A Study of the Pharmacokinetics, Pharmacodynamics, and Safety of ARC1779 Injection in Patients With Von Willebrand Disease Type 2B - Full Text View

Purpose

To evaluate the effect of ARC1779, a therapeutic oligonucleotide ("aptamer") in patients with Type2B von Willebrand Disease.

Condition	Intervention	Phase
Von Willebrand Disease	Drug: ARC1779	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Study of the Pharmacokinetics, Pharmacodynamics, and Safety of ARC1779 Injection in Patients With Von Willebrand Disease Type 2B

Resource links provided by NLM:

Genetics Home Reference related topics: von Willebrand disease

U.S. FDA Resources

Further study details as provided by Archemix Corp.:

Primary Outcome Measures:

To evaluate the effect of ARC1779 Injection on platelet counts in vWD-2B patients who have thrombocytopenia at baseline. [ Time Frame: 10 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To assess the concentration-response relationships among ARC1779 pharmacokinetic (PK) and pharmacodynamic (PD) parameters [ Time Frame: 10 days ] [ Designated as safety issue: No ]


Estimated Enrollment:	2
Study Start Date:	October 2008
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Group NT3 Patients will receive a total dose of approximately 1.7 mg/kg of ARC1779 over 72 hours to achieve a target plasma concentration of 3 mcg/mL	Drug: ARC1779 Initial stepwise infusion of 0.14 mg/kg given over 60 minutes and subsequent continuous infusion of an additional 1.7 mg/kg given over the remaining 72 hours at a rate of 0.0004 mg/kg/min. Group "NT3"
Experimental: Group T3 Patients will receive a total dose of approximately 1.4 mg/kg of ARC1779 over 72 hours to achieve a target plasma concentration of 3 mcg/mL. The infusion of ARC1779 will be tapered by 50% from 48 hours to 60 hours and again by 50% from 60 hours to 72 hours.	Drug: ARC1779 Initial stepwise infusion of 0.14 mg/kg given over 60 minutes and subsequent continuous infusion of an additional 1.3 mg/kg given over the next 72 hours. Group "T3"
Experimental: Group NT6 Patients will receive a total dose of approximately 3.9 mg/kg of ARC1779 over 72 hours to achieve a target plasma concentration of 6 mcg/mL.	Drug: ARC1779 Initial stepwise infusion of 0.28 mg/kg given over 60 minutes and subsequent continuous infusion of an additional 3.8 mg/kg given over the remaining 72 hours at a rate of 0.0009 mg/kg/min. Group "NT6"
Experimental: Group T6 Patients will receive a total dose of approximately 3.1 mg/kg of ARC1779 over 72 hours to achieve a target plasma concentration of 6 mcg/mL. The infusion of ARC1779 will be tapered by 50% from 48 hours to 60 hours and again by 50% from 60 hours to 72 hours.	Drug: ARC1779 Initial stepwise infusion of 0.28 mg/kg given over 60 minutes and subsequent continuous infusion of an additional 3.0 mg/kg given over the remaining 72 hours. Group "T6"

Detailed Description:

ARC1779 will be investigated in an open-label, uncontrolled study in up to 3 vWD-2B patients. Patients with vWD-2B will be screened for eligibility based primarily upon a single major criterion, i.e., presence of any degree of chronic thrombocytopenia. Eligible patients will be treated by intravenous infusion of ARC1779 for 72 hours.

Eligibility


Ages Eligible for Study:	16 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female patients;
≥ 16 to ≤ 75 years of age;
Diagnosis of VWD-2B according to national expert guidelines for the USA [1] and Europe [2] based on medical history and findings from a matrix of laboratory assays which may include: platelet count, concentration of VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), Factor VIII (FVIII) activity, ristocetin-induced platelet aggregation (RIPA), platelet function analyzer (PFA-100®) closure time, bleeding time (BT), VWF multimer test, VWF: platelet-binding (VWF:PB) activity, etc.)
Thrombocytopenia (defined as a platelet count < 100 per nL on at least 2 occasions within the month preceding enrollment;
Female patients of reproductive age must be enrolled within 1 to 7 days of the cessation of preceding menses;
Female patients must be non-pregnant and willing to use 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;
Male patients must agree to use 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;
All patients must be capable of understanding and complying with the protocol and must have signed the informed consent document.

Exclusion Criteria:

Patients with a possible co-existing or alternative hematologic diagnosis which can account for the laboratory findings of thrombocytopenia, etc.;
Any significant medical co-morbidity which would pose an increased risk of bleeding (e.g., recent trauma or surgery, a history of gastrointestinal ulcers, etc.) or thrombosis (e.g., history of recurrent deep vein thrombosis (DVT).

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.

No Contacts or Locations Provided

More Information

No publications provided


Responsible Party:	Margaret Ragni, MD, University of Pittsburgh
ClinicalTrials.gov Identifier:	NCT00694785 History of Changes
Other Study ID Numbers:	ARC1779-010
Study First Received:	June 6, 2008
Last Updated:	August 20, 2009
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:


Von Willebrand Disease, Type 2 Von Willebrand Diseases Blood Coagulation Disorders Blood Coagulation Disorders, Inherited Blood Platelet Disorders	Coagulation Protein Disorders Genetic Diseases, Inborn Hematologic Diseases Hemorrhagic Disorders

ClinicalTrials.gov processed this record on February 27, 2015