Efficacy and Safety Study of DP-b99 in Treating Acute Ischemic Stroke (MACSI)

This study has been terminated.
(The result of a pre-planned interim futility analysis)
Sponsor:
Information provided by (Responsible Party):
D-Pharm Ltd.
ClinicalTrials.gov Identifier:
NCT00893867
First received: May 4, 2009
Last updated: October 23, 2012
Last verified: October 2012
  Purpose

The purpose of this trial is to determine if intravenous administration of the metal ion trapping agent DP-b99 up to 9 hours following acute ischemic stroke onset, and then for 3 additional days (4 consecutive days in total) is effective in improving long term outcome. Patients will be followed up for 3 months after the stroke.


Condition Intervention Phase
Acute Ischemic Stroke
Drug: DP-b99
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Double Blind, Randomized, Placebo-controlled, Parallel Group, Multicenter Phase 3 Pivotal Study to Assess the Safety and Efficacy of 1mg/kg/Day Intravenous DP-b99 Over 4 Consecutive Days Versus Placebo When Initiated Within Nine Hours of Acute Ischemic Stroke Onset

Further study details as provided by D-Pharm Ltd.:

Primary Outcome Measures:
  • Modified Rankin Scale (mRS) categorical analysis ("shift") [ Time Frame: 90 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Recovery, defined as a score of ≤ 1 on modified Rankin Score [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • Safety and tolerability [ Time Frame: throughout study - baseline until day 90 ] [ Designated as safety issue: Yes ]
    the numbers of patients with treatment-emergent adverse events, results of physical examination, 12-lead electrocardiogram, vital signs and laboratory tests (complete blood count, chemistry and urinalysis)

  • recovery as assessed by an NIHSS of not more than 1 [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • 'home time' [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    exploratory endpoint of 'home time', which measures the length of time (as number of nights)spent at home/relatives' home between hospital discharge and day 90


Enrollment: 446
Study Start Date: December 2009
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DP-b99 Drug: DP-b99
1mg/kg/day over 4 consecutive days given intravenously and initiated up to 9 hours following acute stroke onset.
Placebo Comparator: Mannitol Drug: Placebo
1mg/kg/day over 4 consecutive days given intravenously and initiated up to 9 hours following acute stroke onset.

Detailed Description:

This will be a randomized, double-blind, placebo-controlled, multicenter, multi-national, parallel-arm, pivotal study comparing a placebo group to a DP-b99 group treated with intravenous 1.0 mg/kg/d for 4 consecutive days, in acute ischemic stroke patients with an entry National Institutes of Health Stroke Scale (NIHSS) score of 10-16 and a clinical syndrome that includes at least 1 of the following: language dysfunction, visual field defect or Extinction and Inattention (formerly Neglect) (as reflected by at least 1 point on any of the corresponding items of the NIHSS: 9, 3 or 11). An interim analysis for futility will be performed after Day 90 (or last available observation) primary endpoint data have been collected on about 45% of subjects planned to be enrolled. Clinical trial material (CTM) will be administered within 9 hours after the onset of acute ischemic stroke symptoms. Subjects will be randomized at a ratio of 1:1 to receive either DP-b99 or placebo. A data and safety monitoring board (DSMB) will assess the accumulating safety data periodically and will oversee the interim futility analysis.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. M or F age 18 - 85, inclusive
  2. Suffered an acute, likely hemispheric, ischemic stroke, defined as acute, focal, neurological deficit(s), secondary to a presumed vascular event, which must include at least one of the following components (as reflected by at least 1 point on any of the corresponding items of the NIHSS: 3, 9 or 11):

    • Visual
    • Best Language
    • Extinction and Inattention (formerly Neglect)
  3. Suffered the onset of an acute ischemic stroke that can be evaluated and treatment initiated within 9 hours after the onset of acute ischemic stroke symptoms.
  4. Screening NIHSS score of 10 to 16, inclusive
  5. Readily accessible peripheral venous access for clinical trial material (CTM) administration and blood sampling
  6. Ability to understand the requirements of the study and be willing to provide written informed consent as evidenced by signature on an informed consent document approved by an institutional review board or independent ethics committee, and agree to abide by the study restrictions and return for the required assessments.
  7. Provided written authorization for use and disclosure of protected health information in accordance with the Health Insurance Portability and Accountability Act in the United States and the Personal Information Protection and Electronic Documents Act in Canada

Exclusion Criteria:

  1. An intracerebral or subarachnoid hemorrhage per screening/baseline computerized tomography scan or susceptibility-weighted magnetic resonance imaging
  2. A candidate for either:

    1. thrombolytic therapy, or have been treated with thrombolytic therapy for the current stroke
    2. mechanical thromboembolectomy, or have been treated with mechanical thromboembolectomy for the current stroke
  3. Delirious, comatose or stuporous or demented, or having a mental impairment that in the investigator's opinion renders the subject incapable to participate in the study
  4. Have seizure(s) anytime from stroke onset to screening/baseline NIHSS evaluation
  5. Neurological or non-neurological comorbidities that in the investigator's opinion may lead, independent of the current stroke, to further deterioration in the subject's neurological status during the trial period, or may render the study's neurological assessments inconclusive for the purpose of evaluating solely the stroke's effects
  6. Likely to undergo a procedure involving cardiopulmonary bypass during the study period
  7. Suffered a myocardial infarction in the last 90 days
  8. Any medical condition that in the investigator's opinion may threaten the subject's ability to complete the study (e.g., concurrent significant or life-threatening diseases, such as malignancies or end stage organ failure)
  9. Rapid spontaneous improvement of neurological signs during screening/baseline assessments
  10. Premorbid neurological deficits and functional limitations assessed by a pre-stroke Modified Rankin Scale score of > 1
  11. Suffered a stroke within 90 days of the screening/baseline assessments that is either diagnostically confirmed or assumed to be in the same cerebral territory as is the current acute stroke
  12. Either severe hypertension or hypotension, as measured by at least 2 consecutive supine measurements taken 10 minutes apart prior to randomization.
  13. Significant current renal or hepatic disease(s): a serum creatinine concentration of >2.5 mg/dL; alanine aminotransferase, aspartate aminotransferase, or gamma-glutamyl transferase values that are three times greater than the upper limit of normal.
  14. Have a platelet count of <100,000/mm3 or, for patients on oral anticoagulants at study entry, INR of >4
  15. Female of childbearing potential who is not willing to use adequate and effective birth control measures for the duration of the trial. Effective birth control measures include hormonal contraception, a barrier method such as a diaphragm, intrauterine device and/or condom with spermicide
  16. Positive urine pregnancy test at screening/baseline or be a lactating female
  17. Currently dependent on, or abusing, alcohol or one or more of the following: sympathomimetic amines, cannabis, cocaine, hallucinogens, inhalants, opioids, phencyclidine, sedatives and hypnotics
  18. Received an investigational drug or product or participated in an investigational drug study within a period of 30 days prior to receiving study medication or have previously participated in a clinical trial involving DP-b99
  19. Severe anemia as measured by a hemoglobin value of < 7 g/dl.
  20. In a dependent relationship with the physician or the study sponsor.
  21. Known hypersensitivity to any component of the investigational product.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00893867

  Show 154 Study Locations
Sponsors and Collaborators
D-Pharm Ltd.
Investigators
Principal Investigator: Ashfaq Shuaib, MD University of Alberta Hospital, Edmonton, Canada
Principal Investigator: Vasco Salgado, MD Hospital Professor Doutor Fernando Fonseca, EPE, Amadora, Portugal
Principal Investigator: Philippe Lyrer, Prof. Dr. Universitätsspital Basel, Neurologie, Basel, Switzerland
Principal Investigator: Tobien Schreuder, MD Atrium MC Parkstad, Heerlen, Netherlands
Principal Investigator: Maria S Rocha, MD Hospital Santa Marcelina, Sao Paulo, Brasil
Principal Investigator: Hugues Chabriat, Prof. Hôpital Lariboisière - Service Neurologie, Paris, France
  More Information

Publications:
Responsible Party: D-Pharm Ltd.
ClinicalTrials.gov Identifier: NCT00893867     History of Changes
Other Study ID Numbers: Ptcl-01373
Study First Received: May 4, 2009
Last Updated: October 23, 2012
Health Authority: United States: Food and Drug Administration
Israel: Ministry of Health
South Africa: Medicines Control Council
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Austria: Agency for Health and Food Safety
Czech Republic: State Institute for Drug Control
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: The Central Register of Clinical Trials
Slovakia: State Institute for Drug Control
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Switzerland: Swissmedic
Hungary: National Institute of Pharmacy
Portugal: INFARMED - National Authority of Medicines and Health Products
Italy: Agenzia Italiana del Farmaco (AIFA)
Brazil:Agência Nacional de Vigilância Sanitária (Anvisa)

Keywords provided by D-Pharm Ltd.:
acute ischemic stroke
neuroprotective agent

Additional relevant MeSH terms:
Ischemia
Stroke
Cerebral Infarction
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia

ClinicalTrials.gov processed this record on September 22, 2014