Alzheimer DiseasePhase 1MICADNCT04121208
MIcroglial Colony Stimulating Factor-1 Receptor (CSF1R) in Alzheimer's Disease
A Phase 1 study testing JNJ-40346527 in people with Alzheimer Disease and Mild Cognitive Impairment, run by University of Oxford at 3 sites in United Kingdom.
Trial summary
A phase 1 randomised, placebo-controlled, single-blind study to characterise the biomarker effects of the CSF-1 receptor antagonist JNJ-40346527 in participants with mild cognitive impairment. A maximum of 54 participants will be recruited to the two part study. Read more about this study
- Who is it for?
- Ages 50 to 99 years
- Conditions the study is for
- Alzheimer Disease, Mild Cognitive Impairment
- What is being tested?
- JNJ-40346527
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- 7 Apr 2021to 18 Feb 2022
- 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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Any gender over and including 50 years old.
- Willing and able to provide informed consent.
- Clinical Dementia Rating (Scale) (CDR) Global Score = 0.5.
- Self and/or study partner report and impairment on objective cognitive tasks (performance on Hopkin's verbal learning task-revised (HVLT-R) - delay recall and/or free recall > 1 standard deviation (SD) below mean for age/education level).
- Study Partner available, that spends at least 4 hours per week with the participant. The Study Partner must be willing and able to assist with the CDR interview, and will be provided with their own Information Sheet and Informed Consent form.
- Able to read and write in English and with minimum 7 years of formal education.
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- Be considered eligible according to the following Tuberculosis (TB) screening criteria:
- Have no history of latent or active TB at screening. An exception is made for participants who have a history of latent TB (defined for the purpose of this study as having had a positive result from either the tuberculin skin test or the QuantiFERON-TB® Gold test prior to screening) and documentation of having completed an adequate treatment regimen for latent TB within 1 year prior to the first administration of study agent. Adequate treatment for latent TB is defined according to local country guidelines for immunocompromised patients. If no local guidelines for immunocompromised patients exist, United States (US) guidelines must be followed. It is the responsibility of the Investigator to verify the adequacy of previous anti-TB treatment and provide appropriate documentation.
- Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination.
- Have had no recent (within approximately 3 months) close contact with a person with active TB or if there has been such contact, have been evaluated by a physician specialising in TB and found not to have evidence of, or require treatment for latent TB.
- At screening, the results of the following laboratory tests performed at the local laboratory must be within the limits specified below (note: the Investigator may consider the participant eligible if the previously abnormal laboratory test result is within acceptable range on repeat testing. Repeat testing to be done 28 days before dose administration. If results from the laboratory test completed on the same day as the lumbar Puncture are outside the limits specified below, the Investigator may choose to repeat tests and continue the participant in the study, depending on their clinical assessment of any likely outcome/risks).
- Haemoglobin ≥8.5 g/dL (International System of Units [SI]: ≥85 g/L)
- White Blood Cells (WBC) count ≥3.0 x 103 cells/mm3 (SI:≥ 3.0 x 109 cells/L)
- Neutrophils ≥1.5 x 103 cells/mm3 (SI:≥ 1.5 x 109 cells/L)
- Lymphocyte count (absolute) ≥450 cells/mm3 (SI: ≥0.45 x 109 cells/L)
- Platelets ≥100 x 103 cells/mm3 (SI: ≥100 x 109 cells/L)
- Serum alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) levels ≤1.5 x upper limit of normal (ULN)
- Total bilirubin levels ≤1.5 x ULN
- Serum creatinine ≤1.5 mg/dL
- Be otherwise healthy on the basis of clinical laboratory tests performed at screening. If the results of serum chemistry, haematology, or urinalysis tests not specified in the inclusion criteria above are outside of the normal range, the participant may be included only if the Investigator judges the abnormalities or deviations from normal not to be clinically significant or to be appropriate and reasonable for the population under study.
- A woman, before study entry, must be postmenopausal (amenorrhea for at least 18 months). If a man is heterosexually active with a woman of childbearing potential, he must agree to use a double-barrier method of birth control and not to donate sperm during the study and for 6 months after receiving the last dose of study agent.
- Be willing and able to adhere to all of the procedures, prohibitions and restrictions specified in the protocol.
Who cannot join
- Research participants who fulfil diagnostic criteria for any type of dementia (e.g. Alzheimer Dementia, Frontotemporal Dementia (FTD), Diffuse Lewy Body Dementia (DLBD), Vascular Dementia (VAD), etc) CDR ≥1.
- Known carriers of a presenilin 1 (PSEN1), presenilin 2 (PSEN2) or Amyloid Precursor Protein (APP) mutation associated with Autosomal Dominant AD or any other neurodegenerative disease.
- Prohibited or restricted concomitant medication as detailed in Section 10.1.7.
- Presence of any neurological, psychiatric or medical conditions associated with a long-term risk of significant cognitive impairment or dementia including but not limited to pre-manifest Huntington's disease, multiple sclerosis, Parkinson's disease, Down syndrome, active alcohol/drug abuse or major psychiatric disorders including current major depressive disorder, schizophrenia, schizoaffective or bipolar disorder. To quantify abuse is to define this as history of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th Edition) (DSM-V) criteria within 6 months before screening or positive test result for alcohol and/or drugs of abuse at screening/admission.
- History of latent or active infection of one of the following infectious diseases at screening: Listeria infection, Histoplasma, Coccidioides, Paracoccidioides, Pneumocystis, nontuberculous mycobacteria, Blastomyces, Aspergillus, cytomegalovirus generalised or Herpes zoster infection
- Any cancer or history of cancer in the preceding 5 years (excluding cutaneous basal or squamous cell cancer resolved by excision).
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- Any conditions that are clinically significant and may deem the participant's participation in an investigational trial unsafe, e.g., symptomatic cardiovascular disease (including re-vascularisation procedures within the previous year), severe renal or hepatic failure, any clinically relevant abnormalities in blood parameters included in local routine assessments, severe loss of vision, hearing or communicative ability, conditions preventing co-operation or completing the required assessments in the trial, as judged by the Investigator.
- Any contraindications for Lumbar Puncture.
- Any evidence of intracranial pathology which may affect cognition including but not limited to brain tumours (benign or malignant), aneurysm or arteriovenous malformations, territorial stroke (excluding smaller watershed strokes), history of or recovering haemorrhage (parenchymal or subdural), or obstructive hydrocephalus. Research participants with an MRI scan demonstrating markers of small vessel disease (e.g. white matter changes or lacunar infarcts) judged to be clinically insignificant, or microbleeds are allowed.
- Participation in a clinical trial with an Investigational Medicinal Product (IMP) in the last 30 days or 90 days in case of biologics.
- Diminished decision-making capacity that renders the individual not capable of consenting.
- Any other factors in the opinion of the Investigator that could contraindicate the participation of the research participant into this trial.
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
Cambridgeshire and Peterborough NHS Foundation Trust
Cambridge
South London and Maudsley Hospital NHS Foundation Trust
London
Oxford Health NHS Trust
Oxford
About this study
Official title: A Randomised, Placebo-controlled, Single-blind Study to Characterise the Biomarker Effects of the Colony Stimulating Factor-1 (CSF-1) Receptor Antagonist JNJ-40346527 in Participants With Mild Cognitive Impairment
A phase 1 randomised, placebo-controlled, single-blind study to characterise the biomarker effects of the CSF-1 receptor antagonist JNJ-40346527 in participants with mild cognitive impairment. A maximum of 54 participants will be recruited to the two part study. The first part of the study will identify whether it is possible to identify biomarkers that may be used in future studies with JNJ-40346527 and part 2 will investigate a minimal efficacious JNJ-40346527 dose.
Read the detailed description
Alzheimer's disease (AD) is a slow, progressive disease that profoundly affects memory and everyday function. There are treatments available that can help manage symptoms, but at present there is no cure, and no treatment that is effective at slowing the progression of AD. AD can begin to cause brain damage decades before symptoms such as memory loss become apparent.
The trial will investigate the effect of the drug JNJ-40346527 on CSF-1R (colony stimulating factor-1 receptor), which is a protein on the outside of cells present in the brain. CSF-1R is responsible for the regulation of various cells, including microglial cells. Recent research suggests that reducing numbers of these microglial cells may be beneficial in slowing the progression of Alzheimer's disease. The Investigators want to see how well JNJ-40346527 is able to block CSF-1R, and in turn suppress these microglial cells. The study is designed to investigate whether or not it is possible to identify changes in levels of proteins which interact with CSF-1R, and changes in the activity or number of affected microglial cells present in the brain. This evidence may provide useful "biomarkers", measures of change in the body, which the Investigators could track to see how the drug is working. These "biomarkers" could then be used in further larger studies to more thoroughly test the benefits of the drug JNJ-40346527. The present study is not designed to test whether or not this drug can slow the progression of Alzheimer's disease.
If biomarkers are identified in the study, further studies will be designed to test whether JNJ-40346527 can slow or prevent the progression of Alzheimer's disease.
- Conditions
- Alzheimer Disease, Mild Cognitive Impairment
- Being tested
- JNJ-40346527, Placebo
- Medical subject headings
- Alzheimer Disease, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
JNJ-40346527Drug
Active study drug
PlaceboOther
Non-active study drug
| Study group | Role | What they receive |
|---|---|---|
| Active drug: JNJ-40346527 | Active comparator | A single initial randomisation site will be set up for Part 1 that will assign participants to JNJ-40346527 300 mg Bis in die - twice a day (BID) or placebo in a 2:1 ratio.
A second randomisation site will be setup for Part 2 depending on which scenario is adopted.
Either a "Part 2, Scenario 1" site will assign participants to JNJ-40346527 150 mg BID, JNJ-40346527 50 mg BID or placebo in a 2:2:1 ratio or a "Part 2, Scenario 2" site will assign participants to JNJ-40346527 150-50 mg BID or placebo in a 2:1 ratio. Receives: Drug: JNJ-40346527 |
| Placebo | Placebo comparator | Non-active study drug Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Placebo-controlled change from baseline in cerebrospinal fluid (CSF) protein marker concentration levels.
Change from baseline in concentration levels of CSF fluid protein markers including but not limited to interleukin (IL)-34 and CSF-1.
Measured: Baseline and visit 3 (Days 14)
Secondary outcomes (5)
Placebo-controlled change from baseline in CSF and blood biomarker concentration levels
Measured: Baseline and visit 3 (Days 14)
Placebo-controlled change from baseline in amount of CSF extracellular vesicles and cell population.
Measured: Baseline and visit 3 (Days 14)
Measurement of plasma/CSF JNJ-40346527 levels
Measured: Baseline and visit 3 (Days 14)
Measurement of cerebrospinal fluid (CSF) protein marker concentration levels following different JNJ-40346527 doses
Measured: Baseline and visit 3 (Days 14)
Occurrence of adverse events during the study
Safety and tolerability will be assessed by monitoring adverse events identified using key safety assessments: physical and neurological examinations, vital sign measurements, clinical laboratory tests and 12-lead ECGs
Measured: Baseline and visit 3 (Days 14). Serious Adverse Events (Day 14 plus 30 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2019
- Study start7 Apr 2021
- Primary completion18 Feb 2022
- Study completion18 Feb 2022
Why it stopped: Delayed due to COVID19. Study drug expired before could be used.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by University of OxfordThe 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Phase 1b, randomised, single-blind, placebo-controlled parallel-group trial with JNJ-40346527 in adults with Mild Cognitive Impairment (MCI)
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen Pharmaceutica
- Responsible party
- Sponsor
- Investigators
- Vanessa Raymont, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04121208
- Sponsor's protocol ID
- 40346527ALZ1001
- Other IDs
- 2018-004149-17, 2018
- Acronym
- MICAD
- Status last verified
- May 2024
- First submitted
- 3 Jul 2019
- Last updated
- 9 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Study terminated early after 2 participants recruited. No usable data, therefore no data will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Placebo-controlled, Single-blind Study to Characterise the Biomarker Effects of the Colony Stimulating Factor-1 (CSF-1) Receptor Antagonist JNJ-40346527 in Participants With Mild Cognitive Impairment
- ClinicalTrials.gov ID
- NCT04121208
- Acronym / sponsor ID
- MICAD / 40346527ALZ1001
- Conditions
- Alzheimer Disease, Mild Cognitive Impairment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Delayed due to COVID19. Study drug expired before could be used.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Janssen Pharmaceutica
- Study start
- 7 Apr 2021 (actual)
- Primary completion
- 18 Feb 2022 (actual)
- Study completion
- 18 Feb 2022 (actual)
- First posted
- 9 Oct 2019 (actual)
- 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.
A phase 1 randomised, placebo-controlled, single-blind study to characterise the biomarker effects of the CSF-1 receptor antagonist JNJ-40346527 in participants with mild cognitive impairment. A maximum of 54 participants will be recruited to the two part study. The first part of the study will identify whether it is possible to identify biomarkers that may be used in future studies with JNJ-40346527 and part 2 will investigate a minimal efficacious JNJ-40346527 dose.
Detailed description
Alzheimer's disease (AD) is a slow, progressive disease that profoundly affects memory and everyday function. There are treatments available that can help manage symptoms, but at present there is no cure, and no treatment that is effective at slowing the progression of AD. AD can begin to cause brain damage decades before symptoms such as memory loss become apparent.
The trial will investigate the effect of the drug JNJ-40346527 on CSF-1R (colony stimulating factor-1 receptor), which is a protein on the outside of cells present in the brain. CSF-1R is responsible for the regulation of various cells, including microglial cells. Recent research suggests that reducing numbers of these microglial cells may be beneficial in slowing the progression of Alzheimer's disease. The Investigators want to see how well JNJ-40346527 is able to block CSF-1R, and in turn suppress these microglial cells. The study is designed to investigate whether or not it is possible to identify changes in levels of proteins which interact with CSF-1R, and changes in the activity or number of affected microglial cells present in the brain. This evidence may provide useful "biomarkers", measures of change in the body, which the Investigators could track to see how the drug is working. These "biomarkers" could then be used in further larger studies to more thoroughly test the benefits of the drug JNJ-40346527. The present study is not designed to test whether or not this drug can slow the progression of Alzheimer's disease.
If biomarkers are identified in the study, further studies will be designed to test whether JNJ-40346527 can slow or prevent the progression of Alzheimer's disease.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Phase 1b, randomised, single-blind, placebo-controlled parallel-group trial with JNJ-40346527 in adults with Mild Cognitive Impairment (MCI)
| Arm | Type | Receives |
|---|---|---|
| Active drug: JNJ-40346527 | Active comparator | Drug: JNJ-40346527A single initial randomisation site will be set up for Part 1 that will assign participants to JNJ-40346527 300 mg Bis in die - twice a day (BID) or placebo in a 2:1 ratio. A second randomisation site will be setup for Part 2 depending on which scenario is adopted. Either a "Part 2, Scenario 1" site will assign participants to JNJ-40346527 150 mg BID, JNJ-40346527 50 mg BID or placebo in a 2:2:1 ratio or a "Part 2, Scenario 2" site will assign participants to JNJ-40346527 150-50 mg BID or placebo in a 2:1 ratio. |
| Placebo | Placebo comparator | Other: PlaceboNon-active study drug |
Who may qualify
- Ages
- 50 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Any gender over and including 50 years old.
- Willing and able to provide informed consent.
- Clinical Dementia Rating (Scale) (CDR) Global Score = 0.5.
- Self and/or study partner report and impairment on objective cognitive tasks (performance on Hopkin's verbal learning task-revised (HVLT-R) - delay recall and/or free recall > 1 standard deviation (SD) below mean for age/education level).
- Study Partner available, that spends at least 4 hours per week with the participant. The Study Partner must be willing and able to assist with the CDR interview, and will be provided with their own Information Sheet and Informed Consent form.
Key exclusion criteria (12 listed)
- Research participants who fulfil diagnostic criteria for any type of dementia (e.g. Alzheimer Dementia, Frontotemporal Dementia (FTD), Diffuse Lewy Body Dementia (DLBD), Vascular Dementia (VAD), etc) CDR ≥1.
- Known carriers of a presenilin 1 (PSEN1), presenilin 2 (PSEN2) or Amyloid Precursor Protein (APP) mutation associated with Autosomal Dominant AD or any other neurodegenerative disease.
- Prohibited or restricted concomitant medication as detailed in Section 10.1.7.
- Presence of any neurological, psychiatric or medical conditions associated with a long-term risk of significant cognitive impairment or dementia including but not limited to pre-manifest Huntington's disease, multiple sclerosis, Parkinson's disease, Down syndrome, active alcohol/drug abuse or major psychiatric disorders including current major depressive disorder, schizophrenia, schizoaffective or bipolar disorder. To quantify abuse is to define this as history of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th Edition) (DSM-V) criteria within 6 months before screening or positive test result for alcohol and/or drugs of abuse at screening/admission.
- History of latent or active infection of one of the following infectious diseases at screening: Listeria infection, Histoplasma, Coccidioides, Paracoccidioides, Pneumocystis, nontuberculous mycobacteria, Blastomyces, Aspergillus, cytomegalovirus generalised or Herpes zoster infection
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-40346527Active study drug | Drug | Active drug: JNJ-40346527 |
| PlaceboNon-active study drug | Other | Placebo |
Primary outcome
Placebo-controlled change from baseline in cerebrospinal fluid (CSF) protein marker concentration levels.
Time frame: Baseline and visit 3 (Days 14)
Change from baseline in concentration levels of CSF fluid protein markers including but not limited to interleukin (IL)-34 and CSF-1.
5 secondary outcomes
Placebo-controlled change from baseline in CSF and blood biomarker concentration levels
Time frame: Baseline and visit 3 (Days 14)
Placebo-controlled change from baseline in amount of CSF extracellular vesicles and cell population.
Time frame: Baseline and visit 3 (Days 14)
Measurement of plasma/CSF JNJ-40346527 levels
Time frame: Baseline and visit 3 (Days 14)
Measurement of cerebrospinal fluid (CSF) protein marker concentration levels following different JNJ-40346527 doses
Time frame: Baseline and visit 3 (Days 14)
Occurrence of adverse events during the study
Time frame: Baseline and visit 3 (Days 14). Serious Adverse Events (Day 14 plus 30 days)
Results and safety
The study was stopped early (reason given: Delayed due to COVID19. Study drug expired before could be used.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2024.
- Individual participant dataSharing planned: No. Study terminated early after 2 participants recruited. No usable data, therefore no data will be shared.
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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.
Vanessa Raymont principal investigator
University of Oxford
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing JNJ-40346527 in people with Alzheimer Disease and Mild Cognitive Impairment, run by University of Oxford at 3 sites in United Kingdom.
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 22 inclusion and 12 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: stopped early, as of the sponsor's last update on 9 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. 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 was stopped early (reason given: Delayed due to COVID19. Study drug expired before could be used.). Results are not available in the source record.
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?
Placebo-controlled change from baseline in cerebrospinal fluid (CSF) protein marker concentration levels. (time frame: Baseline and visit 3 (Days 14)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 May 2024.