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

• ClinicalTrials.gov Identifier: NCT04346654
• Recruitment Status: Recruiting
• First Posted: April 15, 2020
• Last Update Posted: June 23, 2021
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Immune Thrombocytopenia (ITP)	Drug: Eltrombopag; Drug: Dexamethasone	Phase 2

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 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 106 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: October 9, 2020
• Estimated Primary Completion Date: October 3, 2022
• Estimated Study Completion Date: December 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Eltrombopag + Dexamethasone; 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.	Drug: Eltrombopag; Eltrombopag is for oral use and comes in 25, 50 and 75 mg tablets. Prescribed dose is taken once daily.; Other Name: ETB115; Drug: Dexamethasone; Dexamethasone is for oral use and comes in 8 mg tablets. Prescribed dose is taken once daily.
Active Comparator: Dexamethasone; Patients will be treated with a standard high-dose dexamethasone (1-3 cycles: 40 mg QD day 1-4 every 14-28 days) to induce sustained response off treatment	Drug: Dexamethasone; Dexamethasone is for oral use and comes in 8 mg tablets. Prescribed dose is taken once daily.

Outcome Measures

Primary Outcome Measures :

1. Percentage of patients with sustained response off treatment at 52 weeks [ Time Frame: Study treatment discontinuation until week 52 ]
   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

Secondary Outcome Measures :

1. Percentage of patients with overall response at Week 52 [ Time Frame: Study treatment discontinuation until 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
2. Duration of sustained response off treatment [ Time Frame: Study treatment discontinuation until lost of response (up to 78 weeks) ]
   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
3. Percentage of patients with sustained response off treatment at Week 78 [ Time Frame: Study treatment discontinuation until 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
4. Overall response by Week 4 [ Time Frame: Screening up to 4 weeks ]
   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
5. Complete response by Week 4 [ Time Frame: Baseline up to 4 weeks ]
   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
6. Absolute changes in platelet count from screening to baseline and toto various time points [ Time Frame: Screening, baseline, 1, 2, 4, 12, 26, and 52 weeks ]
   Absolute changes in platelet count from screening to baseline and to 1, 2, 4, 12, 26 and 52 weeks
7. Relative changes in platelet count from screening to baseline and to various time points [ Time Frame: Screening, baseline, 1, 2, 4, 12, 26, and 52 weeks ]
   Relative changes in platelet count from screening to baseline and to 1, 2, 4, 12, 26, and 52 weeks
8. Time to overall response [ Time Frame: Time from starting study treatment to achievement of overall response (up to 78 weeks) ]
   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
9. Time to complete response [ Time Frame: Time from starting study treatment to achievement of complete response (up to 78 weeks) ]
   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
10. Duration of overall and complete response [ Time Frame: Achievement of overall or complete response until lost of response (up to 78 weeks) ]
    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
11. Change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionaire [ Time Frame: Baseline to 1, 2, 4, 12, 26, and 52 weeks ]
    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
12. Change from baseline in Short Form 36 Health Survey (SF-36v2) questionaire [ Time Frame: Baseline to 1, 2, 4, 12, 26, and 52 weeks ]
    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
13. Incidence and severity of bleeding events [ Time Frame: Baseline up to 78 weeks ]
    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)

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. 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

Contacts and Locations

Contacts

Contact: Novartis Pharmaceuticals; +41613241111; novartis.email@novartis.com

Contact: Novartis Pharmaceuticals

Locations

Germany

Novartis Investigative Site; Recruiting

Regensburg, Bavaria, Germany, 93053

Novartis Investigative Site; Recruiting

Muenchen, Bayern, Germany, 80634

Novartis Investigative Site; Recruiting

Aachen, Germany, 52074

Novartis Investigative Site; Recruiting

Augsburg, Germany, 86179

Novartis Investigative Site; Recruiting

Berlin, Germany, 13353

Novartis Investigative Site; Recruiting

Chemnitz, Germany, 09113

Novartis Investigative Site; Recruiting

Donauwoerth, Germany, 86609

Novartis Investigative Site; Recruiting

Dortmund, Germany, 44263

Novartis Investigative Site; Recruiting

Dresden, Germany, 01307

Novartis Investigative Site; Recruiting

Frankfurt, Germany, 60590

Novartis Investigative Site; Recruiting

Frechen, Germany, 50226

Novartis Investigative Site; Recruiting

Giessen, Germany, 35392

Novartis Investigative Site; Recruiting

Goslar, Germany, 38642

Novartis Investigative Site; Recruiting

Halle Saale, Germany, 06112

Novartis Investigative Site; Recruiting

Heilbronn, Germany, 74072

Novartis Investigative Site; Recruiting

Jena, Germany, 07740

Novartis Investigative Site; Recruiting

Kiel, Germany, 24116

Novartis Investigative Site; Recruiting

Kronach, Germany, 96317

Novartis Investigative Site; Recruiting

Köln, Germany, 50674

Novartis Investigative Site; Recruiting

Oldenburg, Germany, 26121

Sponsors and Collaborators

Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04346654
• Other Study ID Numbers: CETB115JDE01
• First Posted: April 15, 2020
• Last Update Posted: June 23, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

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

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

ITP; Eltrombopag; Dexamethasone; Sustained response off treatment; TFR; Adult; ETB115; Platelets; Thrombocytopenic; Thrombopoietin receptor Agonist; Newly-diagnosed; Blood bleeding disorder

Additional relevant MeSH terms:

Thrombocytopenia; Immune System Diseases; Purpura, Thrombocytopenic, Idiopathic; Blood Platelet Disorders; Hematologic Diseases; Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Thrombotic Microangiopathies; Hemorrhagic Disorders; Autoimmune Diseases; Hemorrhage; Pathologic Processes; Skin Manifestations; Dexamethasone; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents