Clinical Outcome Study of ARC1779 Injection in Patients With Thrombotic Microangiopathy

Sponsor

Archemix Corp. (Industry)

Overall Status

Terminated

CT.gov ID

NCT00726544

Collaborator

(none)

100

Enrollment

Locations

Arms

26.9

Duration (Months)

5.9

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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 Drug: ARC1779 Injection Drug: ARC1779 Injection	Phase 2

Study Design

Study Type:

Interventional

Anticipated 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 :

Dec 1, 2008

Anticipated Primary Completion Date :

Dec 1, 2010

Anticipated Study Completion Date :

Mar 1, 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

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 Outcome Measures

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.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

	Site	City	State	Country	Postal Code
1	Northwestern University	Chicago	Illinois	United States	60611
2	Indiana University Simon Cancer Center	Indianapolis	Indiana	United States	46202
3	Washington University	St. Louis	Missouri	United States	63110
4	New York Medical College	Valhalla	New York	United States	10595
5	The Ohio State University Research Foundation	Columbus	Ohio	United States	43235
6	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
7	The Methodist Hospital	Houston	Texas	United States	77030
8	University of Vienna	Vienna		Austria	1090
9	QEII CDHA Centre	Halifax	Nova Scotia	Canada	B3H 2Y9
10	CICM/Hospital Charles LeMoyne	Greenfield Park	Quebec	Canada	J4V 2H1
11	CHA-Hospital de L'Enfant-Jesus	Quebec		Canada	G1J 1Z4
12	Ospedale Ferrarotto	Catania		Italy	95100
13	Fondazione Ospedale Maggiore Policlinico	Milano		Italy	20122
14	Policlinico Mangiagalli Regina Elena-Fondazione L.Villa	Milan		Italy
15	Azienda Ospedaliera S.Maria Nuova	Reggio Emilia		Italy	42100
16	Università Cattolica del Sacro Cuore	Rome		Italy
17	University College London Hospital	London		United Kingdom	W1T 4EU