A Study to Assess Efficacy and Safety of Eltrombopag in Combination With a Short Course of Dexamethasone in Patients With Newly Diagnosed ITP

Immune Thrombocytopenia (ITP) Clinical Trial

— XPAG-ITP  

Official title:

A Phase II, Randomized (1:1) Open Label Study to Assess the Efficacy and Safety of Eltrombopag in Combination With Dexamethasone Compared to Dexamethasone, as First-line Treatment in Adult Patients With Newly Diagnosed Immune Thrombocytopenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04346654
• Other study ID #: CETB115JDE01
• Secondary ID: 2019-002658-21
• Status: Completed
• Phase: Phase 2
• Start date: October 9, 2020
• Est. completion date: September 22, 2023

Study information

• Verified date: January 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the ability of eltrombopag in combination with a short course of high-dose dexamethasone to induce sustained response off treatment in patients with newly-diagnosed ITP versus 1-3 cycles of dexamethasone monotherapy. The unmet clinical need and the potential for eltrombopag when added to steroids to improve the treatment outcome and the potential to induce sustained response off treatment serve as the basis for clinical investigation of eltrombopag in first-line ITP.

Description:

This is a Phase II, multicenter, 1:1 randomized, open-label study to compare the efficacy and safety of eltrombopag in combination with a short course of high-dose dexamethasone to 1-3 cycles of high-dose dexamethasone monotherapy, as first-line treatment in adult patients with newly diagnosed ITP. Adult patients with newly diagnosed ITP who have platelet counts < 30 × 109/L and require treatment will be screened, and if eligible, will be randomized to either Arm A (eltrombopag in combination with a short course of dexamethasone) or Arm B (1-3 cycles of dexamethasone monotherapy). The study will be conducted in the following periods: Screening Period: Patients will be screened for 14 days based on the inclusion and exclusion criteria Treatment Period: Arm A: Patients will be treated for 26 weeks during the treatment period. Patients who reach platelet counts ≥ 30 × 109/L and maintain counts ≥ 30 × 109/L during the tapering phase will be eligible for treatment discontinuation. Duration of tapering before treatment discontinuation at Week 26 will be 6 weeks. Arm B: Patients will be treated up to 12 weeks during the treatment period. Patients who reach platelet counts ≥ 30 × 109/L and maintain counts ≥ 30 × 109/L after 1-3 cycles of dexamethasone treatment will be eligible for treatment discontinuation. Patients with platelet counts < 30 × 109/L after 3 cycles of dexamethasone treatment will be offered a course of eltrombopag treatment within the study and will discontinue from study at week 52. Observation period: After completion of treatment period, all patients will be observed for sustained response off treatment until week 52. Only patients with sustained response at week 52 will be followed for another 26 weeks. Patients who relapse between Week 52 and Week 78 will discontinue the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: September 22, 2023
• Est. primary completion date: September 22, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

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

2. Men and women = 18 years of age

3. Newly diagnosed with primary ITP (time from diagnosis within 3 months)

4. Platelet count < 30 × 109/L at screening and a need for treatment (per physician's discretion) Note: If pre-treatment is necessary, platelet count data performed directly before pre-treatment (can be used for study inclusion (screening value). Treatment-naïve patients will be included based on their platelet counts performed at screening

Exclusion Criteria:

1. Previous history of treatment for ITP, except any ITP-directed therapy for a maximum of 3 days within 7 days before randomization

2. Patients with diagnosis of secondary thrombocytopenia

3. Patients who have life threatening bleeding complications per physician´s discretion

4. Patients with a history of thromboembolic events or known risk factors for thromboembolism

5. Serum creatinine > 1.5 mg/dL

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

7. Aspartate transaminase (AST) > 3.0 × ULN

8. Alanine transaminase (ALT) > 3.0 × ULN

9. Patients who are human immun deficiency virus (HIV),hepatitis C virus (HCV) or hepatitis B surface antigen (HBsAg) positive

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

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

12. History of current diagnosis of cardiac disease or impaired cardiac function denoted

13. Patients who have active malignancy

14. Patients with evidence of current alcohol/drug abuse

15. 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

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

Related Conditions & MeSH terms

• Immune Thrombocytopenia (ITP)
• Purpura, Thrombocytopenic, Idiopathic
• Thrombocytopenia

Intervention

Drug:
• Eltrombopag
Eltrombopag is for oral use and comes in 25, 50 and 75 mg tablets. Prescribed dose is taken once daily.
• Dexamethasone
Dexamethasone is for oral use and comes in 8 mg tablets. Prescribed dose is taken once daily.

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Aachen
Germany	Novartis Investigative Site	Aschaffenburg	Bayern
Germany	Novartis Investigative Site	Chemnitz
Germany	Novartis Investigative Site	Donauwoerth
Germany	Novartis Investigative Site	Dortmund
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Jena
Germany	Novartis Investigative Site	Kiel
Germany	Novartis Investigative Site	Kronach

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients with sustained response off treatment at 52 weeks	Sustained response off treatment at 52 weeks is defined as maintain platelet count = 30 × 109/L after treatment discontinuation in the absence of bleeding events = Grade II or use of any rescue medication at all visits until Week 52	Study treatment discontinuation until week 52
Secondary	Percentage of patients with overall response at Week 52	Overall response at week 52 is defined as platelet count = 30 × 109/L and = 2 fold increase of screeening platelets after treatment discontinuation in the absence of bleeding events = Grade II and no rescue therapy at all visits until Week 52	Study treatment discontinuation until week 52
Secondary	Duration of sustained response off treatment	Duration of sustained response off treatment is defined as time of treatment discontinuation until platelet count < 30 × 109/L or bleeding events = Grade II or use of any rescue therapy	Study treatment discontinuation until lost of response (up to 78 weeks)
Secondary	Percentage of patients with sustained response off treatment at Week 78	Sustained response off treatment at week 78 is defined as maintain platelet count = 30 × 109/L after treatment discontinuation in the absence of bleeding events = Grade II or use of any rescue medication at all visits until Week 78	Study treatment discontinuation until week 78
Secondary	Overall response by Week 4	Overall response by week 4 is defined as platelet count = 30 × 109/L and = 2 fold increase of screening platelet count and absence of bleeding and no rescue therapy at least once by Week 4	Screening up to 4 weeks
Secondary	Complete response by Week 4	Complete Response by week 4 is defined as platelet count = 100 × 109/L and absence of bleeding and no rescue therapy at least once by Week 4	Baseline up to 4 weeks
Secondary	Absolute changes in platelet count from screening to baseline and to various time points	Absolute changes in platelet count from screening to baseline and to 1, 2, 4, 12, 26 and 52 weeks	Screening, baseline, 1, 2, 4, 12, 26, and 52 weeks
Secondary	Relative changes in platelet count from screening to baseline and to various time points	Relative changes in platelet count from screening to baseline and to 1, 2, 4, 12, 26, and 52 weeks	Screening, baseline, 1, 2, 4, 12, 26, and 52 weeks
Secondary	Time to overall response	Time to overall response is defined as time from starting study treatment to time of achievement of overall response. Overall response is defined as a platelet count = 30 × 109/L and = 2 fold increase of baseline platelet count and absence of bleeding and no rescue therapy	Time from starting study treatment to achievement of overall response (up to 78 weeks)
Secondary	Time to complete response	Time to complete response is defined as time from starting study treatment to time of achievement of complete response. Complete response is defined as a platelet count = 100 × 109/L and absence of bleeding and no rescue therapy	Time from starting study treatment to achievement of complete response (up to 78 weeks)
Secondary	Duration of overall and complete response	Duration of overall or complete response is defined as time of achievement of overall or complete response (as defined above) until lost of overall or complete response	Achievement of overall or complete response until lost of response (up to 78 weeks)
Secondary	Change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionaire	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. Items are scored on a 0-4 response scale (4=not at all to 0=very much) where the total possible score ranges from 0-52 (alle items are summed up to create the total score); higher scores represent better HRQoL	Baseline to 1, 2, 4, 12, 26, and 52 weeks
Secondary	Change from baseline in Short Form 36 Health Survey (SF-36v2) questionaire	SF-36v2 is a validated instrument with 36 questions to measure general physical and mental health status 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. The SF-36 is scored using norm-based scoring procedures and scores ranging from 0-100; higher scores represent better HRQoL	Baseline to 1, 2, 4, 12, 26, and 52 weeks
Secondary	Incidence and severity of bleeding events	Incidence and severity of bleeding assessed by the modified World Health Organization (WHO) Bleeding Scale; Bleeding is graded based on a 1-4 scale (1=minor bleeding to 4=severe bleeding)	Baseline up to 78 weeks