Immune Thrombocytopenia
Conditions
Keywords
Baricitinib, High-dose dexamethasone
Brief summary
A randomized, open-label, multicenter, phase 2 trial to compare the efficacy and safety of baricitinib plus high-dose dexamethasone compared to high-dose dexamethasone monotherapy for the first-line treatment of adults with primary immune thrombocytopenia (ITP).
Detailed description
This is a parallel group, multicenter, randomized, controlled trial of patients with ITP in China. Patients were randomly assigned to receive baricitinib plus high-dose dexamethasone or high-dose dexamethasone monotherapy. Treatment will be discontinued if very severe or life-threatening adverse events developed or at the patients' request. The primary endpoint is durable response, defined as the maintenance of platelet count ≥30,000/μL and at least 2-fold increase of the baseline count, the absence of bleeding, and no need for rescue medication at the 6-month follow-up.
Interventions
DRUGBaricitinib 2 MG
Baricitinib 2 mg q.d., p.o., for 6 consecutive months.
DRUGDexamethasone
Dexamethasone 40 mg q.d. for 4 consecutive days (the 4-day course of dexamethasone will be repeated in the case of lack of response by day 10)
Sponsors
Beijing Luhe Hospital
Chinese PLA General Hospital
Navy General Hospital, Beijing
Beijing Hospital
Beijing Friendship Hospital
Peking University First Hospital
Peking University Third Hospital
China-Japan Friendship Hospital
Beijing Tsinghua Changgeng Hospital
Peking University People's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients are randomly assigned at a 1:1 ratio to receive baricitinib plus high-dose dexamethasone or high-dose dexamethasone alone. Each group requires 66 patients (considering 10% drop-off).
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Confirmed newly-diagnosed, treatment-naive ITP; 2. A platelet count \<30,000/μL, or a platelet count \<50,000/μL with clinically significant bleeding symptoms (WHO bleeding scale 2 or above) at the enrollment; 3. Willing and able to sign written informed consent.
Exclusion criteria
1. Received chemotherapy or anticoagulants or other drugs affecting the platelet counts within 6 months before the screening visit; 2. Have a known diagnosis of other autoimmune diseases, established in the medical history and laboratory findings with positive results for the determination of antinuclear antibodies, anti-cardiolipin antibodies, lupus anticoagulant or direct Coombs test; 3. Active or a history of malignancy; 4. Pregnancy or lactation; 5. Received first-line and second-line ITP-modifying therapy; 6. Previously received corticosteroids or immunosuppressive agents for non-ITP diseases within 6 months before enrollment; 7. A history of clinically significant adverse reactions to previous corticosteroid therapy; 8. Unstable or uncontrolled disease or condition related to or impacting cardiac function (e.g., unstable angina, congestive heart failure, uncontrolled hypertension or cardiac arrhythmia); 9. Current or recent (\<4 weeks prior to screening) clinically serious viral, bacterial, fungal, or parasitic infection; 10. A history of symptomatic herpes zoster infection within 12 weeks prior to screening; 11. Active or chronic viral infection from hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV); 12. Have evidence of active tuberculosis (TB), or have previously had evidence of active TB and did not receive appropriate and documented treatment, or have had household contact with a person with active TB and did not receive appropriate and documented prophylaxis for TB; 13. Have experienced a clinically significant thrombotic event within 24 weeks of screening or are on anticoagulants and in the opinion of the investigator are not well controlled; 14. Myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage IV heart failure; 15. A history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that, in the opinion of the investigator, could constitute an unacceptable risk when taking investigational product or interfere with the interpretation of data; 16. Any of the following specific abnormalities on screening laboratory tests: 1\) ALT or AST \>2 x ULN, or total bilirubin ≥1.5 x ULN 2) hemoglobin \<9 g/dL, or total white blood cell (WBC) count \<2,500/µL, or neutropenia (absolute neutrophil count \<1,200/µL), or lymphopenia (lymphocyte count \<750/µL) 3) eGFR \<50 mL/min/1.73 m\^2.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Durable response | 6 months | The maintenance of a platelet count ≥30,000/μL, at least 2-fold increase of the baseline count, the absence of bleeding, and no need for rescue medication at the 6-month follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Early response | 7 days | Achievement of CR or R at day 7 |
| Initial response | 28 days | Achievement of CR or R at day 28 |
| Bleeding events | From the start of study treatment (Day 1) to the end of week 26 | Clinically significant bleeding as assessed using the world health organization (WHO) bleeding scale. |
| Health-related quality of life (HRQoL) | From the start of study treatment (Day 1) to the end of week 26 | ITP-PAQ is used to assess the Health Related Quality of Life (HRQoL) before and after treatment. |
| Duration of response | 6 months | Duration of response at 6-month follow up. |
| Complete response (CR) | 1 month | A platelet count over 100,000/μL and absence of bleeding. |
| Response (R) | 1 month | A platelet count over 30,000/μL and at least 2-fold increase of the baseline count and absence of bleeding. |
| Time to response | 6 months | The time from starting treatment to time of achievement of CR or R. |
| Adverse events | From the start of study treatment (Day 1) to the end of week 26 | Adverse events (AEs) are reported and graded in accordance with the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. |
Countries
China
Contacts
Primary ContactXiaohui Zhang
Backup ContactPeng Zhao
Outcome results
None listed