This study has been transitioned to CTIS with ID 2024-511770-76-00 check the CTIS register for the current data. Primary* To assess safety and tolerability of IBC-Ab002 following single and multiple ascending doses in persons with early ADSecondary…
ID
Source
Brief title
Condition
- Dementia and amnestic conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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 outcome
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)
Background summary
Alzheimer*s disease (AD) is the most common type of neurodegenerative dementia.
The greatest risk factor for AD is increasing age. Gender too is a risk factor
with more women than men developing the disease. In Europe, the prevalence of
AD is estimated at 5.05%. In the Netherlands, in 2019, it was estimated that
about 265,000 people had dementia (mainly AD) and that that number would grow
to 420,000 in 2030 and 520,000 in 2040. In association with this increase in
prevalence, the healthcare costs would rise from ¤6.6 billion to ¤15.6 billion
in 2040. The initial and most common presenting symptom of AD is episodic
short-term memory loss with relative sparing of long-term memory. Short-term
memory impairment is followed by impairment in problem-solving, judgment,
executive functioning, lack of motivation and disorganization, leading to
problems with multitasking and abstract thinking. Acetylcholinesterase
inhibitors (AChEi), the mainstay of treatment that are approved for early AD
have modest effects on symptoms of the disease and there is therefore an unmet
need for new and novel treatment options . Recent clinical development programs
have focused on treatments that target the pathological manifestations
associated with amyloid beta or aggregated tau; however, despite the successful
reduction of amyloid plaque burden in patients, only minimal meaningful effects
have been observed on cognitive function. IBC-Ab002 represents a novel
therapeutic approach for AD. The aim of IBC-Ab002 administration is to break
age/disease related adaptive immune suppression by blocking the Programmed cell
death protein 1 (PD-1)/ Programmed death-ligand 1 (PD-L1) inhibitory immune
checkpoint pathway.
Study objective
This study has been transitioned to CTIS with ID 2024-511770-76-00 check the CTIS register for the current data.
Primary
* To assess safety and tolerability of IBC-Ab002 following single and multiple
ascending doses in persons with early AD
Secondary
* To assess the pharmacokinetics of IBC-Ab002 following a single and multiple
ascending doses in persons with early AD
Exploratory
* To evaluate the pharmacodynamic effect of single and multiple doses of
IBC-Ab002 in persons with early AD
* To support the proposed mechanism of action and biological effect of IBC-Ab002
* To evaluate initial effect of IBC-Ab002 on selected efficacy measures in
persons with early AD
Study design
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 IV doses of IBC-Ab002 in persons with early
Alzheimer's disease. The study will have both Single- and Multiple- Ascending
Dose components.
The study will have an adaptive design and will be carried out in two parts.
Part A will be comprised of a Single-Ascending-Dose (SAD) study and Part B will
continue dosing of Part A subjects as a Multiple-Ascending Dose (MAD) study.
Adaptive features may include 1) modification of dosage levels in Parts A and B
based upon emerging PK variability and PD data, 2) the ability to add or expand
cohorts at the higher dose levels based on emerging safety, PK and PD data.
Part A will be preceded by a Screening Period of up to 8 weeks during which
subject eligibility will be assessed.
A Study Monitoring Team (SMT) will review safety, tolerability and PK data
prior to opening new dosing cohorts or initiating dosing in the multiple-dose
portion of the study. The SMT will meet at specified intervals to monitor study
progress, and, in particular, the emerging safety and tolerability profile of
IBC-Ab002. The SMT will consist at least of the Study Director, the Study
Principal Investigator, the Study Statistician, Pharmacometrician, Medical
Monitor and an Oncologist experienced in checkpoint inhibitor clinical trials.
Subjects in five (5) sequential cohorts of 8 subjects each will be assigned in
a 3:1 ratio to receive either IBC-Ab002 or matching placebo four (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.
Intervention
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 the five study cohorts will be as follows:
Cohort #1: IBC-Ab002 1 mg/kg or placebo - Single dose (Part A) and then 3 doses
Q12W (Part B)
Cohort #2: IBC-Ab002 3 mg/kg or placebo - Single dose (Part A) and then 3 doses
Q12W (Part B)
Cohort #3: IBC-Ab002 7 mg/kg or placebo - Single dose (Part A) and then 3 doses
Q12W (Part B)
Cohort #4: IBC-Ab002 15 mg/kg or placebo - Single dose (Part A) and then 3
doses Q12W (Part B)
Cohort #5: IBC-Ab002 30 mg/kg or placebo - Single dose (Part A) and then 3
doses Q12W (Part B)
Study drug will be infused over a period of 2 hours. Study drug administration
in Part A of the study may be prolonged by up to 15 minutes but should not be
less than 2 hours in duration. For Part B of the study, should safety and
tolerability allow, the infusion rate may be shortened to 1 hour. This decision
will be at the discretion of the Study Monitoring Team (SMT) and will only be
considered after all subjects have received their Part A dosing. Infusion rates
may be slowed, or individual infusions may be interrupted for up to * hour, at
the discretion of the Investigator in the event that infusion reactions are
observed, in keeping with local protocols. Subjects assigned to receive placebo
will be administered 100 mL of normal saline
Study burden and risks
it is not possible to predict all of the risks and side effects that might
happen if you are given IBC-Ab002. However, humans who have taken
investigational medications called *Immune Checkpoint Inhibitors* that work in
a similar manner to IBC-Ab002 for the treatment of cancer have had certain side
effects, which may include certain immune-related disorders. Since IBC-Ab002 is
dosed only once every 12 weeks, instead of once every 2 or 3 weeks as Immune
Checkpoint Inhibitors are dosed for treatment of cancer, it may be that the
pattern and kind of side effects you could experience may be different.
Data on potential effects of IBC Ab002 on male and female fertility and the
potential for IBC-Ab002 administration to cause fetal abnormalities receiving
IBC Ab002 is unknown at this time.
Immune Checkpoint Inhibitors, which work in a similar way to IBC-Ab002 are
considered immunostimulants (stimulating an immune response) and may
potentially enhance the response to vaccines such as the influenza vaccine.
However, there is no evidence to suggest that such an enhanced immune response
can lead to a serious over stimulation of the immune system.
As with taking any medication, there is a risk of allergic reaction. If you
have a very serious allergic reaction, you may be at risk of death. The study
staff are trained to recognise the symptoms and take any necessary action
during the infusion to treat a serious allergic reaction.
You should not expect any clinical benefit from being in the study. It is
possible that you may get better, stay the same, or get worse. The intention
of this study is to determine how the study medication works and how safe it
is. If you take part in this study, the results of the study will be used for
further development of treatments for AD and other people with AD may be helped
in case it is determined that the treatment will be safe and effective.
200 E. 61st Street 38F
New York NY 10065
US
200 E. 61st Street 38F
New York NY 10065
US
Listed location countries
Age
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 < 1000 pg/mL and pTau181 > 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
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
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-511770-76-00 |
| EudraCT | EUCTR2021-006580-19-NL |
| ClinicalTrials.gov | NCT05551741 |
| CCMO | NL78640.056.22 |