A Proof of Concept Study to Evaluate the Safety of Afamelanotide in Patients With Acute Arterial Ischaemic Stroke (AIS)
Condition: Arterial Ischemic Stroke
MeSH terms: Stroke; Ischemic Stroke; Cerebral Infarction; Ischemia
Intervention: Afamelanotide
Intervention description: 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.
Intervention MeSH terms: Afamelanotide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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.