XPAG-ITP

A Phase II, randomized (1:1) open-label study to assess the efficacy and safety of eltrombopag in combination with dexamethasone compared to dexamethasone, as first-line treatment in adult patients with newly diagnosed immune thrombocytopenia (XPAG-ITP)

Specifications

• Sponsor: Novartis Pharma GmbH

  EudraCT-No.: 2019-002658-21

   

  Principal inclusion criteria:

  • Signed informed consent must be obtained prior to participation in the study
  • Men and women ≥ 18 years of age
  • Newly diagnosed with primary ITP (time from diagnosis within 3 months)
  • Platelet count < 30 × 10^9/L and a need for treatment (per physician’s discretion)

  
  Principal exclusion criteria:

  • Previous history of treatment for ITP.
    Note: Patients in need of immediate treatment for thrombocytopenia while diagnosis or eligibility are being determined may receive treatment with any ITP-directed therapy 3 days before randomization. These therapies must be discontinued, and a platelet count test done to ensure that the level is within applicable range for inclusion to the study [see Incl#4] before the patient receives the first dose of study treatment
  • Patients with diagnosis of secondary thrombocytopenia
  • Patients who have life threatening bleeding complications per physician´s discretion
  • Patients with a history of thromboembolic events or known risk factors for thromboembolism (e.g. Factor V Leiden, ATIII deficiency, antiphospholipid syndrome) are excluded. Patients with other risk factors which may pose an increased thromboembolic event (TEE) risk (prolonged periods of immobilization, malignancies, contraceptives and hormone replacement therapy, surgery/trauma, obesity and smoking) would be excluded according to the discretion of the investigator.
  • Presence of moderate to severe impaired renal function as indicated by any or all of the following criteria:
    • Creatinine clearance < 45 mL/min as calculated using Cockcroft-Gault formula
    • Serum creatinine > 1.5 mg/dL
  • Total bilirubin (TBIL) > 1.5 × upper limit of normal (ULN)
  • Aspartate transaminase (AST) > 3.0 × ULN
  • Alanine transaminase (ALT) > 3.0 × ULN
  • Patients who are human immunodeficiency virus (HIV), HCV or hepatitis B surface antigen (HBsAg) positive
  • Patients with hepatic impairment (Child-Pugh score > 5)
  • Patients with known active or uncontrolled infections not responding to appropriate therapy
  • History of current diagnosis of cardiac disease or impaired cardiac function denoted by any of the following:
    • Corrected QTc >450 msec using Fridericia correction (QTcF) on the screening electrocardiogram (ECG)
    • History of myocardial infarction and unstable angina within 6 months prior to starting study treatment
    • Clinically significant cardiac arrhythmias or other clinically significant cardiovascular disease (e.g., congestive heart failure, uncontrolled hypertension) within the six months prior to starting study treatment
  • Patients who have active malignancy
  • Patients with evidence of current alcohol/drug abuse
  • Any serious and/or unstable pre-existing medical (including any advanced malignancy other than the disease under study), psychiatric disorder, or other conditions that could interfere with subject’s safety, obtaining informed consent or compliance with the study procedures.
  • Patients with a known immediate or delayed hypersensitivity reaction or idiosyncrasy to eltrombopag or drugs chemically related to eltrombopag or excipients that contraindicate their participation
  • Patients with pre-existing medical conditions that are known precautions with corticosteroid use, in whom the potential risks of participating in the study outweigh the potential benefits as determined by the investigator
  • Female subjects 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
  • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and for 7 days after stopping medication. Highly effective contraception methods include:
    • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of Ovulation [1]:
    - oral
    - intravaginal
    - transdermal
  • • progestogen-only hormonal contraception associated with inhibition of Ovulation[1]:
    - oral
    - injectable
    - implantable[2]
  • • intrauterine device (IUD)[2]
  • • intrauterine hormone-releasing system (IUS)[2]
  • • bilateral tubal occlusion[2]
  • • vasectomised Partner[2,3]
  • • sexual abstinence[4]
  • [1]Hormonal contraception may be susceptible to interaction with the IMP, which may reduce the efficacy of the contraception method (see section 4.3).
  • [2] Contraception methods that in the context of this guidance are considered to have low user dependency.
  • [3] Vasectomised partner is a highly effective birth control method provided that partner is the sole sexual partner of the WOCBP trial participant and that the vasectomised partner has received medical assessment of the surgical success.
  • [4] In the context of this guidance sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject