Zanubrutinib and Eltrombopag as Second-line Treatment in Adults With Primary Immune Thrombocytopenia

Zanubrutinib and Eltrombopag as Second-line Treatment for Patients With Immune Thrombocytopenia: a Multicentre, Open-label,Randomised, Controlled, Phase 2 Trial

Randomized, open-label, multicenter study to compare the efficacy and safety of zanubrutinib plus eltrombopag compared to eltrombopag monotherapy for the first-line treatment of adults with chronic immune thrombocytopenia (ITP).

Study Overview

• Status: Not yet recruiting
• Conditions: Immune Thrombocytopenia
• Intervention / Treatment: Drug: Zanubrutinib; Drug: Eltrombopag

Detailed Description

The investigators are undertaking a prospective trial of patients with ITP in China. Zanubrutinib is administered as 80 mg po. qd for 6 weeks. Eltrombopag is given with 50 mg once daily for up to 6 weeks. Platelet count, bleeding and other symptoms were evaluated before and after treatment. Adverse events are also recorded throughout the study. This study assessed the efficacy and safety of eltrombopag plus zanubrutinib.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100010
      • Peking University Insititute of Hematology, Peking University People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Primary immune thrombocytopenia (ITP) confirmed by excluding other supervened causes of thrombocytopenia;
2. Patients with chronic low platelet count (less than 30,000/µL) for 6 months who have failed at least one treatment for chronic low platelet count

2. 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 3. Willing and able to sign written informed consent

Exclusion Criteria:

1. Secondary immune thrombocytopenia (e.g., patients with HIV, HCV, Helicobacter pylori infection or patients with systemic lupus erythematosus)
2. congestive heart failure
3. severe arrhythmia
4. nursing or pregnant women
5. aspartate aminotransferase and alanine transaminase levels ≥ 3× the upper limit of the normal threshold criteria
6. creatinine or serum bilirubin levels each 1•5 times or more than the normal range
7. active or previous malignancy
8. Unable to do blood routine test for the sake of time, distance, economic issues or other reasons
9. History of clotting disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Zanubrutinib and eltrombopag; Zanubrutinib 80mg po qd 6 weeks and eltrombopag 50 mg qd for up to 6 weeks.	Drug: Zanubrutinib; Zanubrutinib 80mg po qd 6 weeks; Other Names: BTK inihibitor; Drug: Eltrombopag; eltrombopag 50 mg qd for up to 6 weeks. The eltrombopag dose could be increased from 50 mg to 75 mg after 3 weeks in patients whose platelet counts were less than 50 000 per μL. Treatment was discontinued in patients who attained a platelet count greater than 200 000 per μL.
ACTIVE_COMPARATOR: Eltrombopag monotherapy; Eltrombopag is given as 50 mg qd for up to 6 weeks.	Drug: Eltrombopag; eltrombopag 50 mg qd for up to 6 weeks. The eltrombopag dose could be increased from 50 mg to 75 mg after 3 weeks in patients whose platelet counts were less than 50 000 per μL. Treatment was discontinued in patients who attained a platelet count greater than 200 000 per μL.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment response	The proportion of patients who had an increase in platelet counts to 50 000 per μL or more after 6 weeks of treatment	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response	The maintenance of platelet count ≥ 30 x 10^9/L, at least 2-fold increase of the baseline count, the absence of bleeding, and no need for rescue medication after 6 weeks of treatment	6 weeks
Complete response (CR)	Complete response (CR) was defined as platelet count more than 100,000 per cubic millimeter and absence of bleeding	6 weeks
Time to response	The time from starting treatment to time of achievement of Response	6 weeks
Sustained response	The maintenance of platelet count ≥ 30 x 10^9/L, at least 2-fold increase of the baseline count, the absence of bleeding, and no need for rescue medication at the 12-month follow-up	12 month
Number of patients with bleeding	Number of patients with bleeding complication ( WHO bleeding score)	12 months
Number of patients with adverse events	Number of patients with adverse events	12 months
Duration of response (DOR)	Duration of response at 12-month follow up	12 months
Loss of response	Platelet counts below 100 x 109/L or bleeding (from CR) or platelet counts below 30 x 109/L, less than 2-fold increase of baseline platelet count or bleeding (from R)	12 months

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Collaborators: Qilu Hospital of Shandong University; Beijing Tongren Hospital; Beijing Hospital; Navy General Hospital, Beijing; Beijing Aerospace General Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): June 1, 2022
• Primary Completion (ANTICIPATED): June 1, 2025
• Study Completion (ANTICIPATED): December 30, 2025

Study Registration Dates

• First Submitted: May 6, 2022
• First Submitted That Met QC Criteria: May 6, 2022
• First Posted (ACTUAL): May 11, 2022

Study Record Updates

• Last Update Posted (ACTUAL): May 11, 2022
• Last Update Submitted That Met QC Criteria: May 6, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: BTK inhibitor; Thrombopoietin-receptor agonist
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Zanubrutinib
• Other Study ID Numbers: Zan-Eltro-ITP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No