Alzheimer disease dementia
Conditions
Interventions
IBC-Ab002/placebo will be administered IV. Each subjects will receive 4 dosages
of the study drug or placebo throughout the study with an interval of 12 weeks
between doses.
The assigned doses for t
Sponsors
ImmunoBrain Checkpoint, Inc
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Age range: 50-80 years of age at the Screening visit 2. Diagnosis of early AD based on the NIA-AA Research Framework criteria, regardless of APOE gene status a. Biomarker classification A+T+N+ or A+T+N- based upon Screening CSF profile consistent with AD defined by either of the following criteria: i. CSF Aβ42 19 pg/mL ii. CSF pTau181/Aβ42 ratio > 0.020 b. AD Clinical Stage 3 or 4 based on the National Institute on Aging and Alzheimer's Association (NIA-AA) Research Framework criteria i. Gradual and progressive change in memory function reported by the participant or informant for >=6 months ii. Have a Mini-Mental State Examination (MMSE) score at Screening between 20-28 inclusive iii. Clinical Dementia Rating Scale (CDR) global score at Screening of 0.5 or 1 with memory box score >= 0.5 3. Able to speak, read and write the local language fluently 4. With respect to symptomatic treatment for Alzheimer*s disease, subjects 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) other than anti-Ab antibodies 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 5. Subject has a study partner who spends at least 10 hours/week with the patient, and can attend all visits with the patient, report accurately on the subject*s status and ensure compliance with all study requirements
Exclusion criteria
Exclusion criteria: 1. Females who are not postmenopausal at Screening as defined by amenorrhea for at least 12 consecutive months or who have not been sterilized surgically (i.e. bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before Screening) 2. Males who are fertile but refuse to practice double-barrier methods of contraception with female partners of childbearing potential 3. Other than AD, neurologic or medical disorder which may impair cognition including: head trauma, seizure disorder, neurodegenerative disease, hydrocephalus, cerebral / spinal hematoma, inflammatory disease, CNS infection (e.g. 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 4. As assessed by the central MRI reader, a. Magnetic Resonance Imaging (MRI) evidence of a) more than three lacunar infarcts, b) territorial infarct or macroscopic hemorrhage, or c) deep white matter lesions corresponding to a Fazekas score = 3 b. Presence of any structural lesion that could potentially explain the subject*s cognitive impairment, or place the subject at risk for AEs during the trial. Examples include but are not limited to: cerebral contusion, encephalomalacia, aneurysm or vascular malformation, infective lesion, intraparenchymal tumor, meningioma or arachnoid cyst larger than 1 cm in longest diameter c. More than 5 Amyloid-Related Imaging Abnormalities-Hemorrhages (ARIA-H) (including microbleeds and areas of leptomeningeal hemosiderosis (LH)) or more than 3 areas of LH 5. Any contra-indication to undergo MRI, as judged by local PI or radiologist, including but not limited to presence of pacemaker, aneurysm clips, artificial heart valves, ear implants, ventriculoperitoneal shunt, foreign metal objects in the eyes, skin or body or any other circumstance which would contraindicate an MRI scan or impair MRI image quality, or history of claustrophobia or of not tolerating MRI scanning procedures
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Assessment of safety by determining the number of subjects with any Adverse Events (AE), Serious Adverse Events (SAE) and fatal SAE, clinical laboratory tests, cognitive worsening and electrocardiograms; CSF cell counts, development of new abnormalities on brain MRI (high-res T1, T2*, FLAIR) scans and the Columbia Suicidality Rating Scale (C-SSRS) | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic (PK) Parameters IBC-Ab002 concentration in serum will be measured by a validated ELISA method: o Serum antibody concentrations o Area under the concentration-time curve from time zero to infinity (AUCinf) o Area under the concentration-time curve from time zero to the time of the last measurable sample (AUClast) o Maximum observed concentration (Cmax) o Time to reach maximum observed concentration (Tmax) o Terminal elimination half-life (T1/2) o Clearance (CL) o Volume of distribution (Vd) o Concentrations of IBC-Ab002 in CSF at selected time points Serological Parameters o Number of subjects with positive serum anti-IBC-Ab002 antibodies (i.e. Anti-drug Antibodies-ADAs) | — |
Countries
Netherlands
Outcome results
None listed