A phase II dose escalation study: use of eltrombopag in pediatric patients with severe aplastic anemia or recurrent aplastic anemia

• Register: EUCTR
• Last refreshed on: 5 April 2021
• Main ID: EUCTR2015-003166-91-NL
• Date of registration: 08/08/2017
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma AG
• Public title: A phase II dose escalation study: use of eltrombopag in pediatric patients with severe aplastic anemia or recurrent aplastic anemia
• Scientific title: A phase II, open-label, non-controlled, intra-patient dose escalation study to characterize the pharmacokinetics after oral administration of eltrombopag in pediatric patients with refractory, relapsed or treatment naïve severe aplastic anemia or recurrent aplastic anemia.
• Date of first enrolment: 14/11/2018
• Target sample size: 60
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-003166-91
• 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; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Hong Kong, Netherlands, Portugal, Russian Federation, Thailand, United Kingdom, United States

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion Criteria specific to Cohort A (patients with relapsed/refractory
SAA or recurrent AA):
1. Prior history of diagnosis of SAA
2. Diagnosis of relapsed/refractory SAA or recurrent AA following IST for
SAA at the time of enrollment. Patients with
recurrent AA (e.g., losing their response) are exempt from meeting the
diagnostic criteria for relapsed SAA at the time
of enrollment, but must have been previously diagnosed with SAA.
3. Agree to concurrent eltrombopag treatment with appropriate,
investigator-selected IST with either hATG + CsA or CsA.
Inclusion Criteria specific to Cohort B (patients with previously
untreated SAA):
4. Diagnosis of SAA at the time of enrollment.
5. Patients must not have been previously treated for SAA
6. Patients must agree to treatment with hATG + CsA concurrent with
eltrombopag.
Inclusion Criteria for all patients regardless of cohort:
7. Age 1 to <18 years
8. Where appropriate, assessments to rule out congenital/inherited bone
marrow failure syndromes and other causes of immune-mediated
pancytopenia, which may be treated with transplant, must be completed
prior to enrollment.
9. Hematopoietic stem cell transplantation (HSCT) is not available or
suitable as a treatment option or has been refused by the patient.
(Candidacy for HSCT will be determined as per local practice.)
10. Bone marrow aspirate/biopsy at any time during the 4 weeks prior
to first dose of eltrombopag
11. Normal karyotype with FISH for chromosomes 7 and 8
12. Performance status score: Karnofsky =50 or Lansky =50 (depending
on age)
13. Serum creatinine = 2.5 x ULN
14. Total bilirubin = 1.5 x ULN
15. Written informed consent signed by a parent or legal guardian prior
to initiation of any study specific procedure.
Are the trial subjects under 18? yes
Number of subjects for this age range: 60
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Prior and/or active medical history of:
• Fanconi anemia (via chromosomal breakage test or growth arrest by flow cytometry)
• Other known underlying congenital/inherited marrow failure syndromes (such as, but not limited to, Dyskeratosis Congenita, Congenital Amegakaryocytic Thrombocytopenia, or Shwachman-Diamond Syndrome).
• Symptomatic Paroxysmal Nocturnal Hemoglobinuria (PNH) and/or PNH clones >50% of PMN or RBC at time of enrollment
• Any cytogenetic abnormalities, including but not limited to chromosome 7 or myelodysplasia, in bone marrow within 4 weeks of study enrollment
• Myelodysplastic syndrome (MDS)
• Other known or suspected underlying primary immunodeficiency
• Any malignancy
2. Active infection not responding to appropriate therapy
3. Prior eltrombopag or other thrombopoietin receptor (TPO-R) agonist treatment for at least 2 months and a lack of response.
4. Any out of range lab values Creatinine >2.5 × upper limit of normal (ULN), Total bilirubin >1.5 × ULN Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 × ULN.


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

Health Condition(s) or Problem(s) studied

Refractory, relapsed or treatment naïve severe aplastic anemia (SAA) or recurrent aplastic anemia (AA)
MedDRA version: 20.0 Level: PT Classification code 10002967 Term: Aplastic anaemia System Organ Class: 10005329 - Blood and lymphatic system disorders

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: 496775-61-2
Current Sponsor code: ETB115
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: 496775-61-2
Current Sponsor code: ETB115
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: 496775-61-2
Current Sponsor code: ETB115
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Trade Name: REVOLADE
Product Name: Eltrombopag
Product Code: ETB115
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: ELTROMBOPAG
CAS Number: 496775-61-2
Current Sponsor code: ETB115
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: 496775-61-2
Current Sponsor code: ETB115
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: 496775-61-2
Current Sponsor code: ETB115
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 12.5-

Trade Name: REVOLADE
Product Name: Eltrombopag
Product Code: ETB115
Pharmaceutical Form:

Primary Outcome(s)

Primary end point(s): Eltrombopag PK parameters, including AUCtau, Cmax and Ctrough, 2 weeks and 12 weeks after initiation of dosing (capturing steady-state PK at starting dose and highest dose achieved).

Secondary Objective: Key secondary objectives:
1. To determine the safety and tolerability of eltrombopag given orally in pediatric patients with SAA.
2. To assess the efficacy defined as overall response (ORR).
Other secondary endpoints:
3. To assess hematologic counts.
4. To evaluate PLT and RBC transfusion independence.
5. To assess bone marrow cellularity, morphology (trephine biopsy) and cytogenetics.
6. To assess the acceptability and palatability for the PfOS.
7. To assess clonal evolution to PNH.
8. To characterize the exposure-response relationship of eltrombopag and overall response and PLT response.
9. To assess the efficacy defined as the alternate overall response (aORR).

Main Objective: To characterize the PK of eltrombopag at steady state after oral administration in pediatric patients with SAA.

Timepoint(s) of evaluation of this end point: At 2 weeks and 12 weeks after dose initiation.

Secondary Outcome(s)

Secondary end point(s): a) To determine the safety and tolerability of eltrombopag given orally in pediatric patients with SAA.
b) To assess the efficacy of eltrombopag defined as overall response rate (ORR)

Timepoint(s) of evaluation of this end point: a) Assessed throughout the study.
b) At Week 12, Week 26, Week 52, and Week 78.

Secondary ID(s)

NCT03025698

CETB115E2201

2015-003166-91-GB

Source(s) of Monetary Support

Novartis Pharma AG

Ethics review

Status: Approved
Approval date: 14/11/2018
Contact: