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

Primary Purpose

Acute Ischemic Stroke

Status

Terminated

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

DP-b99

Placebo

About this trial

This is an interventional treatment trial for Acute Ischemic Stroke focused on measuring acute ischemic stroke, neuroprotective agent

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

M or F age 18 - 85, inclusive
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)
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.
Screening NIHSS score of 10 to 16, inclusive
Readily accessible peripheral venous access for clinical trial material (CTM) administration and blood sampling
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.
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:

An intracerebral or subarachnoid hemorrhage per screening/baseline computerized tomography scan or susceptibility-weighted magnetic resonance imaging
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
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
Have seizure(s) anytime from stroke onset to screening/baseline NIHSS evaluation
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
Likely to undergo a procedure involving cardiopulmonary bypass during the study period
Suffered a myocardial infarction in the last 90 days
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)
Rapid spontaneous improvement of neurological signs during screening/baseline assessments
Premorbid neurological deficits and functional limitations assessed by a pre-stroke Modified Rankin Scale score of > 1
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
Either severe hypertension or hypotension, as measured by at least 2 consecutive supine measurements taken 10 minutes apart prior to randomization.
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.
Have a platelet count of <100,000/mm3 or, for patients on oral anticoagulants at study entry, INR of >4
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
Positive urine pregnancy test at screening/baseline or be a lactating female
Currently dependent on, or abusing, alcohol or one or more of the following: sympathomimetic amines, cannabis, cocaine, hallucinogens, inhalants, opioids, phencyclidine, sedatives and hypnotics
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
Severe anemia as measured by a hemoglobin value of < 7 g/dl.
In a dependent relationship with the physician or the study sponsor.
Known hypersensitivity to any component of the investigational product.

Sites / Locations

Research Center of Southern California
Associated Neurologists, P.C.
Memorial Health University Medical Center
The University of Kentucky The Methodist Hospital
University of Louisville, Kentucky Neuroscience Research
Tufts Medical Center
Capital Health Regional Medical Center Neuroscience Institute
Presbitarian Hospital
St. Elizabeth's Medical Center
Legacy Meridian Park Medical Center
Thomas Jefferson University
The Methodist Hospital
Carilion Clinic
Medizinische Universität Innsbruck
Landeskrankenhaus Klagenfurt
Abt. Neurologie und Psychiatrie
LKH St. Pölten Department of Neurology
Santa Casa de Misericordia de Belo Horizonte Departamento de Neurologia
Hospital de Clinicas de Porto Alegre
Hospital Moinhos de Vento
Hospital Mãe de Deus
Santa Casa de Misericórdia de Porto Alegre Policlinica Santa Clara Sala de Neurologia
Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto Unidade de Emergência Centro de Estudos
UNIFESP
Hospital São José de Joinville
Hospital Santa Marcelina
Hamilton Health Sciences Centre
Grey Nun's Community Hospital
University of Alberta Hospital
Hamilton Health Sciences Centre
Kingston General Hospital
Chinook Regional Hospital
CHA- Hôpital de l'Enfant-Jésus
University Hospital Brno
University Hospital Hradec Kralove, Clinic of Neurology
Hospital Jihlava Clinic of Neurology
Hospital Vítkovice Clinic of Neurology
County Hospital Pardubice Clinic of Neurology
Clinic of Neurology, Stroke Center, Charles University
University Hospital Kralovske Vinohrady
University Hospital Motol Clinic of Neurology
CHU Jean Minjoz Besançon
Hopital Pellegrin-Tripode
CHU Henri Mondor
Hopital Gui de Chauliac
Hôpital Bichat
Hôpital Lariboisière - Service Neurologie
Hôpital Saint Jean
Ärztlicher Direktor Neurologische Klinik, Neurologische Klink GmbH der Rhoen-Klinikum AG
Marien-Krankenhaus gGmbH, Abteilung für Neurologie
DRK Kliniken Berlin, Klinik fuer Neurologie
Vivantes Klinikum Neukölln, Klinik für Neurologie, Stroke Unit
Klinikum Bremen-Mitte
Klinikum Bremerhaven-Reinkenheide gGmbH, Neurologische Klinik
Klinikum Chemnitz GmbH Chefarzt Klinik für Neurologie
Helios Klinikum Erfurt GmbH
Universitätsklinikum Erlangen, Neurologische klinik
Universitätsklinikum Essen, Klinik und Poliklinik für Neurologie
Neurologische Universitätsklinik Freiburg, Neurozentrum
Klinikum Fulda, Neurologische Klinik
Evangelische Kliniken Gelsenkirchen GmbH Klinik für Neurologie und Klinische Neurophysiologie
Georg-August-Universitat Gottingen Neurologische Klinik
Ernst Moritz Arndt University
Askepios Klinik Altona
Askepios Klinik Heidberg
Klinikum Köln Merheim, Department of Neurology
Universitätsklinikum Leipzig AöR, Klinik und Poliklinik für Neurologie
Klinikum der Otto-von-Guericke-Universität Magdeburg, Neurologische Universitätsklinik
Johannes Gutenberg Universitat, Klinik und Poliklinik fur Neurologie
Klinikum 1 Minden, Neurologische Klinik
Universität Rostock Chefarzt Abteilung Neurologie
ASKLEPIOS Fachklinikum Teupitz
Krankenhaus der Bramherzigen Brüder
Universitätsklinikum Ulm, Abteilung für Neurologie im RKU
Heinrich Braun Klinikum Zwickau
Fővárosi Önkormányzat Péterfy Sándor utcai Kórház- Rendelőintézet és Baleseti Központ
Állami Egészségügyi Központ
Kenezy Korhaz Rendelointezet Egezsegugyi Szolgaltato Nonprofit Kft.
University of Debrecen, Medical and Health Science Center
Aladár Petz County Teaching Hospital
PM Flór Ferenc County Hospital
Borsod-Abaúj-Zemplén County Hospital Miskolc
Pécsi Tudományegyetem Klinikai Központ
Zala Megyei Kórház
Bnai Zion Medical Center
Neurological Dept. Edith Wolfson Medical Center
Meir Medical Center
Sourasky Medical Center
Chaim Sheba Medical Center
Ospedale Regionale Valle d'Aosta
Dipartimento di Neuroscienze, Ospedale di Brotzu
Ospedale di Circolo di Varese
Istituto Scientifico San Raffaele - Stroke Unit
Istituto Neurologico C. Mondino
Università di Perugia, Division of Internal and Cardiovascular Medicine - Stroke Unit
Presidio Ospedaliero di Piacenza
Azienda Ospedaliera Sant'Andrea, Stroke Unit
Istituto Patologia Generale U.C.S.C
U.O.C. Stroke Unit
Università di Roma "La Sapienza" - Stroke Unit
Azienda Ospedaliera Universitaria "Santa Maria della Misericordia" Stroke Unit
Dong-A Medical Center
Inje University BUSAN Paik Hospital
Inje University ILSAN Paik Hospital
Chonnam National University Hospital
Inha University Hospital
Seoul National University Bundang Hospital
ASAN Medical Center
Severance Hospital
The Catholic University of Korea Seoul St. Mary's hospital
Catharina Ziekenhuis Neurologie
Medisch Spectrum Twente Hoofd Afdeling Vasculaire Neurologie
Atrium MC Parkstad
Isala Klinieken Ploikliniek Neurologie
Pomerania Traumatology Center, Regional Specialist Hospital im. Nicolaus Copernicus
Medical University of Lublin, Department of Neurology, Stroke Unit
Samodzielny Publiczny Zespol Zakladow Opieki Zdrowotnej w Sandomierzu
Szpital Powiatowy im. Marii Curie - Skłodowskiej w Skarżysku-Kamiennej
Wojewodzki Szpital Specjalistyczny Nr 1 im. Prof. Jozefa Gasinskiego
Instytut Psychiatrii i Neurologii Oddział Neurologiczny z Pododdziałem Udarowym
Medical University of Warsaw, Department of Neurology
Szpital Wolski im. dr Anny Gostyńskiej Samodzielny Publiczny Zakład Opieki Zdrowotnej, Oddział Neurologii
Wojskowy Instytut Medyczny, Oddział Neurologii
Hospital Professor Doutor Fernando Fonseca, EPE
Centro Hospitalar de Coimbra EPE
Hospitais da Universidadde de Coimbra, EPE
Centro de Estudos Egas Moniz - Hospital de Santa Maria
Hospital de São Sebastião, EPE
Neurology Clinic, Faculty Hospital in Martin
University Hospital Nitra
Hospital un Poliklinic
Faculty Hospital Trnava
Neurology dept.,Hospital Zilina
Fichmed
Constantiaberg Medi-clinic
Union Hospital
Helderberg Research Institute
Triervlei Trial Centre
Clinical Projects Research
Hospital Universitario de Albacete
Hospital De La Santa Ta Creu i Sant Pau
Hospital del Mar
Hospital Germans Triasy Pujol
Hospital Vall D'hebron
Hospital Gregorio Maranon
Hospital La Princesa
Hospital Ramon y Cajal
Hospital Universitario Clinico San Carlos
Hospital Universitario La Paz
Hospital Clinico Universitario de Santiago
Consorcio Hospital General Universitario Valencia
Hospital Clinico Universitario De Valladolid
Universitätsspital Basel, Neurologie
Universitätsspital Zürich, Klinik für Neurologie

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

DP-b99

Mannitol

Arm Description

Outcomes

Primary Outcome Measures

Modified Rankin Scale (mRS) categorical analysis ("shift")

Secondary Outcome Measures

Recovery, defined as a score of ≤ 1 on modified Rankin Score

Safety and tolerability

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

'home time'

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

Full Information

NCT ID

NCT00893867

First Posted

May 4, 2009

Last Updated

October 23, 2012

Sponsor

D-Pharm Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT00893867

Brief Title

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

Acronym

MACSI

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2012

Overall Recruitment Status

Terminated

Why Stopped

The result of a pre-planned interim futility analysis

Study Start Date

December 2009 (undefined)

Primary Completion Date

April 2012 (Actual)

Study Completion Date

April 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

D-Pharm Ltd.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Ischemic Stroke

Keywords

acute ischemic stroke, neuroprotective agent

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

446 (Actual)

8. Arms, Groups, and Interventions

Arm Title

DP-b99

Arm Type

Experimental

Arm Title

Mannitol

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

DP-b99

Intervention Description

1mg/kg/day over 4 consecutive days given intravenously and initiated up to 9 hours following acute stroke onset.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

1mg/kg/day over 4 consecutive days given intravenously and initiated up to 9 hours following acute stroke onset.

Primary Outcome Measure Information:

Title

Modified Rankin Scale (mRS) categorical analysis ("shift")

Time Frame

90 days

Secondary Outcome Measure Information:

Title

Recovery, defined as a score of ≤ 1 on modified Rankin Score

Time Frame

90 days

Title

Safety and tolerability

Description

Time Frame

throughout study - baseline until day 90

Title

recovery as assessed by an NIHSS of not more than 1

Time Frame

90 days

Title

'home time'

Description

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

Time Frame

90 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria: M or F age 18 - 85, inclusive 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) 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. Screening NIHSS score of 10 to 16, inclusive Readily accessible peripheral venous access for clinical trial material (CTM) administration and blood sampling 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. 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: An intracerebral or subarachnoid hemorrhage per screening/baseline computerized tomography scan or susceptibility-weighted magnetic resonance imaging A candidate for either: thrombolytic therapy, or have been treated with thrombolytic therapy for the current stroke mechanical thromboembolectomy, or have been treated with mechanical thromboembolectomy for the current stroke 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 Have seizure(s) anytime from stroke onset to screening/baseline NIHSS evaluation 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 Likely to undergo a procedure involving cardiopulmonary bypass during the study period Suffered a myocardial infarction in the last 90 days 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) Rapid spontaneous improvement of neurological signs during screening/baseline assessments Premorbid neurological deficits and functional limitations assessed by a pre-stroke Modified Rankin Scale score of > 1 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 Either severe hypertension or hypotension, as measured by at least 2 consecutive supine measurements taken 10 minutes apart prior to randomization. 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. Have a platelet count of <100,000/mm3 or, for patients on oral anticoagulants at study entry, INR of >4 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 Positive urine pregnancy test at screening/baseline or be a lactating female Currently dependent on, or abusing, alcohol or one or more of the following: sympathomimetic amines, cannabis, cocaine, hallucinogens, inhalants, opioids, phencyclidine, sedatives and hypnotics 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 Severe anemia as measured by a hemoglobin value of < 7 g/dl. In a dependent relationship with the physician or the study sponsor. Known hypersensitivity to any component of the investigational product.

Overall Study Officials: