Objective of this dose-escalation study with Lu AA24493 is to evaluate the safety, tolerability, immunogenicity and pharmacokinetics of multiple doses Lu AA 24493 in patients with acute ischemic stroke. In addition patient outcome on National…
ID
Source
Brief title
Condition
- Central nervous system vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety and tolerability, assessed in terms of AEs, clinical safety laboratory
tests, vital signs, body weight, and physical examination.
Secondary outcome
Immunogenicity and pharmacokinetics of Lu AA24493. Patient outcome in terms of
NIHSS and mRS. Exploration of mechanistic biomarkers in blood for efficacy and
safety.
Background summary
Acute ischemic stroke is a major cause of mortality and of long-term
disability. The only intervention currently available is limited to
thrombolysis within 3 hours after symptom onset. Lu AA24493 (CEPO) is
chemically modified erythropoietin (EPO), by cabamylation of lysine residues.
It has been hypothesized that erythropoietin may have cytoprotecive properties
in case of ischemia. Animal models have shown a time-window of at least 24
hours.
Study objective
Objective of this dose-escalation study with Lu AA24493 is to evaluate the
safety, tolerability, immunogenicity and pharmacokinetics of multiple doses Lu
AA 24493 in patients with acute ischemic stroke. In addition patient outcome on
National Institutes of Health Stroke Scale (NIHSS) en modified Rankin Scale
(mRS) will be followed.
Study design
The study is an international multi-centre, randomised, double-blind,
placebo-controlled, multiple-dose, dose-escalation study. Patients will be
randomised to receive 5 daily dosages Lu AA24493 or placebo, according to the
following dose-escalation scheme: 0.5 mcg/kg (6 active: 2 placebo), 5 mcg/kg
(6:2) and 50 mcg/kg (6:2). First dose will be administered within 48 hours
after onset of symptoms. Patients will be under close observation during the
treatment period and are to stay in the hospital for at least 6 days. Patients
will be followed-up for 60 days. Patients showing an antibody response will be
followed as deemed necessary by the Data Management Committee.
Intervention
Multiple dose (5 daily dosages on consecutive days) of Lu AA24493 or placebo,
administered as an IV infusion.
Study burden and risks
At Baseline medical/neurological history is taken, temperature, blood pressure,
pulse rate, height and weight are assessed; an ECG is recorded, and blood
samples are taken for laboratory testing. A physical and neurological exam are
conducted. NIHSS and mRS are assessed. When a patient is considered eligible,
IMP is administered as once-daily IV dose for 5 consecutive days. Temperature,
blood pressure and pulse rate are assessed 15, 30, and 60 minutes, and 2, 4, 8,
10 and 12 hours after IMP administration on day 1, once daily after IMP
administration on days 2, 3, 4, and 5, as well as on days 6 and 30. One hour
after IMP administration, and on day 6, an ECG is recorded. Blood samples are
taken for PK analysis 30 minutes before, and 15, 30 and 60 minutes, and 2, 3,
5, 8, and 12 hours after IMP administration on day 1 and day 5, pre-dose on
days 2-4, and on day 6 24 hours after last dose. Blood samples for haematology
and clinical chemistry are taken on days 2, 4, 6, 14, 30 and 60, for
pharmacodynamic assessments daily on days 2 - 6 and on day 30. NIHSS is
administered on days 2, 3, 4, 5, 6, 14 and 30. mRS is administered on days 6,
14 and 30. After 6, 14 and 30 days, a physical and neurological exam are
conducted. In patients, showing an antibody response, monthly blood sampling
takes place after the regular study period as long as deemed necessary by the
Data Management Committee. At each study visit AEs and concomitant medication
are recorded.
Except for the normal risks, associated with study procedures like regular
blood sampling, the most important risk, anticipated for this study, is
eliciting an antibody response due to administration of a (modified)
glycoprotein drug.
Benefit of participation is a potential clinical improvement in patients,
suffering from a life threatening and disabling disorder, for whom currently no
treatment modality is available.
Postbus 12021
1100 AA Amsterdam
NL
Postbus 12021
1100 AA Amsterdam
NL
Listed location countries
Age
Inclusion criteria
Male or female patients, aged 50-90 years; clinical diagnosis of acute ischemic stroke; measurable stroke-related deficit at the start of treatment; stable condition; treatment can be initiated 0-48 hours after onset of stroke symptoms; acceptance of hospital stay of at least 120 hours after first IMP dose (for full inclusion criteria refer to study protocol, page 28)
Exclusion criteria
Treatment with a thrombolytic within the previous 24 hours; previous treatment with erythropoietin of Lu AA24493; score >0 on the NIHSS consciousness item; pre-stroke mRS score >1, indicating previous disability; uncontrolled hypertension; history or imaging evidence of various CNS abnormalities (for further details, and full exclusion criteria, refer to study protocol, page 28)
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-003390-81-NL |
| CCMO | NL23854.056.08 |