Arterial Ischemic Stroke
Conditions
Brief summary
The primary study objective is to assess the safety of afamelanotide while the secondary objective is to assess whether the therapy affects the size of the penumbra, by increasing blood flow, restoring oxygen supply to the brain, and reducing the amount of cerebral oedema (fluid) which is seen as a result of the stroke. Positive findings would indicate that the drug is able to support brain tissue-at-risk and provide overall neuroprotection and benefit to stroke patients.
Interventions
DRUGAfamelanotide
Six adult patients with clots located in the higher segments of the brain and who are ineligible for alternative treatments will be enrolled in the study and evaluated for six weeks. The study will assess patients' brain injury with computed tomography (CT) scans and magnetic resonance imaging (MRI), as well as using recognised methods of clinical evaluation to measure changes in patients' neurological and cognitive function following treatment.
Sponsors
Clinuvel Pharmaceuticals Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Male or female subjects with a diagnosis of first AIS due to distal \[M2 segment and beyond\] occlusion or perforator occlusion * Perfusion abnormalities observed on Computed Tomography Perfusion (CTP) * Mild to moderate stroke severity * Pre-stroke mRS \<4 * Written informed consent obtained from patient and/or medical treatment decision maker prior to study-start (upon admission).
Exclusion criteria
* Administration of intravenous thrombolytic therapy in distal occlusion as etiology of AIS * Intervention by endovascular thrombectomy (EVT) * Known allergy or anaphylaxis to adrenocorticotropic hormone (ACTH) or melanocortins or any of the excipients listed in the Investigator's Brochure * Any evidence of hepatic (defined as three times standard range) or renal impairment (defined as estimated glomerular filtration rate (eGFR) \<50 mL/min/1.73 m²) * Any other medical condition which may interfere with the study protocol * Female who is pregnant (confirmed by positive serum beta human chorionic gonadotropin (β-HCG) pregnancy test prior to baseline) or lactating * Females of child-bearing potential (pre-menopausal, not surgically sterile) not using adequate contraceptive measures (i.e. oral contraceptives, diaphragm plus spermicide, intrauterine device) or a lifestyle excluding pregnancy * Unable to undergo MRI brain evaluation * Not suitable for trial participation according to judgment of the Principal Investigator (PI) * Patients starting afamelanotide 24 hours or more from ictus.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Changes in Volume of Infarct | From Day 0 to Day 3 and Day 0 to Day 9 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes of Neurological Function as Measured by the National Institutional Health Stroke Scale (NIHSS). | From baseline to Day 42 | 0: No stroke symptoms 1-15: Mild to Moderate stroke 16-20: Moderate to severe stroke 21- 42: Severe stroke |
| Changes of Daily Activities as Measured by the Modified Rankin Scale (mRS) | From baseline to Day 42 | The mRS indicates the degree of disability or dependence in the daily activities of patients who have suffered a stroke or other causes of neurological disability. The scale runs from 0-6, running from perfect health without symptoms (0) to death (+6). |
Countries
Australia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SCENESSE® (Afamelanotide 16mg) Six adult patients with clots located in the higher segments of the brain and who are ineligible for alternative treatments will be enrolled in the study and evaluated for six weeks. The study will assess patients' brain injury with computed tomography (CT) scans and magnetic resonance imaging (MRI), as well as using recognised methods of clinical evaluation to measure changes in patients' neurological and cognitive function following treatment. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | SCENESSE® (Afamelanotide 16mg) |
|---|---|
| Age, Continuous | 76.0 years |
| Race/Ethnicity, Customized Race Caucasian | 5 Participants |
| Race/Ethnicity, Customized Race Unknown or Not Reported | 1 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 6 |
| other Total, other adverse events | 5 / 6 |
| serious Total, serious adverse events | 1 / 6 |
Outcome results
Primary
Changes in Volume of Infarct
Time frame: From Day 0 to Day 3 and Day 0 to Day 9
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SCENESSE® (Afamelanotide 16mg) | Changes in Volume of Infarct | Median change from baseline to Day 3 | 9.97 mL |
| SCENESSE® (Afamelanotide 16mg) | Changes in Volume of Infarct | Median change from baseline to Day 9 | 4.06 mL |
p-value: 0.0313Wilcoxon (Mann-Whitney)
p-value: 0.0625Wilcoxon (Mann-Whitney)
Secondary
Changes of Daily Activities as Measured by the Modified Rankin Scale (mRS)
The mRS indicates the degree of disability or dependence in the daily activities of patients who have suffered a stroke or other causes of neurological disability. The scale runs from 0-6, running from perfect health without symptoms (0) to death (+6).
Time frame: From baseline to Day 42
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SCENESSE® (Afamelanotide 16mg) | Changes of Daily Activities as Measured by the Modified Rankin Scale (mRS) | Pre-stroke score 0 | 4 Participants |
| SCENESSE® (Afamelanotide 16mg) | Changes of Daily Activities as Measured by the Modified Rankin Scale (mRS) | Pre-stroke score 1 | 1 Participants |
| SCENESSE® (Afamelanotide 16mg) | Changes of Daily Activities as Measured by the Modified Rankin Scale (mRS) | Pre-stroke score 2 | 1 Participants |
| SCENESSE® (Afamelanotide 16mg) | Changes of Daily Activities as Measured by the Modified Rankin Scale (mRS) | Day 42 score 3 | 3 Participants |
| SCENESSE® (Afamelanotide 16mg) | Changes of Daily Activities as Measured by the Modified Rankin Scale (mRS) | Day 42 score 4 | 2 Participants |
| SCENESSE® (Afamelanotide 16mg) | Changes of Daily Activities as Measured by the Modified Rankin Scale (mRS) | Day 42 score 6 | 1 Participants |
Secondary
Changes of Neurological Function as Measured by the National Institutional Health Stroke Scale (NIHSS).
0: No stroke symptoms 1-15: Mild to Moderate stroke 16-20: Moderate to severe stroke 21- 42: Severe stroke
Time frame: From baseline to Day 42
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SCENESSE® (Afamelanotide 16mg) | Changes of Neurological Function as Measured by the National Institutional Health Stroke Scale (NIHSS). | -4.5 Score on a scale |