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

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

Sponsors

Lead Sponsor: Novartis Pharmaceuticals

Source Novartis
Brief 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.

Detailed 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 for 40 weeks 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.

Overall Status Recruiting
Start Date October 9, 2020
Completion Date December 31, 2023
Primary Completion Date October 3, 2022
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Percentage of patients with sustained response off treatment at 52 weeks Study treatment discontinuation until week 52
Secondary Outcome
Measure Time Frame
Percentage of patients with overall response at Week 52 Study treatment discontinuation until week 52
Duration of sustained response off treatment Study treatment discontinuation until lost of response (up to 78 weeks)
Percentage of patients with sustained response off treatment at Week 78 Study treatment discontinuation until week 78
Overall response by Week 4 Baseline up to 4 weeks
Complete response by Week 4 Baseline up to 4 weeks
Absolute changes in platelet count from baseline to various time points Baseline, 1, 2, 4, 12, 26, and 52 weeks
Relative changes in platelet count from baseline to various time points Baseline, 1, 2, 4, 12, 26, and 52 weeks
Time to overall response Time from starting treatment to achievement of overall response (up to 78 weeks)
Time to complete response Time from starting treatment to achievement of complete response (up to 78 weeks)
Duration of overall and complete response Achievement of overall or complete response until lost of response (up to 78 weeks)
Change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionaire Baseline to 1, 2, 4, 12, 26, and 52 weeks
Change from baseline in Short Form 36 Health Survey (SF-36v2) questionaire Baseline to 1, 2, 4, 12, 26, and 52 weeks
Incidence and severity of bleeding events Baseline up to 78 weeks
Enrollment 106
Condition
Intervention

Intervention Type: Drug

Intervention Name: Eltrombopag

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

Arm Group Label: Eltrombopag + Dexamethasone

Other Name: ETB115

Intervention Type: Drug

Intervention Name: Dexamethasone

Description: Dexamethasone is for oral use and comes in 8 mg tablets. Prescribed dose is taken once daily.

Eligibility

Criteria:

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 and a need for treatment (per physician's discretion)

Exclusion Criteria:

1. Previous history of treatment for ITP, except any ITP-directed therapy 3 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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Contact

Last Name: Novartis Pharmaceuticals

Phone: +41613241111

Email: [email protected]

Location
Facility: Status:
Novartis Investigative Site | Berlin, 13353, Germany Recruiting
Novartis Investigative Site | Jena, 07740, Germany Recruiting
Location Countries

Germany

Verification Date

October 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Eltrombopag + Dexamethasone

Type: Experimental

Description: Patients will be treated with eltrombopag in combination with a standard high-dose dexamethasone (1 cycle: 40 mg QD from day 1-4) to induce sustained response off treatment.

Label: Dexamethasone

Type: Active Comparator

Description: Patients will be treated with a standard high-dose dexamethasone (1-3 cycles: 40 mg QD day 1-4 every 28 days) to induce sustained response off treatment

Acronym XPAG-ITP
Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov