Clinical trial NCT05852847: Low-dose Baricitinib Plus Danazol for Steroid-resistant/Relapse Immune Thrombocytopenia
Official title: Low-dose Baricitinib Plus Danazol Versus Danazol for Patients With Steroid-resistant/Relapse Immune Thrombocytopenia: A Multicenter, Randomized, Open-label Phase 2 Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Immune Thrombocytopenia
Keywords: Immune Thrombocytopenia
baricitinib
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: 2023-05-10
Enrollment: 216
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 danazol or danazol alone. Each group requires 108 patients (considering 20% drop-off) to achieve the superiority comparison.
Primary purpose: TREATMENT

Brief summary: This is a prospective, multicenter, randomized, controlled phase 2 trial to compare the efficacy and safety profiles in ITP patients receiving baricitinib plus danazol to those receiving danazol alone.

Detailed description: This is a prospective, multicenter, randomized, controlled design of 216 adult patients with steroid-resistant/relapse ITP in China. Patients are randomly assigned at a 1:1 ratio to receive baricitinib plus danazol or danazol alone. Patients in the combination therapy group receive oral baricitinib at a dose of 2 mg daily and oral danazol at a dose of 200 mg twice a day. Those in the monotherapy group receive oral danazol at 200 mg twice daily. The treatment lasts for 6 months. 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, 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. Primary immune thrombocytopenia (ITP) confirmed by excluding other supervened causes of thrombocytopenia;
2. Patients with chronic low platelet count (\<30,000/μL) for 6 months who have failed at least one treatment for chronic low platelet count;
3. Patients who did not achieve a sustained response to treatment with full-dose corticosteroids for a minimum duration of 4 weeks or who relapsed during steroid-tapering or after its discontinuation;
4. Patients with a platelet count \<30,000/μL or a platelet count \<50,000/μL with clinically significant bleeding symptoms at the enrollment;
5. Willing and able to provide written informed consent, and agreeable to the schedule of assessment.

Exclusion Criteria:

1. Secondary immune thrombocytopenia (e.g. patients with HIV, HCV, Helicobacter pylori infection or patients with confirmed autoimmune disease);
2. Active or a history of malignancy;
3. Pregnancy or lactation;
4. Current or recent (\<4 weeks prior to screening) clinically serious viral, bacterial, fungal, or parasitic infection;
5. A history of symptomatic herpes zoster infection within 12 weeks prior to screening;
6. Active or chronic viral infection from hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV);
7. 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;
8. 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;
9. Myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage IV heart failure;
10. 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;
11. 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: Initial response
timeFrame: 28 days
measure: Bleeding events
timeFrame: 6 months
measure: Health-related quality of life (HRQoL)
timeFrame: 6 months
measure: Adverse events
timeFrame: 6 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Insititute of Hematology, Peking University People's Hospital
state: Beijing
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, MD
role: PRINCIPAL_INVESTIGATOR
References: