Last updated: 11/04/2018 12:55:38
RAISE: Randomized Placebo-Controlled Idiopathic Thrombocytopenic Purpura (ITP) Study with EltrombopagRAISE
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A randomized, double-blind, placebo-controlled phase III study, to evaluate the efficacy, safety and tolerability of eltrombopag olamine (SB-497115-GR), a thrombopoietin receptor agonist, administered for 6 months as oral tablets once daily in adult subjects with previously treated chronic ITP.
Trial description: The rationale for this Phase III study is to evaluate the 6 month safety and efficacy of eltrombopag in the treatment of previously treated subjects with chronic ITP. The starting dose of eltrombopag, 50 mg, once daily was selected based upon the observed efficacy, safety and pharmacokinetics in a dose-finding Study (TRA100773). This Phase III study is a randomized, double-blind, placebo-controlled, Phase III study, to evaluate efficacy, safety and tolerability of eltrombopag, initially administered as 50 mg oral tablets once daily for six months in adult subjects with previously treated chronic ITP. Subjects will be randomized 2:1, eltrombopag to placebo, and will be stratified based upon splenectomy status, use of ITP medication at baseline and baseline platelet count less than or equal to 15,000/µL. Subjects will receive study medication for 6 months, during which the dose of study medication may be adjusted based upon individual platelet counts. In addition, subjects may taper off concomitant ITP medications and may receive any rescue treatments as dictated by local standard of care. After discontinuation of study medication, subjects will complete follow-up visits at weeks 1, 2, 4 and months 3 and 6.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Percentage of Responders
Timeframe: Baseline; each on-therapy treatment day; Weeks 10, 14, 18, 22, and 26; and Weeks 1, 2, and 4 post-treatment
Secondary outcomes:
Summary of median platelet counts
Timeframe: Baseline; Day 8 through Week 26 on-treatment; and 1, 2, 4 week follow-up visits
Percentage of participants initiating rescue treatment on-therapy
Timeframe: Anytime from Day 1 to Week 26
Maximum and total weeks of platelet response
Timeframe: Day 1 through Week 26 on-treatment
Percentage of participants with a reduction in use of baseline ITP medication
Timeframe: From Day 1 through Week 26 on-treatment
WHO bleeding scale
Timeframe: Baseline, all nominal visits on-therapy defined as Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Week 10, Week 14, Week 18, Week 22, Week 26, and 1, 2 and 4 week follow-up visits
HR-QoL instrument and domain scores from the SF-36v2 questionnaire at Baseline, Week 6, Week 14, and Week 26 or early discontinuation from study treatment
Timeframe: Baseline, Week 6, Week 14, and Week 26/Early Withdrawal
HR-QoL instrument and domain scores from the FACIT-F questionnaire at Baseline, Week 6, Week 14, and Week 26 or early discontinuation from study treatment
Timeframe: Baseline, Week 6, Week 14, and Week 26/Early Withdrawal
HR-QoL instrument and domain scores for the FACT-Th questionnaire at Baseline, Week 6, Week 14, and Week 26 or early discontinuation from study treatment
Timeframe: Baseline, Week 6, Week 14, and Week 26/Early Withdrawal
HR-QoL instrument and domain scores from the MEI-SF questionnaire at Baseline, Week 6, Week 14, and Week 26 or early discontinuation from study treatment
Timeframe: Baseline, Week 6, Week 14, and Week 26/Early Withdrawal
Interventions:
Drug: eltrombopag
Drug: Placebo
Enrollment:
197
Observational study model:
Not applicable
Primary completion date:
2008-18-07
Time perspective:
Not applicable
Clinical publications:
Cheng G, Saleh MN, Marcher C, Vasey S, Mayer B, Aivado M, Arning M, Stone NL, Bussel JB. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet. 2011;377(9763):393-402.
Haselboeck J, Pabinger I, Ay C, Koder S, Panzer S. Platelet Activation and Function during Eltrombopag Treatment in Immune Thrombocytopenia. Ann Hematol. 2011;91(1):109-113.
Siobhan Hayes, Daniele Ouellet, Jianping Zhang, Mary Wire, Ekaterina Gibiansky . Population PK/PD Modeling of Eltrombopag in Healthy Volunteers and Patients with Immune Thrombocytopenic Purpura and Optimization of Response-Guided Dosing. J Clin Pharmacol. 2010;
Tarantino M, Fogarty P, Mayer B, Vasey SY, Brainsky A. Efficacy of Eltrombopag in Management of Bleeding Symptoms Associated With Chronic Immune Thrombocytopenia. Blood Coagul Fibrinolysis. 2013;24(3):284-296.
Medical condition
Purpura, Thrombocytopaenic, Idiopathic
Product
eltrombopag
Collaborators
Not applicable
Study date(s)
November 2006 to July 2008
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- A subject will be eligible for inclusion in this study only if all of the following criteria apply:
- Subject has signed and dated a written informed consent.
- A subject will NOT be eligible for inclusion in this study if any of the following criteria apply:
- Any clinically relevant abnormality, other than ITP, identified on the screening examination or any other medical condition or circumstance, which in the opinion of the investigator makes the subject unsuitable for participation in the study or suggests another primary diagnosis (e.g., thrombocytopenia is secondary to another disease).
Inclusion and exclusion criteria
Inclusion criteria:
- A subject will be eligible for inclusion in this study only if all of the following criteria apply:
- Subject has signed and dated a written informed consent.
- Adults (≥18 years) diagnosed with chronic ITP according to the American Society for Hematology/British Committee for Standards in Hematology (ASH/BCSH) guidelines [George, 1996; BCSH, 2003], and platelet count < 30,000/μL on Day 1 (or within 24 hours prior to dosing on Day 1). In addition, a peripheral blood smear should support the diagnosis of ITP with no evidence of other causes of thrombocytopenia (e.g. pseudothrombocytopenia, myelofibrosis). The physical examination should not suggest any disease which may cause thrombocytopenia other than ITP.
- Subjects who have previously received one or more prior ITP therapies. Previous treatments for ITP include but are not limited to corticosteroids, immunoglobulins, azathioprine, danazol, cyclophosphamide and/or rituximab.
- Subjects must have either initially responded (platelet count > 100,000/μL) to a previous ITP therapy or have had a bone marrow examination consistent with ITP within 3 years to rule out myelodysplastic syndromes or other causes of thrombocytopenia.
- Previous therapy for ITP with immunoglobulins (IVIg and anti-D) must have been completed at least 1 week prior to randomization and the platelet count must show a clear downward trend after the last treatment with immunoglobulins. Previous treatment for ITP with splenectomy, rituximab and cyclophosphamide must have been completed at least 4 weeks prior to randomization, or clearly be ineffective.
- Subjects treated with concomitant ITP medication (e.g. corticosteroids or azathioprine) must be receiving a dose that has been stable for at least 4 weeks prior to randomization. Subjects treated with cyclosporine A, mycophenolate mofetil or danazol must be receiving a dose that has been stable for at least 3 months prior to randomization. The medication should be continued with a stable dose for the initial 6 weeks of study "Concomitant ITP Therapy")
- Prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT) must be within 80 to 120% of the normal range with no history of hypercoagulable state.
- A complete blood count (CBC), within the reference range (including WBC differential not indicative of a disorder other than ITP), with the following exceptions:
- < 30,000 platelets/μL on Day 1 (or within 24 hours of Day 1) is required for inclusion,
- Hemoglobin: Subjects with hemoglobin levels between 10 g/dL (100 g/L) and the lower limit of normal are eligible for inclusion, if anemia is clearly attributable to ITP (excessive blood loss).
- ANC ≥ 1500/μL (1.5 x 10^9/L) is required for inclusion (elevated WBC/ANC due to steroid treatment is acceptable).
- The following clinical chemistries MUST NOT exceed the upper limit of normal (ULN) reference range by more than 20%: creatinine, ALT, AST, total bilirubin, and alkaline phosphatase. In addition, total albumin must not be below the lower limit of normal (LLN) by more than 10%.
- Subject is practicing an acceptable method of contraception (documented in chart). Female subjects (or female partners of male subjects) must either be of non-childbearing potential (hysterectomy, bilateral oophorectomy, bilateral tubal ligation or post-menopausal > 1 year), or of childbearing potential and use one of the following highly effective methods of contraception (i.e., Pearl Index <1.0%) from two weeks prior to administration of study medication, throughout the study, and 28 days after completion or premature discontinuation from the study:
- Complete abstinence from intercourse;
- Intrauterine device (IUD);
- Two forms of barrier contraception (diaphragm plus spermicide, and for males condom plus spermicide);
- Male partner is sterile prior to entry into the study and is the only partner of the female;
- Systemic contraceptives (combined or progesterone only). Subject is able to understand and comply with protocol requirements and instructions and intends to complete the study as planned.
Exclusion criteria:
- A subject will NOT be eligible for inclusion in this study if any of the following criteria apply:
- Any clinically relevant abnormality, other than ITP, identified on the screening examination or any other medical condition or circumstance, which in the opinion of the investigator makes the subject unsuitable for participation in the study or suggests another primary diagnosis (e.g., thrombocytopenia is secondary to another disease).
- Concurrent malignant disease and/or history of cancer treatment with cytotoxic chemotherapy and/or radiotherapy.
- Any prior history of arterial or venous thrombosis (stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis or pulmonary embolism), AND ≥ two of the following risk factors: hormone replacement therapy, systemic contraception (containing estrogen), smoking, diabetes, hypercholesterolemia, medication for hypertension, cancer, hereditary thrombophilic disorders (e.g., Factor V Leiden, ATIII deficiency, etc), or any other family history of arterial or venous thrombosis.
- Pre-existing cardiovascular disease (congestive heart failure, New York Heart Association [NYHA] Grade III/IV), or arrhythmia known to increase the risk of thromboembolic events (e.g. atrial fibrillation), or subjects with a QTc >450 msec.
- Female subjects who are nursing or pregnant (positive serum or urine b-human chorionic gonadotrophin pregnancy test) at screening or pre-dose on Day 1.
- History of alcohol/drug abuse.
- Treatment with an investigational drug within 30 days or five half-lives (whichever is longer) preceding the first dose of study medication.
- Subject treated with drugs that affect platelet function (including but not limited to aspirin, clopidogrel and/or NSAIDs) or anti-coagulants for > 3 consecutive days within 2 weeks of the study start and until the end of the study.
- History of platelet agglutination abnormality that prevents reliable measurement of platelet counts.
- All subjects with secondary immune thrombocytopenia, including those with laboratory or clinical evidence of HIV infection, anti-phospholipid antibody syndrome, chronic hepatitis B infection, hepatitis C virus infection, or any evidence for active hepatitis at the time of subject screening. If a potential subject has no clinical history that would support HIV infection or hepatitis infection, no further laboratory screening is necessary; however, standard medical practice would suggest further evaluation of patients who have risk factors for these infections.
- Previous participation in a clinical study with eltrombopag.
- Patients planning to have cataract surgery.
- In France, a subject is neither affiliated with nor a beneficiary of a social security category.
Trial location(s)
Location
GSK Investigational Site
New York, New York, United States, 10029
Status
Terminated/Withdrawn
Location
GSK Investigational Site
New York, New York, United States, 10065
Status
Study Complete
Location
GSK Investigational Site
Dallas, Texas, United States, 75137
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Buffalo, New York, United States, 14215
Status
Study Complete
Location
GSK Investigational Site
Plymouth, Devon, United Kingdom, PL6 8DH
Status
Study Complete
Location
GSK Investigational Site
Worcester, Massachusetts, United States, 01655
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Hollywood, Florida, United States, 33021
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Willow Grove, Pennsylvania, United States, 19090
Status
Study Complete
Location
GSK Investigational Site
San Francisco, California, United States, 94143
Status
Study Complete
Location
GSK Investigational Site
Washington, District of Columbia, United States, 20007
Status
Study Complete
Location
GSK Investigational Site
St. Louis, Missouri, United States, 63110
Status
Study Complete
Location
GSK Investigational Site
Savannah, Georgia, United States, 31405
Status
Study Complete
Location
GSK Investigational Site
Greenfield Park, Québec, Canada, J4V 2H1
Status
Study Complete
Location
GSK Investigational Site
Weston, Ontario, Canada, M9N 1N8
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Houston, Texas, United States, 77030
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Washington, District of Columbia, United States, 20010-2975
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Seattle, Washington, United States, 98109
Status
Study Complete
Location
GSK Investigational Site
Taunton, Somerset, United Kingdom, TA1 5DA
Status
Study Complete
Location
GSK Investigational Site
Honolulu, Hawaii, United States, 96813
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Atlanta, Georgia, United States, 30341
Status
Study Complete
Location
GSK Investigational Site
Arlington, Virginia, United States, 22205
Status
Study Complete
Location
GSK Investigational Site
Albano Laziale (Roma), Lazio, Italy, 00041
Status
Study Complete
Location
GSK Investigational Site
Hradec Kralove, Czech Republic, 500 05
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Boston, Massachusetts, United States, 02114
Status
Study Complete
Location
GSK Investigational Site
Portland, Oregon, United States, 97227
Status
Study Complete
Location
GSK Investigational Site
Los Angeles, California, United States, 90033
Status
Study Complete
Location
GSK Investigational Site
Saarbruecken, Saarland, Germany, 66113
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Burnaby, British Columbia, Canada, V5H 4K7
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Lubbock, Texas, United States, 79415
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Montreal, Québec, Canada, H3T 1E2
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Duarte, California, United States, 91010
Status
Study Complete
Location
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30625
Status
Study Complete
Location
GSK Investigational Site
Lawton, Oklahoma, United States, 73505
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Tacoma, Washington, United States, 98405
Status
Study Complete
Location
GSK Investigational Site
Saint John's, Newfoundland and Labrador, Canada, A1B 3V6
Status
Terminated/Withdrawn
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2008-18-07
Actual study completion date
2008-18-07
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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