Overview
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.
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 at screening
- Requires pharmacologic treatment from the perspective of the treating clinician.
Need to treat is at the discretion of the investigator, but there should be clinical
equipoise about the use of eltrombopag vs standard treatment options (patients should not,
in the opinion of the investigator, require concomitant therapy at time of enrollment).
- Treatment options include one of three standard therapies, (IVIg, steroids, or
Anti-D). For example, if patient has previously shown no response to IVIg or steroids
and is Rh-negative, patient would not be eligible for study.
- Patient population includes both:
1. Upfront treatment: Patient within 10 days of ITP diagnosis who has not received
previous treatment OR
2. Treatment failure: Patients who have failed standard management (observation or
treatment with one or more first-line agents)
- Failure of observation: no platelet recovery (>30 x 10^9/L) with observation
>10 days from diagnosis, with need to treat
- Poor response to first-line agent (platelets remain <30 x10^9/L)
- Initial response to first-line agent, but response wanes and platelets fall
below 30 x10^9/L
- Family willing and able to return for required lab studies
Exclusion Criteria:
- Severe bleeding: Buchanan Overall Grade 4 or 5 bleeding, or severe bleeding requiring
emergent treatment at the discretion of the provider. (e.g., intracranial hemorrhage,
pulmonary hemorrhage, bleeding with ongoing need for pRBC transfusion)
- Prior treatment with TPO-RA (eltrombopag or romiplostim)
- Known secondary ITP (due to lupus, CVID, ALPS)
- Known HIV (or history of HIV positivity) or Hepatitis C (screening not required if no
clinical suspicion)
- Evans Syndrome: positive direct Coombs with evidence of active hemolysis (elevated
lactate dehydrogenase (LDH) or reticulocyte count not attributable to recent treatment
or bleeding)
- Any Malignancy
- History of stem cell transplant or solid organ transplant
- aspartate aminotransferase (AST) or ALT >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