EFAVIRENZ for Alzheimer's Disease

Inclusion criteria

• {"criterion_text":"- Age range: 50-75 years of age at the Screening Visit."}
• {"criterion_text":"- Males, or females who are post-menopausal or otherwise not of child-bearing potential."}
• {"criterion_text":"- Diagnosis of AD based on the NIA-AA Research Framework criteria: Biomarker classification A+T+N+ or A+T+N- based upon: a.\tCSF profile consistent with AD (an Aβ42 concentration of <1000 pg/mL AND phosphorylated tau (p-Tau) >19 pg/mL, or a ratio of p-Tau/Aβ42 of ≥0.020) taken during the Screening period prior to the day of the first dose of study medication or, b.\tDocumented evidence of a CSF profile consistent with AD obtained within the previous 12 months, or c.\tDocumented amyloid positron emission tomography (PET) scan evidence acquired within the previous 12 months."}
• {"criterion_text":"- AD Clinical Stage 3 or 4 based on the NIA-AA Research Framework criteria a.\tHave a mini-mental state examination (MMSE) score at Screening and baseline ≥20. b.\tCDR global score 0.5 up to 1.0"}
• {"criterion_text":"- Able to speak, read and write the local language fluently."}
• {"criterion_text":"- Patients should either be: a.\tNot treated with any approved treatments for AD with a reasonable expectation that, based on the course of illness, need for treatment is not imminent and the patient should not be initiated on treatment for the length of the study, or b.\tStabilized on an approved medication(s) for the treatment of AD for at least 3 months prior to baseline. The dose of the AD treatment should remain the same after entering the study."}
• {"criterion_text":"- Patient and care partner are willing to consent to all study procedures."}

Exclusion criteria

• {"criterion_text":"- Other than AD, neurologic or medical disorder which may impair cognition including: head trauma, seizure disorder, neurodegenerative disease, hydrocephalus, cerebral/spinal hematoma, inflammatory disease, central nervous system infection (eg, encephalitis or meningitis), neoplasm, toxic exposure, metabolic disorder (including hypoxic or hypoglycemic episodes), or endocrine disorder, or any significant medical conditions that, in the opinion of the Investigator, would prohibit their participation in the study."}
• {"criterion_text":"- Regular use of cannabis or cannabis products, including non-prescription products containing cannabidiol."}
• {"criterion_text":"- History of drug (including cannabis) or alcohol abuse within the last 5 years."}
• {"criterion_text":"- Has an active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection a.\tNote: A subject being screened for this study who had a documented, positive polymerase chain reaction (PCR) or serology test for SARS-CoV-2 may be enrolled provided the subject has: i.\tRecovered from COVID-19 ie, all COVID-19 related symptoms and major clinical findings which could potentially affect the safety of the subject should be resolved to baseline, and ii.\tA negative result from a health authority-authorized nucleic acid amplification (PCR) test for SARS-CoV-2 taken."}
• {"criterion_text":"- Any contra-indication to undergo magnetic resonance imaging (MRI), as judged by Investigator or radiologist."}
• {"criterion_text":"- MRI of the brain indicative of significant abnormality, including, but not limited to, prior hemorrhage or infarct >1 cm3, >3 lacunar infarcts, deep white matter lesions corresponding to a Fazekas score of 3, cerebral contusion, encephalomalacia, aneurysm, vascular malformation, subdural hematoma, hydrocephalus, space-occupying lesion (eg, abscess or brain tumor such as meningioma). Small incidental meningiomas may be allowed if discussed and approved by the PI."}
• {"criterion_text":"- History of any of the following neurological, psychiatric or medical conditions: a.\tHistory of large vessel stroke b.\tHistory of myocardial infarction or unstable angina within the previous 12 months c.\tType 1 diabetes or uncontrolled type 2 diabetes (hemoglobin A1c [HbA1c] >8%) d.\tSystemic blood pressure >150/90 mmHg on 3 separate determinations e.\tHistory of hyperaldosteronism f.\tSignificant renal or hepatic dysfunction g.\tCurrent or previous hepatitis B infection (defined as positive test for hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (anti-HBc)+. Subjects with immunity to hepatitis B (if due to natural infection defined as negative HBsAg, positive hepatitis B antibody [anti-HBs] and positive anti-HBc; if due to vaccination defined as negative HBsAg, negative anti-HCV and positive anti-HBs) are eligible to participate in the study h.\tHistory or positive test at Screening for hepatitis C virus antibody (anti-HCV) i.\tHistory or positive test at Screening for human immunodeficiency virus (HIV) j.\tDiagnosed with cancer with metastatic potential within the last 5 years other than carcinoma in situ of the breast or cervix, or basal cell carcinoma of the skin that has been completely excised k.\tMajor depressive episode requiring initiation of medication or hospitalization within the previous 90 days l.\tPresence of hallucinations or delusions m.\tSurgery within 12 weeks of Screening"}
• {"criterion_text":"- Any of the following laboratory abnormalities at Screening a.\tClinically significant (as determined by a cardiologist or local PI) 12-lead ECG abnormalities b.\tAny serum chemistry value (eg, aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, creatine kinase [CK], total bilirubin etc) >2x the upper limit of normal (ULN) on 2 successive determinations less than 2 weeks apart c.\tSerum creatinine above the ULN or estimated glomerular filtration rate (eGFR) <60 mL/min d.\tPlatelet count, international normalized ratio (INR), prothrombin time (PT) or partial thromboplastin time (PTT) not within the normal range or other risk for increased or uncontrolled bleeding"}
• {"criterion_text":"- Presence of contraindication to lumbar puncture as judged by local PI."}
• {"criterion_text":"- Any other significant medical conditions that, in the opinion of the Investigator, would prohibit participation in the study, including inability to tolerate the MRI scan or lumbar puncture procedures."}
• {"criterion_text":"- Taking any of the following medications a.\tAntipsychotic agents, including pimavanserin b.\tStimulant medications c.\tAntidepressant medications whose dose has not been stable for at least 90 days d.\tImmunosuppressant medications, including chronic corticosteroids e.\tInjected or infused antibody therapies, including but not limited antibodies directed against tumor necrosis factor (TNF), anti-interleukin(IL)-6, natalizumab, rituximab and similar agents f.\tAnticoagulant or anti-platelet medications including warfarin, heparanoids and direct coagulation factor inhibitors (eg, apixaban, dagibatran, rivaroxaban); either aspirin at a dose of ≤100 mg/day or clopidogrel at a dose of 75 mg/day, but not both in combination is permitted. g.\tAny lipid-altering therapies h. CYP3A4 inhibitors i.\tterfenadine, astemizole, cisapride, midazolam, triazolam, pimozide, bepridil, or ergot alkaloids (for example, ergotamine, dihydroergotamine, ergonovine, and methylergonovine)"}
• {"criterion_text":"- Participation in any other interventional clinical trial, or treatment with any investigational drug or investigational use of an approved therapy within 30 days (or 5 half-lives of such agent) prior to the first Screening visit."}

Primary endpoints

• {"endpoint_text":"- Change From Baseline Levels in 24-Hydroxycholesterol in CSF","definition_or_measurement_approach":"Change from baseline in levels of 24-hydroxycholesterol in cerebrospinal fluid (CSF) at Day 84 compared with baseline (primary PD endpoint)."}

Secondary endpoints

• {"endpoint_text":"- Changes from levels in 24-hydroxycholesterol at 3h, 6h, 24h, 7d, 28d, 56d, and 84d","definition_or_measurement_approach":"Serial measurements of 24-hydroxycholesterol at specified timepoints (3h, 6h, 24h, 7d, 28d, 56d, 84d) compared with baseline."}
• {"endpoint_text":"- Change From Baseline Levels in AD Biomarkers in CSF: pTau, tTau, Ab42, Ab40, Ab42/40, NFL, NRGN, GFAP, YKL-40, inflammatory cytokines","definition_or_measurement_approach":"Measurement of specified AD biomarkers in CSF with change from baseline assessed."}
• {"endpoint_text":"- Change From Baseline Levels in AD Biomarkers in Plasma: pTau, tTau, Ab40, Ab42, Ab42/40m NFL","definition_or_measurement_approach":"Measurement of specified AD biomarkers in plasma with change from baseline assessed."}
• {"endpoint_text":"- Exploratory cognition endpoints: MSSE","definition_or_measurement_approach":"Cognitive assessment using the MSSE instrument (exploratory)."}
• {"endpoint_text":"- PK in plasma and CSF","definition_or_measurement_approach":"Pharmacokinetic sampling and analysis in plasma and CSF."}

Methods

• Social media posts (documents present: 'L2_Other subject information_Social media post_V1_11NOV2025', 'L2_Other subject information_Social media post_V2_12JAN2026_TC') — digital channel targeting potential participants (patients with early Alzheimer's disease) and their care partners in the Netherlands.
• Website text (documents present: 'L2_Other subject information material Website tekst Dutch', 'L2_Other subject information material Website tekst English') — website information in Dutch and English for potential participants and care partners.
• Flyer text (documents present: 'L2_Other subject information_Flyertekst_V1_11NOV2025', 'L2_Other subject information_Flyertekst_V2_12JAN2025_TC') — printed recruitment material for patients and care partners.
• Newsletter text (documents present: 'L2_Other subject information_Nieuwsbrief tekst_V1_11NOV2025', 'L2_Other subject information_Nieuwsbrief tekst_V2_12JAN2026_TC') — communications via newsletters targeting potential participants/caregivers.
• Patient-facing document and subject information / ICF (documents present: 'L1_SIS and ICF 50-75 yrs_redacted version', 'L2_Other subject information_Flyertekst...') — direct recruitment via provision of study information and informed consent materials to eligible patients and their care partners.

Netherlands

Earliest CTIS Part Ii Submission Date

29-05-2024

Latest Decision Or Authorization Date

06-02-2026

Processing Time Days

618

Number Of Sites

1

Number Of Participants

40

Primary sponsor

Full Name

Amsterdam UMC

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands