Clinical trial NCT05932524: Low-dose Baricitinib Plus High-dose Dexamethasone for Patients With Newly Diagnosed Immune Thrombocytopenia
Official title: Low-dose Baricitinib Plus High-dose Dexamethasone as First-line Treatment for Patients With Newly Diagnosed Immune Thrombocytopenia: a Multicenter, Open-label, Randomized, Controlled, Phase 2 Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Immune Thrombocytopenia
Keywords: Baricitinib
High-dose dexamethasone
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
Collaborators: name: Beijing Luhe Hospital
name: Chinese PLA General Hospital
name: Navy General Hospital, Beijing
name: Beijing Hospital
name: Beijing Friendship Hospital
name: Peking University First Hospital
name: Peking University Third Hospital
name: China-Japan Friendship Hospital
name: Beijing Tsinghua Changgeng Hospital
First posted: 2023-07-06
Enrollment: 132
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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).
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Durable response
timeFrame: 6 months
Secondary outcomes:
measure: Complete response (CR)
timeFrame: 1 month
measure: Response (R)
timeFrame: 1 month
measure: Time to response
timeFrame: 6 months
measure: Duration of response
timeFrame: 6 months
measure: Early response
timeFrame: 7 days
measure: Initial response
timeFrame: 28 days
measure: Bleeding events
timeFrame: From the start of study treatment (Day 1) to the end of week 26
measure: Health-related quality of life (HRQoL)
timeFrame: From the start of study treatment (Day 1) to the end of week 26
measure: Adverse events
timeFrame: From the start of study treatment (Day 1) to the end of week 26
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Insititute of Hematology, Peking University People's Hospital
city: Beijing
country: China
facility: Beijing Friendship Hospital
city: Beijing
country: China
facility: Beijing Hospital
city: Beijing
country: China
facility: Beijing Luhe Hospital
city: Beijing
country: China
facility: Beijing Tsinghua Changgeng Hospital
city: Beijing
country: China
facility: China-Japan Friendship Hospital
city: Beijing
country: China
facility: Chinese PLA General Hospital
city: Beijing
country: China
facility: Peking University First Hospital
city: Beijing
country: China
facility: Peking University Third Hospital
city: Beijing
country: China
facility: The Sixth Medical Center of PLA General Hospital
Study officials:
affiliation: Peking University Institute of Hematology, Peking University People's Hospital
name: Xiaohui Zhang
role: PRINCIPAL_INVESTIGATOR
References: