Alzheimer DiseasePhase 1NCT01978548
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
A Phase 1 study testing JNJ-54861911 10 mg and JNJ-54861911 50 mg in people with Alzheimer Disease, run by Janssen Research & Development, LLC at 10 sites in 4 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 50 to 90 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- JNJ-54861911 10 mg and JNJ-54861911 50 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 10 sitesin 4 countries
- Study dates
- Dec 2013to Apr 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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)
Trial locations and contacts
10 sites in 4 countries.
10 sites in 4 countries
Spain4 sites
Study site
Barcelona
Study site
Madrid
Study site
Terrassa
Study site
Valencia
About this study
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
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).
Read the 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.
- Conditions
- Alzheimer Disease
- Being tested
- JNJ-54861911 10 mg, JNJ-54861911 50 mg, Placebo
- Keywords
- Alzheimer Disease, Prodromal Alzheimer Disease, Safety, Tolerability, Pharmacokinetic, Proof of Mechanism, JNJ-54861911
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
JNJ-54861911 10 mgDrug
JNJ-54861911 10 mg will be administered as two 5 mg oral tablets once daily.
JNJ-54861911 50 mgDrug
JNJ-54861911 50 mg will be administered as two 25 mg oral tablets once daily.
PlaceboDrug
Matching placebo will be administered as 2 oral tablets once daily.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: JNJ-54861911 10 mg |
| JNJ-54861911 50 mg | Experimental | Not described Receives: Drug: JNJ-54861911 50 mg |
| Placebo | Placebo comparator | Patients will receive matching placebo. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Levels of amyloid beta 1-40 in cerebrospinal (CSF) after treatment at the intended target dose range
Measured: Up to 4 weeks
Levels of amyloid beta 1-40 in plasma after treatment at the intended target dose range
Measured: 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
Measured: 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
Measured: 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)
Measured: 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
Measured: Up to 4 weeks
Cerebrospinal fluid exposure of JNJ-54861911
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Up to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2013 (estimated)
- Study startDec 2013
- Primary completionApr 2015
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01978548
- Sponsor's protocol ID
- CR103012
- Other IDs
- 54861911ALZ1005, 2013-003036-69
- Status last verified
- Jun 2015
- First submitted
- 31 Oct 2013
- Last updated
- 25 Jun 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 30134967
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01978548
- Acronym / sponsor ID
- CR103012
- Conditions
- Alzheimer Disease
- Keywords
- Alzheimer Disease, Prodromal Alzheimer Disease, Safety, Tolerability, Pharmacokinetic, Proof of Mechanism, JNJ-54861911
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- Dec 2013
- Primary completion
- Apr 2015 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 7 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| JNJ-54861911 10 mg | Experimental | Drug: JNJ-54861911 10 mgFrom 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). |
| JNJ-54861911 50 mg | Experimental | Drug: JNJ-54861911 50 mg |
| Placebo | Placebo comparator | Drug: PlaceboPatients will receive matching placebo. |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| JNJ-54861911 10 mgJNJ-54861911 10 mg will be administered as two 5 mg oral tablets once daily. | Drug | JNJ-54861911 10 mg |
| JNJ-54861911 50 mgJNJ-54861911 50 mg will be administered as two 25 mg oral tablets once daily. | Drug | JNJ-54861911 50 mg |
| PlaceboMatching placebo will be administered as 2 oral tablets once daily. | Drug | Placebo |
Primary outcome
Levels of amyloid beta 1-40 in cerebrospinal (CSF) after treatment at the intended target dose range
Time frame: 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
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
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
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)
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
Cerebrospinal fluid exposure of JNJ-54861911
Time frame: 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
4 secondary outcomes
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
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2015.
- Derived from this study: PubMed 30134967Timmers 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.
Related trials for Alzheimer Disease
Not yet recruiting
Virtual Reality to Advance Dementia Care and Quality of Life
Dementia, Agitation
RecruitingPhase 2
Neuroplasticity Enhancement From Cognitive Training Reinforced by Psilocybin
Alzheimer's Disease
RecruitingObservational study
Amyloid PET Imaging in the Baltimore Longitudinal Study of Aging
Aging
Recruiting
The Effects of Successful OSA Treatment on Memory and AD Biomarkers in Older Adults Study
Obstructive Sleep Apnea, Cognitive Decline
Active, not recruiting
Promoting Physical Activity in Older Hispanic/Latino(a) Adults
Sedentary Behavior, Physical Inactivity
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
10 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing JNJ-54861911 10 mg and JNJ-54861911 50 mg in people with Alzheimer Disease, run by Janssen Research & Development, LLC at 10 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Spain, Belgium, Sweden, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Levels of amyloid beta 1-40 in cerebrospinal (CSF) after treatment at the intended target dose range (time frame: Up to 4 weeks). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01978548, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2015.