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

Archemix

Status and phase: Withdrawn; Phase 2

Conditions: Von Willebrand Disease

Treatments: Drug: ARC1779

Study type: Interventional

Funder types: Industry

Identifiers

NCT00694785

ARC1779-010

Details and patient eligibility

About

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

Full 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.

Enrollment: 2 estimated patients

Sex: All

Ages: 16 to 75 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

2 participants in 4 patient groups

Group NT3

Experimental group

Description:

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

Treatment:

Drug: ARC1779

Drug: ARC1779

Drug: ARC1779

Drug: ARC1779

Group T3

Experimental group

Description:

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.

Treatment:

Drug: ARC1779

Drug: ARC1779

Drug: ARC1779

Drug: ARC1779

Group NT6

Experimental group

Description:

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.

Treatment:

Drug: ARC1779

Drug: ARC1779

Drug: ARC1779

Drug: ARC1779

Group T6

Experimental group

Description:

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.

Treatment:

Drug: ARC1779

Drug: ARC1779

Drug: ARC1779

Drug: ARC1779