RAISE: Randomized Placebo-Controlled Idiopathic Thrombocytopenic Purpura (ITP) Study With Eltrombopag

NCT00370331 | Completed Phase 3 Results

• 1 other identifier: TRA102537
• Study Type: interventional
• Target: 197
• Locations: 25 countries
• Sites: 115

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.

Conditions

Purpura, Thrombocytopaenic, Idiopathic

Keywords

ITP; idiopathic; platelets; purpura; thrombocytopenia; Idiopathic Thrombocytopenic Purpura; thrombocytopenic

Outcome Measures

Primary Outcomes (1)

• Percentage of Responders

  The percentage of evaluable participants who achieved a platelet response (defined as a platelet count between 50,000 and 400,000 microliter) at each nominal on-therapy day and 4 weeks post-treatment

  Baseline; each on-therapy treatment day; Weeks 10, 14, 18, 22, and 26; and Weeks 1, 2, and 4 post-treatment

Secondary Outcomes (9)

• Summary of Median Platelet Counts

  Baseline; Day 8 through Week 26 on-treatment; and 1, 2, 4 week follow-up visits

• Percentage of Participants Initiating Rescue Treatment On-therapy

  Anytime from Day 1 to Week 26

• Maximum and Total Weeks of Platelet Response

  Day 1 through Week 26 on-treatment

• Percentage of Participants With a Reduction in Use of Baseline ITP Medication

  From Day 1 through Week 26 on-treatment

• WHO Bleeding Scale

  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

Study Arms (2)

Treatment arm plus standard of care

EXPERIMENTAL

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.

Drug: eltrombopag

placebo plus standard of care

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

eltrombopag DRUG

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 arm plus standard of care

Placebo DRUG

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

placebo plus standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (115)

GSK Investigational Site

Duarte, California, 91010, United States

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GSK Investigational Site

Los Angeles, California, 90033, United States

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San Francisco, California, 94143, United States

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Washington D.C., District of Columbia, 20007, United States

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Washington D.C., District of Columbia, 20010-2975, United States

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Hollywood, Florida, 33021, United States

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Atlanta, Georgia, 30341, United States

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Savannah, Georgia, 31405, United States

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Honolulu, Hawaii, 96813, United States

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Boston, Massachusetts, 02114, United States

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Worcester, Massachusetts, 01655, United States

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St Louis, Missouri, 63110, United States

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Buffalo, New York, 14215, United States

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New York, New York, 10029, United States

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New York, New York, 10065, United States

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Cleveland, Ohio, 44106, United States

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Lawton, Oklahoma, 73505, United States

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Portland, Oregon, 97227, United States

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Willow Grove, Pennsylvania, 19090, United States

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Dallas, Texas, 75137, United States

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Houston, Texas, 77030, United States

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Lubbock, Texas, 79410, United States

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Lubbock, Texas, 79415, United States

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Arlington, Virginia, 22205, United States

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Seattle, Washington, 98109, United States

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Tacoma, Washington, 98405, United States

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Vienna, A-1090, Austria

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Burnaby, British Columbia, V5H 4K7, Canada

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St. John's, Newfoundland and Labrador, A1B 3V6, Canada

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Hamilton, Ontario, L8N 3Z5, Canada

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Weston, Ontario, M9N 1N8, Canada

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Greenfield Park, Quebec, J4V 2H1, Canada

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Laval, Quebec, H7M 3L9, Canada

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Montreal, Quebec, H2L 4M1, Canada

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Montreal, Quebec, H3T 1E2, Canada

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Jiang Su Province, 215006, China

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Shanghai, 200025, China

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Tianjin, 300020, China

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Brno, 625 00, Czechia

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Hradec Králové, 500 05, Czechia

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Olomouc, 775 20, Czechia

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Prague, 128 20, Czechia

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Odense, 5000, Denmark

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Kuopio, 70210, Finland

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Bobigny, 93003, France

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Caen, 14033, France

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Créteil, 94010, France

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Pessac, 33604, France

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Munich, Bavaria, 80639, Germany

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Giessen, Hesse, 35392, Germany

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Hanover, Lower Saxony, 30625, Germany

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Saarbrücken, Saarland, 66113, Germany

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Berlin, State of Berlin, 13353, Germany

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Athens, 10676, Greece

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Athens, 11527, Greece

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Athens, 15123, Greece

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Heraklion, Crete, 71201, Greece

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Thessaloniki, 57010, Greece

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Shatin, Hong Kong

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Bangalore, 560002, India

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Manipal, 576 104, India

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Napoli, Campania, 80131, Italy

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Bologna, Emilia-Romagna, 40138, Italy

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Albano Laziale (Roma), Lazio, 00041, Italy

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Milan, Lombardy, 20132, Italy

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Padua, Veneto, 35128, Italy

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Vicenza, Veneto, 36100, Italy

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Amersfoort, 3816 CP, Netherlands

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Nijmegen, 6525 GA, Netherlands

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Zwolle, 8025 AB, Netherlands

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Auckland, 1309, New Zealand

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Auckland, 1701, New Zealand

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Christchurch, 8011, New Zealand

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Grafton, 1003, New Zealand

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Lima, Lima Province, Lima 41, Peru

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Lima, Lima 27, Peru

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Gdansk, 80-952, Poland

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Krakow, 31-501, Poland

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Legnica, 59-200, Poland

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Opole, 45-372, Poland

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Słupsk, 76-200, Poland

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Torun, 87-100, Poland

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Wroclaw, 50-367, Poland

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Moscow, 125167, Russia

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Novosibirsk, 630087, Russia

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Saint Petersburg, 193024, Russia

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Košice, 041 90, Slovakia

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Martin, 036 59, Slovakia

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Prešov, 080 01, Slovakia

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Madrid, 28006, Spain

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Madrid, 28040, Spain

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Palma de Mallorca, 07014, Spain

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Taipei, 100, Taiwan

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Taipei, 110, Taiwan

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Taipei, 114, Taiwan

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Taipei, Taiwan

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Sfax, 3029, Tunisia

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Sousse, 4000, Tunisia

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Tunis, 1008, Tunisia

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Dnipropetrovsk, 49102, Ukraine

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Kyiv, 03150, Ukraine

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Kyiv, 04112, Ukraine

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Lviv, 79044, Ukraine

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Odesa, 65025, Ukraine

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Plymouth, Devon, PL6 8DH, United Kingdom

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Taunton, Somerset, TA1 5DA, United Kingdom

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Leed, LS1 3EX, United Kingdom

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London, E1 1BB, United Kingdom

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London, NW1 2BU, United Kingdom

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London, SE5 9RS, United Kingdom

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Manchester, M13 9WL, United Kingdom

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Morriston, SA6 6NL, United Kingdom

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Reading, RG1 5AN, United Kingdom

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Rhyl, Denbighshire, United Kingdom

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Ho Chi Minh City, Vietnam

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Related Publications (6)

• 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.

  PMID: 20739054 BACKGROUND

• 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.

  PMID: 21553010 BACKGROUND

• 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.

  PMID: 21148042 BACKGROUND

• 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.

  PMID: 23492914 BACKGROUND

• 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.

  PMID: 22117897 DERIVED

• 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.

  PMID: 21533818 DERIVED

MeSH Terms

Conditions

Purpura; Thrombocytopenia; Purpura, Thrombocytopenic, Idiopathic

Interventions

eltrombopag

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms; Blood Platelet Disorders; Cytopenia; Purpura, Thrombocytopenic; Thrombotic Microangiopathies; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2006
• First Posted: August 31, 2006
• Study Start: November 1, 2006
• Primary Completion: July 1, 2008
• Study Completion: July 1, 2008
• Last Updated: April 18, 2017
• Results First Posted: February 23, 2010

Record last verified: 2017-03

Locations

DK (1); VN (1); NL (3); CZ (4); CA (8); FR (4); FI (1); IT (6); HK (1); IN (2); SL (3); TU (3); GB (10); ES (3); TW (4); UA (5); US (26); NZ (4); PL (7); DE (5); RU (3); CN (3); AU (1); PE (2); GR (5)