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

NCT03520049 | Unknown Phase 3

• 1 other identifier: ITP30
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Immune Thrombocytopenia

Keywords

Thrombocytopenia; ITP; Platelets; Bleeding; Immune; Oseltamivir; Glycoprotein; Sialylation; Antibody; Autoantibody

Outcome Measures

Primary Outcomes (1)

• Mean platelet glycoprotein sialyation

  Mean platelet glycoprotein sialyation

  Day 0 and Day 5

Secondary Outcomes (11)

• Percentage of eligible patients successfully recruited

  Screening and Day 0

• Number of patients recruited per month

  Screening and Day 0

• Percentage of patients who received the study drug within 12 hours of randomization

  Day 0

• Percentage of patients who received every scheduled dose of the study drug in a blinded fashion

  Day 0 and Day 5

• Percentage of patients who had complete follow-up 12 months after randomization

  Day 0, Day 5 and Follow up

Study Arms (2)

Oseltamivir

EXPERIMENTAL

Oseltamivir capsule administered orally at 75 mg twice daily for five consecutive days.

Drug: Oseltamivir

Placebo

PLACEBO COMPARATOR

Placebo capsule administered orally twice daily for five consecutive days.

Drug: Placebo

Interventions

Oseltamivir DRUG

Also known as: Oseltamivir phosphate, Tamiflu®

Oseltamivir

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients ≥ 18 years of age;
• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Unity Health Toronto: lead
• Li Ka Shing Knowledge Institute: collaborator
• University of Toronto: collaborator

Study Sites (1)

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

RECRUITING

Related Publications (2)

• Li J, van der Wal DE, Zhu G, Xu M, Yougbare I, Ma L, Vadasz B, Carrim N, Grozovsky R, Ruan M, Zhu L, Zeng Q, Tao L, Zhai ZM, Peng J, Hou M, Leytin V, Freedman J, Hoffmeister KM, Ni H. Desialylation is a mechanism of Fc-independent platelet clearance and a therapeutic target in immune thrombocytopenia. Nat Commun. 2015 Jul 17;6:7737. doi: 10.1038/ncomms8737.

  PMID: 26185093 BACKGROUND

• Shao L, Wu Y, Zhou H, Qin P, Ni H, Peng J, Hou M. Successful treatment with oseltamivir phosphate in a patient with chronic immune thrombocytopenia positive for anti-GPIb/IX autoantibody. Platelets. 2015;26(5):495-7. doi: 10.3109/09537104.2014.948838. Epub 2014 Aug 28.

  PMID: 25166956 BACKGROUND

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Hemorrhage

Interventions

Oseltamivir

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2017
• First Posted: May 9, 2018
• Study Start: November 1, 2016
• Primary Completion: September 1, 2021
• Study Completion: September 1, 2021
• Last Updated: October 22, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)