CytopaeniaPhase 2NCT02148133
A Study to Assess the Safety and Efficacy of Eltrombopag in Japanese Subjects With Refractory, Moderate or More Severe Aplastic Anemia
A Phase 2 study testing Eltrombopag 12.5 mg and Eltrombopag 25 mg in people with Cytopaenia, run by Novartis Pharmaceuticals at 12 sites in Japan.
Trial summary
This was a non-randomized, open-label, phase II study to assess the efficacy and safety of eltrombopag in Japanese moderate or more severe aplastic anemia (AA) subjects with a platelet count <30,000/microliter who were refractory to anti-thymocyte globulin (ATG)-based immunosuppressive therapy (IST), who have relapsed… Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Cytopaenia
- What is being tested?
- Eltrombopag 12.5 mg and Eltrombopag 25 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 12 sitesJapan
- Study dates
- 23 Jul 2014to 5 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 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject has given written informed consent. If a subject is under 20 years, both the subject and the subject's legally acceptable representative have to give informed consent.
- Japanese subjects aged >=18 and <80 years at the time of informed consent.
- Diagnosis of moderate (stage II) or more Aplastic Anemia (AA) with platelet count <30,000/microliter (based on the diagnosis criteria of AA established by the Study Group on Idiopathic Hematopoietic Disorder as a part of Research on Measures for Intractable Diseases supported by Health and Labor Science Research Grants).
- Subjects who became refractory to Anti-thymocyte globulin (ATG)-based Immunosuppressive therapy (IST), who have relapsed after ATG-based IST, or who are ineligible for ATG-based IST. Note: Refractory or relapsed subjects to whom re-treatment with ATG is indicated should not be enrolled in the study. Subjects who have a sibling donor with matched human leukocyte antigen (HLA) should not be enrolled in the study. However, such subjects may be enrolled if the disease relapsed after hematopoietic stem cell transplantation (HSCT), if HSCT is not indicated, or the subject does not want to undergo HSCT.
- Adequate organ function at screening and Day 1 as defined as follows: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=3 × central laboratory upper limit of normal (ULN); Creatinine, total bilirubin, and alkaline phosphatase (ALP) <1.5 × central laboratory ULN (total bilirubin <2.5 × central laboratory ULN with Gilbert's Syndrome)
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0 or 1
- Subjects with QT interval corrected for heart rate by Fridericia's formula (QTcF) <450 milliseconds (msec) or QTcF<480 msec with branch block. Corrected QT interval duration (QTc) is QT interval corrected by Fridericia formula (QTcF), machine or manual over read. QTcF is based on single or averaged QTc value of triplicate electrocardiogram (ECG).
- 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 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 unit /milliliter (mIU/mL) or estradiol <40 picogram (pg)/mL (<140 picomole /Liter (pmole/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 study treatment. It is recommended that the pregnancy test should be performed as close as possible to the first dose of study treatment. 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 study treatment until 28 days after the last dose of eltrombopag.
Who cannot join
- Treatment with ATG in the past 12 months. Note: Subjects who are receiving cyclosporine or anabolic steroids (excluding danazol) at a stable dose may be enrolled if laboratory values are stable at screening.
- Congenital aplastic anemia (e.g., Fanconi anemia, congenital dyskeratosis)
- Paroxysmal nocturnal hemoglobinuria (PNH) granulocyte clone size determined by flow cytometry >=50%
- Presence of chromosomal aberration (-7/7q- detected by fluorescence in situ hybridization (FISH), or other aberrations detected by Giemsa (G)-band staining) Note: Subjects with the result by G-band staining (bone marrow aspiration) not adopted into the abnormal clone definition of An International System for Human Cytogenetic Nomenclature (ISCN) can be enrolled as no chromosomal aberration.
- Past history of thromboembolism or current use of anticoagulants. Note: Subjects with antiphospholipid antibody syndrome (APS) should not be enrolled.
- Past or current history of malignant tumor. Note: Subjects who have a history of completely resected malignant tumor and have been disease-free for 5 years are eligible.
Show all 16Show fewer
- Subjects who test positive for hepatitis B surface (HBs) antigen, hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antibody at screening. Note: Subjects with inactive hepatitis B may be enrolled. Judgment of inactive hepatitis B will be done by the medical advisor.
- Subjects with concurrent uncontrollable severe infection (e.g., sepsis)
- Hepatic cirrhosis
- Cardiac disorder (congestive heart disease of New York Heart Association (NYHA) functional classification Grade II/III/IV), or arrhythmia with a risk of thrombosis (e.g., atrial fibrillation). Note: Subjects with NYHA Grade II due to cardiac disorder should not be enrolled but those with NYHA Grade II due to Aplastic Anemia (AA) may be enrolled.
- Alcohol or drug abuse
- Pregnant women (a positive serum or urine pregnancy test within 7 days prior to the first dose of study treatment) or lactating women. Note: Female subjects who are lactating are eligible to participate if they discontinue nursing prior to the first dose of study treatment and refrain from nursing until 5 days after the treatment completion.
- Past history of immediate or delayed hypersensitivity to compounds chemically similar to eltrombopag or their activators
- Treatment with another investigational product within 30 days or the period 5-fold longer than the half-life of the investigational product, whichever longer, prior to the first dose of eltrombopag
- Prior treatment with eltrombopag, romiplostim, or any other Thrombopoietin (TPO) receptor agonist
- Use of prohibited concomitant medications.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
Japan12 sites
Novartis Investigative Site
Aichi, 453-8511
Novartis Investigative Site
Aichi, 460-0001
Novartis Investigative Site
Hyōgo, 664-8540
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, Open-label, Phase II Study to Assess the Safety and Efficacy of Eltrombopag in Japanese Subjects With Refractory, Moderate or More Severe Aplastic Anemia
This was a non-randomized, open-label, phase II study to assess the efficacy and safety of eltrombopag in Japanese moderate or more severe aplastic anemia (AA) subjects with a platelet count <30,000/microliter who were refractory to anti-thymocyte globulin (ATG)-based immunosuppressive therapy (IST), who have relapsed after ATG-based IST, or who are ineligible for ATG-based IST.
Eltrombopag was expected to improve trilineage blood cells and decrease transfusion frequency based on the result from the previous study in patients with severe AA. This study used the hematologic response rate, defined as the proportion of subjects showing improvement in at least one of the three blood cell lineages or a decrease in blood transfusion volume, as the primary endpoint.
A total of 36 subjects were screened and 21 were enrolled in the study. Treatment with eltrombopag started at 25 milligram (mg)/day and increased by 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day. Response assessment was performed at 3 months after starting the study treatment (Week 13). Subjects in whom the treatment was assessed as effective continued with the study treatment. Subjects in whom the treatment was assessed as effective (when meeting any of the response criteria) at 6 months after starting the study treatment (Week 26) might enter the extension phase and continue the treatment with eltrombopag. The primary endpoint was the hematologic response rate at Week26.
- Conditions
- Cytopaenia
- Being tested
- Eltrombopag 12.5 mg, Eltrombopag 25 mg
- Keywords
- Eltrombopag, Aplastic Anemia (AA), Thrombocytopenia, Thrombopoietin, Bone Marrow, Bone Marrow Biopsy, Hematopoietic Stem Cells, Mature Blood Cells, Pancytopenia, Leukopenia, Platelets
- Medical subject headings
- Anemia, Aplastic, Thrombocytopenia, Jacobs syndrome, Pancytopenia, Leukopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eltrombopag 12.5 mgDrug
Also called Revolade
White, round, film-coated tablets containing 12.5 mg of eltrombopag free acid (SB-497115-GR, eltrombopag) in each tablet
Eltrombopag 25 mgDrug
Also called Revolade
White, round, film-coated tablets containing 25 mg of eltrombopag free acid (SB-497115-GR, eltrombopag) in each tablet
| Study group | Role | What they receive |
|---|---|---|
| Eltrombopag | Experimental | Subjects were assigned the investigational product (eltrombopag 25 mg/day) orally once a day under fasting condition. The dose adjustment was done every 2 weeks according to the platelet count (increased by eltrombopag 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day). Receives: Drug: Eltrombopag 12.5 mg; Drug: Eltrombopag 25 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hematological Response at Week 26
Hematologic response rate at 6 months (at WeeK 26) after the start of study treatment was defined as the percentage of subjects who met any of the response criteria (Platelet count, Hemoglobin level, Neutrophil count). 1 ) Platelet count: an increase from baseline by 20,000/μL or more (In the absence of platelet transfusion), or no platelet transfusion requirements for 8 weeks; 2) Hemoglobin: When the baseline hemoglobin level is <9 g/dL: Without RBC transfusion at baseline, an increase from baseline by 1.5 g/dL or more; With RBC transfusion at baseline, a decrease of at least 4 units in RBC transfusions in the post-treatment 8-week period compared to the pre-treatment 8-week period (1 unit = RBC derived from 200 mL blood); 3) Neutrophil count: an increase from baseline by 500/μL or more (in the absence of granulocyte colony-stimulating factor (G-CSF)), or (if < 500/μL at baseline) an increase by 100 % or more. Only descriptive analysis done.
Measured: D183 (Week 26)
Secondary outcomes (15)
Change in Platelet Count From Baseline in the Absence of Platelet Transfusion Over Time
The changes in observed values for Platelet Count were summarized. The measurements were followed up to Week 26 and thereafter in the extension part (Up to the launch of the product after approval, which will be approximately up to two and a half years). Only descriptive analysis done.
Measured: Up to 2.5 years
Change in Hemoglobin From Baseline in the Absence of Red Blood Cell (RBC) Transfusion Over Time
The changes in observed values for Hemoglobin were summarized. The measurements were followed up to Week 26 and thereafter in the extension part (Up to the launch of the product after approval, which will be approximately up to two and a half years). Only descriptive analysis done.
Measured: Up to 2.5 years
Change in Neutrophil Count From Baseline in the Absence of Granulocyte-colony Stimulating Factor (G-CSF) Over Time
The changes in observed values for Neutrophil Count were summarized. The measurements were followed up to Week 26 and thereafter in the extension part (Up to the launch of the product after approval, which will be approximately up to two and a half years). Only descriptive analysis done.
Measured: Up to 2.5 years
Hematological Response at Week 13 in Terms of the Platelet Count, Hemoglobin Level and Neutrophil Count
The frequency and percentage were calculated with 95% confidence interval (CI) of responses (which meet each response criteria) of platelet count, hemoglobin and neutrophil count at Week 13.
Measured: Week 13
Duration of Hematological Response in Participants Who Responded at the Week 13
The duration of haematological response was defined, for subjects who responded at the Week 13 visit, as the number of months from the first date of a response until the first date of a relapse or the date the subject was last assessed. Only subjects with at least 2 response assessments were included in the duration of response assessment. The measurements were followed up to Week 26 and thereafter in the extension part (Up to the launch of the product after approval, which will be approximately up to two and a half years). Only descriptive analysis done.
Measured: Up to 2.5 years
Volume of (Platelet and RBC) Transfusion in Each Period
The amount of blood transfusion (platelets, RBC) were summarized. The measurements were followed up to Week 26 and thereafter in the extension part (Up to the launch of the product after approval, which will be approximately up to two and a half years). Only descriptive analysis done.
Measured: Day 1, Day 92 (Week 13), Day 183 (Week 26), Extension W39 and Extension W52
Frequency of (Platelet and RBC) Transfusion in Each Period
The frequency of blood transfusion (platelets, RBC) were summarized. The measurements were followed up to Week 26 and thereafter in the extension part (Up to the launch of the product after approval, which will be approximately up to two and a half years). Only descriptive analysis done.
Measured: Day 1, Day 92 (Week 13), Day 183 (Week 26), Extension W39 and Extension W52
Percentage of Participants With Reduced Volume of Transfusion (Platelet and RBC)
The proportion of the participants for whom the amount of blood transfusion (platelets and RBC) is decreased was measured and reported as a percentage. The measurements were followed up to Week 26 and thereafter in the extension part (Up to the launch of the product after approval, which will be approximately up to two and a half years). Only descriptive analysis done. This analysis was performed for the subjects who were baseline transfusion dependent.
Measured: Up to 2.5 years
Percentage of Participants Who Become Transfusion (Platelet and RBC) Independent
The proportion of participants for whom blood transfusion (platelets and RBC) became unnecessary was measured and reported as a percentage. The measurements were followed up to Week 26 and thereafter in the extension part (Up to the launch of the product after approval, which will be approximately up to two and a half years). Only descriptive analysis done. This analysis was performed for the subjects who were baseline transfusion dependent.
Measured: Up to 2.5 years
Long-term Safety and Tolerability of Eltrombopag
The frequency and percentage of subjects who experienced adverse events (AEs), serious adverse events (SAEs) and deaths by primary system organ class (SOC) and MedDRA preferred term were summarized.
Measured: Up to 30 days after last dose of study treatment
Number of Participants With Bleeding Events and Severity of Bleeding
The measurements were followed up to Week 26 and thereafter in the extension part.
Measured: Up to 30 days after last dose of study treatment
Maximum Observed Plasma Concentration (Cmax) for Eltrombopag
At some study sites, full blood sampling for pharmacokinetic (PK) evaluation of Eltrombopag was performed on Day 14 to calculate Cmax, tmax, AUC(0-t), and AUC(0-tau). PK parameters were calculated from plasma concentration-time data using non-compartmental methods.
Measured: Day 14 at 25 mg QD (-0.05, 0.15, 0.30, 0.45, 1.00, 1.30 and 24.00), at 50,75 and 100 mg QD (pre-dose)
Time to Reach the Maximum Plasma Concentration (Tmax) for Eltrombopag
At some study sites, full blood sampling for pharmacokinetic (PK) evaluation of Eltrombopag was performed on Day 14 to calculate Cmax, tmax, AUC(0-t), and AUC(0-tau). PK parameters were calculated from plasma concentration-time data using non-compartmental methods.
Measured: Day 14 at 25 mg QD (-0.05, 0.15, 0.30, 0.45, 1.00, 1.30 and 24.00), at 50,75 and 100 mg QD (pre-dose)
Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Within a Subject Across All Treatments (AUC 0-t) and Over the Dosing Interval (AUC 0-tau) for Eltrombopag
At some study sites, full blood sampling for pharmacokinetic (PK) evaluation of Eltrombopag was performed on Day 14 to calculate Cmax, tmax, AUC(0-t), and AUC(0-tau). PK parameters were calculated from plasma concentration-time data using non-compartmental methods.
Measured: Day 14 at 25 mg QD (-0.05, 0.15, 0.30, 0.45, 1.00, 1.30 and 24.00), at 50,75 and 100 mg QD (pre-dose)
Mean Change in Eltrombopag Concentration in Pharmacokinetic Serum Samples Over Time at Days 14 and 15
At every study center, blood samples was be collected on Day 15 of multiple doses of eltrombopag 25 mg to determine the plasma eltrombopag concentration prior to the next dose (trough concentration). In addition, one-point pre-dose blood sampling was performed at every study center on Day 15 of multiple doses of eltrombopag 50 mg, 75 mg and 100 mg to determine trough concentrations. PK parameters were calculated from plasma concentration-time data using non-compartmental methods.
Measured: Day 14 (pre-dose, 1, 2, 4, 6, 8 and 24 post-dose), Day 15 (pre-dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2014 (estimated)
- Study start23 Jul 2014
- Primary completion10 Sep 2015
- Study completion5 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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CytopaeniaStudies 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
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 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
- NCT02148133
- Sponsor's protocol ID
- 200926
- Other IDs
- CETB115E1201
- Status last verified
- Jan 2019
- First submitted
- 22 May 2014
- Last updated
- 3 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Yamazaki H, Ohta K, Iida H, Imada K, Obara N, Tokumine Y, Tomiyama Y, Usuki K, Imajo K, Miyamura K, Sasaki O, Fanghong Z, Hattori T, Tajima T, Matsuda A, Nakao S. Hematologic recovery induced by eltrombopag in Japanese patients with aplastic anemia refractory or intolerant to immunosuppressive therapy. Int J Hematol. 2019 Aug;110(2):187-196. doi: 10.1007/s12185-019-02683-1. Epub 2019 Jun 10.
PubMed 31183813
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Non-randomized, Open-label, Phase II Study to Assess the Safety and Efficacy of Eltrombopag in Japanese Subjects With Refractory, Moderate or More Severe Aplastic Anemia
- ClinicalTrials.gov ID
- NCT02148133
- Acronym / sponsor ID
- 200926
- Conditions
- Cytopaenia
- Keywords
- Eltrombopag, Aplastic Anemia (AA), Thrombocytopenia, Thrombopoietin, Bone Marrow, Bone Marrow Biopsy, Hematopoietic Stem Cells, Mature Blood Cells
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 23 Jul 2014 (actual)
- Primary completion
- 10 Sep 2015 (actual)
- Study completion
- 5 Sep 2017 (actual)
- First posted
- 28 May 2014 (estimated)
- Results
- Posted 3 May 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 a non-randomized, open-label, phase II study to assess the efficacy and safety of eltrombopag in Japanese moderate or more severe aplastic anemia (AA) subjects with a platelet count <30,000/microliter who were refractory to anti-thymocyte globulin (ATG)-based immunosuppressive therapy (IST), who have relapsed after ATG-based IST, or who are ineligible for ATG-based IST.
Eltrombopag was expected to improve trilineage blood cells and decrease transfusion frequency based on the result from the previous study in patients with severe AA. This study used the hematologic response rate, defined as the proportion of subjects showing improvement in at least one of the three blood cell lineages or a decrease in blood transfusion volume, as the primary endpoint.
A total of 36 subjects were screened and 21 were enrolled in the study. Treatment with eltrombopag started at 25 milligram (mg)/day and increased by 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day. Response assessment was performed at 3 months after starting the study treatment (Week 13). Subjects in whom the treatment was assessed as effective continued with the study treatment. Subjects in whom the treatment was assessed as effective (when meeting any of the response criteria) at 6 months after starting the study treatment (Week 26) might enter the extension phase and continue the treatment with eltrombopag. The primary endpoint was the hematologic response rate at Week26.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eltrombopag | Experimental | Drug: Eltrombopag 12.5 mg, Drug: Eltrombopag 25 mgSubjects were assigned the investigational product (eltrombopag 25 mg/day) orally once a day under fasting condition. The dose adjustment was done every 2 weeks according to the platelet count (increased by eltrombopag 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day). |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Subject has given written informed consent. If a subject is under 20 years, both the subject and the subject's legally acceptable representative have to give informed consent.
- Japanese subjects aged >=18 and <80 years at the time of informed consent.
- Diagnosis of moderate (stage II) or more Aplastic Anemia (AA) with platelet count <30,000/microliter (based on the diagnosis criteria of AA established by the Study Group on Idiopathic Hematopoietic Disorder as a part of Research on Measures for Intractable Diseases supported by Health and Labor Science Research Grants).
- Subjects who became refractory to Anti-thymocyte globulin (ATG)-based Immunosuppressive therapy (IST), who have relapsed after ATG-based IST, or who are ineligible for ATG-based IST. Note: Refractory or relapsed subjects to whom re-treatment with ATG is indicated should not be enrolled in the study. Subjects who have a sibling donor with matched human leukocyte antigen (HLA) should not be enrolled in the study. However, such subjects may be enrolled if the disease relapsed after hematopoietic stem cell transplantation (HSCT), if HSCT is not indicated, or the subject does not want to undergo HSCT.
- Adequate organ function at screening and Day 1 as defined as follows: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=3 × central laboratory upper limit of normal (ULN); Creatinine, total bilirubin, and alkaline phosphatase (ALP) <1.5 × central laboratory ULN (total bilirubin <2.5 × central laboratory ULN with Gilbert's Syndrome)
Key exclusion criteria (16 listed)
- Treatment with ATG in the past 12 months. Note: Subjects who are receiving cyclosporine or anabolic steroids (excluding danazol) at a stable dose may be enrolled if laboratory values are stable at screening.
- Congenital aplastic anemia (e.g., Fanconi anemia, congenital dyskeratosis)
- Paroxysmal nocturnal hemoglobinuria (PNH) granulocyte clone size determined by flow cytometry >=50%
- Presence of chromosomal aberration (-7/7q- detected by fluorescence in situ hybridization (FISH), or other aberrations detected by Giemsa (G)-band staining) Note: Subjects with the result by G-band staining (bone marrow aspiration) not adopted into the abnormal clone definition of An International System for Human Cytogenetic Nomenclature (ISCN) can be enrolled as no chromosomal aberration.
- Past history of thromboembolism or current use of anticoagulants. Note: Subjects with antiphospholipid antibody syndrome (APS) should not be enrolled.
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 |
|---|---|---|
| Eltrombopag 12.5 mgAlso: RevoladeWhite, round, film-coated tablets containing 12.5 mg of eltrombopag free acid (SB-497115-GR, eltrombopag) in each tablet | Drug | Eltrombopag |
| Eltrombopag 25 mgAlso: RevoladeWhite, round, film-coated tablets containing 25 mg of eltrombopag free acid (SB-497115-GR, eltrombopag) in each tablet | Drug | Eltrombopag |
Primary outcome
Hematological Response at Week 26
Time frame: D183 (Week 26)
Hematologic response rate at 6 months (at WeeK 26) after the start of study treatment was defined as the percentage of subjects who met any of the response criteria (Platelet count, Hemoglobin level, Neutrophil count). 1 ) Platelet count: an increase from baseline by 20,000/μL or more (In the absence of platelet transfusion), or no platelet transfusion requirements for 8 weeks; 2) Hemoglobin: When the baseline hemoglobin level is <9 g/dL: Without RBC transfusion at baseline, an increase from baseline by 1.5 g/dL or more; With RBC transfusion at baseline, a decrease of at least 4 units in RBC transfusions in the post-treatment 8-week period compared to the pre-treatment 8-week period (1 unit = RBC derived from 200 mL blood); 3) Neutrophil count: an increase from baseline by 500/μL or more (in the absence of granulocyte colony-stimulating factor (G-CSF)), or (if < 500/μL at baseline) an increase by 100 % or more. Only descriptive analysis done.
15 secondary outcomes
Change in Platelet Count From Baseline in the Absence of Platelet Transfusion Over Time
Time frame: Up to 2.5 years
Change in Hemoglobin From Baseline in the Absence of Red Blood Cell (RBC) Transfusion Over Time
Time frame: Up to 2.5 years
Change in Neutrophil Count From Baseline in the Absence of Granulocyte-colony Stimulating Factor (G-CSF) Over Time
Time frame: Up to 2.5 years
Hematological Response at Week 13 in Terms of the Platelet Count, Hemoglobin Level and Neutrophil Count
Time frame: Week 13
Duration of Hematological Response in Participants Who Responded at the Week 13
Time frame: Up to 2.5 years
Volume of (Platelet and RBC) Transfusion in Each Period
Time frame: Day 1, Day 92 (Week 13), Day 183 (Week 26), Extension W39 and Extension W52
Frequency of (Platelet and RBC) Transfusion in Each Period
Time frame: Day 1, Day 92 (Week 13), Day 183 (Week 26), Extension W39 and Extension W52
Percentage of Participants With Reduced Volume of Transfusion (Platelet and RBC)
Time frame: Up to 2.5 years
Percentage of Participants Who Become Transfusion (Platelet and RBC) Independent
Time frame: Up to 2.5 years
Long-term Safety and Tolerability of Eltrombopag
Time frame: Up to 30 days after last dose of study treatment
Number of Participants With Bleeding Events and Severity of Bleeding
Time frame: Up to 30 days after last dose of study treatment
Maximum Observed Plasma Concentration (Cmax) for Eltrombopag
Time frame: Day 14 at 25 mg QD (-0.05, 0.15, 0.30, 0.45, 1.00, 1.30 and 24.00), at 50,75 and 100 mg QD (pre-dose)
Time to Reach the Maximum Plasma Concentration (Tmax) for Eltrombopag
Time frame: Day 14 at 25 mg QD (-0.05, 0.15, 0.30, 0.45, 1.00, 1.30 and 24.00), at 50,75 and 100 mg QD (pre-dose)
Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Within a Subject Across All Treatments (AUC 0-t) and Over the Dosing Interval (AUC 0-tau) for Eltrombopag
Time frame: Day 14 at 25 mg QD (-0.05, 0.15, 0.30, 0.45, 1.00, 1.30 and 24.00), at 50,75 and 100 mg QD (pre-dose)
Mean Change in Eltrombopag Concentration in Pharmacokinetic Serum Samples Over Time at Days 14 and 15
Time frame: Day 14 (pre-dose, 1, 2, 4, 6, 8 and 24 post-dose), Day 15 (pre-dose)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31183813Yamazaki H, Ohta K, Iida H, Imada K, Obara N, Tokumine Y, Tomiyama Y, Usuki K, Imajo K, Miyamura K, Sasaki O, Fanghong Z, Hattori T, Tajima T, Matsuda A, Nakao S. Hematologic recovery induced by eltrombopag in Japanese patients with aplastic anemia refractory or intolerant to immunosuppressive therapy. Int J Hematol. 2019 Aug;110(2):187-196. doi: 10.1007/s12185-019-02683-1. Epub 2019 Jun 10.
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
12 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 12.5 mg and Eltrombopag 25 mg in people with Cytopaenia, run by Novartis Pharmaceuticals at 12 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 8 inclusion and 16 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 3 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 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 3 May 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?
Hematological Response at Week 26 (time frame: D183 (Week 26)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02148133, which also lists 1 linked publication.
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 3 May 2019.