Primary immune thrombocytopenia
Conditions
Interventions
Case Lusutrombopag:Lusutrombopag
Sponsors
Institute of Hematology& Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Males and females >= 18 years of age 2. Subjects > 60 years must have had a diagnostic bone marrow aspiration in the last 3 years or responded to treatment (platelet count >50 x 10^9/L) 3. Diagnosed with primary persistent or chronic ITP at least 3 months prior to screening and excluding other secondary thrombocytopenia such as MDS, AA, SLE, etc 4. Persistent or chronic immune thrombocytopenia (ITP) that is relapsed or refractory following at least one prior line of therapy, with or without splenectomy. 5. Prior rescue therapies for ITP (including but not limited to corticosteroids, platelet transfusions, immunoglobulins, immunomodulators, and cyclophosphamide) must have been discontinued at least 1 week before the new treatment initiation ?or? demonstrated no clinical efficacy within 1 week of administration. 6. Subjects are permitted to receive stable doses of immunosuppressive agents including cyclosporine, mycophenolate mofetil, azathioprine, or danazol. All such medications must have been maintained at a stable dose for =4 weeks prior to the first visit (Day 1). 7.Subjects receiving Chinese herbal medicine (CHM) must discontinue treatment =1 week prior to the first dose. Use of CHM is prohibited during the treatment period. 8. Subjects receiving steroid maintenance therapy during the study may be enrolled, as long as corticosteroids have been received at a stable dose (change=for 2 weeks. 9. During the screening visit, if no hormone maintenance therapy is received: an average of 2 PLTs < 30x10^9/L during the screening period (a single PLT count shall not be greater than 35x10^9/L) and if you are receiving hormone therapy, an average of 2 PLTs < 50x10^9/L during the screening period. The second test was within 96 hours from visit 1 (day 1), and the interval between the first and second monitoring was 2-14 days. 10. Prothrombin time (PT) and activated partial thromboplastin time (APTT) within 20% of the upper limit of normal (ULN) at Screening,or PT did not exceed normal value by +/-3s and APTT by +/-10s;No other history of coagulation state except ITP 11. A complete blood count within the reference range (including white blood count [WBC] differential not indicative of a disorder other than ITP), with the following exceptions: a) Hemoglobin: participants with hemoglobin levels between 10 g/dL (100 g/L) and the lower limit of normal (LLN) are eligible for inclusion; participants with anemia(hemoglobin levels <10g/dl )clearly attributable to ITP (excessive blood loss) are also eligible for inclusion; b) Absolute neutrophil count (ANC) greater than or equal to 1500/uL (1.5x10^9/L) (elevated WBC/ANC due to corticosteroid treatment is acceptable). 12. All subjects must agree to take progestin or barrier contraception: patients with potential fertility (excluding hysterectomy, bilateral salpingectomy, bilateral tubal ligation or postmenopausal women for more than one year; Men with bilateral vasectomy) must take effective contraceptive measures at least 2 weeks before taking the study drug for the first time, throughout the study and within 28 days after the end of the study (or early termination of the study); Women with potential fertility must have a negative pregnancy test during the screening period and on the 0 th day of the trial. 13. A signed and dated written consent obtained prior to the performance of Screening procedures
Exclusion criteria
Exclusion criteria: 1. History of inherited or acquired, clinically important hemorrhagic clotting disorder 2. Females who were pregnant or lactating, or receiving other hormone/chemical ontraceptives 3. Patients with potential fertility refused to take contraceptive methods 4. Use the following medications or treatments before the first visit (Day 1): Laboratory abnormalities with clinical significance (1)Abnormal peripheral blood smear (2)Total bilirubin >1.5×ULN (upper limit of normal) (3)Alanine aminotransferase (ALT) >1.5×ULN (4) Aspartate aminotransferase (AST) >1.5×ULN (5) Creatinine >1.5×ULN (6) HIV-positive (7)Human immunodeficiency virus positive Subjects who are positive for hepatitis A immunoglobulin M antibody (HAV IgM), hepatitis B surface antigen (HbsAg) and hepatitis B virus DNA copy number >= 1000IU/ml, or hepatitis C antibody (HCV) positive and have a history of acute hepatitis, cirrhosis, portal hypertension or chronic active hepatitis. (8)Thyroid-stimulating hormone (TSH) >1.5×ULN (9) Free thyroxine (T4) > 1.5 x ULN 5. Exposure to a small platepoietin (TPO) mimetic or agonist such as rhTPO, romiplostim, eltrombopag, avatrombopag, or hetrombopag within 4 weeks prior to Day 1 dosing. If the platelets < 30×10^9/L after TPO drug withdrawal, the investigator can judge that the group can be enrolled in advance. 6. Subjects unresponsive to previous TPO mimetics/agonists 7. 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): (1) Within 12 weeks - alemtuzumab, multi-drug systemic chemotherapy, stem cell therapy (2) Within 12weeks - rituximab; 8. History of clinically significant cardiovascular or thromboembolic disease within 26 weeks prior to Initial Screening 9. Splenectomy within 4 weeks prior to Initial Screening 10. Other abnormalities except ITP or situations that investigators deem inappropriate to participate in this study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of subjects with (d29) PLT >= 50x10^9/L after 4 weeks or PLT >= 250x10^9/L over 4 weeks; | — |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of participants who achieved a platelet count of >=50x10^9 /L after 12 weeks (Day85);Percentage of Participants Who at least once Achieved a Platelet Count of >=100x10^9 /L from week1 to week4 ;Change From Baseline in Platelet Counts Within 1-12 weeks;Percentage of Participants Who at least once Achieved a Platelet Count of >=50x10^9 /L during week 1-4 and week 5-12;Percentage of Participants Who at least once Achieved a Platelet Count of >=100x10^9 /L during week 1-4 and week 5-12;Time to first Achieve a Platelet Count of >= 50x10^9/L from baseline;Time to first Achieve a Platelet Count of >=100x10^9 /L from baseline;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;durable platelet response (platelet count >=50 × 10^9/L in >=75% of weeks);Accumulated days of response(PLT >=50x10^9/L);Percentage of concomitant ITP medications reduced compared with baseline;The proportion of rescue therapy ;The incidence and rating of bleeding events (WHO);At the end of the last follow -up, adverse events, clinical laboratory assessment, vital signs, electrocardiogram, physical examination, ophthalmological examination, bone marrow biopsy, etc. within the week;quality of life was assessed by ITP-PAG,FACIT-F from baseline to week16; | — |
Countries
China
Contacts
Public ContactLei Zhang
Institute of Hematology& Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Outcome results
None listed