A Study to Assess the Ability of Eltrombopag to Induce Sustained Response Off Treatment in Subjects With ITP

NCT ID: NCT03524612

Last Updated: 2025-01-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-02
• Study Completion Date: 2022-10-03

Brief Summary

The purpose of this trial was to assess the ability of eltrombopag to induce sustained treatment-free remission in immune thrombocytopenia purpura (ITP) subjects who relapsed or failed to respond to an initial treatment with steroids.

Detailed Description

Protocol Amendment 01 added a follow-up period of 12 months for patients with sustained response off treatment at month 12 to obtain further data on response duration.

The starting dose was eltrombopag 50 mg daily (25 mg daily for Asian patients and 12.5 mg daily for Japanese patients in Japan). The starting dose for this study was consistent with the dosing guidelines approved for eltrombopag use in ITP. An increase of eltrombopag dose up to 75 mg was allowed for patients who did not respond to standard-dosage treatment and to reduce the risk of bleeding. The rationale for this increased dose was to use the minimal efficacious dosage of eltrombopag in order to achieve a platelet count ≥ 100×10^9/L and maintain it around 100×10^9/L (no counts below 70×10^9/L) for 2 months in order to allow patients to start the eltrombopag tapering and withdrawal process.

Patients who reached a platelet count of >= 100 × 10^9/L and maintained counts around 100×10^9/L for 2 months with no platelet count < 70 × 10^9/L were eligible for tapering-off and treatment discontinuation, which occurred via 25 mg reduction every 2 weeks up to 25 mg on alternate days for 2 weeks until treatment discontinuation.

Patients who successfully discontinue eltrombopag and maintained platelet count >= 30 × 10^9/L in the absence of bleeding or use of rescue therapy were followed to month 12. If a relapse (defined as platelet count <30 × 10^9/L) occurred during the 12-month treatment period, they were offered a new course of eltrombopag treatment within this timeframe at the appropriate starting dose. If a patient relapsed in the post 12-month follow-up period, no further attempts for tapering and achieving sustained response off treatment were made.

The taper-off scheme followed recommendations within the current established dosing regimen for when to consider dose adjustment.

Conditions

Immune Thrombocytopenic Purpura (ITP)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

eltrombopag

Participants were treated with eltrombopag to induce sustained response off treatment to reach a target platelet count of \>=100×10\^9/L (CR), after 1st line steroids had failed.

Group Type: OTHER

eltrombopag

Intervention Type: DRUG

12.5, 25, 50 and 75 mg tablets for oral use once daily

Interventions

eltrombopag

12.5, 25, 50 and 75 mg tablets for oral use once daily

Intervention Type: DRUG

Other Intervention Names

ETB115

Eligibility Criteria

Inclusion Criteria

1. Signed informed consent must be obtained prior to participation in the study

2. Patients ≥ 18 years old

3. Patients with a confirmed diagnosis of primary ITP, who are not responsive or in relapse after a first line of steroid therapy ± intravenous immunoglobulin (IVIG) (used as a rescue therapy)

4. Platelet count < 30×10^9/L and assessed as needing treatment (per physician's discretion

Exclusion Criteria

1. ITP patients previously treated with any ITP second-line therapies, thrombopoietin receptor (TPO-R) agonists for ITP, except steroids / IVIG

2. Patients who relapsed more than one year after the end of first-line full course of steroid therapy

3. Patients with a diagnosis of secondary thrombocytopenia

4. Patients who have life threatening bleeding complications per investigator discretion

5. Patients who had a deep vein thrombosis or arterial thrombosis in the 6 months preceding enrollment

6. Serum creatinine ≥ 1.5 mg/dL

7. Total bilirubin > 1.5 × upper limit of normal (ULN)

8. Aspartate transaminase (AST) > 3.0 × ULN

9. Alanine transaminase (ALT) > 3.0 × ULN

10. Patients who are human immune deficiency virus (HIV), hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg) positive

11. Patients with hepatic impairment (Child-Pugh score > 5)

12. Patients who have active malignancy

13. Patients with any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions that could interfere with subject's safety, obtaining informed consent or compliance with the study procedures per investigator discretion

14. History or current diagnosis of cardiac disease indicating significant risk of safety for Patients participating in the study

15. Patients with known active or uncontrolled infections not responding to appropriate therapy

16. Patients with evidence of current alcohol/drug abuse

17. Women of child-bearing potential and sexually active males unwilling to use adequate contraception during the study

18. Female Patients who are nursing or pregnant (positive serum or urine B-human chorionic gonadotrophin (B-hCG) pregnancy test) at screening or pre-dose on Day 1

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Hematology Oncology Association of Rockland

Nyack, New York, United States

Case Western Reserve

Cleveland, Ohio, United States

Novartis Investigative Site

Linz, , Austria

Novartis Investigative Site

Salvador, Estado de Bahia, Brazil

Novartis Investigative Site

Rio de Janeiro, Rio de Janeiro, Brazil

Novartis Investigative Site

São Paulo, São Paulo, Brazil

Novartis Investigative Site

Temuco, Región de la Araucanía, Chile

Novartis Investigative Site

Viña del Mar, Región de Valparaíso, Chile

Novartis Investigative Site

Caen, , France

Novartis Investigative Site

Pessac, , France

Novartis Investigative Site

Athens, , Greece

Novartis Investigative Site

Pátrai, , Greece

Novartis Investigative Site

Bologna, BO, Italy

Novartis Investigative Site

Trieste, TS, Italy

Novartis Investigative Site

Nagoya, Aichi-ken, Japan

Novartis Investigative Site

Guadalajara, Jalisco, Mexico

Novartis Investigative Site

Mexico City, , Mexico

Novartis Investigative Site

Muscat, , Oman

Novartis Investigative Site

Moscow, , Russia

Novartis Investigative Site

Saint Petersburg, , Russia

Novartis Investigative Site

Málaga, Andalusia, Spain

Novartis Investigative Site

Salamanca, Castille and León, Spain

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Murcia, , Spain

Novartis Investigative Site

Bern, , Switzerland

Novartis Investigative Site

Aydin, , Turkey (Türkiye)

Novartis Investigative Site

Edirne, , Turkey (Türkiye)

Novartis Investigative Site

Kocaeli, , Turkey (Türkiye)

Novartis Investigative Site

London, , United Kingdom

Countries

United States; Austria; Brazil; Chile; France; Greece; Italy; Japan; Mexico; Oman; Russia; Spain; Switzerland; Turkey (Türkiye); United Kingdom

References

Cooper N, Ghanima W, Vianelli N, Valcarcel D, Yavasoglu I, Melikyan A, Ruiz EY, Haenig J, Somenzi O, Lee J, Clark J, Zhang Y, Zaja F. Sustained response off-treatment in eltrombopag-treated adult patients with ITP who are refractory or relapsed after first-line steroids: Primary, final, and ad-hoc analyses of the Phase II TAPER trial. Am J Hematol. 2024 Jan;99(1):57-67. doi: 10.1002/ajh.27131. Epub 2023 Nov 28.

Reference Type: DERIVED

PMID: 38014779 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-000452-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CETB115J2411

Identifier Type: -

Identifier Source: org_study_id