A Study to Assess the Ability of Eltrombopag to Induce Sustained Remission in Subjects With ITP (TAPER)

• ClinicalTrials.gov Identifier: NCT03524612
• Recruitment Status: Active, not recruiting
• First Posted: May 15, 2018
• Last Update Posted: April 14, 2021
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

This study will assess the ability of eltrombopag to induce sustained treatment-free remission in ITP subjects who relapsed or failed to respond to an initial treatment with steroids.

There is limited, mainly retrospective evidence that earlier use of eltrombopag after ITP diagnosis, will allow a larger proportion of subjects to achieve sustained remission after tapering off drug. Clinically there is a need for a less toxic regimen that will provide responses and sustained remission with a shorter treatment interval. This trial is designed to assess this.

Condition or disease	Intervention/treatment	Phase
Immune Thrombocytopenic Purpura (ITP)	Drug: eltrombopag	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 105 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Open-label, Prospective, Single-arm, Study to Assess Ability of Eltrombopag to Induce Sustained Remission in Subjects With ITP Who Are Refractory or Relapsed After First-line Steroids
• Actual Study Start Date: November 2, 2018
• Estimated Primary Completion Date: November 30, 2022
• Estimated Study Completion Date: November 30, 2022

Arms and Interventions

Arm	Intervention/treatment
eltrombopag; Participants will be treated with eltrombopagto to induce sustained remission to reach a target platelet count of ≥ 100×109/L (CR), after 1st line steroids have failed.	Drug: eltrombopag; eltrombopag is for oral use and comes in 12.5, 25, 50 and 75 mg tablets; prescribed dose is taken once daily; Other Name: ETB115

Outcome Measures

Primary Outcome Measures :

1. Percentage of participants with sustained remission (R) by 12 months [ Time Frame: 12 months ]
   Sustained remission is defined as reach platelet count ≥ 100×109/L (complete response [CR]) and then maintain platelet counts around 100×109/L for 2 months (no counts below 70×109/L) AND then taper off the drug until treatment discontinuation while, maintain platelet count ≥ 30×109/L in the absence of bleeding (no bleeding AEs) or use of any rescue therapy until month 12.

Secondary Outcome Measures :

1. Median duration of sustained remission [ Time Frame: Last dose of eltrombopag to 12 months ]
   Duration of sustained remission (in weeks) counted from last dose of eltrombopag to month 12 for participants with sustained remission (R).
2. Percentage of participants with platelet count ≥ 50×109/L [ Time Frame: By 1 month ]
   Percentage of subjects who reach platelet count ≥ 50×109/L at least once within the first month (month 1) without bleeding events and no rescue therapy
3. Percentage of participants with at least one platelet count ≥ 30×109/L after eltrombopag is re-introduced without bleeding and no rescue medication [ Time Frame: 12 months ]
   Percentage of subjects with at least one platelet count ≥ 30×109/L after eltrombopag is re-introduced, in case of loss of response (< 30×109/L and/or bleeding event) without bleeding events and no rescue therapy
4. Absolute and relative change in platelet count from baseline to various time points [ Time Frame: Baseline 3, 6, 9, 12 months ]
   Quantify platelet count from baseline to different time points; box plots for absolute and/or relative change in platelet counts from baseline to different time points
5. Percentage of participants who maintain a platelet count ≥ 30×109/L without bleeding and no rescue medication [ Time Frame: From first time of reaching the level to 3, 6, 9, 12 months ]
   Ability of eltrombopag to maintain platelet count ≥ 30×109/L within 12 months.
6. Change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionaire [ Time Frame: Baseline to 3, 6, 9, 12 months ]
   The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) instrument is a 13-item validated tool used to measure an individual's level of fatigue during usual daily activities over the past 7 days (Cella 2002, Webster 2003). FACIT-Fatigue is a subscale of the FACIT measurement system. FACIT-fatigue is scored using a 4-point Likert scale (4=not at all fatigued to 0=very much fatigued) where the total possible score ranges from 0-5; higher scores represent better HRQoL.
7. Change from baseline in Functinal Assessment of Cancer Therapy- Thrombocytopenia (FACT-Th6) questionnaire [ Time Frame: Baseline to 3, 6, 9, 12 months ]
   FACT-Th6 instrument is used to measure worry/concern about bleeding and bruising, and the impact of this worry/concern on physical and social activity (Cella 2006). FACT-Th6 is a 6-item subset of the more detailed FACT-Th, which is an 18-item subscale of the validated FACT that specifically measures concerns related to thrombocytopenia in the past 7 days. The FACT-Th6 is scored using a 5-level Likert scale (0=not at all to 4=very much) and is calculated by summing scores for the 6-items; therefore, scores can range from 0-24, with higher scores representing better HRQoL
8. Change from baseline in Short Form 36 Health Survey (SF-36v2) questionnaire [ Time Frame: Baseline to 3, 6, 9, 12 months ]
   SF-36v2 is a validated instrument used to measure general physical and mental health status (Ware 2000) via assessment of 8 domains-Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, and Mental Health-over the past 4 weeks or 7 days. The SF-36 is scored using norm-based scoring procedures and scores ranging from 0-100; higher scores represent better HRQoL
9. Overall change from baseline of the overall impact of side effects on treatment via Functional Assessment of Cancer Therapy-G (GP5) [ Time Frame: Baseline, 12 months or end of study ]
   The GP5 is a single question used to assess the overall bothersomeness of treatment side effects. The GP5 is scored using a 5-point rating scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; and 4 = very much), where lower scores reflect less bothersomeness from treatment side effects.
10. Overall change of treatment satisfaction using Treatment Satisfaction Questionnaire (TSQM-9) [ Time Frame: Baseline, 12 months or end of study ]
    TSQM-9 will be used to assess treatment satisfaction with medication. The three scales of the TSQM-9 include the effectiveness scale, convenience scale, and global satisfaction scale

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Signed informed consent must be obtained prior to participation in the study
2. Subjects ≥ 18 years old
3. Subjects 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 < 30×109/L and assessed as needing treatment (per physician's discretion

Exclusion Criteria:

1. ITP subjects previously treated with any ITP second-line therapies, thrombopoietin receptor (TPO-R) agonists for ITP, except steroids / IVIG
2. Subjects who relapsed more than one year after the end of first-line full course of steroid therapy
3. Subjects with a diagnosis of secondary thrombocytopenia
4. Subjects who have life threatening bleeding complications per investigator discretion
5. Subjects 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. Subjects who are human immune deficiency virus (HIV), hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg) positive
11. Subjects with hepatic impairment (Child-Pugh score > 5)
12. Subjects who have active malignancy
13. Subjects 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 subjects participating in the study
15. Subjects with known active or uncontrolled infections not responding to appropriate therapy
16. Subjects 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 subjects 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

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

United States, New York

Hematology Oncology Association of Rockland Drug Shipment

Nyack, New York, United States, 10960

United States, Ohio

Case Western Reserve SC - 2

Cleveland, Ohio, United States, 44106-5000

Austria

Novartis Investigative Site

Linz, Austria, 4010

Brazil

Novartis Investigative Site

Salvador, BA, Brazil, 41253-190

Novartis Investigative Site

Rio de Janeiro, RJ, Brazil, 20211-030

Novartis Investigative Site

Sao Paulo, SP, Brazil

Chile

Novartis Investigative Site

Temuco, Araucania, Chile, 4810469

Novartis Investigative Site

Vina del Mar, Valparaiso, Chile, 2540364

France

Novartis Investigative Site

Caen Cedex, France, 14033

Novartis Investigative Site

Pessac Cedex, France, 33604

Greece

Novartis Investigative Site

Athens, Greece, 115 27

Novartis Investigative Site

Patras, Greece, 265 00

Italy

Novartis Investigative Site

Bologna, BO, Italy, 40138

Novartis Investigative Site

Trieste, TS, Italy, 34129

Japan

Novartis Investigative Site

Nagoya-city, Aichi, Japan, 466-8650

Mexico

Novartis Investigative Site

Guadalajara, Jalisco, Mexico, 44160

Novartis Investigative Site

Ciudad de Mexico, Mexico, 14000

Oman

Novartis Investigative Site

Muscat, Oman, 123

Russian Federation

Novartis Investigative Site

Moscow, Russian Federation, 125167

Novartis Investigative Site

St Petersburg, Russian Federation, 191024

Spain

Novartis Investigative Site

Salamanca, Castilla Y Leon, Spain, 37007

Novartis Investigative Site

Barcelona, Catalunya, Spain, 08035

Novartis Investigative Site

Majadahonda, Madrid, Spain, 28222

Novartis Investigative Site

Madrid, Spain, 28009

Novartis Investigative Site

Madrid, Spain, 28046

Novartis Investigative Site

Malaga, Spain, 29010

Novartis Investigative Site

Murcia, Spain, 30008

Switzerland

Novartis Investigative Site

Bern, Switzerland, 3010

Turkey

Novartis Investigative Site

Aydin, Turkey, 09100

Novartis Investigative Site

Edirne, Turkey, 22030

Novartis Investigative Site

Kocaeli, Turkey, 41380

United Kingdom

Novartis Investigative Site

London, United Kingdom, W12 0HS

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03524612
• Other Study ID Numbers: CETB115J2411; 2018-000452-18 ( EudraCT Number )
• First Posted: May 15, 2018
• Last Update Posted: April 14, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Thrombocytopenic; Immune; Platelets; Bleeding; ITP; eltrombopag; ETB115; induce sustained remission; refractory or relapsed; first-line steroids

Additional relevant MeSH terms:

Thrombocytopenia; Immune System Diseases; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic; Blood Coagulation Disorders; Hematologic Diseases; Hemorrhage; Pathologic Processes; Skin Manifestations; Thrombotic Microangiopathies; Blood Platelet Disorders; Hemorrhagic Disorders; Autoimmune Diseases