A Phase II study to investigate the efficacy and safety of eltrombopag in combination with dexamethasone as first-line treatment in adult patients with newly diagnosed primary ITP (XPAG-ITP)

Objective Eltrombopag is an oral thrombopoietin receptor agonist (TPO-RA) that increases platelet production (Erickson-Miller et al., 2010, Sun et al., 2012). Eltrombopag is approved in Europe for the treatment of thrombocytopenia, from 6 months following diagnosis, in patients with primary ITP who are refractory to other treatments.

The aim of this trial (NCT04346654) is to compare the ability of eltrombopag in combination with a short course of high-dose dexamethasone to induce a sustained response off treatment in comparison to dexamethasone monotherapy in newly diagnosed primary ITP patients.

Material and Methods This is a Phase II, multicenter, randomized (1:1), open-label study (see Figure 1).

Treatment/Tapering Period:

Arm A: Patients who have platelet counts < 30.000/µl will receive eltrombopag (50 mg QD) in combination with a short course of high-dose dexamethasone (40 mg QD for 4 consecutive days) beginning at day 1.

Arm B: Treatment in the control arm consists of 1-3 cycles of high-dose dexamethasone administered orally at a dose of 40 mg QD for 4 consecutive days at 4 weeks intervals.

Patients who reach platelet counts ≥ 30.000/µl and maintain them during the tapering phase (week 20 – week 26) will be eligible for treatment discontinuation starting from week 26. During the tapering phase, eltrombopag will be decreased by 25 mg every 2 weeks to a minimum dose of 25 mg every other day for all patients.

Observation period:

Sustained response off treatment is defined as:

omaintain platelet counts ≥ 30.000/µl after treatment discontinuation and

ono bleeding events ≥ Grade II and

owithout the use of any rescue therapy until week 52 and week 78 respectively, after study start

Results The primary objective is the rate of sustained responses off treatment at 52 weeks. Key secondary objectives include the duration of sustained response off treatment, the rate of sustained response off treatment at 78 weeks as well as patient-oriented outcomes for health-related quality of life.

Currently, the study is recruiting patients in Germany, expected to be completed by 2021.

Conclusion This trial will evaluate the potential of eltrombopag in combination with steroids to increase the rate of sustained response off treatment in comparison to steroids alone in patients with previously untreated primary ITP.

Fig. 1 Study design. Abbreviations: ITP: Immune thrombocytopenia; EPAG: Eltrombopag; HD-DEX: High-dose dexamethasone; PLT: Platelets; QD: Daily (quaque die); R: Randomization; TPO-RA: Thrombopoietin receptor agonist.