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

Primary Purpose

Alzheimer's Disease

Status

Recruiting

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

IBC-Ab002

Placebo

About this trial

This is an interventional treatment trial for Alzheimer's Disease focused on measuring anti-PD-L1 monoclonal antibody, IBC-Ab002, early Alzheimer's Disease

Eligibility Criteria

50 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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 care partner who spends at least 15 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 care partner must each independently be able to understand the study requirements and provide informed consent

Exclusion Criteria:

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.
1. Immunosuppressant medications, including chronic systemic corticosteroids (chronic use of topical steroids is allowed)
2. 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
3. Aducanumab, (aducanumab-avwa) intravenous injection (brand name: Aduhelm™), or any other experimental or approved anti-amyloid antibody
4. Insulin
5. 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
Regular nonmedical use of cannabis or cannabis products unless such products are documented by the manufacturer's label not to contain tetrahydrocannabinol or its derivatives or analogs
History of drug (including cannabis) or alcohol abuse within the last 5 years
Positive urine drug test for drugs of abuse at Screening. Subjects who test positive for benzodiazepines or opioids in urine drug testing need not be excluded if in the clinical opinion of the investigator, this is due to the subject taking prior/concomitant medications containing benzodiazepines or opioids for a medical condition and not due to drug abuse
Subjects who answer "yes" to Columbia Suicidality Rating Scale (C-SSRS) suicidal ideation Type 4 or 5, or any suicidal behavior assessment within 6 months before Screening, at Screening, or has been hospitalized or treated for suicidal behavior in the past 5 years before Screening
Unwillingness to comply with study requirements or history of noncompliance in prior clinical trials

Sites / Locations

Barzilai Medical CenterRecruiting
Rambam Health Care CampusRecruiting
Rabin Medical CenterRecruiting
Sheba Medical CenterRecruiting
Tel-Aviv Sourasky Medical CenterRecruiting
University Hospital Southampton NHS Foundation TrustRecruiting
RICE - Research Institute for the Care of Older PeopleRecruiting
King's College London - Institute of Psychiatry, Psychology & Neuroscience (IoPPN)Recruiting
Dementia Research Centre, National Hospital for Neurology and NeurosurgeryRecruiting
Sheffield teaching Hospitals NHS TrustRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Cohort 4

Cohort 5

Arm Description

IBC-Ab002 low dose or placebo

IBC-Ab002 mid low dose or placebo

IBC-Ab002 mid dose or placebo

IBC-Ab002 mid high dose or placebo

IBC-Ab002 high dose or placebo

Outcomes

Primary Outcome Measures

Incidence of subjects with adverse events, serious adverse events

Safety Outcome

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

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).

Incidence of subjects with clinically significant changes in urinalysis parameters

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

Incidence of subjects with clinically significant changes in vital signs

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

Incidence of subjects with clinically significant changes in physical examination

Safety Outcome

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

Safety Outcome

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

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).

Secondary Outcome Measures

IBC-Ab002 levels in serum.

Pharmacokinetic Outcome - Area under the concentration-time curve from time zero to infinity, Area under the concentration-time curve from time zero to the time of the last measurable sample, maximum observed concentration, time to reach maximum observed concentration, terminal elimination half-life, clearance, volume of distribution,

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

Pharmacokinetic Outcome

Full Information

NCT ID

NCT05551741

First Posted

July 14, 2022

Last Updated

October 12, 2023

Sponsor

Immunobrain Checkpoint

Collaborators

National Institute on Aging (NIA), Alzheimer's Association

1. Study Identification

Unique Protocol Identification Number

NCT05551741

Brief Title

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

Official Title

A First in Human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of IBC-Ab002 in Persons With Early Alzheimer's Disease (AD)

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

February 23, 2023 (Actual)

Primary Completion Date

October 1, 2024 (Anticipated)

Study Completion Date

December 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Immunobrain Checkpoint

Collaborators

National Institute on Aging (NIA), Alzheimer's Association

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

Subjects in 5 sequential cohorts of 8 subjects each will be assigned in a 3:1 ratio to receive either IBC-Ab002 or matching placebo 4 times. Part A will be a single-ascending dose study and Part B will be a multiple ascending dose study. The two parts of the study will be intercalated such that subjects will be dosed once every 12 weeks. However, repeated dosing at any dose level will not begin until the anticipated cumulative dose for that cohort has been equaled or exceeded in Part A and/or B of the study, and appropriate safety review of data from all preceding doses in prior subjects has taken place. All subjects randomized into Part A of the study will automatically continue into Part B unless dosing is halted at the individual or group level due to safety or other concerns.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alzheimer's Disease

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Model Description

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

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1

Arm Type

Experimental

Arm Description

IBC-Ab002 low dose or placebo

Arm Title

Cohort 2

Arm Type

Experimental

Arm Description

IBC-Ab002 mid low dose or placebo

Arm Title

Cohort 3

Arm Type

Experimental

Arm Description

IBC-Ab002 mid dose or placebo

Arm Title

Cohort 4

Arm Type

Experimental

Arm Description

IBC-Ab002 mid high dose or placebo

Arm Title

Cohort 5

Arm Type

Experimental

Arm Description

IBC-Ab002 high dose or placebo

Intervention Type

Biological

Intervention Name(s)

IBC-Ab002

Intervention Description

An anti-PD-L1 monoclonal antibody

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Normal Saline

Primary Outcome Measure Information:

Title

Incidence of subjects with adverse events, serious adverse events

Description

Safety Outcome

Time Frame

48 weeks

Title

Incidence of subjects with clinically significant changes in hematology parameters

Description

Time Frame

48 weeks

Title

Incidence of subjects with clinically significant changes in biochemistry parameters

Description

Time Frame

48 weeks

Title

Incidence of subjects with clinically significant changes in urinalysis parameters

Description

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

Time Frame

48 weeks

Title

Incidence of subjects with clinically significant changes in vital signs

Description

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

Time Frame

48 weeks

Title

Incidence of subjects with clinically significant changes in physical examination

Description

Safety Outcome

Time Frame

48 weeks

Title

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

Description

Safety Outcome

Time Frame

48 weeks

Title

Incidence of subjects with development of new abnormalities on brain MRI

Description

Time Frame

48 weeks

Title

Incidence of subjects with increased suicidality

Description

Time Frame

48 weeks

Secondary Outcome Measure Information:

Title

IBC-Ab002 levels in serum.

Description

Time Frame

Pre-dose and up to Day 84 post-dose

Title

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

Description

Pharmacokinetic Outcome

Time Frame

48 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 care partner who spends at least 15 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 care partner must each independently be able to understand the study requirements and provide informed consent Exclusion Criteria: 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 Regular nonmedical use of cannabis or cannabis products unless such products are documented by the manufacturer's label not to contain tetrahydrocannabinol or its derivatives or analogs History of drug (including cannabis) or alcohol abuse within the last 5 years Positive urine drug test for drugs of abuse at Screening. Subjects who test positive for benzodiazepines or opioids in urine drug testing need not be excluded if in the clinical opinion of the investigator, this is due to the subject taking prior/concomitant medications containing benzodiazepines or opioids for a medical condition and not due to drug abuse Subjects who answer "yes" to Columbia Suicidality Rating Scale (C-SSRS) suicidal ideation Type 4 or 5, or any suicidal behavior assessment within 6 months before Screening, at Screening, or has been hospitalized or treated for suicidal behavior in the past 5 years before Screening Unwillingness to comply with study requirements or history of noncompliance in prior clinical trials

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Dalia Bracha

Phone

+972547831876

dalia@immunobrain.com

First Name & Middle Initial & Last Name or Official Title & Degree

Kinga Barsony

kinga.barsony@worldwide.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Tommaso Croese, MD

Organizational Affiliation

Immunobrain Checkpoint

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Catherine Mummery, MD

Organizational Affiliation

Dementia Research Centre, UCL, London

Official's Role

Principal Investigator

Facility Information:

Facility Name

Barzilai Medical Center

City

Ashkelon

Country

Israel

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Vered Loew Shavit

Phone

+97286745117

Facility Name

Rambam Health Care Campus

City

Haifa

Country

Israel

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Merav Shor

Phone

+972-50-7773471

m_shor@rambam.health.gov.il

Facility Name

Rabin Medical Center

City

Petach Tikva

Country

Israel

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sara Mola

Saramol@clalit.org.il

Facility Name

Sheba Medical Center

City

Ramat Gan

Country

Israel

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Efrat Tal

Phone

+972-54-6881186

Efrat.Tal@sheba.health.gov.il

Facility Name

Tel-Aviv Sourasky Medical Center

City

Tel Aviv

Country

Israel

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Noa Trablus

Phone

+972-54-7324473

noat@tlvmc.gov.il

Facility Name

University Hospital Southampton NHS Foundation Trust

City

Southampton

State/Province

Hampshire

Country

United Kingdom

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Christopher Kipps

Phone

02381204989

Christopher.kipps@uhs.nhs.uk

Facility Name

RICE - Research Institute for the Care of Older People

City

Bath

ZIP/Postal Code

BA1 3NG

Country

United Kingdom

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Nicola Youlden

Phone

+44 (0)1225476420

ny247@bath.ac.uk

Facility Name

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

City

London

ZIP/Postal Code

SE5 8AF

Country

United Kingdom

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Miguel Vasconcelos Da Silva

Phone

02078480024

miguel.1.dasilva@kcl.ac.uk

Facility Name

Dementia Research Centre, National Hospital for Neurology and Neurosurgery

City

London

Country

United Kingdom

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Marivic Ricamara

Marivic.ricamara@nhs.net

First Name & Middle Initial & Last Name & Degree

Miguel Paz-Alvarez

miguel.paz-alvarez@nhs.net

First Name & Middle Initial & Last Name & Degree

Catherine Mummery, MD PhD FRCP

Facility Name

Sheffield teaching Hospitals NHS Trust

City

London

Country

United Kingdom

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Daisy Priest

Phone

+44-114 22 65580

Daisy.priest1@nhs.net

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Individual study data will be shared with qualified researchers upon review of the request by the trial sponsor

IPD Sharing Time Frame

After the end of the study, submission of the clinical study report and publication of the study results

IPD Sharing Access Criteria

Upon review of the qualifications of the requesting researcher and the purpose of the research

Learn more about this trial

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

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