PB2251 A PHASE II, OPEN-LABEL, PROSPECTIVE STUDY (TAPER) TO ASSESS THE ABILITY OF ELTROMBOPAG TO INDUCE SUSTAINED TREATMENT-FREE REMISSION IN ITP PATIENTS WITH INSUFFICIENT RESPONSE TO CORTICOSTEROIDS
Authors: N. Cooper, W. Ghanima, J. Haenig, J. Jha, J. Lee, F. Zaja
Journal: HemaSphere (2019)

Background: Corticosteroids and intravenous immunoglobulins (IVIG) remain the first-line standard of care for immune thrombocytopenia (ITP) despite high relapse rates (∼50% of adult patients (pts) with ITP relapsed by 6 months with an additional 25% relapsed by >1 year; Cuker A 2015) and significant morbidity, highlighting an unmet medical need in the management of ITP, particularly to improve sustained remission (SR) after treatment discontinuation. Few studies (Bussel JB 2015, Gonzalez-Lopez T 2015) indicate that treatment with thrombopoietin receptor agonist (TPO-RA) earlier in the course of the disease produced a stable response and SR in pts with ITP after treatment discontinuation. Eltrombopag (EPAG), an oral TPO-RA, is approved for treatment of chronic ITP (in Europe: primary ITP lasting 6 months or longer) in pts who are refractory to or relapsed with other treatments (such as corticosteroids, immunoglobulins). However, studies assessing the ability of EPAG to induce SR after treatment discontinuation in this pt population are limited (Lucchini E 2018). Aims: This study (NCT03524612) will assess the ability of EPAG to induce SR after treatment discontinuation in pts with ITP who are refractory to or relapsed after first-line steroid therapy. Methods: Adult pts (≥18 years) with primary ITP with platelet count <30 × 109/L who are not responsive to or in relapse after a first-line steroid therapy (overall steroid exposure ≤3 months) will be included in the study. Key exclusion criteria: pts with ITP previously treated with any second-line therapies, pts who relapsed ≥1 year after the end of steroid therapy. Overall, 101 pts are planned to be enrolled in the study. EPAG will be administered at a starting dose of 50 mg QD (Asian pts, 25 mg QD) for 2 weeks to reach a target platelet count of ≥100 × 109/L (complete response; CR). EPAG dose up to 75 mg will be allowed for pts who do not respond to standard dosage. EPAG will be administered at a minimal dose required to reach, and maintain CR for 2 months. Pts attaining this will be eligible for taper-off and treatment discontinuation: a reduction of 25 mg every 2 weeks up to 25 mg on alternate days for 2 weeks until treatment discontinuation. EPAG dose tapering scheme is summarized in Figure A & B. Steroids/IVIG and PLT transfusion are allowed along with EPAG for the first 14 days in case of very low platelet count (<10 × 109/L) and/or significant bleeding. Primary endpoint will be proportion of pts with SR by month 12. Key secondary endpoints include duration of SR after treatment discontinuation by months 12 and 24, proportion of pts maintaining a SR after treatment discontinuation through month 24, and proportion of pts with platelet count ≥50 × 109/L at least once by month 1 without bleeding and no rescue therapy. Safety set will include all pts who received at least one dose of EPAG. Key exploratory endpoints are analysis of lymphocytes cell subset changes and monocyte profiling in ITP pts before and after EPAG, change from baseline in the immunoglobulin levels, and in the serum iron parameters. The first pt first visit was on November 2, 2018. Currently, the study is recruiting pts, expected to be completed by first quarter of 2020.Summary/Conclusion: This trial will help to generate prospective data on the ability of EPAG to achieve SR after treatment discontinuation, and also on the proportion of pts who can discontinue EPAG if administered early. Further, it will provide exploratory data such as the immunomodulatory effects of EPAG and its association with the clinical response.