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

Inclusion Criteria:

• Male or female subjects with a diagnosis of first AIS due to distal [M2 segment andbeyond] 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 makerprior to study-start (upon admission).

Exclusion Criteria:

• Administration of intravenous thrombolytic therapy in distal occlusion as etiology ofAIS
• Intervention by endovascular thrombectomy (EVT)
• Known allergy or anaphylaxis to adrenocorticotropic hormone (ACTH) or melanocortins orany 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 usingadequate 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 PrincipalInvestigator (PI)
• Patients starting afamelanotide 24 hours or more from ictus.