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

• Sponsor: Clinuvel Pharmaceuticals Limited (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04962503
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arm: 1
• Actual Duration (Months): 8.1
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Arterial Ischemic Stroke	Drug: Afamelanotide	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: Jun 3, 2021
• Actual Primary Completion Date: Feb 4, 2022
• Actual Study Completion Date: Feb 4, 2022

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Afamelanotide

Drug: Afamelanotide; 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.

Outcome Measures

Primary Outcome Measures

1. Evaluate the safety of afamelanotide by monitoring and recording treatment-emergent adverse events (TEAEs). [From baseline to Day 42.]

   TEAEs will be recorded and coded as MedDRA Preferred Terms.

Secondary Outcome Measures

1. Changes in blood volume of the infarcted area. [From baseline to Day 42.]

   Evaluation will be made by comparing imaging (CT and MRI).

2. Changes of neurological function as measured by the National Institutional Health Stroke Scale (NIHSS). [From baseline to Day 42.]

   The validated NIHSS records the level of impairment caused by a stroke in 11 items: A score equal or less than 8 represents mild AIS, a score between 9 and 15 represents moderate AIS, a score equal or above 16 represents severe AIS.

3. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Alfred	Melbourne		Australia

Sponsors and Collaborators

• Clinuvel Pharmaceuticals Limited

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Clinuvel Pharmaceuticals Limited
• ClinicalTrials.gov Identifier: NCT04962503
• Other Study ID Numbers: CUV801
• First Posted: Jul 15, 2021
• Last Update Posted: Feb 23, 2022
• Last Verified: Feb 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Stroke; Ischemic Stroke; Cerebral Infarction; Ischemia; Afamelanotide

Study Results

No Results Posted as of Feb 23, 2022