A Study to Assess the Ability of Eltrombopag to Induce Sustained Response Off Treatment in Subjects With ITP

A Phase II, Open-label, Prospective, Single-arm, Study to Assess Ability of Eltrombopag to Induce Sustained Remission in Subjects With ITP Who Are Refractory or Relapsed After First-line Steroids

The purpose of this trial was to assess the ability of eltrombopag to induce sustained treatment-free remission in immune thrombocytopenia purpura (ITP) subjects who relapsed or failed to respond to an initial treatment with steroids.

Protocol Amendment 01 added a follow-up period of 12 months for patients with sustained response off treatment at month 12 to obtain further data on response duration.

The starting dose was eltrombopag 50 mg daily (25 mg daily for Asian patients and 12.5 mg daily for Japanese patients in Japan). The starting dose for this study was consistent with the dosing guidelines approved for eltrombopag use in ITP. An increase of eltrombopag dose up to 75 mg was allowed for patients who did not respond to standard-dosage treatment and to reduce the risk of bleeding. The rationale for this increased dose was to use the minimal efficacious dosage of eltrombopag in order to achieve a platelet count ≥ 100×10^9/L and maintain it around 100×10^9/L (no counts below 70×10^9/L) for 2 months in order to allow patients to start the eltrombopag tapering and withdrawal process.

Patients who reached a platelet count of >= 100 × 10^9/L and maintained counts around 100×10^9/L for 2 months with no platelet count < 70 × 10^9/L were eligible for tapering-off and treatment discontinuation, which occurred via 25 mg reduction every 2 weeks up to 25 mg on alternate days for 2 weeks until treatment discontinuation.

Patients who successfully discontinue eltrombopag and maintained platelet count >= 30 × 10^9/L in the absence of bleeding or use of rescue therapy were followed to month 12. If a relapse (defined as platelet count <30 × 10^9/L) occurred during the 12-month treatment period, they were offered a new course of eltrombopag treatment within this timeframe at the appropriate starting dose. If a patient relapsed in the post 12-month follow-up period, no further attempts for tapering and achieving sustained response off treatment were made.

The taper-off scheme followed recommendations within the current established dosing regimen for when to consider dose adjustment.

Inclusion Criteria:

1. Signed informed consent must be obtained prior to participation in the study
2. Patients ≥ 18 years old
3. Patients with a confirmed diagnosis of primary ITP, who are not responsive or in relapse after a first line of steroid therapy ± intravenous immunoglobulin (IVIG) (used as a rescue therapy)
4. Platelet count < 30×10^9/L and assessed as needing treatment (per physician's discretion

Exclusion Criteria:

1. ITP patients previously treated with any ITP second-line therapies, thrombopoietin receptor (TPO-R) agonists for ITP, except steroids / IVIG
2. Patients who relapsed more than one year after the end of first-line full course of steroid therapy
3. Patients with a diagnosis of secondary thrombocytopenia
4. Patients who have life threatening bleeding complications per investigator discretion
5. Patients who had a deep vein thrombosis or arterial thrombosis in the 6 months preceding enrollment
6. Serum creatinine ≥ 1.5 mg/dL
7. Total bilirubin > 1.5 × upper limit of normal (ULN)
8. Aspartate transaminase (AST) > 3.0 × ULN
9. Alanine transaminase (ALT) > 3.0 × ULN
10. Patients who are human immune deficiency virus (HIV), hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg) positive
11. Patients with hepatic impairment (Child-Pugh score > 5)
12. Patients who have active malignancy
13. Patients with any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions that could interfere with subject's safety, obtaining informed consent or compliance with the study procedures per investigator discretion
14. History or current diagnosis of cardiac disease indicating significant risk of safety for Patients participating in the study
15. Patients with known active or uncontrolled infections not responding to appropriate therapy
16. Patients with evidence of current alcohol/drug abuse
17. Women of child-bearing potential and sexually active males unwilling to use adequate contraception during the study
18. Female Patients who are nursing or pregnant (positive serum or urine B-human chorionic gonadotrophin (B-hCG) pregnancy test) at screening or pre-dose on Day 1

Other protocol-defined inclusion/exclusion criteria may apply.