Clinical trial NCT03524612: A Study to Assess the Ability of Eltrombopag to Induce Sustained Response Off Treatment in Subjects With ITP
Official title: A Phase II, Open-label, Prospective, Single-arm, Study to Assess Ability of Eltrombopag to Induce Sustained Remission in Subjects With ITP Who Are Refractory or Relapsed After First-line Steroids
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Immune Thrombocytopenic Purpura (ITP)
Keywords: Thrombocytopenic
Immune
Platelets
Bleeding
ITP
eltrombopag
ETB115
induce sustained response off treatment
refractory or relapsed
first-line steroids
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2018-05-15
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this trial was to assess the ability of eltrombopag to induce sustained treatment-free remission in immune thrombocytopenia purpura (ITP) subjects who relapsed or failed to respond to an initial treatment with steroids.

Detailed description: Protocol Amendment 01 added a follow-up period of 12 months for patients with sustained response off treatment at month 12 to obtain further data on response duration.

The starting dose was eltrombopag 50 mg daily (25 mg daily for Asian patients and 12.5 mg daily for Japanese patients in Japan). The starting dose for this study was consistent with the dosing guidelines approved for eltrombopag use in ITP. An increase of eltrombopag dose up to 75 mg was allowed for patients who did not respond to standard-dosage treatment and to reduce the risk of bleeding. The rationale for this increased dose was to use the minimal efficacious dosage of eltrombopag in order to achieve a platelet count ≥ 100×10\^9/L and maintain it around 100×10\^9/L (no counts below 70×10\^9/L) for 2 months in order to allow patients to start the eltrombopag tapering and withdrawal process.

Patients who reached a platelet count of \>= 100 × 10\^9/L and maintained counts around 100×10\^9/L for 2 months with no platelet count \< 70 × 10\^9/L were eligible for tapering-off and treatment discontinuation, which occurred via 25 mg reduction every 2 weeks up to 25 mg on alternate days for 2 weeks until treatment discontinuation.

Patients who successfully discontinue eltrombopag and maintained platelet count \>= 30 × 10\^9/L in the absence of bleeding or use of rescue therapy were followed to month 12. If a relapse (defined as platelet count \<30 × 10\^9/L) occurred during the 12-month treatment period, they were offered a new course of eltrombopag treatment within this timeframe at the appropriate starting dose. If a patient relapsed in the post 12-month follow-up period, no further attempts for tapering and achieving sustained response off treatment were made.

The taper-off scheme followed recommendations within the current established dosing regimen for when to consider dose adjustment.

Eligibility criteria: Inclusion Criteria:

1. Signed informed consent must be obtained prior to participation in the study
2. Patients ≥ 18 years old
3. Patients with a confirmed diagnosis of primary ITP, who are not responsive or in relapse after a first line of steroid therapy ± intravenous immunoglobulin (IVIG) (used as a rescue therapy)
4. Platelet count \< 30×10\^9/L and assessed as needing treatment (per physician's discretion

Exclusion Criteria:

1. ITP patients previously treated with any ITP second-line therapies, thrombopoietin receptor (TPO-R) agonists for ITP, except steroids / IVIG
2. Patients who relapsed more than one year after the end of first-line full course of steroid therapy
3. Patients with a diagnosis of secondary thrombocytopenia
4. Patients who have life threatening bleeding complications per investigator discretion
5. Patients who had a deep vein thrombosis or arterial thrombosis in the 6 months preceding enrollment
6. Serum creatinine ≥ 1.5 mg/dL
7. Total bilirubin \> 1.5 × upper limit of normal (ULN)
8. Aspartate transaminase (AST) \> 3.0 × ULN
9. Alanine transaminase (ALT) \> 3.0 × ULN
10. Patients who are human immune deficiency virus (HIV), hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg) positive
11. Patients with hepatic impairment (Child-Pugh score \> 5)
12. Patients who have active malignancy
13. Patients with 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 per investigator discretion
14. History or current diagnosis of cardiac disease indicating significant risk of safety for Patients participating in the study
15. Patients with known active or uncontrolled infections not responding to appropriate therapy
16. Patients with evidence of current alcohol/drug abuse
17. Women of child-bearing potential and sexually active males unwilling to use adequate contraception during the study
18. Female Patients 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

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Participants With Sustained Response Off Treatment (SRoT) by 12 Months
timeFrame: Month 12
Secondary outcomes:
measure: Median Duration of Sustained Response Off Treatment (SRoT) After Treatment Discontinuation for Participants With Sustained Response Off Treatment
timeFrame: From last dose of eltrombopag to month 12
measure: Estimated Median Duration of Sustained Response Off Treatment (SRoT) for Participants With Sustained Response Off Treatment at Month 12 and Who Enter 12 Months Follow-up Period
timeFrame: From last dose of eltrombopag to relapse, assessed up to month 24
measure: Estimated Median Duration of Sustained Response Off Treatment (SRot) for All Patients
timeFrame: From last dose of eltrombopag to month 24
measure: Percentage of Participants With Sustained Response Off Treatment Until Month 24
timeFrame: Month 15, 18, 21 and 24
measure: Percentage of Participants With Early Response Within First Month
timeFrame: By 1 month
measure: Percentage of Participants With Recovery Response in Case of Loss of Response During or After Tapering of Eltrombopag Until Month 24
timeFrame: Up to month 24
measure: Relative Change From Baseline in Platelet Count Over Time
timeFrame: Baseline, month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders
measure: Percentage of Participants Who Maintain Platelet Counts Level Within 12 Months and Every 3 Months Until Month 24
timeFrame: From first time of reaching the level to month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionaire
timeFrame: Baseline to month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders
measure: Change From Baseline in Functional Assessment of Cancer Therapy- Thrombocytopenia (FACT-Th6) Questionnaire
timeFrame: Baseline to month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders
measure: Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire: Bodily Pain (BP) Score
timeFrame: Baseline to month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders
measure: Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire: General Health (GH) Score
timeFrame: Baseline to month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders
measure: Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire: Mental Health (MH) Score
timeFrame: Baseline to month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders
measure: Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire: Physical Functioning (PF) Score
timeFrame: Baseline to month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders
measure: Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire: Role Emotional (RE) Score
timeFrame: Baseline to month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders
measure: Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire: Role Physical (RP) Score
timeFrame: Baseline to month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders
measure: Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire: Social Functioning (SF) Score
timeFrame: Baseline to month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders
measure: Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire: Vitality (VT) Score
timeFrame: Baseline to month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders
measure: Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire: Physical Component Summary (PCS) Score
timeFrame: Baseline to month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders
measure: Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire: Mental Component Summary (MCS) Score
timeFrame: Baseline to month 3, 6, 9, 12 (End of Treatment Visit for non-responders), 15, 18, 21 and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders
measure: Percentage of Participants With Worst Post-baseline Value in Functional Assessment of Cancer Therapy-G (GP5)
timeFrame: Baseline to end of treatment visit, assessed up to 12 months for non-responders and up to 24 months for responders
measure: Overall Change of Treatment Satisfaction Using Treatment Satisfaction Questionnaire (TSQM-9)
timeFrame: Baseline to month 12 (End of Treatment Visit for non-responders) and 24 (End of Treatment Visit for responders), assessed up to 12 months for non-responders and up to 24 months for responders
Other outcomes:
Locations:
city: Nyack
country: United States
facility: Hematology Oncology Association of Rockland
state: New York
city: Cleveland
country: United States
facility: Case Western Reserve
state: Ohio
city: Linz
country: Austria
facility: Novartis Investigative Site
city: Salvador
country: Brazil
facility: Novartis Investigative Site
state: BA
city: Rio de Janeiro
country: Brazil
facility: Novartis Investigative Site
state: RJ
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Temuco
country: Chile
facility: Novartis Investigative Site
state: Araucania
city: Vina del Mar
country: Chile
facility: Novartis Investigative Site
state: Valparaiso
city: Caen
country: France
facility: Novartis Investigative Site
city: Pessac Cedex
country: France
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Patras
country: Greece
facility: Novartis Investigative Site
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Trieste
country: Italy
facility: Novartis Investigative Site
state: TS
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Guadalajara
country: Mexico
facility: Novartis Investigative Site
state: Jalisco
city: Ciudad de Mexico
country: Mexico
facility: Novartis Investigative Site
city: Muscat
country: Oman
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Salamanca
country: Spain
facility: Novartis Investigative Site
state: Castilla Y Leon
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Murcia
country: Spain
facility: Novartis Investigative Site
city: Bern
country: Switzerland
facility: Novartis Investigative Site
city: Aydin
country: Turkey
facility: Novartis Investigative Site
city: Edirne
country: Turkey
facility: Novartis Investigative Site
city: Kocaeli
country: Turkey
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: