Aplastic AnemiaPhase 2NCT02404025
Eltrombopag in Combination With Rabbit Anti-thymocyte Globulin/Cyclosporine A in Naive Aplastic Anemia (AA) Subjects
A Phase 2 study testing Eltrombopag, Rabbit ATG and CsA in people with Aplastic Anemia, run by Novartis Pharmaceuticals at 11 sites in Japan.
Trial summary
This was an open label, non-randomized, phase II study of eltrombopag in combination with rabbit ATG/CsA in subjects with moderate or more severe AA who did not received prior ATG/ALG-based immunosuppressive therapy. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Aplastic Anemia
- What is being tested?
- Eltrombopag, Rabbit ATG and CsA
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 11 sitesJapan
- Study dates
- 12 May 2015to 6 Sep 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Japanese subjects aged >=18 and <71 years at the time of informed consent. Note: subjects aged >=71 and <75 may be eligible when clinically indicated at the discretion of the investigator by mutual agreement with Novartis medical advisor.
- Diagnosed with moderate or more severe AA according to the diagnostic criteria of AA. The severity classification is: Stage I - Mild - Other than the stages below; Stage II - Moderate - At least two of the following conditions are met: Reticulocyte <60,000/microliter, Neutrophil <1,000/microliter, Platelet <50,000/microliter; Stage III - Moderately severe - At least two of the following conditions are met and regular red blood cell transfusion (a need for transfusion of >=2 units per month) is required: Reticulocyte <60,000/microliter, Neutrophil <1,000/microliter, Platelet <50,000/microliter; Stage IV - Severe - At least two of the following conditions are met: Reticulocyte <20,000/microliter, Neutrophil <500/microliter, Platelet <20,000/microliter; Stage V - Very severe - At least one of the following conditions is met in addition to neutrophil <200/microliter: Reticulocyte <20,000/microliter, Platelet <20,000/microliter.
- Subjects who are considered an indication for the treatment with rabbit ATG and CsA.
- Adequate baseline organ function defined by the following criteria: Alanine aminotransferase (ALT), aspartate aminotransferase (AST)<=3 × local upper limit of normal (ULN) Creatinine, total bilirubin, and alkaline phosphatase (ALP) <1.5 × local ULN (total bilirubin <2.5 × local ULN with Gilbert's Syndrome)
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0 or 1
- Subjects with QTcF<450 millisecond (msec) or QTcF<480 msec with branch block: QTc is QT interval corrected by Fridericia formula (QTcF), machine ,or manual overread. QTcF is based on single or averaged QTc value of triplicate ECG.
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- Subjects are able to understand and comply with protocol requirements and instructions.
- Subjects have signed and dated informed consent.
- Subjects who meet one of the following conditions: Male subjects who have a female partner of childbearing potential must either have a prior vasectomy or agree to use an acceptable method of contraception from time of enrollment in the study until 16 weeks after the last dose of eltrombopag (based upon the lifecycle of sperm). Female subjects of non-childbearing potential (who are physiologically unable to become pregnant) defined as: Premenopausal women with documented bilateral oophorectomy, bilateral tubal ligation, or hysterectomy; or postmenopausal women after at least 12 months of natural amenorrhea [if uncertain, postmenopausal state should be confirmed by hematology result of follicle stimulating hormone (FSH) >40 milli-international units (mIU)/milliliter (mL) or estradiol <40 picogram (pg)/mL (<140 picomoles (pmol)/L)]. Female subjects of childbearing potential: Defined as those not meeting the definition of non-childbearing potential. Female subjects of childbearing potential must have a negative serum human chorionic gonadotropin (hCG) or urine pregnancy test within 7 days prior to the first dose of ATG/CsA. It is recommended that the pregnancy test should be performed as close as possible to the first dose of ATG/CsA. Female subjects with a positive pregnancy test must be excluded from the study. Subjects with a negative pregnancy test must use acceptable contraception including abstinence after the pregnancy test. Subjects must agree to use the acceptable contraception including abstinence from 14 days prior to the first dose of ATG/CsA until 28 days after the last dose of eltrombopag.
Who cannot join
- Diagnosis of congenital AA (e.g. Fanconi anemia or Dyskeratosis congenital).
- Subjects who have a sibling donor with matched human leukocyte antigen (HLA) or who underwent hematopoietic stem cell transplantation (HSCT) previously. However, such subjects may be enrolled if HSCT is not indicated, or the subject does not want to undergo HSCT.
- Subjects with abnormal chromosome (monosomy 7 detected by fluorescence in situ hybridization (FISH), or other aberrations detected by G-band staining). Note: Subjects with abnormal chromosome which is not adopted into the clone definition of An International System for Human Cytogenetic Nomenclature (ISCN) may be enrolled after consulting with medical monitor.
- Previous ATG/ALG-based immunosuppressive therapy or steroid pulse therapy for AA.
- Treatment with CsA within 6 months before administration of ATG.
- Subjects with a paroxysmal nocturnal hemoglobinuria (PNH) clone size in granulocytes of >50% by flow cytometric analysis.
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- Pre-existing cardiac disease (congestive heart failure New York Heart Association (NYHA) Grade II/III/IV), or arrhythmias known to involve the risk of thromboembolic events (e.g. atrial fibrillation)
- Past history of thromboembolic event (including anti-phospholipid antibody syndrome) and current use of anticoagulants.
- Subjects with past or current malignancy. Note : Subjects who have a history of completely resected malignant tumor and have been disease-free for 5 years are eligible.
- Subjects who test positive for hepatitis B surface (HBs) antigen, hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antibody at screening.
- Infection not adequately responding to appropriate therapy.
- Subject with liver cirrhosis
- Subjects with any clinically significant severe cardiac, renal, or hepatic medical condition.
- Pregnant women (a positive serum or urine pregnancy test within 7 days prior to the first dose of ATG/CsA or lactating women) Note: Female subjects who are lactating are eligible to participate if they discontinue nursing prior to the first dose of ATG/CsA and refrain from nursing until 5 days after the completion of treatment with eltrombopag.
- Known hypersensitivity, intolerance or allergy to rabbit ATG, cyclosporine A, eltrombopag or any of their excipients.
- Current alcohol or drug abuse.
- Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) proceeding the first dose of ATG/CsA.
- Subjects who is not candidates for ATG.
- Subjects who is not candidates for CsA.
- History of treatment with eltrombopag, romiplostim or other thrombopoietin-receptor (TPO-R) agonists.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
Japan11 sites
Novartis Investigative Site
Aichi, 453-8511
Novartis Investigative Site
Aichi, 460-0001
Novartis Investigative Site
Ibaraki, 305-8576
Novartis Investigative Site
Ishikawa, 920-8641
Novartis Investigative Site
Miyagi, 981-1293
Novartis Investigative Site
Okayama, 700-0962
Novartis Investigative Site
Osaka, 530-0012
Novartis Investigative Site
Osaka, 543-8555
Novartis Investigative Site
Osaka, 565-0871
Novartis Investigative Site
Tochigi, 329-0498
Novartis Investigative Site
Tokyo, 141-8625
About this study
Official title: A Non-randomized, Phase II Study of Eltrombopag in Combination With Rabbit Anti-thymocyte Globulin/Cyclosporine A (ATG/CsA) in Subjects With Moderate or More Severe Aplastic Anemia Who Have Not Received Prior ATG/Anti-lymphocyte Globulin (ALG)-Based Immunosuppressive Therapy
This was an open label, non-randomized, phase II study of eltrombopag in combination with rabbit ATG/CsA in subjects with moderate or more severe AA who did not received prior ATG/ALG-based immunosuppressive therapy. The objective was to assess additive effects of eltorombopag on overall response rate (ORR) at 6 months (Week 26) of treatment with ATG/CsA. Subjects were assessed at least weekly for safety during the period from the start of ATG/CsA to 4 weeks after the start of administration of eltrombopag. After that, subjects had visits every 2 weeks until Week 26. Subjects in whom the treatment was assessed as effective at Week 26 could continued treatment with eltrombopag after 6 months when clinically indicated at the discretion of the investigator. There were five follow-up visits: at discontinuation of the treatment of eltrombopag, and Weeks 1, 2, 3, 4 and 26 after treatment discontinuation. As this study was the first Japanese phase II study in which this product was administered in combination with ATG/CsA to subjects with naive moderate or more severe AA, the subject number of this study was determined to be 10 based on the feasibility survey.
- Conditions
- Aplastic Anemia
- Being tested
- Eltrombopag, Rabbit ATG, CsA
- Keywords
- Eltrombopag, rabbit anti-thymocyte globulin, additive effect, cyclosporine A, bone marrow, hematopoietic stem cells, pancytopenia, leukopenia, platelets, throbocytopenia, mature blood cells, bone marrow biopsy
- Medical subject headings
- Anemia, Aplastic, Pancytopenia, Leukopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EltrombopagDrug
Eltrombopag was provided as white round film-coated tablets containing 12.5 mg or 25 mg of eltrombopag free acid (SB-497115-GR, eltrombopag).
Rabbit ATGDrug
Rabbit ATG, as an intravenous drip infusion, diluted by 500 mL of saline or 5% glucose injection was administered at a dose of 2.5 to 3.75 mg per kg per day as a slow intravenous infusion over 6 hours.
CsADrug
CsA as capsules, oral solution, or fine granule, was administered at a dose of 3 mg per kg twice a day.
| Study group | Role | What they receive |
|---|---|---|
| Eltrombopag+rabbit ATG/CsA arm | Experimental | Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag wasadministered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26.After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion. Receives: Drug: Eltrombopag; Drug: Rabbit ATG; Drug: CsA |
What is being measured
The primary outcome is the main question the study is designed to answer.
ORR at 6 Months: Overall Response Rate (ORR) Defined as the Number of Participants Who Met the Criteria of Either Complete Response (CR) or Partial Response (PR) at Week 26
ORR will be calculated after 6 months of eltrombopag administration by measuring platelet, reticulocyte, neutrophil and transfusion independence. ORR includes Complete Response (CR) and Partial Response (PR) Rate.
Measured: Week 26
Secondary outcomes (25)
ORR at 3 Months
ORR will be calculated after 3 months of eltrombopag administration by measuring platelet, reticulocyte, neutrophil and transfusion independence.
Measured: Week 14
Complete Response (CR), and Partial Response (PR) Rate at 3 Months
CR and PR will be calculated after 3 months of eltrombopag administration by measuring platelet, reticulocyte, neutrophil and transfusion independence.
Measured: Week 14
CR Rate Based on the Criteria Used in NIH 12-H-0150 Study at 6 Months
CR criteria used in NIH 12-H-150 study is as follows: Hemoglobin >10 gram (g)/ deciliter (dL), and Absolute neutrophil count (ANC) >1,000/microliter, and Platelets >100,000/microliter.
Measured: Week 26
Changes in Hematology Parameters (Haemoglobin) in the Absence of Platelet Transfusion
The change in hematology values ( haemoglobin) were evaluated.
Measured: Week 26 and week 104
Changes in Hematology Parameters in the Absence of Platelet Transfusion
The change in hematology values from baseline for platelets, neutrophils and reticulocytes were evaluated.
Measured: Week 26 and week 104
Frequency of Platelet and Red Blood Cells (RBC) Transfusions
RBC transfusion dependency defined as at least one RBC transfusion within 8 weeks prior to D1. Platelet or RBC transfusions will be based on physician's subjective judgement. Platelet transfusion will be done if the platelet count is less than 10×10^9/liter (L) with significant bleeding tendency or the platelet count is less than 20×10^9/L with pyrexia. RBC transfusion will be done to keep the hemoglobin concentration at over 7 g/dL or in the presence of clinical symptoms such as dyspnea.
Measured: Baseline, Week 26
Volume of Platelet and RBC Transfusions
Platelet or RBC transfusions will be based on physician's subjective judgement. Platelet transfusion will be done if the platelet count is less than 10×10^9/L with significant bleeding tendency or the platelet count is less than 20×10^9/L with pyrexia. RBC transfusion will be done to keep the hemoglobin concentration at over 7 g/dL or in the presence of clinical symptoms such as dyspnea.
Measured: Baseline, Week 26
The Proportion of Subjects Whose Transfusion Unit (or Volume) Are Decreased or Who Became Transfusion (Platelet, RBC) Independent
The proportions of the subjects for whom the amount of blood transfusion (platelets and RBC) decreased or the proportions of the subjects for whom blood transfusion (platelets and RBC) became unnecessary. Platelet transfusion will be done if the platelet count is less than 10×10^9/L with significant bleeding tendency or the platelet count is less than 20×10^9/L with pyrexia. RBC transfusion will be done to keep the hemoglobin concentration at over 7 g/dL or in the presence of clinical symptoms such as dyspnea.
Measured: Week 26
Duration of Hospitalization
Duration of hospitalization is the time period from the administration of ATG up to discharge.
Measured: Week 26
Time to Onset of CR and PR
The time to onset of CR and PR will be determined by measuring platelet, reticulocyte, neutrophil and transfusion independence.
Measured: Week 26
Duration of CR or PR
Duration for CR or PR will be determined by measuring platelet, reticulocyte, neutrophil and transfusion independence.
Measured: Week 104
Degree of Exposure to Eltrombopag : Average Daily Dose
Measured: Week 104
Degree of Exposure to Eltrombopag : Cumulative Dose
The cumulative dose of drug administered to the subject will be calculated.
Measured: Week 104
Degree of Exposure to Eltrombopag : Days on Study
Measured: Week 104
Number of Participants With Adverse Events
Adverse events will be collected from the start of study treatment until the approval.
Measured: though study completion , approximately 2 years
Vital Signs (Blood Pressure) as a Measure of Safety and Tolerability
Vital sign measurements : blood pressure
Measured: baseline and Week 26
12-lead Electrocardiogram (ECG) as Measure of Safety and Tolerability
Triplicate 12-lead ECGs will be obtained at designated time points during the study using an ECG machine that calculates the heart rate and measures PR, QRS, QT, and QT interval corrected by Fridericia formula (QTcF) intervals.
Measured: Baseline, Week 26
The Trough Concentrations of Eltrombopag Following Repeat Doses of at 75 mg, 50 mg and 25 mg
Blood samples will be collected after repeat (14 days) doses of eltrombopag 75, 50, 25 mg to determine the plasma eltrombopag concentration prior to the next dose.
Measured: day 15
The Concentration After 4 Hours of Dose of Eltrombopag 75 mg
Blood sample will be collected at 4 hours after repeat (14 days) dose of eltrombopag 75 mg
Measured: day 15
Composite of Laboratory Parameters Assessment as a Safety Measure (Haemoglobin and Albumin).
The laboratory test values (haemoglobin and albumin) were calculated at each time point of evaluation.
Measured: Baseline, Week 26
Composite of Laboratory Parameters Assessment as a Safety Measure (Lymphocytes and Neutrophils).
The laboratory test values (lymphocytes and neutrophils) were calculated at each time point of evaluation.
Measured: Baseline, Week 26
Composite of Laboratory Parameters Assessment as a Safety Measure (Alcaline Phosphatase and Aspartate Amino Transferase) .
The laboratory test values (Alcaline Phosphatase and Aspartate Amino Transferase) were calculated at each time point of evaluation.
Measured: Baseline, Week 26
Composite of Laboratory Parameters Assessment as a Safety Measure.
The laboratory test values (hematological /biochemical examinations) were calculated at each time point of evaluation.
Measured: Baseline, Week 26
Vital Signs (Temperature) as a Measure of Safety and Tolerability
Vital sign measurements : temperature
Measured: baseline and Week 26
Vital Signs (Pulse Rate) as a Measure of Safety and Tolerability
Vital sign measurements : pulse rate.
Measured: baseline and Week 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2015 (estimated)
- Study start12 May 2015
- Primary completion5 Jul 2016
- Study completion6 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Aplastic AnemiaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02404025
- Sponsor's protocol ID
- 201793
- Status last verified
- May 2019
- First submitted
- 26 Feb 2015
- Last updated
- 26 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Non-randomized, Phase II Study of Eltrombopag in Combination With Rabbit Anti-thymocyte Globulin/Cyclosporine A (ATG/CsA) in Subjects With Moderate or More Severe Aplastic Anemia Who Have Not Received Prior ATG/Anti-lymphocyte Globulin (ALG)-Based Immunosuppressive Therapy
- ClinicalTrials.gov ID
- NCT02404025
- Acronym / sponsor ID
- 201793
- Conditions
- Aplastic Anemia
- Keywords
- Eltrombopag, rabbit anti-thymocyte globulin, additive effect, cyclosporine A, bone marrow, hematopoietic stem cells, pancytopenia, leukopenia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 12 May 2015 (actual)
- Primary completion
- 5 Jul 2016 (actual)
- Study completion
- 6 Sep 2017 (actual)
- First posted
- 31 Mar 2015 (estimated)
- Results
- Posted 26 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was an open label, non-randomized, phase II study of eltrombopag in combination with rabbit ATG/CsA in subjects with moderate or more severe AA who did not received prior ATG/ALG-based immunosuppressive therapy. The objective was to assess additive effects of eltorombopag on overall response rate (ORR) at 6 months (Week 26) of treatment with ATG/CsA. Subjects were assessed at least weekly for safety during the period from the start of ATG/CsA to 4 weeks after the start of administration of eltrombopag. After that, subjects had visits every 2 weeks until Week 26. Subjects in whom the treatment was assessed as effective at Week 26 could continued treatment with eltrombopag after 6 months when clinically indicated at the discretion of the investigator. There were five follow-up visits: at discontinuation of the treatment of eltrombopag, and Weeks 1, 2, 3, 4 and 26 after treatment discontinuation. As this study was the first Japanese phase II study in which this product was administered in combination with ATG/CsA to subjects with naive moderate or more severe AA, the subject number of this study was determined to be 10 based on the feasibility survey.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eltrombopag+rabbit ATG/CsA arm | Experimental | Drug: Eltrombopag, Drug: Rabbit ATG, Drug: CsASubjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag wasadministered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26.After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Japanese subjects aged >=18 and <71 years at the time of informed consent. Note: subjects aged >=71 and <75 may be eligible when clinically indicated at the discretion of the investigator by mutual agreement with Novartis medical advisor.
- Diagnosed with moderate or more severe AA according to the diagnostic criteria of AA. The severity classification is: Stage I - Mild - Other than the stages below; Stage II - Moderate - At least two of the following conditions are met: Reticulocyte <60,000/microliter, Neutrophil <1,000/microliter, Platelet <50,000/microliter; Stage III - Moderately severe - At least two of the following conditions are met and regular red blood cell transfusion (a need for transfusion of >=2 units per month) is required: Reticulocyte <60,000/microliter, Neutrophil <1,000/microliter, Platelet <50,000/microliter; Stage IV - Severe - At least two of the following conditions are met: Reticulocyte <20,000/microliter, Neutrophil <500/microliter, Platelet <20,000/microliter; Stage V - Very severe - At least one of the following conditions is met in addition to neutrophil <200/microliter: Reticulocyte <20,000/microliter, Platelet <20,000/microliter.
- Subjects who are considered an indication for the treatment with rabbit ATG and CsA.
- Adequate baseline organ function defined by the following criteria: Alanine aminotransferase (ALT), aspartate aminotransferase (AST)<=3 × local upper limit of normal (ULN) Creatinine, total bilirubin, and alkaline phosphatase (ALP) <1.5 × local ULN (total bilirubin <2.5 × local ULN with Gilbert's Syndrome)
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0 or 1
Key exclusion criteria (20 listed)
- Diagnosis of congenital AA (e.g. Fanconi anemia or Dyskeratosis congenital).
- Subjects who have a sibling donor with matched human leukocyte antigen (HLA) or who underwent hematopoietic stem cell transplantation (HSCT) previously. However, such subjects may be enrolled if HSCT is not indicated, or the subject does not want to undergo HSCT.
- Subjects with abnormal chromosome (monosomy 7 detected by fluorescence in situ hybridization (FISH), or other aberrations detected by G-band staining). Note: Subjects with abnormal chromosome which is not adopted into the clone definition of An International System for Human Cytogenetic Nomenclature (ISCN) may be enrolled after consulting with medical monitor.
- Previous ATG/ALG-based immunosuppressive therapy or steroid pulse therapy for AA.
- Treatment with CsA within 6 months before administration of ATG.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EltrombopagEltrombopag was provided as white round film-coated tablets containing 12.5 mg or 25 mg of eltrombopag free acid (SB-497115-GR, eltrombopag). | Drug | Eltrombopag+rabbit ATG/CsA arm |
| Rabbit ATGRabbit ATG, as an intravenous drip infusion, diluted by 500 mL of saline or 5% glucose injection was administered at a dose of 2.5 to 3.75 mg per kg per day as a slow intravenous infusion over 6 hours. | Drug | Eltrombopag+rabbit ATG/CsA arm |
| CsACsA as capsules, oral solution, or fine granule, was administered at a dose of 3 mg per kg twice a day. | Drug | Eltrombopag+rabbit ATG/CsA arm |
Primary outcome
ORR at 6 Months: Overall Response Rate (ORR) Defined as the Number of Participants Who Met the Criteria of Either Complete Response (CR) or Partial Response (PR) at Week 26
Time frame: Week 26
ORR will be calculated after 6 months of eltrombopag administration by measuring platelet, reticulocyte, neutrophil and transfusion independence. ORR includes Complete Response (CR) and Partial Response (PR) Rate.
25 secondary outcomes
ORR at 3 Months
Time frame: Week 14
Complete Response (CR), and Partial Response (PR) Rate at 3 Months
Time frame: Week 14
CR Rate Based on the Criteria Used in NIH 12-H-0150 Study at 6 Months
Time frame: Week 26
Changes in Hematology Parameters (Haemoglobin) in the Absence of Platelet Transfusion
Time frame: Week 26 and week 104
Changes in Hematology Parameters in the Absence of Platelet Transfusion
Time frame: Week 26 and week 104
Frequency of Platelet and Red Blood Cells (RBC) Transfusions
Time frame: Baseline, Week 26
Volume of Platelet and RBC Transfusions
Time frame: Baseline, Week 26
The Proportion of Subjects Whose Transfusion Unit (or Volume) Are Decreased or Who Became Transfusion (Platelet, RBC) Independent
Time frame: Week 26
Duration of Hospitalization
Time frame: Week 26
Time to Onset of CR and PR
Time frame: Week 26
Duration of CR or PR
Time frame: Week 104
Degree of Exposure to Eltrombopag : Average Daily Dose
Time frame: Week 104
Degree of Exposure to Eltrombopag : Cumulative Dose
Time frame: Week 104
Degree of Exposure to Eltrombopag : Days on Study
Time frame: Week 104
Number of Participants With Adverse Events
Time frame: though study completion , approximately 2 years
Vital Signs (Blood Pressure) as a Measure of Safety and Tolerability
Time frame: baseline and Week 26
12-lead Electrocardiogram (ECG) as Measure of Safety and Tolerability
Time frame: Baseline, Week 26
The Trough Concentrations of Eltrombopag Following Repeat Doses of at 75 mg, 50 mg and 25 mg
Time frame: day 15
The Concentration After 4 Hours of Dose of Eltrombopag 75 mg
Time frame: day 15
Composite of Laboratory Parameters Assessment as a Safety Measure (Haemoglobin and Albumin).
Time frame: Baseline, Week 26
Composite of Laboratory Parameters Assessment as a Safety Measure (Lymphocytes and Neutrophils).
Time frame: Baseline, Week 26
Composite of Laboratory Parameters Assessment as a Safety Measure (Alcaline Phosphatase and Aspartate Amino Transferase) .
Time frame: Baseline, Week 26
Composite of Laboratory Parameters Assessment as a Safety Measure.
Time frame: Baseline, Week 26
Vital Signs (Temperature) as a Measure of Safety and Tolerability
Time frame: baseline and Week 26
Vital Signs (Pulse Rate) as a Measure of Safety and Tolerability
Time frame: baseline and Week 26
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Eltrombopag, Rabbit ATG and CsA in people with Aplastic Anemia, run by Novartis Pharmaceuticals at 11 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ORR at 6 Months: Overall Response Rate (ORR) Defined as the Number of Participants Who Met the Criteria of Either Complete Response (CR) or Partial Response (PR) at Week 26 (time frame: Week 26). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2019.