The study is aimed to evaluate the efficacy of different doses of hetrombopag compared to placebo, measured by the proportion of subjects that can complete two planned consecutive chemotherapy cycles with no modification of chemotherapy regimen (i.e., delayed start, dose reduction, omission, or discontinuation) because of thrombocytopenia \[platelet count \<100×109/L\], to determine an optimal dose of hetrombopag and to demonstrate its superiority over placebo.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Stage 1: Hetrombopag lower dose; Hetrombopag higher dose Stage 2: Hetrombopag X mg (dose to be determined based on Stage 1 results)
Matching placebo(Stage 1;Stage 2)
Proportion of treatment "responders" who do not require modification of chemotherapy regimen because of thrombocytopenia (PC <100×109/L) during two planned consecutive chemotherapy cycles without the use of rescue treatment.
Cochran-Mantel-Haenszel (CMH) test will be used to make a comparison between each hetrombopag group and the placebo group.
Time frame: 56 days after the first dose of study drug
Time to first platelet response, defined by PC ≥100×109/L.
Will be analyzed by a log-rank test stratified by the randomization stratification factors. The Kaplan-Meier (KM) method will be used to describe the time-to-event data.
Time frame: 56 days after the first dose of study drug
Proportion of subjects achieving PC ≥100×109/L.
Will be analyzed with the CMH test
Time frame: 14 days after the first dose of study drug
Time duration of PC ≥100×109/L.
Will be analyzed with the log rank test and KM plots
Time frame: 42 days after the start of the first chemotherapy cycle
PC nadir from the start of the first on-study chemotherapy cycle through the end of the double-blind treatment period.
An Analysis of Covariance (ANCOVA) will be used.
Time frame: 42 days after the start of the first chemotherapy cycle]
Time duration of severe thrombocytopenia, defined as a PC of 50×109/L
Will be analyzed with the log rank test and KM plots.
Time frame: 56 days after the first dose of study drug
Proportion of subjects without serious bleeding events, defined as grade ≥ 2, according to the World Health Organization Bleeding scale.
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Will be analyzed with the CMH test.
Time frame: 56 days after the first dose of study drug
Proportion of subjects with at least single incidence of platelet transfusion or other rescue treatment.
Will be analyzed with the CMH test.
Time frame: 56 days after the first dose of study drug
Proportion of patients without chemotherapy regimen modifications due to any cause.
Will be analyzed with the CMH test.
Time frame: 14 days after the first dose of study drug
Number adverse events (AEs) as assessed by CTCAE v5.0.
Arithmetic summary statistics will be provided.
Time frame: up to 140 days of treatment with study drug plus 6 months of follow-up.