A clinical trial to determine the distribution through the patient’s body, safety and effectiveness of rVWF and rFVIII in treatment of bleeding episodes in patient’s diagnosed with the Von Willebrand Disease.

Phase 3

• Conditions: severe hereditary Von Willebrand Disease

• Registration Number: CTRI/2012/01/002390
• Lead Sponsor: Baxter Healthcare Corporation

Brief Summary

This is a Phase 3,multi-center, open-label study to evaluate Pharmacokinetics, safety andeffectiveness in the treatment of bleeding episodes in patients with severetype 3 VWD, non-type 3 WVD and type 2N VWD disease. The study will be dividedin 2 parts (A&B). Approximately 45 patients will be enrolled. The primaryendpoint is a pharmacokinetic measurement.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-02-15
• Last Update Posted: 2016-02-02

Recruitment & Eligibility

• Status: Other
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

• •The subject has been diagnosed with: o type 3 VWD (VWF:Ag ≤3 IU/dl) or o severe non-type 3 VWD (VWF:RCo <20 IU/dL) or o type 2N VWD (FVIII:C <10% and historically documented genetics) •The subject, who participates for the treatment for bleeding episodes, has had a minimum of 6 documented bleeds (medical history) requiring VWF coagulation factor replacement therapy during the previous3 years prior to enrollment.
• •The subject has a Karnofsky score ≥60.
• •If female of childbearing potential, subject presents with a negative pregnancy test •The subject agrees to employ adequate birth control measures for the duration of the study.
• •Subject is willing and able to comply with the requirements of the protocol.

Exclusion Criteria

• •The subject has been diagnosed with pseudo VWD or another hereditary or acquired coagulation disorder other than VWD (eg qualitative and quantitative platelet disorders or elevated PT/international normalized ratio [INR] >1.4).
• •The subject has a documented history of a VWF:RCo half-life of <6 hours.
• •The subject has a history or presence of a VWF inhibitor at screening.
• •The subject has a history or presence of a factor VIII (FVIII) inhibitor with a titer ≥0.4 BU (by Nijmegen assay) or ≥0.6 BU (by Bethesda assay).
• •The subject has a known hypersensitivity to any of the components of the study drugs, such as to mouse or hamster proteins.
• •The subject has a medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis, mild asthma, food allergies or animal allergies.
• •The subject has a medical history of a thromboembolic event.
• •The subject is HIV positive with an absolute CD4 count <200/mm3.
• •The subject has been diagnosed with cardiovascular disease (New York Heart Association [NYHA] classes 1-4) •The subject has an acute illness (eg, influenza, flu-like syndrome, allergic rhinitis/conjunctivitis, non-seasonal asthma) at screening.
• •The subject has been diagnosed with significant liver disease as evidenced by any of the following: serum alanine aminotransferase (ALT) 5 times the upper limit of normal; hypoalbuminemia; portal vein hypertension (eg, presence of otherwise unexplained splenomegaly, history of esophageal varices).
• •The subject has been diagnosed with renal disease, with a serum creatinine level ≥2 mg/dL.
• •In the judgment of the investigator, the subject has another clinically significant concomitant disease (eg, uncontrolled hypertension) that may pose additional risks for the subject.
• •The subject has been treated with an imunomodulatory drug, excluding topical treatment (eg, ointments, nasal sprays), within 30 days prior to signing the informed consent.
• •Subject is pregnant or lactating at the time of enrollment.
• •Subject has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an investigational product or investigational device during the course of this study.
• •The subject has a history of drug or alcohol abuse within the 2 years prior to enrollment.
• •The subject is identified by the investigator as being unable or unwilling to cooperate with study procedures.
• •The subject suffers from a mental condition rendering him/her unable to understand the nature, scope and possible consequences of the study and/or evidence of an uncooperative attitude.
• •The subject is in prison or compulsory detention by regulatory and/or juridical order.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Number of subjects with a treatment success for treated bleeding episodes.	12 month

Secondary Outcome Measures

Name	Time	Method
Number of treated bleeding episodes with an efficacy rating of excellent or good	12 month
Number of infusions and rVWF:rFVIII and/or rVWF units per bleeding episode	12 month
Development of inhibitory and total binding anti-VWF antibodies	12 month
Development of inhibitory antibodies to FVIII, Time-points	12 month
Development of antibodies to Chinese hamster ovary (CHO) proteins, mouse immunoglobulin G (IgG) and rFurin	12 month
Occurrence of thrombotic events, Time-points	12 month
Other IP related AEs, such as clinically significant changes in routine laboratory parameters (hematology and clinical chemistry) and vital signs	12 month
Area under the plasma concentration/time curve from time 0 to infinity (AUC0-∞/Dose); area under the plasma concentration/time curve from time 0 to 96 hours (AUC0-96h/Dose); mean residence time (MRT); clearance (CL); incremental recovery (IR), elimination phase half-life (T1/2); volume of distribution at steady state (Vss) of VWF Ristocetin cofactor (VWF:RCo), VWF antigen (VWF:Ag), VWF collagen-binding (VWF:CB), and FVIII	6 month
In vivo recovery (IVR) of VWF:RCo, VWF:Ag and VWF:CB	12 month
Comparison of intra-subject PK of VWF:RCo, VWF:CB and VWF:Ag at baseline and after 6 months in a subset of at least 20 subjects with severe VWD (minimum 6 subjects with type 3 VWD)	6 month

Trial Locations

Locations (3)

Christian Medical College; 🇮🇳 Vellore, TAMIL NADU, India

Jehangir Clinical Development Centre; 🇮🇳 Pune, MAHARASHTRA, India

Sahyadri Specialty Hospital; 🇮🇳 Pune, MAHARASHTRA, India

Christian Medical College

🇮🇳Vellore, TAMIL NADU, India

Dr Alok Srivastava

Principal investigator

0416228235

aloks@cmcvellore.ac.in