Clinical Outcome Study of ARC1779 Injection in Patients With Thrombotic Microangiopathy

NCT00726544 | Terminated Phase 2 DMC

• 1 other identifier: ARC1779-006
• Study Type: interventional
• Target: 100
• Locations: 5 countries
• Sites: 17

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.

Conditions

Thrombotic Microangiopathy; Thrombotic Thrombocytopenic Purpura

Keywords

thrombocytopenia; microangiopathic hemolytic anemia; von Willebrand Factor; ADAMTS13

Outcome Measures

Primary Outcomes (1)

• The incidence of the clinical composite of death (all-cause mortality), stroke, coma, seizures, renal failure, or acute myocardial infarction (AMI)

  6 weeks post randomization

Secondary Outcomes (4)

• Neurocognitive function is to be assessed with the CogState® test system.

  Once during the hospitalization period and again at the 6 week clinic visit.

• The incidence of death, stroke, or acute renal failure/injury requiring dialysis is to be assessed.

  During the extended clinical follow-up for each patient from the time of the 6 week clinic visit until the study is closed.

• 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.

  During initial hospitalization and at 6 week clinic visit.

• 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.

  During initial hospitalization and at the 6 week clinic visit.

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Drug: ARC 1779 Placebo

Low Dose

ACTIVE COMPARATOR

Drug: ARC1779 Injection

Medium Dose

ACTIVE COMPARATOR

Drug: ARC1779 Injection

High Dose

ACTIVE COMPARATOR

Drug: ARC1779 Injection

Interventions

ARC 1779 Placebo DRUG

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.

Placebo

ARC1779 Injection DRUG

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.

Low Dose

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Archemix Corp.: lead

Study Sites (17)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

The Ohio State University Research Foundation

Columbus, Ohio, 43235, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

The Methodist Hospital

Houston, Texas, 77030, United States

Location

University of Vienna

Vienna, 1090, Austria

Location

QEII CDHA Centre

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

CICM/Hospital Charles LeMoyne

Greenfield Park, Quebec, J4V 2H1, Canada

Location

CHA-Hospital de L'Enfant-Jesus

Québec, Quebec, G1J 1Z4, Canada

Location

Ospedale Ferrarotto

Catania, 95100, Italy

Location

Policlinico Mangiagalli Regina Elena-Fondazione L.Villa

Milan, Italy

Location

Fondazione Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Azienda Ospedaliera S.Maria Nuova

Reggio Emilia, 42100, Italy

Location

Università Cattolica del Sacro Cuore

Rome, Italy

Location

University College London Hospital

London, W1T 4EU, United Kingdom

Location

MeSH Terms

Conditions

Thrombotic Microangiopathies; Purpura, Thrombotic Thrombocytopenic; Thrombocytopenia; Anemia, Hemolytic

Interventions

ARC 1779

Condition Hierarchy (Ancestors)

Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia; Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Thrombophilia; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms; Anemia

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: July 30, 2008
• First Posted: August 1, 2008
• Study Start: December 1, 2008
• Primary Completion: December 1, 2010
• Study Completion: March 1, 2011
• Last Updated: November 26, 2009

Record last verified: 2009-11

Locations

US (7); AU (1); IT (5); GB (1); CA (3)