Avatrombopag for the Treatment of Chemotherapy-Induced Thrombocytopenia in Adults With Active Non-Hematological Cancers

Phase 3

Completed

Brief Summary: Phase 3 randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of avatrombopag in subjects with chemotherapy-induced thrombocytopenia receiving chemotherapy for the treatment of ovarian, lung (small cell and non-small cell) and bladder cancer.

Detailed Description: Subjects will receive placebo controlled test treatment for one cycle of chemotherapy followed by an observational cycle. Subjects will have the option to continue into an open label extension period for all remaining chemotherapy cycles within the current regimen. After the follow-up visit, all subjects will continue to a long-term safety follow-up period.

Recruitment & Eligibility

Inclusion Criteria

Men and women greater than or equal to 18 years of age;
A diagnosis of ovarian, lung (small cell or non-small cell) or bladder cancer requiring systemic chemotherapy
Participant receiving a chemotherapy regimen given in a 21 or 28-day cycle, including 1 or more of the following agents or class of agents:
- Nucleoside analog, including gemcitabine and fluorouracil;
- Carboplatin or cisplatin;
- Anthracycline; or
- Alkylating agent;
Participant experienced severe thrombocytopenia, defined as 2 platelet counts <50 x 109/L measured at least 24 hours apart, during the qualifying chemotherapy cycle, of their current chemotherapy regimen
ECOG performance status <=2

Exclusion Criteria

Participant has experienced >=Grade 2 CIT other than during the current chemotherapy treatment regimen within 6 months of Screening;
Participant has any history of hematologic malignancies, including leukemia, myeloma, myeloproliferative disease, lymphoma, or myelodysplastic diseases;
Participant has received >2 previous lines of chemotherapy or is receiving whole brain radiation during the study treatment period;
Participant has a known medical history of genetic prothrombotic syndromes
Participant has a history of arterial or venous thrombosis within 3 months of screening;
Use of vitamin K antagonists;
Participant has previously received a thrombopoietin receptor agonist or recombinant human thrombopoietin for the treatment of CIT within 3 months of screening

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo Oral Tablet	Study is 2:1 randomization ratio (avatrombopag to placebo). Investigational product administered orally once daily for 5 days prior to chemotherapy and 5 days following chemotherapy treatment.
Avatrombopag	Avatrombopag	Study is 2:1 randomization ratio (avatrombopag to placebo). Investigational product administered orally once daily for 5 days prior to chemotherapy and 5 days following chemotherapy treatment.

Primary Outcome Measures

Name	Time	Method
Percentage of Subjects Who do Not Require Platelet Transfusion, Dose Reduction in Chemotherapy by 15%, or Chemotherapy Delay by >=4 Days	Randomization up to 33 days

Secondary Outcome Measures

Name	Time	Method
Duration of Severe Thrombocytopenia Defined as a Platelet Count <50 x 10^9/L	Randomization up to 33 days	The duration of severe thrombocytopenia is defined as the total number of days with a platelet count \<50×10\^9/L during the period after post-chemotherapy study drug treatment in Cycle X+1 through Chemotherapy Day of Cycle X+2.
Change in Platelet Count From Baseline (Nadir)	Randomization up to 33 days	Comparison of avatrombopag 60 mg vs. placebo, adjusted for the number of chemotherapy agents currently receiving per IWRS (1, ≥2). Cycle X nadir is defined as the lowest platelet count value prior to the first dose of study drug; Cycle X+1 nadir is defined as the lowest platelet count value during the period after post-chemotherapy study drug treatment in Cycle X+1 through Chemotherapy Day in Cycle X+2.
Percentage of Subjects Who Did Not Have Major or Non-major Clinically Relevant Bleeding During the Period After Post-chemotherapy Study Drug Treatment in Cycle X+1 Through Chemotherapy Day of Cycle X+2.	Randomization up to 33 days