Proof-of-Concept: A Pilot, Randomized, Double-Blind Study of Oseltamivir Versus Placebo for Immune Thrombocytopenia

• Status: Recruiting
• Trial end date: 2021-09-01
• Target enrollment: 0
• Participant gender: All

Summary

Immune Thrombocytopenia (ITP) is a disorder resulting in impaired platelet production and enhanced destruction on the basis of autoantibody-mediated mechanisms. Patients with ITP are at increased risk of bleeding and infection. First line therapy includes glucocorticoids, with or without the addition of intravenous immune globulin (IVIg) when a prompt platelet response is desired. The likelihood of stable and safe disease after first-line treatment ranges from 30-60% and risk of relapse requiring additional therapy occurs in 50-80% of patients. Moreover, the toxicity associated with first and subsequent therapy for ITP is substantial.

Oseltamivir is an attractive drug for ITP since it specifically targets a pathophysiologic mechanism that appears to be important for the development of ITP and has a benign side effect profile compared to standard ITP therapy.

Oseltamivir has never been rigorously tested in humans to determine its efficacy in the management of ITP. The investigators therefore propose the first randomized, double blind study to assess the impact of oseltamivir on biological markers in adult patients with ITP. This study will also provide information about the feasibility of recruitment into a definitive trial, which would be coordinated by St. Michael's Hospital.

The research question is: Do adults (≥ 18 years) with ITP treated with oseltamivir at 75mg twice daily for 5 consecutive days have an increase in their mean platelet glycoprotein sialylation compared to those receiving placebo?

This pilot, proof-of-concept, randomized controlled clinical trial will enroll 30 individuals with ITP. Randomization and allocation will occur at a ratio of 1:1. Analysis of the primary outcome measure will occur via analysis of covariance (ANCOVA).

This study has the potential to dramatically change the treatment of ITP. If the results from this study demonstrate a biological effect, and results from the subsequent definitive study are positive, The investigators envision a move away from non-specific immune-blunting therapy such as prednisone, towards tailored therapy with oseltamivir. It could diminish the lifelong summative immunosuppressive therapy burden, associated drug toxicity and improve long- and short-term health outcomes for these patients.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: St. Michael's Hospital, Toronto; Unity Health Toronto
• Collaborators: Li Ka Shing Knowledge Institute; University of Toronto
• Treatments: Oseltamivir

Criteria

Inclusion Criteria:

• Patients ≥ 18 years of age;

• Patients with primary or secondary (i.e. ITP due to a secondary cause) ITP (autoimmune disorder characterized by isolated thrombocytopenia with no other causes or disorders that can be associated with thrombocytopenia; diagnosis of exclusion);

• Individuals with lack of sustained complete remission - platelet count <100 x E9/L despite first line therapy (prednisone, dexamethasone, IVIG);

• Patient's median platelet count over the last 12 months is <100 x E9/L, and must be <100 x E9/L on screening day.

Exclusion Criteria:

• Concurrent medical or surgical treatment for ITP (e.g. prednisone, dexamethasone, IVIG, anti-RhD immune globulin, azathioprine, cyclosporine, cyclophosphamide, danazol, dapsone, mycophenylate mofetil, rituximab, thrombopoietin mimetics, any investigational agents for ITP, splenectomy);

• Patient with a platelet count of <20 x E9/L with active significant bleeding based on a bleeding assessment score of Grade 2 at any site by the ITP Bleeding Scale (IBLS);

• Any immunosuppressive or immunomodulating therapy (not aforementioned) over the last 3 months;

• Oseltamivir therapy over the last 3 months;

• Pregnant females (oseltamivir is a class C drug in pregnancy);

• Lactating females (oseltamivir is detected in low quantities in breast milk).