Back to resultsA Study to Assess Efficacy and Safety of Eltrombopag in Combination With a Short Course of Dexamethasone in Patients With Newly Diagnosed ITP (XPAG-ITP)
Primary Purpose
Immune Thrombocytopenia (ITP)
Status
Active
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Eltrombopag
Dexamethasone
Sponsored by
About this trial
This is an interventional treatment trial for Immune Thrombocytopenia (ITP) focused on measuring ITP, Eltrombopag, Dexamethasone, Sustained response off treatment, TFR, Adult, ETB115, Platelets, Thrombocytopenic, Thrombopoietin receptor Agonist, Newly-diagnosed, Blood bleeding disorder
Eligibility Criteria
Inclusion Criteria:
- Signed informed consent must be obtained prior to participation in the study.
- Men and women ≥ 18 years of age
- Newly diagnosed with primary ITP (time from diagnosis within 3 months)
- 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:
- Previous history of treatment for ITP, except any ITP-directed therapy for a maximum of 3 days within 7 days before randomization
- Patients with diagnosis of secondary thrombocytopenia
- Patients who have life threatening bleeding complications per physician´s discretion
- Patients with a history of thromboembolic events or known risk factors for thromboembolism
- Serum creatinine > 1.5 mg/dL
- Total bilirubin (TBIL) > 1.5 × upper limit of normal (ULN)
- Aspartate transaminase (AST) > 3.0 × ULN
- Alanine transaminase (ALT) > 3.0 × ULN
- Patients who are human immun deficiency virus (HIV),hepatitis C virus (HCV) or hepatitis B surface antigen (HBsAg) positive
- Patients with hepatic impairment (Child-Pugh score > 5)
- Patients with known active or uncontrolled infections not responding to appropriate therapy
- History of current diagnosis of cardiac disease or impaired cardiac function denoted
- Patients who have active malignancy
- Patients with evidence of current alcohol/drug abuse
- 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
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Eltrombopag + Dexamethasone
Dexamethasone
Arm 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.
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
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
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
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
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
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
Absolute changes in platelet count from screening to baseline and toto various time points
Absolute changes in platelet count from screening to baseline and to 1, 2, 4, 12, 26 and 52 weeks
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
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 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
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
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
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
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)
Full Information
NCT ID
NCT04346654
First Posted
April 12, 2020
Last Updated
October 16, 2023
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT04346654
Brief Title
A Study to Assess Efficacy and Safety of Eltrombopag in Combination With a Short Course of Dexamethasone in Patients With Newly Diagnosed ITP
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 9, 2020 (Actual)
Primary Completion Date
January 3, 2024 (Anticipated)
Study Completion Date
January 3, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Immune Thrombocytopenia (ITP)
Keywords
ITP, Eltrombopag, Dexamethasone, Sustained response off treatment, TFR, Adult, ETB115, Platelets, Thrombocytopenic, Thrombopoietin receptor Agonist, Newly-diagnosed, Blood bleeding disorder
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Eltrombopag + Dexamethasone
Arm Type
Experimental
Arm 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.
Arm Title
Dexamethasone
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Eltrombopag
Other Intervention Name(s)
ETB115
Intervention Description
Eltrombopag is for oral use and comes in 25, 50 and 75 mg tablets. Prescribed dose is taken once daily.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Dexamethasone is for oral use and comes in 8 mg tablets. Prescribed dose is taken once daily.
Primary Outcome Measure Information:
Title
Percentage of patients with sustained response off treatment at 52 weeks
Description
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
Time Frame
Study treatment discontinuation until week 52
Secondary Outcome Measure Information:
Title
Percentage of patients with overall response at Week 52
Description
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
Time Frame
Study treatment discontinuation until week 52
Title
Duration of sustained response off treatment
Description
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
Time Frame
Study treatment discontinuation until lost of response (up to 78 weeks)
Title
Percentage of patients with sustained response off treatment at Week 78
Description
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
Time Frame
Study treatment discontinuation until week 78
Title
Overall response by Week 4
Description
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
Time Frame
Screening up to 4 weeks
Title
Complete response by Week 4
Description
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
Time Frame
Baseline up to 4 weeks
Title
Absolute changes in platelet count from screening to baseline and toto various time points
Description
Absolute changes in platelet count from screening to baseline and to 1, 2, 4, 12, 26 and 52 weeks
Time Frame
Screening, baseline, 1, 2, 4, 12, 26, and 52 weeks
Title
Relative changes in platelet count from screening to baseline and to various time points
Description
Relative changes in platelet count from screening to baseline and to 1, 2, 4, 12, 26, and 52 weeks
Time Frame
Screening, baseline, 1, 2, 4, 12, 26, and 52 weeks
Title
Time to overall response
Description
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 Frame
Time from starting study treatment to achievement of overall response (up to 78 weeks)
Title
Time to complete response
Description
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 Frame
Time from starting study treatment to achievement of complete response (up to 78 weeks)
Title
Duration of overall and complete response
Description
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
Time Frame
Achievement of overall or complete response until lost of response (up to 78 weeks)
Title
Change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionaire
Description
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
Time Frame
Baseline to 1, 2, 4, 12, 26, and 52 weeks
Title
Change from baseline in Short Form 36 Health Survey (SF-36v2) questionaire
Description
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
Time Frame
Baseline to 1, 2, 4, 12, 26, and 52 weeks
Title
Incidence and severity of bleeding events
Description
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)
Time Frame
Baseline up to 78 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed informed consent must be obtained prior to participation in the study.
Men and women ≥ 18 years of age
Newly diagnosed with primary ITP (time from diagnosis within 3 months)
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:
Previous history of treatment for ITP, except any ITP-directed therapy for a maximum of 3 days within 7 days before randomization
Patients with diagnosis of secondary thrombocytopenia
Patients who have life threatening bleeding complications per physician´s discretion
Patients with a history of thromboembolic events or known risk factors for thromboembolism
Serum creatinine > 1.5 mg/dL
Total bilirubin (TBIL) > 1.5 × upper limit of normal (ULN)
Aspartate transaminase (AST) > 3.0 × ULN
Alanine transaminase (ALT) > 3.0 × ULN
Patients who are human immun deficiency virus (HIV),hepatitis C virus (HCV) or hepatitis B surface antigen (HBsAg) positive
Patients with hepatic impairment (Child-Pugh score > 5)
Patients with known active or uncontrolled infections not responding to appropriate therapy
History of current diagnosis of cardiac disease or impaired cardiac function denoted
Patients who have active malignancy
Patients with evidence of current alcohol/drug abuse
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
Facility Information:
Facility Name
Novartis Investigative Site
City
Aschaffenburg
State/Province
Bayern
ZIP/Postal Code
63739
Country
Germany
Facility Name
Novartis Investigative Site
City
Aachen
ZIP/Postal Code
52074
Country
Germany
Facility Name
Novartis Investigative Site
City
Chemnitz
ZIP/Postal Code
09113
Country
Germany
Facility Name
Novartis Investigative Site
City
Donauwoerth
ZIP/Postal Code
86609
Country
Germany
Facility Name
Novartis Investigative Site
City
Dortmund
ZIP/Postal Code
44263
Country
Germany
Facility Name
Novartis Investigative Site
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Novartis Investigative Site
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
Novartis Investigative Site
City
Jena
ZIP/Postal Code
07740
Country
Germany
Facility Name
Novartis Investigative Site
City
Kiel
ZIP/Postal Code
24116
Country
Germany
Facility Name
Novartis Investigative Site
City
Kronach
ZIP/Postal Code
96317
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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
Learn more about this trial
A Study to Assess Efficacy and Safety of Eltrombopag in Combination With a Short Course of Dexamethasone in Patients With Newly Diagnosed ITP
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