A study to evaluate the effect and safety of obicetrapib in patients with early Alzheimer's disease (Hetero/Homozygote APOE4 carriers)
- Conditions
- Alzheimer's diseaseTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2021-002687-41-NL
- Lead Sponsor
- ewAmsterdam Pharma BV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 15
1.Age range: 50-75 years of age at the Screening Visit.
2.Males, or females who are post-menopausal or otherwise not of child-bearing potential.
a.Women are not considered to be of childbearing potential if they meet 1 of the following criteria as documented by the Investigator:
i.They have had a hysterectomy or tubal ligation at a minimum of 1 cycle prior to signing the ICF; or
ii.They are postmenopausal, defined as =1 year since their last menstrual period for women =55 years of age or =1 year since their last menstrual period and have a follicle stimulating hormone (FSH) level in the postmenopausal range for women <55 years of age
b.Men whose partners are of childbearing potential must agree to use an effective method of avoiding pregnancy from screening to 90 days after the last visit. Effective methods of avoiding pregnancy are contraceptive methods with a Pearl index of <1 used consistently and correctly (including implantable contraceptives, injectable contraceptives, oral contraceptives, transdermal contraceptives, intrauterine devices, diaphragm with spermicide, male or female condoms with spermicide, or cervical cap) or a sterile sexual partner;
3.Diagnosis of AD based on the NIA-AA Research Framework criteria:
Biomarker classification A+T+N+ or A+T+N- based upon:
a.CSF profile consistent with AD (an Aß42 concentration of <1000 pg/mL AND phosphorylated tau (p-Tau) >19 pg/mL, or a ratio of p-Tau/Aß42 of =0.020 taken during the Screening period prior to the day of the first dose of study medication or,
b.Documented evidence of a CSF profile consistent with AD obtained within the previous 12 months, or
c.Documented amyloid positron emission tomography (PET) scan evidence acquired within the previous 12 months.
4.AD Clinical Stage 3 or 4 based on the NIA-AA Research Framework criteria
a.Clinical Dementia Rating scale global score =0.5 and =1
b.Mini-mental state examination (MMSE) score at Screening and baseline =20
5.Able to speak, read and write the local language fluently.
6.Have an APOE genotype of E4/E4 or E3/E4.
7.Patients should either be:
a.Not 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.Stabilized 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.
8.Patient and study partner are willing to consent to all study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 7
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8
1.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 would prohibit their participation in the study.
2.Any contra-indication to undergo magnetic resonance imaging (MRI)
3.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 Principal Investigator (PI).
4.History of any of the following:
a.large vessel stroke
b.myocardial infarction or unstable angina within the previous 12 months
c.Type 1 diabetes and uncontrolled type 2 diabetes (hemoglobin A1c [HbA1c] >8%)
d.Systemic blood pressure >150/90 mmHg on 3 separate determinations
e.hyperaldosteronism
f.Significant renal or hepatic dysfunction
g.Current 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.History or positive test at Screening for hepatitis C virus antibody (anti-HCV)
i.History or positive test at Screening for human immunodeficiency virus (HIV)
j.Diagnosed 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.Major depressive episode requiring initiation of medication or hospitalization within the previous 90 days
l.Presence of hallucinations or delusions
m.Surgery within 12 weeks of Screening
5.Any of the following laboratory abnormalities at Screening
a.Clinically significant (as determined by a cardiologist or local PI) 12-lead ECG abnormalities
b.Any 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.Serum creatinine above the ULN or estimated glomerular filtration rate (eGFR) <60 mL/min
d.Platelet 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
e.Not carrying an APOE4 allele (eg, E3/E3; E3/E2/ E2/E2).
6.Contraindication to lumbar puncture.
7.Any other significant medical conditions that would prohibit participation.
8.Taking any of the following medications
a.Antipsychotic agents
b.Stimulant medications
c.Antidepressant medications whose dose has not been stable for at least 90 days
d.Immunosuppressant medications
e.Injected o
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method