Safety Study of Carbamylated Erythropoietin (CEPO) to Treat Patients With Acute Ischemic Stroke

Study Overview
=================
Brief Summary
-----------------
The primary purpose of the study is to determine whether carbamylated erythropoietin (CEPO) is a safe treatment for patients who have suffered an acute ischemic stroke.

Detailed Description
-----------------
Acute ischemic stroke is a major cause of death and severe disability. There is only one approved pharmacological treatment, Alteplase, which has to be administered within 3 hours from symptom onset. Consequently, only about 2-3% of patients world wide with ischemic strokes are treated. The naturally occurring hormone, erythropoietin (EPO), is able to protect various neuronal tissues from ischemic injury and is beneficial in animal models of acute ischemic stroke. However, treatment of stroke with EPO is undesirable due to its ability to stimulate production of red blood cells and to promote the blood to coagulate. Lu AA24493 is a modified (carbamylated) version of EPO, neuroprotective but without the haematopoietic side effects. Lu AA24493 is developed for treatment of patients with acute ischemic stroke. In this safety study of single doses with Lu AA24493, patients will receive Lu AA24493 within 12-48 hours from symptom onset.

Official Title
-----------------
Randomised, Double-blind, Placebo-controlled, Single-dose, Dose-escalation Study of the Safety, Tolerability, and Pharmacokinetics of Lu AA24493 in Acute Ischemic Stroke

Conditions
-----------------
Acute Ischemic Stroke

Intervention / Treatment
-----------------
* Drug: Lu AA24493 (CEPO)
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age between 50 and 90 years Clinical diagnosis of acute ischemic stroke Measurable stroke-related deficit Patient is stable Treatment can be initiated between 12 hours and 48 hours after the onset of stroke Expected hospital stay of at least 72 hours after study medication If female then not of childbearing potential Exclusion Criteria: Primary intracerebral haemorrhage (ICH), or parenchymal haemorrhagic transformation of infarction (type PHI or PHII as defined in ECASS), subarachnoid haemorrhage (SAH), arterio-venous malformation (AVM), cerebral aneurysm, or cerebral neoplasm Treated with a thrombolytic <24 hours (if >24 hours excluded ICH then eligible) Score >0 on the NIHSS item 1a Pre-stroke mRS score >1 Uncontrolled hypertension Previous treatment with erythropoietin Clinically significant abnormal ECG Cerebral pathology Received or donated blood within previous 3 months

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lu AA24493 (CEPO): 0.005 mcg/kg<br> | Drug: Lu AA24493 (CEPO)<br>* 0.005 - 50.0 mcg/kg body weight, IV, within 12-48 hrs from symptom onset<br>|
| Experimental: Lu AA24493 (CEPO): 0.05 mcg/kg<br> | Drug: Lu AA24493 (CEPO)<br>* 0.005 - 50.0 mcg/kg body weight, IV, within 12-48 hrs from symptom onset<br>|
| Experimental: Lu AA24493 (CEPO): 0.5 mcg/kg<br> | Drug: Lu AA24493 (CEPO)<br>* 0.005 - 50.0 mcg/kg body weight, IV, within 12-48 hrs from symptom onset<br>|
| Experimental: Lu AA24493 (CEPO): 5.0 mcg/kg<br> | Drug: Lu AA24493 (CEPO)<br>* 0.005 - 50.0 mcg/kg body weight, IV, within 12-48 hrs from symptom onset<br>|
| Experimental: Lu AA24493 (CEPO): 50.0 mcg/kg<br> | Drug: Lu AA24493 (CEPO)<br>* 0.005 - 50.0 mcg/kg body weight, IV, within 12-48 hrs from symptom onset<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Vials with solution for IV infusion<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS) |  | Baseline, Day 7, Day 30; for NIHSS also Day 2 and 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics, immunogenicity and mechanistic biomarkers (S-100b, glial fibrillary acidic protein (GFAP), matrix metalloproteinase 9 (MMP-9)) |  | Baseline, Day 1-4, Day 7 and Day 30 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Acute ischemic stroke, Erythropoietin, Carbamylated, Neuroprotection