A First in Human Study of IBC-Ab002 in Persons With Early Alzheimer's Disease (AD)

NCT05551741 | Completed Phase 1 DMC

• 5 other identifiers: IBC-01-011R01AG071810-012021-006580-19PTCG-20-701033U1111-1303-6922
• Study Type: interventional
• Target: 40
• Locations: 3 countries
• Sites: 10

Brief Summary

This is a randomized, double-blind, placebo-controlled first-in-human, Phase 1, safety, tolerability, pharmacokinetic (PK) and preliminary exploratory activity study of escalating multiple intravenous (IV) doses of IBC-Ab002 in persons with early Alzheimer's disease. The study will have both Single- and Multiple-Ascending Dose components.

Conditions

Alzheimer's Disease

Keywords

anti-PD-L1 monoclonal antibody; IBC-Ab002; early Alzheimer's Disease

Outcome Measures

Primary Outcomes (9)

• Incidence of subjects with adverse events, serious adverse events

  Safety Outcome

  48 weeks

• Incidence of subjects with clinically significant changes in hematology parameters

  Safety Outcome - complete blood count, white blood cells, red blood cells, platelets, hematocrit, mean corpuscular hemoglobin (MCH), neutrophiles percent, neutrophiles absolute, lymphocytes percent, lymphocytes absolute, monocytes percent, monocytes absolute, eosinophils percent, eosinophils absolute, basophils percent, basophils absolute, mean platelet volume

  48 weeks

• Incidence of subjects with clinically significant changes in biochemistry parameters

  Safety Outcome - sodium, potassium, calcium, phosphorus, glucose, alanine aminotransferase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), bilirubin, creatine, albumin, total protein, amylase, total cholesterol, triglycerides, thyroid function tests (T3, T4, TSH), coagulation panel International normalized ratio (INR) and partial thromboplastin time (PTT).

  48 weeks

• Incidence of subjects with clinically significant changes in urinalysis parameters

  Safety Outcome - protein, nitrates, glucose, specific gravity, ketones, urobilinogen, bilirubin, pH, hemoglobin

  48 weeks

• Incidence of subjects with clinically significant changes in vital signs

  Safety outcome - weight, heart rate, respiratory rate, body temperature, systolic and diastolic blood pressure

  48 weeks

• Incidence of subjects with clinically significant changes in physical examination

  Safety Outcome

  48 weeks

• Incidence of subjects with clinically significant changes in electrocardiogram (EEG)

  Safety Outcome

  48 weeks

• Incidence of subjects with development of new abnormalities on brain MRI

  Safety Outcome - lacunar infarcts, territorial infarct, macroscopic hemorrhage, deep white matter lesions, cerebral contusion, encephalomalacia, infective lesion, aneurysm or vascular malformation, intraparenchymal tumor, meningioma or arachnoid cyst, inflammation, edema

  48 weeks

• Incidence of subjects with increased suicidality

  Safety Outcome - measured using Columbia Suicidality Rating Scale. Part 1 of the scale (Suicidal Ideation) is comprised of 5 yes/no questions with "yes" indicating suicidal ideation and "no" indicating no suicidal ideation. Part 2 of the scale (Intensity of Ideation) is comprised of 5 items which should be rated with respect to the most severe type if ideation (with 5 being the most severe intensity and 1 being the least intensity). Part 3 of thee scale (Suicidal Behavior) is comprised of 5 yes/no items with "yes" indicating suicidal behavior and "no" indicating no suicidal behavior. Part 4 of the scale (Actual Attempts) is comprised of 2 items which should be rated with respect to the most severe outcome of the suicide attempt (with the highest score indicating the most severe outcome and 0 indicating no harm).

  48 weeks

Secondary Outcomes (2)

• IBC-Ab002 levels in serum.

  Pre-dose and up to Day 84 post-dose

• Number of subjects with positive serum anti-IBC-Ab002 antibodies

  48 weeks

Study Arms (5)

Cohort 1

EXPERIMENTAL

IBC-Ab002 low dose or placebo

Biological: IBC-Ab002; Other: Placebo

Cohort 2

EXPERIMENTAL

IBC-Ab002 mid low dose or placebo

Biological: IBC-Ab002; Other: Placebo

Cohort 3

EXPERIMENTAL

IBC-Ab002 mid dose or placebo

Biological: IBC-Ab002; Other: Placebo

Cohort 4

EXPERIMENTAL

IBC-Ab002 mid high dose or placebo

Biological: IBC-Ab002; Other: Placebo

Cohort 5

EXPERIMENTAL

IBC-Ab002 high dose or placebo

Biological: IBC-Ab002; Other: Placebo

Interventions

IBC-Ab002 BIOLOGICAL

An anti-PD-L1 monoclonal antibody

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

Placebo OTHER

Normal Saline

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of early Alzheimer's disease based on the National Institute on Aging and Alzheimer's Association) (NIA-AA Research Framework criteria, regardless of apolipoprotein E (APOE) gene status.
• Able to speak, read and write the local language fluently.
• With respect to symptomatic treatment for Alzheimer's disease, subjects should either be not treated with any approved treatments for AD or stabilized on approved medication(s) other than anti-Ab antibodies for the treatment of AD for at least 3 months prior to Baseline.
• Subject has a study partner who spends at least 10 hours/week with the subject, and can attend all visits with the subject, report accurately on the subject's status, and ensure compliance with all study requirements
• Subject and study partner must each independently be able to understand the study requirements and provide informed consent

You may not qualify if:

• 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)
• Other than Alzheimer's disease, any neurologic or medical disorder which may impair cognition.
• Any contra-indication to undergo magnetic resonance imaging (MRI).
• Severe vision or hearing impairment that would prevent the subject from performing psychometric tests or otherwise complying with requirements for study participation and activities.
• History of certain neurological, psychiatric or medical conditions including autoimmune diseases.
• Clinically significant laboratory or electrocardiogram (ECG) abnormalities
• Presence of contraindication to lumbar puncture (LP) including taking anticoagulant or antiplatelet medications other than aspirin at a dose of ≤ 100 mg/day or clopidogrel.
• Taking any of the following medications.
• Immunosuppressant medications, including chronic systemic corticosteroids (chronic use of topical steroids is allowed)
• Injected or infused antibody therapies, including but not limited to antibodies directed against tumor necrosis factor (TNF), anti-interleukin-6 (anti-IL-6), natalizumab, rituximab and similar agents
• Aducanumab, (aducanumab-avwa) intravenous injection (brand name: Aduhelm™), or any other experimental or approved anti-amyloid antibody
• Insulin
• Anticoagulant or anti-platelet medications including warfarin, heparinoids and direct coagulation factor inhibitors (e.g. apixaban, dabigatran, rivaroxaban) within 90 days of the planned first dose of study drug; 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
• 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, whichever is longer, prior to the first Screening visit
• Subject currently smokes more than 5 cigarettes or equivalent tobacco consumption daily

Sponsors & Collaborators

• Immunobrain Checkpoint: lead
• National Institute on Aging (NIA): collaborator
• Alzheimer's Association: collaborator

Study Sites (10)

Barzilai Medical Center

Ashkelon, Israel

Location

Rabin Medical Center

Petah Tikva, Israel

Location

Sheba Medical Center

Ramat Gan, Israel

Location

Tel-Aviv Sourasky Medical Center

Tel Aviv, Israel

Location

Brain Research Center

Amsterdam, Netherlands

Location

University Hospital Southampton NHS Foundation Trust

Southampton, Hampshire, United Kingdom

Location

RICE - Research Institute for the Care of Older People

Bath, BA1 3NG, United Kingdom

Location

King's College London - Institute of Psychiatry, Psychology & Neuroscience (IoPPN)

London, SE5 8AF, United Kingdom

Location

Dementia Research Centre, National Hospital for Neurology and Neurosurgery

London, United Kingdom

Location

Sheffield teaching Hospitals NHS Trust

London, United Kingdom

Location

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Tommaso Croese, MD

  Immunobrain Checkpoint

  STUDY DIRECTOR

• Catherine Mummery, MD

  Dementia Research Centre, UCL, London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Within each cohort subjects are randomized to either active investigational product or placebo in a ratio 3:1

Study Record Dates

• First Submitted: July 14, 2022
• First Posted: September 23, 2022
• Study Start: February 23, 2023
• Primary Completion: December 16, 2025
• Study Completion: December 16, 2025
• Last Updated: December 24, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: After the end of the study, submission of the clinical study report and publication of the study results
• Access Criteria: Upon review of the qualifications of the requesting researcher and the purpose of the research

Locations

NL (1); IL (4); GB (5)