An Open Label, Multi Center Study on the Efficacy and Safety of a Liquid, Ready-to-Use Intravenously Administered Anti-D Immunoglobulin in Patients with Chronic Immune Thrombocytopenic Purpura.

Introduction

Intravenous anti-Rh₀(D) immune globulin (anti-D) is used as a platelet enhancing therapy in patients with ITP. The following study was designed to assess the efficacy, tolerability and safety of a new, liquid anti-D (ZLB Behring).

Methods

This multicenter study was an open-label, single arm, phase III trial of 98 Rh₀(D)-positive patients with chronic ITP and a platelet count < 30x10⁹/L. Exclusion criteria included previous splenectomy, HIV infection, pregnancy, anemia (hemoglobin < 100 g/L), and positive Coombs test. The study medication was a chromatographically purified, solvent detergent treated and nanofiltered (15 nm) anti-D. This manufacturing process results in a product with a high purity (particularly a very low IgA content) and an excellent viral safety. Anti-D was provided in pre-filled, ready-to-use syringes and administered at a dose of 50 μg/kg body weight as a single intravenous injection.

The primary endpoint was the response rate, defined by the percentage of patients reaching an increase of their platelet count by at least 20x10⁹/L to at least 30x10⁹/L within 15 days. Secondary endpoints included time to platelet response, duration of response and the regression of hemorrhages. For the safety evaluation, blood hemoglobin, serum creatinine and bilirubin levels were closely monitored, in addition to the recording of all adverse events (AE).

Results

The overall response rate was 66 % (95 % CI: 57 to 75 %). The median time to response was 3 days and the median duration of response was 22 days. A regression of hemorrhages was seen in 88 % of the 50 patients having bleeding at baseline. The most frequent drug related AEs were chills, pyrexia, increase in bilirubin levels and headache. They were generally mild or moderate. A slight decrease in hemoglobin levels (median: -8 g/L) and a slight, transient elevation of bilirubin (median: +0.6 mg/dL) were seen in most patients as expected due the mode of action of anti-D. Clinically relevant elevations in serum creatinine level did not occur (median change: < 0.02 mg/dL).

Discussion

The present study has demonstrated that the tested anti-D is safe and efficacious in chronic ITP. Response rate, time to response and duration of response were similar to those reported for other platelet enhancing treatments, including high dose corticosteroids, IVIG and other anti-D products. The increase in platelet count was accompanied by a substantial regression of hemorrhages. Drug related adverse events were mainly mild and expected and no cases of severe hemolysis or deterioration of renal function occurred. The liquid, ready-to-use anti-D is an attractive treatment alternative in ITP, offering the convenience of a fast and easy administration.