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
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Immune Thrombocytopenia (ITP)
Keywords: ITP
Eltrombopag
Dexamethasone
Sustained response off treatment
TFR
Adult
ETB115
Platelets
Thrombocytopenic
Thrombopoietin receptor Agonist
Newly-diagnosed
Blood bleeding disorder
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-04-15
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was 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 that compared 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 had platelet counts \< 30 × 10\^9/L and required treatment were screened, and if eligible, were 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 was conducted in the following periods:

Screening Period: Patients were screened for 14 days based on the inclusion and exclusion criteria.

Treatment Period: Arm A: Patients were treated for 26 weeks during the treatment period. Patients who reached platelet counts ≥ 30 × 10\^9/L and maintained counts ≥ 30 × 10\^9/L during the tapering phase were eligible for treatment discontinuation. Duration of tapering before treatment discontinuation at Week 26 was 6 weeks. Arm B: Patients were treated up to 12 weeks during the treatment period. Patients who reached platelet counts ≥ 30 × 10\^9/L and maintained counts ≥ 30 × 10\^9/L after 1-3 cycles of dexamethasone treatment were eligible for treatment discontinuation. Patients with platelet counts \< 30 × 10\^9/L after 3 cycles of dexamethasone treatment were offered a course of eltrombopag treatment within the study and were discontinued from study at week 52.

Observation period: After completion of the treatment period, all patients were observed for sustained response off treatment until week 52. Only patients with sustained response at week 52 were followed for another 26 weeks.

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 in the 6 months preceding enrollment 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 immune 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
* 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
* Women of child-bearing potential and males unwilling to use adequate contraception during the study

Primary outcomes:
measure: Percentage of Patients With Sustained Response Off Treatment at 52 Weeks
timeFrame: Study treatment discontinuation until week 52
Secondary outcomes:
measure: Percentage of Patients With Overall Response at Week 52
timeFrame: Study treatment discontinuation until week 52
measure: Duration of Sustained Response Off Treatment
timeFrame: from last dose of study treatment until loss of response, approx. 52 weeks
measure: Overall Response by Week 4
timeFrame: By Week 4
measure: Complete Response by Week 4
timeFrame: By Week 4
measure: Absolute Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points
timeFrame: Pre-treatment/screening, Week 1 (baseline), 2, 4, 13, 27, and 53
measure: Relative Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points
timeFrame: Pre-treatment/screening, Week 1 (baseline), 2, 4, 13, 27, and 53
measure: Time to Overall Response (TOR)
timeFrame: Time from starting study treatment to achievement of complete response (up to 52 weeks)
measure: Time to Complete Response
timeFrame: Time from starting study treatment to achievement of complete response (up to 52 weeks)
measure: Duration of Overall Response (OR) and Complete Response (CR)
timeFrame: Achievement of overall or complete response until loss of response (up to 52 weeks)
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaire
timeFrame: Baseline (Week 1), Week 2, 3, 5, 13, 27 and 53
measure: Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM))
timeFrame: Baseline (Week 1), Week 2, 3, 5, 13, 27 and 53
measure: Incidence and Severity of Bleeding Events
timeFrame: Baseline up to 52 weeks
Other outcomes:
Locations:
city: Aschaffenburg
country: Germany
facility: Novartis Investigative Site
state: Bayern
city: Aachen
country: Germany
facility: Novartis Investigative Site
city: Chemnitz
country: Germany
facility: Novartis Investigative Site
city: Donauwoerth
country: Germany
facility: Novartis Investigative Site
city: Dortmund
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Jena
country: Germany
facility: Novartis Investigative Site
city: Kiel
country: Germany
facility: Novartis Investigative Site
city: Kronach
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaacueticals
role: STUDY_DIRECTOR
References: