The study will determine if subjects are able to stop eltrombopag treatment while maintaining acceptable platelet levels after their disease has become resistant to treatment (refractory) or has a reoccurrence of symptoms after initial treatment with steroids (relapse)

• Register: EUCTR
• Last refreshed on: 8 March 2021
• Main ID: EUCTR2018-000452-18-AT
• Date of registration: 17/07/2018
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma AG
• Public title: The study will determine if subjects are able to stop eltrombopag treatment while maintaining acceptable platelet levels after their disease has become resistant to treatment (refractory) or has a reoccurrence of symptoms after initial treatment with steroids (relapse)
• Scientific 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 (TAPER)
• Date of first enrolment: 26/09/2018
• Target sample size: 101
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-000452-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Brazil, Chile, France, Germany, Greece, Italy, Japan, Mexico, Oman, Russian Federation, Saudi Arabia, Spain, Switzerland, Turkey, United Kingdom, United States

Contacts

• Name: Drug Regulatory Affairs
• Affiliation: Novartis Pharma GmbH

• Name: Drug Regulatory Affairs
• Affiliation: Novartis Pharma GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1. Signed informed consent must be obtained prior to participation in the study
2. Subjects = 18 years old
3. Subjects 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 < 30×109/L and assessed as needing treatment (per physician’s discretion

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 66
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 35

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 are unable to participate in assessments/biological
studies
5. Patients who have life threatening bleeding complications per
investigator discretion
6. Patients who had a deep vein thrombosis or arterial thrombosis in the
6 months preceding enrollment
7. Presence of moderate to severe impaired renal function as indicated
by any or all of the following criteria:
? Creatinine clearance < 45 mL/min as calculated using Cockcroft-Gault
formula
? Serum creatinine > 1.5 mg/dL
8. Total bilirubin > 1.5 × upper limit of normal (ULN)
9. Aspartate transaminase (AST) > 3.0 × ULN
10. Alanine transaminase (ALT) > 3.0 × ULN
11. Subjects who are human immune deficiency virus (HIV), hepatitis C
virus (HCV), hepatitis B surface antigen (HBsAg) positive
12. Subjects with hepatic impairment (Child-Pugh score > 5)
13. Subjects who have active malignancy
14. Subjects 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
15. History or current diagnosis of cardiac disease indicating significant
risk of safety for subjects participating in the study
16. Subjects with known active or uncontrolled infections not responding
to appropriate therapy
17. Subjects with evidence of current alcohol/drug abuse
18. Women of child-bearing potential and sexually active males unwilling
to use adequate contraception during the study
19. 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
Other protocol-defined inclusion/exclusion criteria may apply


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

immune thrombocytopenia
MedDRA version: 23.0 Level: LLT Classification code 10050245 Term: Autoimmune thrombocytopenia System Organ Class: 100000004851
MedDRA version: 22.1 Level: LLT Classification code 10036735 Term: Primary thrombocytopenia System Organ Class: 100000004851

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Intervention(s)

Trade Name: REVOLADE
Product Name: Eltrombopag
Product Code: ETB115
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ELTROMBOPAG
CAS Number: 496775-62-3
Current Sponsor code: ETB115
Other descriptive name: ELTROMBOPAG OLAMINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 12.5-

Trade Name: REVOLADE
Product Name: Eltrombopag
Product Code: ETB115
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ELTROMBOPAG
CAS Number: 496775-62-3
Current Sponsor code: ETB115
Other descriptive name: ELTROMBOPAG OLAMINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Trade Name: REVOLADE
Product Name: Eltrombopag
Product Code: ETB115
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ELTROMBOPAG
CAS Number: 496775-62-3
Current Sponsor code: ETB115
Other descriptive name: ELTROMBOPAG OLAMINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Trade Name: REVOLADE
Product Name: Eltrombopag
Product Code: ETB115
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ELTROMBOPAG
CAS Number: 496775-62-3
Current Sponsor code: ETB115
Other descriptive name: ELTROMBOPAG OLAMINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 75-

Trade Name: REVOLADE
Product Name: Eltrombopag
Product Code: ETB115
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ELTROMBOPAG
CAS Number: 496775-62-3
Current Sponsor code: ETB115
Other descriptive name: ELTROMBOPAG OLAMINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 12.5-

Trade Name: REVOLADE
Product Name: Eltrombopag
Product Code: ETB115
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ELTROMBOPAG
CAS Number: 496

Primary Outcome(s)

Secondary Objective: assess 1.duration of sustained remission after treatment discontinuation by M12 and 24 2.proportion of patients maintaining a sustained remission after treatment discontinuation until M24 3.ability of eltrombopag to induce early response by month 1 4.ability of eltrombopag to induce a recovery response, in case of loss of response during or after tapering of eltrombopag until M 24 5.platelet count from baseline and every 3M until M24 6.ability of eltrombopag to maintain platelet count = 30×109/L within 12M and every 3M until 24M 7.evaluate patient-Health Related outcome measures for health-related quality of life (fatigue level of the patients through FACIT) & FACT-Th6 and SF-36v2 questionnaires from baseline and every 3M to 24M and end of treatment/ to explore 8.overall impact of side effects on treatment via the GP5 at baseline,M12, and end
of treatment 9.treatment satisfaction with TSQM-9 at baseline, M12, and end of treatment 10.evaluate the safety and tolerability of eltrombopag

Main Objective: To assess ability of eltrombopag to induce sustained remission by month 12 in ITP subjects who relapsed or failed to respond to first-line steroid treatment

Primary end point(s): Proportion of patients with sustained remission (R) by month 12 where
sustained remission is defined as:
? reach platelet count = 100×109/L (complete response [CR]) and then
maintain platelet counts around 100×109/L for 2 months (no counts
below 70×109/L) AND then
? taper off the drug until treatment discontinuation while,
? maintain platelet count = 30×109/L in the absence of bleeding (no
bleeding AEs) or use of any rescue therapy until month 12.

Timepoint(s) of evaluation of this end point: 12 months

Secondary Outcome(s)

Secondary end point(s): 1a. Median duration of sustained remission (weeks) counted from last
dose of eltrombopag to month 12 for patients with sustained remission
(R)
1b. Estimated median duration of sustained remission (weeks) by month
24 for patients who are in sustained remission (R) at month 12 and
enter 12 months follow-up period using Kaplan-Meier method
1c. Estimated median duration of sustained remission (weeks) by month
24 for all patients using Kaplan-Meier method.
2. Proportion of sustained remission (R) patients at months 15, 18, 21,
and 24.
3. Number (%) of patients with platelet count = 50×109/L at least once
by month 1 (first month) without bleeding and no rescue therapy
4. Number (%) of patients with at least one platelet count = 30×109/L
after eltrombopag is re-introduced, in case of loss of response (<
30×109/L and/or bleeding event) without bleeding and no rescue
therapy by month 12 and 24
5. Absolute and relative change in platelet count from baseline to 3, 6,
9,12, 15, 18, 21, and 24 months and end of treatment
6. Number (%) of patients who maintain a platelet count = 30×109/L
from the first time of reaching that level to month 3, 6, 9, 12, 15, 18, 21,
24, and end of treatment without bleeding and no rescue therapy
7. The analysis of HRQoL parameters; fatigue level of the patients
through FACIT & FACT-Th6, SF-36v2 questionnaires. Change in scores
from baseline to month 3, 6, 9, 12, 15, 18, 21, 24, and end of treatment
8. Overall change from baseline to month 12 and end of treatment will
be assessed
9. Overall change from baseline to month 12 and end of treatment will
be assessed
10. Number (%) and severity of patients with AEs, serious AEs (SAEs),
AEs leading to discontinuation, AEs leading to dose adjustments, AEs of
special interest. Change from baseline in vital signs and clinical
laboratory tests

Timepoint(s) of evaluation of this end point: 1. 12 months
1b. 24 months
1c. 24 months
2. at months 15, 18, 21 and 24
3. 1 month
4. 12 and 24 months
5. from baseline to 3, 6, 9,12, 15, 18, 21, and 24 months and end of
treatment
6.from the first time of reaching required platelet level to month 3, 6, 9,
12, 15, 18, 21, 24, and end of treatment
7. from baseline to month 3, 6, 9, 12, 15, 18, 21, 24, and end of
treatment
8. from baseline to month 12 and end of treatment
9. from baseline to month 12 and end of treatment
10. from baseline

Secondary ID(s)

ETB115J2411

Source(s) of Monetary Support

Novartis Pharma AG

Ethics review

Status: Approved
Approval date: 26/09/2018
Contact: