Clinical Outcome Study of ARC1779 Injection in Patients With Thrombotic Microangiopathy

This study has been terminated.
(Enrollment into study was slower than expected.)
Sponsor:
Information provided by:
Archemix Corp.
ClinicalTrials.gov Identifier:
NCT00726544
First received: July 30, 2008
Last updated: November 24, 2009
Last verified: November 2009
  Purpose

The purpose of this ascending-dose research study is to determine whether the administration of ARC1779 Injection improves subject's health profile by protecting the brain, heart, and kidney from damage due to formation of small blood clots in blood vessels. It will also determine the safety of ARC1779 Injection, how ARC1779 Injection enters and leaves the blood and tissue over time, and its effect on laboratory tests related to blood clotting, heart and brain function, and other body systems.


Condition Intervention Phase
Thrombotic Microangiopathy
Thrombotic Thrombocytopenic Purpura
Drug: ARC 1779 Placebo
Drug: ARC1779 Injection
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo Controlled, Clinical Outcome Study of ARC1779 Injection in Patients With Thrombotic Microangiopathy

Resource links provided by NLM:


Further study details as provided by Archemix Corp.:

Primary Outcome Measures:
  • The incidence of the clinical composite of death (all-cause mortality), stroke, coma, seizures, renal failure, or acute myocardial infarction (AMI) [ Time Frame: 6 weeks post randomization ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Neurocognitive function is to be assessed with the CogState® test system. [ Time Frame: Once during the hospitalization period and again at the 6 week clinic visit. ] [ Designated as safety issue: No ]
  • The incidence of death, stroke, or acute renal failure/injury requiring dialysis is to be assessed. [ Time Frame: During the extended clinical follow-up for each patient from the time of the 6 week clinic visit until the study is closed. ] [ Designated as safety issue: No ]
  • Safety- and efficacy-related clinical laboratory parameters and biomarkers will be analyzed in relation to ARC1779 exposure in terms of the dose administered and the observed plasma concentration. [ Time Frame: During initial hospitalization and at 6 week clinic visit. ] [ Designated as safety issue: Yes ]
  • The incidence of the composite of complications associated with plasma exchange therapy (i.e., catheter-related infection, thrombosis, internal hemorrhage, or pneumothorax) is to be assessed. [ Time Frame: During initial hospitalization and at the 6 week clinic visit. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 100
Study Start Date: December 2008
Estimated Study Completion Date: March 2011
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: ARC 1779 Placebo
ARC1779 Injection or placebo is administered intravenously to patients as an initial loading dose followed by continuous infusion of up to 14 days plus 2 day taper.
Active Comparator: Low Dose Drug: ARC1779 Injection
ARC1779 Injection or placebo is administered intravenously to patients as an initial loading dose followed by continuous infusion of up to 14 days plus 2 day taper. Treatment with ARC1779 Injection is to be given at low dosage that is intended to produce target steady-state ARC1779 plasma concentrations during infusion of 3μg/mL.
Active Comparator: Medium Dose Drug: ARC1779 Injection
ARC1779 Injection or placebo is administered intravenously to patients as an initial loading dose followed by continuous infusion of up to 14 days plus 2 day taper. Treatment with ARC1779 Injection is to be given at low dosage that is intended to produce target steady-state ARC1779 plasma concentrations during infusion of 6μg/mL.
Active Comparator: High Dose Drug: ARC1779 Injection
ARC1779 Injection or placebo is administered intravenously to patients as an initial loading dose followed by continuous infusion of up to 14 days plus 2 day taper. Treatment with ARC1779 Injection is to be given at low dosage that is intended to produce target steady-state ARC1779 plasma concentrations during infusion of 12μg/mL.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female;
  • ≥18 to ≤75 years of age;
  • Diagnosis of TMA based on presence of:
  • Thrombocytopenia, defined as a platelet count <100 x 109 per liter;
  • Microangiopathic hemolytic anemia, defined by negative findings on direct antiglobulin test, and evidence of accelerated red blood cell (RBC) production and destruction); AND
  • Absence of a clinically apparent alternative explanation for thrombocytopenia and anemia, e.g., disseminated intravascular coagulation (DIC), eclampsia, HELLP syndrome, Evans syndrome;
  • Females: non-pregnant and commit to use of effective, redundant methods of contraception (i.e., for both self and male partner) throughout the study and for at least 30 days after discontinuation of study drug treatment;
  • Males: commit to use of a medically acceptable contraceptive (abstinence or use of a condom with spermicide) throughout the study and for at least 30 days after discontinuation of study drug treatment;
  • Not received an unlicensed investigational agent (drug, device, or blood-derived product) within 30 days prior to randomization, and may not receive such an investigational agent in the 30 days post-randomization (note: investigational use for treatment of TMA of a licensed immunomodulator, e.g., rituximab, is permitted at any time relative to randomization);
  • Capable of understanding and complying with the protocol, and he/she (or a legal representative) must have signed the informed consent document prior to performance of any study-related procedures.

Patients who have again become acutely ill following recent treatment and achievement of a brief remission of acute TMA may be enrolled in the study if ALL of the following conditions are met:

  • Disease activity in the patient in unabated (e.g. persistent thrombocytopenia and microangiopathic hemolytic anemia with ongoing neurological symptoms and/or troponin elevation);
  • The last plasma exchange of the patient's preceding course of treatment occurred at least 7 days prior;
  • The patient did not undergo splenectomy during the preceding course of treatment;
  • The new course of plasma exchange has not been ongoing for more than 3 days.

Exclusion Criteria:

  • Females: pregnant or <24 hours post-partum, or breastfeeding;
  • History of bleeding diathesis or evidence of active abnormal bleeding within the previous 30 days;
  • Disseminated malignancy or other co-morbid illness limiting life expectancy to ≤3 months independent of the TMA disorder.
  • Diagnosis other than TMA which can account for the findings of thrombocytopenia and hemolytic anemia (e.g., DIC, HELLP syndrome, Evans syndrome);
  • Diagnosis of DIC verified by laboratory values for D-dimer, fibrinogen, prothrombin time (PT), and activated partial thromboplastin time (aPTT).

Patients who have again become acutely ill following recent treatment and achievement of a brief remission of acute TMA may not be enrolled in the study if ANY of the following conditions are met:

  • The last plasma exchange of the patient's preceding course of treatment occurred less than 7 days prior;
  • The patient underwent splenectomy during the preceding course of treatment;
  • The new course of plasma exchange has been ongoing for more than 3 days.
  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: NCT00726544

Locations
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Indiana
Indiana University Simon Cancer Center
Indianapolis, Indiana, United States, 46202
United States, Missouri
Washington University
St. Louis, Missouri, United States, 63110
United States, New York
New York Medical College
Valhalla, New York, United States, 10595
United States, Ohio
The Ohio State University Research Foundation
Columbus, Ohio, United States, 43235
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
The Methodist Hospital
Houston, Texas, United States, 77030
Austria
University of Vienna
Vienna, Austria, 1090
Canada, Nova Scotia
QEII CDHA Centre
Halifax, Nova Scotia, Canada, B3H 2Y9
Canada, Quebec
CICM/Hospital Charles LeMoyne
Greenfield Park, Quebec, Canada, J4V 2H1
Canada
CHA-Hospital de L'Enfant-Jesus
Quebec, Canada, G1J 1Z4
Italy
Ospedale Ferrarotto
Catania, Italy, 95100
Policlinico Mangiagalli Regina Elena-Fondazione L.Villa
Milan, Italy
Fondazione Ospedale Maggiore Policlinico
Milano, Italy, 20122
Azienda Ospedaliera S.Maria Nuova
Reggio Emilia, Italy, 42100
Università Cattolica del Sacro Cuore
Rome, Italy
United Kingdom
University College London Hospital
London, United Kingdom, W1T 4EU
Sponsors and Collaborators
Archemix Corp.
  More Information

No publications provided

Responsible Party: Dr, James Gilbert, Archemix
ClinicalTrials.gov Identifier: NCT00726544     History of Changes
Other Study ID Numbers: ARC1779-006
Study First Received: July 30, 2008
Last Updated: November 24, 2009
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Austria: Agency for Health and Food Safety
Switzerland: Swissmedic
Canada: Health Canada
Italy: Ministry of Health

Keywords provided by Archemix Corp.:
thrombocytopenia
microangiopathic hemolytic anemia
von Willebrand Factor
ADAMTS13

Additional relevant MeSH terms:
Purpura
Purpura, Thrombocytopenic
Purpura, Thrombotic Thrombocytopenic
Vascular Diseases
Thrombotic Microangiopathies
Blood Coagulation Disorders
Hematologic Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Thrombocytopenia
Blood Platelet Disorders
Immune System Diseases
Thrombophilia
Cardiovascular Diseases

ClinicalTrials.gov processed this record on August 28, 2014