Clinical Outcome Study of ARC1779 Injection in Patients With Thrombotic Microangiopathy

• Sponsor: Archemix Corp.
• Information provided by: Archemix Corp.

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Thrombotic Microangiopathy; Thrombotic Thrombocytopenic Purpura	Drug: ARC 1779 Placebo; Drug: ARC1779 Injection	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	100 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, 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
Study Start Date :	December 2008
Estimated Primary Completion Date :	December 2010
Estimated Study Completion Date :	March 2011

Arms and Interventions

Arm	Intervention/treatment
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.

Outcome Measures

Primary Outcome Measures :

1. 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 ]

Secondary Outcome Measures :

1. 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. ]
2. 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. ]
3. 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. ]
4. 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. ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 75 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
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

Locations

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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
Fondazione Ospedale Maggiore Policlinico
Milano, Italy, 20122
Policlinico Mangiagalli Regina Elena-Fondazione L.Villa
Milan, Italy
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

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Responsible Party:	Dr, James Gilbert, Archemix
ClinicalTrials.gov Identifier:	NCT00726544 History of Changes
Other Study ID Numbers:	ARC1779-006
First Posted:	August 1, 2008
Last Update Posted:	November 26, 2009
Last Verified:	November 2009

Keywords provided by Archemix Corp.:

thrombocytopenia; microangiopathic hemolytic anemia; von Willebrand Factor; ADAMTS13

Additional relevant MeSH terms:

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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