Primary objective:• To evaluate the safety and tolerability profile of single intravenous doses of AST-004 given as a short loading intravenous infusion followed by a 6-hour continuous intravenous (IV) infusion in healthy adult subjects.Secondary…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
cerebral infarction and traumatic brain injury
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Efficacy is not being assessed in this study. The primary endpoints are the
safe and well tolerated administration of the study medication.
Secondary outcome
PK of AST-004 in plasma and CSF will be important in determining the dose of
the study medication to be used in Phase 2 trials and to be used in any future
Phase 1 studies. PK of AST-004 as well as identification of any major
metabolites in urine and plasma will be obtained.
Mechanistic and pharmacodynamic biomarkers of AST-004 will also be assessed in
the plasma and CSF including changes in cytokine levels.
Background summary
Astrocyte Pharmaceuticals Inc. is developing the small molecule, AST-004, as a
cerebroprotectant for treating patients with acute ischemic stroke (AIS), and
other brain injuries including traumatic brain injury (TBI), concussion, and
neurodegenerative disease. The proprietary, novel approach at Astrocyte
Pharmaceuticals differs significantly from historical neuron-centric
cerebroprotective attempts by focusing on a non-neuronal cell type, the
astrocyte. Astrocytes have only recently received broader attention as an
important cellular target for successful therapeutic research. AST-004 acts via
a novel cerebroprotective mechanism, namely the activation of adenosine A3
receptors (A3R) expressed on astrocytes, leading to enhanced mitochondrial
energy production, and the promotion of multiple intrinsic healing mechanisms.
The small molecule AST-004 is blood-brain barrier (BBB) penetrant.
AST-004 is a promising cerebroprotectant therapeutic demonstrating significant
efficacy in multiple preclinical models of AIS and with a favorable TI that
warrants further investigation in human subjects.
See the IB for further information.
Study objective
Primary objective:
• To evaluate the safety and tolerability profile of single intravenous doses
of AST-004 given as a short loading intravenous infusion followed by a 6-hour
continuous intravenous (IV) infusion in healthy adult subjects.
Secondary objective:
• To characterize the PK profile of AST-004 in plasma, CSF and urine when given
as a short loading intravenous infusion followed by a 6-hour continuous IV
infusion.
Study design
This is an adaptive-design, Phase 1 safety-tolerability, and pharmacokinetic
study, conducted in two study parts:
• Part 1: Single Partially Double-blinded Dose (SD) IV Load infusion followed
by a 6-hour continuous infusion (CI)
• Part 2: Single Dose (SD) IV Load infusion followed by a 6-hour continuous
infusion (CI) with periodic Cerebrospinal Fluid collection (CSF)
Intervention
AST-004 or matching placebo
Study burden and risks
Since the study is being executed in healthy volunteers, there are no
anticipated benefits of the IMP.
There has been one study completed in healthy individuals. Up to now, 42
persons have been administered AST-004. The study drug was well tolerated and
there were no serious side effects identified. Side effects that were reported
during this study are:
• Headache
• Neck and back stiffness
• Increase in liver blood test values. These values returned to normal when
administration of the study drug was stopped.
• Increase in inflammatory marker values that returned to normal when
administration of the study drug was stopped.
• Abnormalities in the heart tracing (ECG).
• Chills without fever
AST-004 can also have side effects that we do not yet know, and these could
also be serious side effects.
Please see the overall benefit risk analysis in the CSP for further
information.
Shennecossett Road 93
Groton CT 06340
US
Shennecossett Road 93
Groton CT 06340
US
Listed location countries
Age
Inclusion criteria
1. Male or female subjects aged >= 18 to <= 65 years at the time of signing the
informed consent form (ICF).
2. Body mass index (BMI) >= 18.0 and <= 30.0 kg/m2.
3. Weight of 50.0 kg - 100.0 kg.
4. Women of childbearing potential who agree to use a highly effective method
of contraception for 3 months after the last dose of study drug or as per the
local regulation.
Exclusion criteria
1. Presence of any contraindication to pharmacokinetic sampling, with
particular attention to lumbar punction in Part 2 (e.g., possible raised
intracranial pressure, thrombocytopenia or other bleeding diathesis, suspected
spinal epidural abscess)
2. History of seizures other than clearly documented febrile seizure prior to 2
years of age, myoclonus or other movement disorders, periodic paralysis,
unexplained loss of consciousness, structural neurological abnormalities,
traumatic brain injury including concussion within the last three years,
history of epilepsy, depression or suicidal ideation
3. Any clinically significant abnormality identified during pre-study (prior to
dosing) on full physical examination, vital signs, laboratory tests, and ECG
4. Any laboratory value noted here: Hgb Neutrophils <1.5 x 10 9/L, Platelets ULN, Total Bilirubin >ULN,
may be up to 1.5x ULN if Direct Bilirubin is repeated x1 during the screening period.
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 |
|---|---|
| EudraCT | EUCTR2023-000028-12-NL |
| CCMO | NL83655.056.23 |