A randomized trial of avatrombopag, an investigational thrombopoietin-receptor agonist, in persistent and chronic immune thrombocytopenia.

Abstract

Stimulation of platelet production by thrombopoietin-receptor agonists (TPO-RAs) is an effective second-line treatment in immune thrombocytopenia (ITP). This 28-day phase 2 study assigned subjects with ITP of ≥3 months to once-daily oral avatrombopag (2.5, 5, 10, or 20 mg), an investigational nonpeptide TPO-RA active in humans, or placebo; subjects completing randomized treatment could enroll in a 24-week extension study. Of 64 randomized subjects, 13% (avatrombopag 2.5 mg), 53% (5 mg), 50% (10 mg), and 80% (20 mg), vs 0% for placebo, achieved a platelet count (PC) response of ≥50 × 10(9)/L with ≥20 × 10(9)/L increase above baseline at day 28. Fifty-three subjects (83%) entered the extension: 52% and 76% had a durable (PC response at ≥75% of their platelet assessments over the last 14 weeks) and overall (stable response or response at any ≥2 consecutive visits) response, respectively. All subjects experienced ≥1 adverse event (AE) (most commonly fatigue, headache, and epistaxis); 19% (n = 12) reported ≥1 serious AE; 10 (16%) withdrew due to an AE (5 due to increased PC). Avatrombopag was active and generally well tolerated, with PC response rates and AE incidence comparable with other TPO-RAs. These studies were registered at www.clinicaltrials.gov as #NCT00441090 and #NCT00625443.

• Authors: James B Bussel, David J Kuter, Louis M Aledort, Craig M Kessler, Adam Cuker, Kelly B Pendergrass, Shande Tang, Joe McIntosh
• Journal: Blood (Blood) Vol. 123 Issue 25 Pg. 3887-94 (Jun 19 2014) ISSN: 1528-0020 [Electronic] United States
• PMID: 24802775 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 by The American Society of Hematology.

Chemical References

• Drugs, Investigational
• Receptors, Thrombopoietin
• Thiazoles
• Thiophenes
• avatrombopag

Topics

• Administration, Oral
• Adult
• Aged
• Chronic Disease
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drugs, Investigational (administration & dosage, adverse effects, therapeutic use)
• Epistaxis (chemically induced)
• Fatigue (chemically induced)
• Female
• Headache (chemically induced)
• Humans
• Male
• Middle Aged
• Platelet Count
• Purpura, Thrombocytopenic, Idiopathic (drug therapy, pathology)
• Receptors, Thrombopoietin (agonists)
• Thiazoles (administration & dosage, adverse effects, therapeutic use)
• Thiophenes (administration & dosage, adverse effects, therapeutic use)
• Time Factors
• Treatment Outcome