MICAD

TerminatedPhase 1

MIcroglial Colony Stimulating Factor-1 Receptor (CSF1R) in Alzheimer's Disease

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

Lead sponsor

University of Oxford

Asset

JNJ-40346527

Listed sites

Recruiting sites

Enrollment

actual

Study population

Alzheimer’s disease, MCI / preclinical Alzheimer’s

Key I/E criterion

•Age 50-99

Primary endpoint

•Placebo-controlled change from baseline in cerebrospinal fluid (CSF) protein

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Eudract number2018-004149-17

Org study ID40346527ALZ1001

NCT IDNCT04121208

Timeline

Milestones

Study first posted2019-10-09actual

Study start2021-04-07actual

Primary completion2022-02-18actual

Study completion2022-02-18actual

Last update posted2024-05-09actual

Assets

Drug assets

JNJ-40346527

Study populations

Who this study enrolls

Alzheimer’s diseaseMCI / preclinical Alzheimer’s

Eligibility

Who can enroll

Minimum age50 Years

Maximum age99 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•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.

•Be considered eligible according to the following Tuberculosis (TB) screening criteria:

1. 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.

2. Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination.

3. 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).

1. Haemoglobin ≥8.5 g/dL (International System of Units [SI]: ≥85 g/L)

2. White Blood Cells (WBC) count ≥3.0 x 103 cells/mm3 (SI:≥ 3.0 x 109 cells/L)

3. Neutrophils ≥1.5 x 103 cells/mm3 (SI:≥ 1.5 x 109 cells/L)

4. Lymphocyte count (absolute) ≥450 cells/mm3 (SI: ≥0.45 x 109 cells/L)

5. Platelets ≥100 x 103 cells/mm3 (SI: ≥100 x 109 cells/L)

6. Serum alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) levels ≤1.5 x upper limit of normal (ULN)

7. Total bilirubin levels ≤1.5 x ULN

8. 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

Exclusion criteria

•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).

•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.

Endpoints (6)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Fluid / digital biomarkers

Safety / tolerability / PK

Fluid / digital biomarkers

5 endpoints

Primary/protocol endpoint

Placebo-controlled change from baseline in cerebrospinal fluid (CSF) protein marker concentration levels.