Clinical trial NCT05551741: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Alzheimer's Disease
Keywords: anti-PD-L1 monoclonal antibody
IBC-Ab002
early Alzheimer's Disease
Lead sponsor: Immunobrain Checkpoint
Sponsor class: INDUSTRY
Collaborators: name: National Institute on Aging (NIA)
name: Alzheimer's Association
First posted: 2022-09-23
Enrollment: 40
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Within each cohort subjects are randomized to either active investigational product or placebo in a ratio 3:1
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. Able to speak, read and write the local language fluently.
3. 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.
4. 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
5. Subject and study partner must each independently be able to understand the study requirements and provide informed consent

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. Other than Alzheimer's disease, any neurologic or medical disorder which may impair cognition.
3. Any contra-indication to undergo magnetic resonance imaging (MRI).
4. Severe vision or hearing impairment that would prevent the subject from performing psychometric tests or otherwise complying with requirements for study participation and activities.
5. History of certain neurological, psychiatric or medical conditions including autoimmune diseases.
6. Clinically significant laboratory or electrocardiogram (ECG) abnormalities
7. 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.
8. 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
9. 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
10. Subject currently smokes more than 5 cigarettes or equivalent tobacco consumption daily
11. 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
12. History of drug (including cannabis) or alcohol abuse within the last 5 years
13. 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
14. 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
15. Unwillingness to comply with study requirements or history of noncompliance in prior clinical trials

Primary outcomes:
measure: Incidence of subjects with adverse events, serious adverse events
timeFrame: 48 weeks
measure: Incidence of subjects with clinically significant changes in hematology parameters
timeFrame: 48 weeks
measure: Incidence of subjects with clinically significant changes in biochemistry parameters
timeFrame: 48 weeks
measure: Incidence of subjects with clinically significant changes in urinalysis parameters
timeFrame: 48 weeks
measure: Incidence of subjects with clinically significant changes in vital signs
timeFrame: 48 weeks
measure: Incidence of subjects with clinically significant changes in physical examination
timeFrame: 48 weeks
measure: Incidence of subjects with clinically significant changes in electrocardiogram (EEG)
timeFrame: 48 weeks
measure: Incidence of subjects with development of new abnormalities on brain MRI
timeFrame: 48 weeks
measure: Incidence of subjects with increased suicidality
timeFrame: 48 weeks
Secondary outcomes:
measure: IBC-Ab002 levels in serum.
timeFrame: Pre-dose and up to Day 84 post-dose
measure: Number of subjects with positive serum anti-IBC-Ab002 antibodies
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
city: Amsterdam
country: Netherlands
facility: Brain Research Center
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
state: Hampshire
city: Bath
country: United Kingdom
facility: RICE - Research Institute for the Care of Older People
city: London
country: United Kingdom
facility: King's College London - Institute of Psychiatry, Psychology & Neuroscience (IoPPN)
city: London
country: United Kingdom
facility: Dementia Research Centre, National Hospital for Neurology and Neurosurgery
city: London
country: United Kingdom
facility: Sheffield teaching Hospitals NHS Trust
Study officials:
affiliation: Immunobrain Checkpoint
name: Tommaso Croese, MD
role: STUDY_DIRECTOR
affiliation: Dementia Research Centre, UCL, London
name: Catherine Mummery, MD
role: PRINCIPAL_INVESTIGATOR
References: