Final Results From a Phase II Trial with the First in Class Recombinant Polyclonal Antibody Product Rozrolimupab in Primary Immune Thrombocytopenia
Authors: Robak Tadeusz , Trelinski Jacek , von Depka Prondzinski Mario , Giagounidis Aristoteles , Doyen Chantal , Janssens Ann , Román Mayte Álvarez , Pueyo Javier Loscertales , Ramos Isidro Jarque , Loscertales Javier , Rus Gloria Pérez , Hellmann Andrzej , Wiktor-Jedrzejczak Wieslaw , Kuliczkowski Kazimierz , Golubovic Lana , Celeketic Dusica , Cucuianu Andrei , Gheorghita Emanuil , Mihaela Lazaroiu , Attias Dina , Shpilberg Ofer , Karyagina Elena , Vilchevska Kateryna , Svetlana Kalinina , Cooper Nichola , Talks Kate , Prabhu Mukyaprana , Prasad Sripada V.S.S , Bharadwaj T. P. Raghava , Flensburg Mimi Folden , Petersen Jorgen , Windyga Jerzy 
Published: October 2019

Abstract
Abstract 527

Background:
Rozrolimupab is the first in-class fully human, recombinant antibody mixture for the treatment of ITP. Rozrolimupab comprises 25 unique human antibodies with documented binding capacity to the Rhesus D antigen on red blood cells, and constitutes a promising, modern counter-part to the blood-derived immunoglobulin products currently used in the treatment of ITP. The antibody mixture constituting rozrolimupab is produced by a novel single batch manufacturing strategy.

Objectives and Endpoints:
The objectives of the trial were to investigate the safety and efficacy of a single dose of rozrolimupab in RhD positive, non-splenectomized adult patients with primary ITP. The primary endpoint was incidence and severity of Adverse Events (AEs) during the 6-week trial period. Secondary endpoints included identification of the optimal dose of rozrolimupab and percentage of patients responding to treatment at 72 hours, 7 and 15 days.

Methods:
Patients from 27 sites in 11 countries were enrolled in this dose escalation (75 μg/kg – 300 μg/kg), multicentre, open label trial. Inclusion criteria included confirmed presence of thrombocytopenia with two individual pre-dose platelet counts of < 30 × 109/L. The patients received a single iv dose of rozrolimupab, and were followed for 6 weeks with frequent evaluations for safety and efficacy. Response was defined as platelet count ≥ 30 ×109/L and increase in platelet count from baseline by > 20 × 109/L.

Results:
A total of 61 ITP patients were treated with rozrolimupab: 75 μg/kg (11 patients), 100 μg/kg (10 patients), 125 μg/kg (10 patients), 150 μg/kg (5 patients), 200 μg/kg (6 patients), 250 μg/kg (6 patients) and 300 μg/kg (13 patients). Data from the 300 μg/kg cohort were not available for this abstract, but will be included in the final presentation.Given the small size of this study, the dose cohorts differed in a number of baseline characteristics. 60–90% of patients were females in all dose cohorts except in the 75 μg/kg cohort where 73% were males. Median platelet count before trial entry ranged from 11.5 to 22.3 × 109/L, and median time from first ITP diagnosis ranged from 5 to 68 months. In the individual dose groups, up to 83% of the patients responded at day 7. Up to 50% and 60% of the patients responded at 24 and 72 hours, respectively, and some responses lasted for the duration of the 6 weeks follow up period. Platelet responses also included patients who had baseline platelet counts below 10 ×109/L. A total of 51 AEs considered related to trial drug were reported in 20 patients. The most frequently reported adverse reactions were headache (7 events in 5 patients) and pyrexia (5 events in 4 patients). All but 2 of the adverse reactions (one headache, one extravascular haemolysis) were of mild or moderate intensity. Four of the 51 adverse reactions were categorized as Serious Adverse Events: One mild haemoglobin decrease in the 100 μg/kg cohort, one extravascular haemolysis in the 200 μg/kg cohort (mentioned above) and two mild to moderate, transient increases in D-dimer with no clinical symptoms in the 250 μg/kg cohort. Laboratory data showed a mean maximum decrease in haemoglobin ranging from 1.1 g/dL to 2.7 g/dL in individual cohorts with a slight dose dependency. A drop in haemoglobin of ≥ 3 g/dL was seen in 2 patients, one of 3.1 g/dL in the 100 μg/kg cohort and one of 4.5 g/dL in the 200 μg/kg cohort.

Conclusions:
Rozrolimupab is well tolerated with a favourable safety profile. In the individual dose groups, up to 83% of patients responded at day 7 including patients who had baseline platelet counts below 10 ×109/L. Final safety and efficacy data from all dose groups in the completed Phase II trial of rozrolimupab in primary ITP patients will be presented.

Disclosures:
Wiktor-Jedrzejczak: Celgene: Honoraria; Janssen-Cilag: Honoraria; Novartis: Honoraria, Research Funding. Flensburg:Symphogen: Employment. Petersen:Symphogen: Employment.