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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00370331




Registration number
NCT00370331
Ethics application status
Date submitted
29/08/2006
Date registered
31/08/2006
Date last updated
18/04/2017

Titles & IDs
Public title
RAISE: Randomized Placebo-Controlled Idiopathic Thrombocytopenic Purpura (ITP) Study With Eltrombopag
Scientific 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.
Secondary ID [1] 0 0
TRA102537
Universal Trial Number (UTN)
Trial acronym
RAISE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Purpura, Thrombocytopaenic, Idiopathic 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - eltrombopag
Treatment: Drugs - Placebo

Experimental: Treatment arm plus standard of care - Subjects will initiate treatment with 50 mg eltrombopag or matching placebo once daily. Based upon the subjects platelet count at each visit, the dose of eltrombopag may be adjusted either up or down.

Placebo comparator: placebo plus standard of care - Subjects will initiate treatment with 50 mg eltrombopag or matching placebo once daily. Based upon the subjects platelet count at each visit, the dose of eltrombopag may be adjusted either up or down.


Treatment: Drugs: eltrombopag
Subjects will initiate treatment with either 50 mg eltrombopag or matching placebo once daily. Based upon the subjects platelet count at each visit, the dose of eltrombopag may be adjusted either up or down.

Treatment: Drugs: Placebo
Subjects will initiate treatment with either 50 mg eltrombopag or matching placebo once daily. Based upon the subjects platelet count at each visit, the dose of eltrombopag may be adjusted either up or down
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Responders
Timepoint [1] 0 0
Baseline; each on-therapy treatment day; Weeks 10, 14, 18, 22, and 26; and Weeks 1, 2, and 4 post-treatment
Secondary outcome [1] 0 0
Summary of Median Platelet Counts
Timepoint [1] 0 0
Baseline; Day 8 through Week 26 on-treatment; and 1, 2, 4 week follow-up visits
Secondary outcome [2] 0 0
Percentage of Participants Initiating Rescue Treatment On-therapy
Timepoint [2] 0 0
Anytime from Day 1 to Week 26
Secondary outcome [3] 0 0
Maximum and Total Weeks of Platelet Response
Timepoint [3] 0 0
Day 1 through Week 26 on-treatment
Secondary outcome [4] 0 0
Percentage of Participants With a Reduction in Use of Baseline ITP Medication
Timepoint [4] 0 0
From Day 1 through Week 26 on-treatment
Secondary outcome [5] 0 0
WHO Bleeding Scale
Timepoint [5] 0 0
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
Secondary outcome [6] 0 0
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
Timepoint [6] 0 0
Baseline, Week 6, Week 14, and Week 26/Early Withdrawal
Secondary outcome [7] 0 0
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
Timepoint [7] 0 0
Baseline, Week 6, Week 14, and Week 26/Early Withdrawal
Secondary outcome [8] 0 0
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
Timepoint [8] 0 0
Baseline, Week 6, Week 14, and Week 26/Early Withdrawal
Secondary outcome [9] 0 0
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
Timepoint [9] 0 0
Baseline, Week 6, Week 14, and Week 26/Early Withdrawal

Eligibility
Key inclusion 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/07/2008
Sample size
Target
Accrual to date
Final
197
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
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Ho Chi Minh

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00370331
Trial related presentations / 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 Jan 29;377(9763):393-402. doi: 10.1016/S0140-6736(10)60959-2. Epub 2010 Aug 23. Erratum In: Lancet. 2011 Jan 29;377(9763):382.
Haselboeck J, Pabinger I, Ay C, Koder S, Panzer S. Platelet activation and function during eltrombopag treatment in immune thrombocytopenia. Ann Hematol. 2012 Jan;91(1):109-13. doi: 10.1007/s00277-011-1249-5. Epub 2011 May 7.
Hayes S, Ouellet D, Zhang J, Wire MB, Gibiansky E. Population PK/PD modeling of eltrombopag in healthy volunteers and patients with immune thrombocytopenic purpura and optimization of response-guided dosing. J Clin Pharmacol. 2011 Oct;51(10):1403-17. doi: 10.1177/0091270010383019. Epub 2010 Dec 8.
Tarantino MD, 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 Apr;24(3):284-96. doi: 10.1097/MBC.0b013e32835fac99.
Fogarty PF, Tarantino MD, Brainsky A, Signorovitch J, Grotzinger KM. Selective validation of the WHO Bleeding Scale in patients with chronic immune thrombocytopenia. Curr Med Res Opin. 2012 Jan;28(1):79-87. doi: 10.1185/03007995.2011.644849. Epub 2011 Dec 20.
Signorovitch J, Brainsky A, Grotzinger KM. Validation of the FACIT-fatigue subscale, selected items from FACT-thrombocytopenia, and the SF-36v2 in patients with chronic immune thrombocytopenia. Qual Life Res. 2011 Dec;20(10):1737-44. doi: 10.1007/s11136-011-9912-9. Epub 2011 May 1.
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00370331