Protocol No.: OCR19569
Sponsor Protocol No.: ETB115JUS33T; ICON3
Protocol Title.: Eltrombopag vs Standard Front Line Management for Newly Diagnosed Immune Thrombocytopenia (ITP) in Children
Principal Investigator: Fort, John
Objective: This is an investigator initiated, multicenter, open label, randomized phase 3 study for subjects with newly diagnosed ITP from ages 1 to less than 18 years old.
Description: This is a prospective, open label, randomized, two-arm, multi-center Phase 3 trial. Patients with newly diagnosed ITP are randomized 2:1 to receive the experimental treatment, eltrombopag, or investigator's choice of 3 standard therapies. The primary objective is to determine if the proportion of patients with platelet response is significantly greater in patients treated with eltrombopag compared to those treated with standard therapies.
Phase: Phase III
Age Group: Children
Age: 1 Year - 18 Years
Experimental: EltrombopagPatients randomized to eltrombopag will be treated for 12 weeks, with the possibility to continue therapy for up to 1 year depending on response.
Active Comparator: Standard first-line therapySubjects randomized to the standard therapy arm will receive one of three treatments at the discretion of the treating physician. Patients who previously failed standard management prior to study entry must be treated with a different agent than their original failed agent. e.g. Patient who failed steroids could receive either IVIg or anti-D if randomized to the standard treatment arm. Standard therapy will be administered as commercially available drug. Investigator may choose amongst the following: IVIg: IVIG 1 g/kg x1 (no steroids for pre-medication or adjunctive therapy) Steroids: Prednisone/Prednisolone 4 mg/kg/day (Max 120 mg/day) x 4 days Rho(D) Immune Globulin: Anti-D globulin 75 mcg/kg x1 (no steroids for pre-medication or adjunctive therapy)
Detailed Eligibility: Inclusion Criteria: - Age: 1- <18 years - Newly diagnosed ITP (<3 months from diagnosis (first abnormal platelet count), per international working group definition17) - Platelets 30 x 10^9/L) with observation >10 days from diagnosis, with need to treat - Poor response to first-line agent (platelets remain 2 x upper limit of normal (ULN) - Total bilirubin >1.5 × ULN - Subjects with liver cirrhosis (as determined by the investigator) - Creatinine >2.5 × ULN - Known active or uncontrolled infections not responding to appropriate therapy - On anticoagulation or anti-platelet agents - Known thrombophilic risk factors. Exception: Subjects for whom the potential benefits of participating in the study outweigh the potential risks of thromboembolic events, as determined by the investigator. - Baseline ophthalmic problems that may potentiate cataract development - Impaired cardiac function, such as: - Known prolonged QTc, with corrected QTc >450 msec - Other clinically significant cardio-vascular disease (e.g., uncontrolled hypertension, history of labile hypertension), - History of known structural abnormalities (e.g. cardiomyopathy). - History or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the study such as uncontrolled or significant cardiac disease, including any of the following: - Recent myocardial infarction (within last 6 months), - Uncontrolled congestive heart failure, - Unstable angina (within last 6 months), - Clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker.) - Long QT syndrome, family history of idiopathic sudden death, congenital long QT syndrome or additional risk factors for cardiac repolarization abnormality, as determined by the investigator. - Known immediate or delayed hypersensitivity reaction to eltrombopag or its excipient. - Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study. Women of childbearing potential (have achieved menarche) must have a negative serum or urine pregnancy test and agree to use basic methods of contraception (if sexually active) or maintain abstinence for the duration of the study. Basic contraception methods include: - Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception - Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment - Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that subject - Barrier methods of contraception: Condom or Occlusive cap. For the UK: with spermicidal foam/gel/film/cream/ vaginal suppository - Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. - Male patients who are sexually active and do not agree to abstinence or to use a condom during intercourse while taking eltrombopag, and for 7 days after stopping treatment. - History of alcohol/drug abuse - Presence of a medical condition that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data. - Concurrent participation in an investigational study within 30 days prior to enrollment or within 5-half-lives of the investigational product, whichever is longer. Note: parallel enrollment in a non-therapeutic trial such as disease registry or biology study is permitted. Other Eligibility Criteria Considerations All patients and/or their parents or legal guardians must sign a written informed consent (and assent when applicable) - Patients and/or parents who are unable to read English at a grade 2 level will be excluded from the patient-reported outcome component of the study. They will not be excluded from all other aspects of the study