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

Phase 1

Completed

• Conditions: Acute Ischemic Stroke
• Interventions: Drug: Placebo; Drug: Lu AA24493 (CEPO)

• Registration Number: NCT00756249
• Lead Sponsor: H. Lundbeck A/S

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.

Study Timeline

• Study Start: 2007-10
• Primary Completion: 2008-09
• Study First Submitted: 2008-09-19
• Study First Submitted QC: 2008-09-19
• Study First Posted: 2008-09-22
• Study Completion: 2008-12
• Status Verified: 2010-09
• Last Update Submitted: 2010-09-24
• Last Update Posted: 2010-09-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Lu AA24493 (CEPO): 50.0 mcg/kg	Lu AA24493 (CEPO)	-
Lu AA24493 (CEPO): 0.005 mcg/kg	Lu AA24493 (CEPO)	-
Lu AA24493 (CEPO): 0.05 mcg/kg	Lu AA24493 (CEPO)	-
Lu AA24493 (CEPO): 0.5 mcg/kg	Lu AA24493 (CEPO)	-
Lu AA24493 (CEPO): 5.0 mcg/kg	Lu AA24493 (CEPO)	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (5)

FR002; 🇫🇷 Paris, France

FI004; 🇫🇮 Helsinki, Finland

GB001; 🇬🇧 Glasgow, United Kingdom

NL005; 🇳🇱 Breda, Netherlands

SG003; 🇸🇬 Singapore, Singapore