Dose tapering to withdrawal stage and long-term efficacy and safety of hetrombopag for the treatment of immune thrombocytopenia: Results from an open-label extension study

J Thromb Haemost. 2022 Mar;20(3):716-728. doi: 10.1111/jth.15602. Epub 2021 Dec 15.

Abstract

Background: The efficacy of hetrombopag in Chinese patients with immune thrombocytopenia (ITP) has been demonstrated in a randomized, double-blind, placebo-controlled, multicenter, phase III trial (NCT03222843).

Objective: This study aimed to report comprehensive data on a ≤6-week dose tapering to withdrawal (Stage 3) and an additional 24-week long-term extension period (Stage 4) in this phase III trial.

Patients/methods: Patients who fulfilled the screening criteria were eligible to enter Stage 3 or 4. During Stage 3, hetrombopag was gradually tapered to withdrawal. During Stage 4, hetrombopag treatment was initiated at 2.5, 3.75, 5, or 7.5 mg once daily. The efficacy endpoints during Stage 3 or 4 and the safety profile during the entire treatment period were reported.

Results: Among 194 patients who entered Stage 3, 171 (88.1%) relapsed. The median time to the first relapse since the start of Stage 3 was 15.0 days (95% CI, 14.0-16.0). In Stage 4, 144 (42.5%) patients responded at ≥75% of their assessments and 254 (74.9%) patients achieved platelet count ≥30 × 109 /L at least once, which was at least twice their baseline platelet count in the hetrombopag group (n = 339). The most common adverse events were upper respiratory tract infection (53.1%), thrombocytopenia (27.1%), and urinary tract infection (21.2%) in the hetrombopag group.

Conclusion: The majority of patients who experienced dose tapering to withdrawal experienced a relapse. Long-term treatment with hetrombopag was effective in increasing and maintaining platelet count within the desired range in Chinese adults with ITP. Hetrombopag was well tolerated.

Keywords: extension period; hetrombopag; immune thrombocytopenia; platelet response; thrombopoietin receptor agonist; withdrawal.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Double-Blind Method
  • Drug Tapering
  • Humans
  • Hydrazones
  • Purpura, Thrombocytopenic, Idiopathic* / diagnosis
  • Purpura, Thrombocytopenic, Idiopathic* / drug therapy
  • Pyrazolones* / therapeutic use
  • Thrombocytopenia* / chemically induced
  • Thrombocytopenia* / diagnosis
  • Thrombocytopenia* / drug therapy
  • Treatment Outcome

Substances

  • Hydrazones
  • Pyrazolones
  • hetrombopag

Associated data

  • ClinicalTrials.gov/NCT03222843