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This exploratory study is to investigate the efficacy, safety and tolerability of Lusutrombopag in the treatment of primary immune thrombocytopenia in Chinese patients who have failed first-line therapy
This is an open-label, single-arm study of lusutrombopag initiated at a dose of 3mg daily titrated to a maximum dose of 6mg daily in the treatment of Chinese adults with persistent or chronic Immune thrombocytopenia (ITP) with or without prior splenectomy after failing first line therapy such corticosteroids and IV immunoglobulin. The study consists of three phases: Screening, Core Study（participants are treated with lusutrombopag 3mg daily for up to 4 weeks), and Titration study (participants are treated with lusutrombopag titrated to a maximum dose of 6mg daily according to their platelet counts）
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lusutrombopag | Experimental | Participants receive lusutrombopag 3 mg administered orally once a day for up to 4 weeks and titrated to a maximum dose of 6 mg during week 5 and week12 based on the platelet count (PLT) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lusutrombopag Oral Tablet | Drug | Participants receive lusutrombopag 3 mg administered orally once a day for up to 4 weeks and doses are adjusted based on platelet counts during week 5-12. If a subject's platelet count remains < 50x10^9 /L, the dose could have been increased up to a maximum dose of 6 mg（2 tablets).If a subject's platelet count reaches ≥ 250x10^9 /L during the first 4 weeks, treatment is stopped and participants are allowed to enter into Titration Study in advance when platelet count drops to ≥100x10^9 /L. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants with a Platelet Response after 4 Weeks | Platelet responses to lusutrombopag was evaluated using the platelet count defined as ≥50x10^9 /L on study drug treatment after 4 weeks of dosing（on Day 29) or prematurely ≥250x10^9 /L prior to Day 29. | on Day 29 of Treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants with a Platelet Response after 12 Weeks (Day 85) | Platelet responses to lusutrombopag was evaluated using the platelet count defined as ≥50x10^9 /L on study drug treatment after 12 weeks of dosing（on Day 85). | on Day 85 of treatment |
| Percentage of Participants Who Achieved a Platelet Count of ≥50×10^9/L After 6 Weeks of Dosing |
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Inclusion Criteria:
Exclusion Criteria:
History of inherited or acquired, clinically important hemorrhagic clotting disorder
Females who were pregnant or lactating, or receiving other hormone/chemical contraceptives
Patients with potential fertility refused to take contraceptive methods
Laboratory abnormalities
Exposure to previous thrombopoietin (TPO) mimetics/agonists (e.g. romiplostim, recombinant human thrombopoietin (rhTPO), avatrombopag, eltrombopag and herombopag) within 4 weeks prior to initial screening.In addition, participants are allowed to be enrolled at the discretion of the investigator when platelet counts are below 30 x 10^9/L within the 4 weeks after withdrawal of thrombopoietin (TPO) mimetics/agonists
Subjects unresponsive to previous TPO mimetics/agonists
Exposure to an investigative medication within 4 weeks prior to the initial Screening Visit or Use of the following drugs or treatment prior to Visit 1 (Day 1):
History of clinically significant cardiovascular or thromboembolic disease within 26 weeks prior to Initial screening
Splenectomy within 4 weeks prior to Initial Screening
Other abnormalities except ITP or situations that investigators deem inappropriate to participate in this study
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| Name | Affiliation | Role |
|---|---|---|
| Zhang Lei, MD | Chinese Academy of Medical Science and Blood Disease Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institute of Hematology & Blood Diseases Hospital | Tianjin | Tianjin Municipality | 300020 | China |
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| ID | Term |
|---|---|
| D016553 | Purpura, Thrombocytopenic, Idiopathic |
| ID | Term |
|---|---|
| D011696 | Purpura, Thrombocytopenic |
| D011693 | Purpura |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
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| ID | Term |
|---|---|
| C000611387 | lusutrombopag |
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Platelet responses to lusutrombopag was evaluated using the platelet count defined as ≥50x10^9 /L after week 6 |
| on Day 43 of treatment |
| Percentage of Participants Who at least once Achieved a Platelet Count of ≥50x10^9/L in Week 1 ,2,3,4 in the Core Study | Platelet responses to lusutrombopag was evaluated using the platelet count defined as ≥50x10^9 /L from baseline to Week 4. | Baseline, Week 4 |
| Change in Platelet Count | Change from baseline in platelet count was assessed at every visit from Baseline to Week 12 | Baseline, 12 Weeks |
| Percentage of Participants Who at least once Achieved a Platelet Count of≥50x10^9 /L during the Treatment | Platelet responses to lusutrombopag was evaluated using the platelet count defined as ≥50x10^9 /L. Participants who at least once achieved a platelet count of ≥50x10^9 /L during the Core Study and Titration Study respectively were assessed. | Baseline, up to 12 Weeks |
| Percentage of Participants Who at least once Achieved a Platelet Count of≥100x10^9 /L during the treatment | Platelet's complete responses to lusutrombopag was evaluated using the platelet count defined as a platelet count ≥100x10^9 /L. Participants who at least once achieved a platelet count of ≥100x10^9 /L during the Core Study and Titration Study respectively were assessed. | Baseline, up to 12 Weeks |
| Time to first Achieve a Platelet Count of ≥ 50x10^9/L | The time to first achieve a response was defined as the Day when participants first reached a platelet count of ≥ 50×10^9/L from baseline. | Baseline, up to 12 Weeks |
| Time to first Achieve a Platelet Count of ≥100x10^9 /L | Defined as the Day when participants first reached a platelet count of ≥ 100×10^9/L from baseline. | Baseline, up to 12 Weeks |
| Percentage of Participants Who at least once Achieved a Platelet Coun platelet count≥30×10^9/L, a≥2-fold increase from baseline within week 1-4 and week 5-12，respectively. | The percentage of partial response were defined as a platelet count of ≥30×10^9/L, a≥2-fold increase from baseline | Baseline, up to 12 Weeks |
| Durable Platelet Response (platelet count ≥50×10^9/L in ≥75% of weeks) Rate | Durable platelet response rate was defined as platelet count ≥50×10^9/L in ≥75% of assessments(weeks) | Baseline, up to 12 Weeks |
| Cumulated Number of Weeks of Response（≥50x10^9/L） | Cumulative number of weeks of platelet response was defined as the total number of weeks in which platelet count is ≥50x10^9/L during the Core Study and Titration Study | Baseline, up to 12 Weeks |
| Percentage of Participants with a Reduction in the use of Concomitant ITP Medications from Baseline | Lusutrombopag dose titration and downward titration of concomitant ITP medications was allowed at Week ,when Titration Study begins. | Day 29，Week 12 |
| The Incidence and Rating of Bleeding Events During the Study | Bleeding assessments were performed by the Investigator according to the World Health Organization (WHO) criteria bleeding scale: Grade 0: no bleeding; Grade 1: petechial bleeding; Grade 2: mild blood loss (clinically significant); Grade 3: gross blood loss, requires transfusion (severe); Grade 4: debilitating blood loss, retinal or cerebral associated with fatality. | Baseline，Week12 |
| Percentage of Participants Who Required Rescue Therapy for Bleeding During the Study | Participants who received rescue therapy for bleeding events during the study. steroids, intravenous immunoglobulin and platelet transfusion were considered as rescue therapy for bleeding events. | Baseline , Week16 |
| Number of Participants With Adverse Events (AEs) | An AE is defined as any untoward medical occurrence in a subject administered a pharmaceutical product during the course of a clinical investigation, including any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product (IP), whether or not thought to be related to the IP. AEs reported after initial study drug administration were considered treatment-emergent. A serious adverse event is defined as any AE that resulted in death, was life-threatening, hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect or an important medical event that, based upon medical judgment, may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed above. A treatment-related AE is any AE determined by the investigator to be possibly related, probably related, or definitely related to study drug. | Baseline through Week 12 while receiving treatment and at Week 16 after discontinuation of treatment. |
| Change in Health-related Quality of Life Assessed by FACIT-F Scale from Baseline to Week 16 | The Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F) assesses the severity of patient's fatigue. The Full version of FACIT-F contains 40 items. Total score is computed by summing 5 subscales: ranging from 0-160.This study assessed the subscale Fatigue (range 0-52), which contains 13 items, The higher the score, the milder the patients' fatigue. | Baseline，Week16 |
| Change in Health-related Quality of Life Assessed by ITP-PAG Scale from Baseline to Week 16 | The Immune Thrombocytopenic Purpura (ITP)-Patient Assessment Questionnaire (ITP-PAG) assesses the overall quality of life (Qol) of patients. Possible scores range from 0 to 100. Higher total score indicates better QoL | Baseline，Week16 |
| D006425 |
| Hemic and Lymphatic Diseases |
| D057049 | Thrombotic Microangiopathies |
| D013921 | Thrombocytopenia |
| D001791 | Blood Platelet Disorders |
| D000095542 | Cytopenia |
| D006474 | Hemorrhagic Disorders |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012877 | Skin Manifestations |
| D012816 | Signs and Symptoms |