, Engelborghs S. Pharmacodynamics of atabecestat (JNJ-54861911), an oral BACE1 inhibitor in patients with early Alzheimer's disease: randomized, double-blind, placebo-controlled study. Alzheimers Res Ther. 2018 Aug 23;10(1):85. doi: 10.1186/s13195-018-0415-6.

  PMID: 30134967 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

atabecestat

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2013
• First Posted: November 7, 2013
• Study Start: December 1, 2013
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: June 25, 2015

Record last verified: 2015-06

Locations

NL (1); SE (2); ES (4); BE (3)