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.