Clinical Outcome Study of ARC1779 Injection in Patients With Thrombotic Microangiopathy

Thrombotic Thrombocytopenic Purpura Clinical Trial

Official title:

A Randomized, Double-blind, Placebo Controlled, Clinical Outcome Study of ARC1779 Injection in Patients With Thrombotic Microangiopathy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00726544
• Other study ID #: ARC1779-006
• Status: Terminated
• Phase: Phase 2
• First received: July 30, 2008
• Last updated: November 24, 2009
• Start date: December 2008
• Est. completion date: March 2011

Study information

• Verified date: November 2009
• Source: Archemix Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyAustria: Agency for Health and Food SafetySwitzerland: SwissmedicCanada: Health CanadaItaly: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 100
• Est. completion date: March 2011
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Purpura, Thrombocytopenic
• Purpura, Thrombotic Thrombocytopenic
• Thrombotic Microangiopathies
• Thrombotic Microangiopathy
• Thrombotic Thrombocytopenic Purpura
• Vascular Diseases

Intervention

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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
Austria	University of Vienna	Vienna
Canada	CICM/Hospital Charles LeMoyne	Greenfield Park	Quebec
Canada	QEII CDHA Centre	Halifax	Nova Scotia
Canada	CHA-Hospital de L'Enfant-Jesus	Quebec
Italy	Ospedale Ferrarotto	Catania
Italy	Policlinico Mangiagalli Regina Elena-Fondazione L.Villa	Milan
Italy	Fondazione Ospedale Maggiore Policlinico	Milano
Italy	Azienda Ospedaliera S.Maria Nuova	Reggio Emilia
Italy	Università Cattolica del Sacro Cuore	Rome
United Kingdom	University College London Hospital	London
United States	Northwestern University	Chicago	Illinois
United States	The Ohio State University Research Foundation	Columbus	Ohio
United States	The Methodist Hospital	Houston	Texas
United States	Indiana University Simon Cancer Center	Indianapolis	Indiana
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Washington University	St. Louis	Missouri
United States	New York Medical College	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
Archemix Corp.

Countries where clinical trial is conducted

United States,  Austria,  Canada,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Neurocognitive function is to be assessed with the CogState® test system.		Once during the hospitalization period and again at the 6 week clinic visit.	No
Secondary	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.	No
Secondary	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.	Yes
Secondary	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.	Yes