A Proof of Concept Study to Evaluate the Safety of Afamelanotide in Patients With Acute Arterial Ischaemic Stroke (AIS)

Study Overview
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Brief Summary
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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.

Official Title
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A Proof of Concept, Phase IIa, Open Label Study to Evaluate the Safety of Afamelanotide in Patients With Acute Arterial Ischaemic Stroke (AIS) Due to Distal [M2 Segment and Beyond] Arterial Large Vessel Occlusion (LVO) or Perforator Occlusion and Who Are Ineligible for Intravenous Thrombolysis (IVT) or Endovascular Thrombectomy (EVT)

Conditions
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Arterial Ischemic Stroke

Intervention / Treatment
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* Drug: Afamelanotide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Afamelanotide<br> | Drug: Afamelanotide<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Volume of Infarct |  | From Day 0 to Day 3 and Day 0 to Day 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | From baseline to Day 42 | 
| 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). | From baseline to Day 42 |