- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04346654
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)
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
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.
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Aachen, Germany, 52074
- Novartis Investigative Site
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Chemnitz, Germany, 09113
- Novartis Investigative Site
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Donauwoerth, Germany, 86609
- Novartis Investigative Site
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Dortmund, Germany, 44263
- Novartis Investigative Site
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Dresden, Germany, 01307
- Novartis Investigative Site
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Frankfurt, Germany, 60590
- Novartis Investigative Site
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Jena, Germany, 07740
- Novartis Investigative Site
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Kiel, Germany, 24116
- Novartis Investigative Site
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Kronach, Germany, 96317
- Novartis Investigative Site
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Bayern
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Aschaffenburg, Bayern, Germany, 63739
- Novartis Investigative Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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.
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Eltrombopag is for oral use and comes in 25, 50 and 75 mg tablets.
Prescribed dose is taken once daily.
Other Names:
Dexamethasone is for oral use and comes in 8 mg tablets.
Prescribed dose is taken once daily.
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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
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Dexamethasone is for oral use and comes in 8 mg tablets.
Prescribed dose is taken once daily.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of patients with sustained response off treatment at 52 weeks
Time Frame: Study treatment discontinuation until week 52
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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
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Study treatment discontinuation until week 52
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Percentage of patients with overall response at Week 52
Time Frame: Study treatment discontinuation until week 52
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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
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Study treatment discontinuation until week 52
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Duration of sustained response off treatment
Time Frame: Study treatment discontinuation until lost of response (up to 78 weeks)
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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
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Study treatment discontinuation until lost of response (up to 78 weeks)
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Percentage of patients with sustained response off treatment at Week 78
Time Frame: Study treatment discontinuation until week 78
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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
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Study treatment discontinuation until week 78
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Overall response by Week 4
Time Frame: Screening up to 4 weeks
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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
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Screening up to 4 weeks
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Complete response by Week 4
Time Frame: Baseline up to 4 weeks
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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
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Baseline up to 4 weeks
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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
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Relative changes in platelet count from screening to baseline and to 1, 2, 4, 12, 26, and 52 weeks
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Screening, baseline, 1, 2, 4, 12, 26, and 52 weeks
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Time to overall response
Time Frame: Time from starting study treatment to achievement of overall response (up to 78 weeks)
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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
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Time from starting study treatment to achievement of overall response (up to 78 weeks)
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Time to complete response
Time Frame: Time from starting study treatment to achievement of complete response (up to 78 weeks)
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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
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Time from starting study treatment to achievement of complete response (up to 78 weeks)
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Duration of overall and complete response
Time Frame: Achievement of overall or complete response until lost of response (up to 78 weeks)
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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
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Achievement of overall or complete response until lost of response (up to 78 weeks)
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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
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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
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Baseline to 1, 2, 4, 12, 26, and 52 weeks
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Change from baseline in Short Form 36 Health Survey (SF-36v2) questionaire
Time Frame: Baseline to 1, 2, 4, 12, 26, and 52 weeks
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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
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Baseline to 1, 2, 4, 12, 26, and 52 weeks
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Incidence and severity of bleeding events
Time Frame: Baseline up to 78 weeks
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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)
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Baseline up to 78 weeks
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Absolute 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
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Absolute changes in platelet count from screening to baseline and to 1, 2, 4, 12, 26 and 52 weeks
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Screening, baseline, 1, 2, 4, 12, 26, and 52 weeks
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Autoimmune Diseases
- Hematologic Diseases
- Hemorrhage
- Hemorrhagic Disorders
- Blood Coagulation Disorders
- Skin Manifestations
- Blood Platelet Disorders
- Thrombotic Microangiopathies
- Purpura, Thrombocytopenic
- Purpura
- Purpura, Thrombocytopenic, Idiopathic
- Thrombocytopenia
- Physiological Effects of Drugs
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Dexamethasone
Other Study ID Numbers
- CETB115JDE01
- 2019-002658-21 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD 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
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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