A Phase II Study to Assess the Sustained Response Off Treatment in Patients with ITP Receiving Eltrombopag, Who Had a Previous Insufficient Response to Corticosteroids (TAPER): A Recruitment Update
Authors: Cooper Nichola , Ghanima Waleed , Haenig Jens , Lee James , Rahman Masiur , Zaja Francesco 
Published: November 2020

Corticosteriods (CSs) remain the standard of care for immune thrombocytopenia (ITP); however, many patients relapse after initial treatment, and long-term CS use is associated with considerable toxicity and tolerability issues (Provan et al. Blood 2010). Clinically, there is a need for a less toxic regimen that will provide sustained response. Eltrombopag is a thrombopoietin receptor agonist (TPO-RA) currently approved in the United States for the treatment of ITP in patients who have had an insufficient response to CSs, immunoglobulins, or splenectomy. Limited evidence from retrospective studies and the phase II ESTIT study (NCT02402998) suggests that earlier use of TPO-RAs after ITP diagnosis may allow a larger proportion of patients to achieve sustained responses after tapering off drug (Červinek et al. Int J Hematol 2015; Gonzalez-Lopez et al. Am J Hematol 2015; Newland et al. Br J Haematol 2016; Lucchini, et al. Haematologica 2019). TAPER (NCT03524612) is an ongoing phase II, open-label, prospective, single-arm study assessing sustained response off treatment in adult patients with ITP receiving eltrombopag, who had relapsed or failed to respond to initial CS treatment.

Eligible patients are adults (≥ 18 years old) with ITP who are not responsive to or are in relapse after first-line CS therapy ± immunoglobulins used as rescue therapy, with platelet counts &lt; 30×109/L, and assessed as needing treatment. Patients receive a starting dose of 50 mg eltrombopag QD (East/Southeast Asian ancestry: 25 mg QD; Japanese patients treated in Japan: 12.5 mg QD per approved starting dose in the Japanese prescribing information).

The primary endpoint is the number (%) of patients with sustained responses off treatment by Month 12. Sustained response is defined as a complete response (platelet count ≥ 100×109/L) with platelet counts ≥ 70×109/L maintained for 2 months, followed by dose reduction and treatment discontinuation while maintaining platelet counts ≥ 30×109/L, without bleeding or rescue therapy, until Month 12. Platelet counts are assessed weekly during the first 8 weeks of treatment, and biweekly thereafter, depending on patient response. Rescue therapy is permitted within the first 14 days of study treatment and does not preclude patients from reaching the primary endpoint criteria, if successful discontinuation of eltrombopag is reached and maintained at Month 12.

The proportion of patients who reach the primary endpoint will be summarized with the 95% confidence interval (Clopper-Pearson method). A binomial test for one proportion, H0: P = 0.15 vs. H1: P &gt; 0.15 will be performed to test if the proportion of remission patients is greater than 15%, using a target alpha level of 0.05. Patients who meet the primary endpoint at 12 months will be followed up for an additional 12 months.Patients who relapse between Months 12 and 24 will be offered retreatment with eltrombopag until the end of Month 24. Secondary endpoints will include measures of quality of life, and exploratory endpoints will include biomarker assessments of immunomodulation.

Here, we report an update on trial recruitment and patient baseline characteristic data from an early data cut (November 15, 2019). An estimated 101 patients across 50 sites will be enrolled; 47 sites are currently active and 3 are pending site initiation visits. As of November 15, 2019, 66 patients had been screened, 53 of whom had been enrolled and had undergone treatment. Of the patients enrolled, 60.4% were female and the mean (± standard deviation) age was 49.4 (± 19.0) years. The majority of patients were White (88.7%). On June 24, 2020, patients from 15 countries worldwide were committed to screening (Figure 1); the number of patients screened had risen to 98, with 82 patients enrolled. The planned study timeline has been disrupted due to the COVID-19 pandemic. Enrollment is expected to complete in November 2020, with final results expected in 2023.

Conclusion: The purpose of this trial is to assess sustained response off treatment following eltrombopag therapy in patients with ITP who failed to respond to or have relapsed after initial treatment with steroids. The data generated by TAPER will provide insights into whether eltrombopag could be a viable treatment option after first-line steroid treatment. If this were confirmed, the earlier use of eltrombopag could have the potential to reduce the toxicity from repeated steroid exposure in patients with ITP.

Disclosures

Cooper: Novartis: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Ghanima:Amgen: Honoraria, Speakers Bureau; Bristol Myers Squibb: Research Funding; Bayer: Research Funding; Novartis: Honoraria, Speakers Bureau; Principia: Honoraria, Speakers Bureau; Pfizer: Honoraria, Research Funding, Speakers Bureau. Haenig:Novartis: Current Employment. Lee:Novartis: Current Employment, Other: Novartis AG equity holder. Rahman:Novartis: Other: Full time employee of IQVIA which provides services to Novartis; IQVIA: Current Employment. Zaja:Kyowa Kirin: Honoraria, Speakers Bureau; Mundipharma: Honoraria, Speakers Bureau; Novartis: Honoraria, Patents & Royalties: Pending patent (No. PAT058521) relating to TAPER trial (NCT03524612), Speakers Bureau; Roche: Honoraria, Speakers Bureau; AbbVie: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Grifols: Honoraria, Speakers Bureau; Bristol Myers Squibb: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Janssen-Cilag: Honoraria, Speakers Bureau.