Efficacy and Safety of Eltrombopag in Patients with Acquired Moderate Aplastic Anemia (EMAA) who are treated with Ciclosporin A Prospective Randomized Multicenter Study comparing Thrombopoetin-Receptor agonist Eltrombopag with Placebo in Patients with Acquired Moderate Aplastic Anemia who are treated with Ciclosporin A

• Register: EUCTR
• Last refreshed on: 16 May 2022
• Main ID: EUCTR2014-000174-19-DE
• Date of registration: 01/09/2014
• Prospective Registration: Yes
• Primary sponsor: Universitätsklinikum Ulm
• Public title: Efficacy and Safety of Eltrombopag in Patients with Acquired Moderate Aplastic Anemia (EMAA) who are treated with Ciclosporin A Prospective Randomized Multicenter Study comparing Thrombopoetin-Receptor agonist Eltrombopag with Placebo in Patients with Acquired Moderate Aplastic Anemia who are treated with Ciclosporin A
• Scientific title: Efficacy and Safety of Eltrombopag in Patients with Acquired Moderate Aplastic Anemia (EMAA) who are treated with Ciclosporin A Prospective Randomized Multicenter Study comparing Thrombopoetin-Receptor agonist Eltrombopagwith Placebo in Patients with Acquired Moderate Aplastic Anemia who are treated with Ciclosporin A - EMAA
• Date of first enrolment: 27/01/2015
• Target sample size: 90
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000174-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany, Switzerland

Contacts

• Name: Britta Höchsmann
• Affiliation: Universitätsklinikum Ulm

• Name: Britta Höchsmann
• Affiliation: Universitätsklinikum Ulm

Key inclusion & exclusion criteria

Inclusion criteria:
1. Current diagnosis of a Moderate Aplastic Anemia requiring standard treatment with CSA without prior specific therapy.

MAA is defined as Aplastic Anemia fulfilling the following criteria:
• no evidence for other disease, causing marrow failure
• hypocellular bone marrow for age
• depression of at least two out of three peripheral blood counts below the normal values in two different blood samples in a time span from at least two weeks:
• absolute neutrophil count (ANC) < 1.2 G/L
• platelet count < 70 G/L
• absolute reticulocyte count < 60 G/L21
• without fulfilling the criteria for SAA (hypocellularity of bone marrow 25 % and depression of two of the three peripheral counts: ANC < 0.5 G/L, platelet count < 20 G/L, reticulocyte count < 20 G/L)

2. In this study need for treatment with CSA is defined as:
a. transfusion-independent MAA and:
• ANC < 1.0 G/L
• or hemoglobin < 8.5 g/dl and reticulocyte count < 60 G/L
• or platelet count < 30 G/L
• or significant clinical symptoms (infections, bleeding, anemia)
b. transfusion-dependent MAA:
• Platelet transfusion dependency is defined as prophylactic transfusion (platelet counts < 10 G/L with no bleeding) or therapeutic transfusion in the 12 weeks prior to study entry.
• Red blood cell transfusion dependency is defined as transfusion of at least 4 units of packed red blood cell
concentrates (PRBC) in the 12 weeks prior to study entry.
3. A signed and dated informed consent is necessary before the conduct of any study-specific procedure.
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 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90

Exclusion criteria:
1. Age < 18 years
2. Constitutional Aplastic Anemia (i.e. Fanconi anemia or Dyskeratosis congenita)
3. Clonal myeloid disorders based on cytogenetic findings performed within 12 weeks of study entry. Especially patients with cytogenetic abnormalities which are recurrent in MDS are not eligible for the
study.
4. Bone marrow reticulin fibrosis of grade 3 or greater
5. Severe concurrent diseases precluding the patient's ability to tolerate protocol therapy
6. ALT > 3 times the upper limit of normal if this elevation is progressive, or persistent during the 4 weeks before study entry or accompanied by increased direct bilirubin, or accompanied by clinical symptoms of liver injury or evidence for hepatic decompensation
7. Infection not adequately responding to appropriate therapy
8. HIV-positivity (patients with Hepatitis B or Hepatitis C are only in combination with hepatic failure - see
criteria 7- excluded)
9. Moribund status with a likely death within 3 months.
10. History of malignancy other than localized tumors diagnosed more than one year previously and treated surgically with curative intent (for instance squamous cell or other skin cancers, stage 1, breast cancer in
situ, cervical carcinoma in situ...).
11. Prior specific treatment of Aplastic Anemia with immuno-suppression or androgens or interleukin2- receptor-antibodies. The use of these drugs in context with other disorders before diagnosis of aplastic anemia is not an exclusion criteria if these treatments were finished longer than 6 months before study entry.
12. Treatment with other hematological effective drugs (including erythropoetin) within 3 months before study
entry as well as treatment with corticosteroids and GCSF within 3 weeks before enrollment.
13. Known hypersensitivity to Eltrombopag or its components
14. Known hypersensitivity to Ciclosporin.
15. Current nursing, pregnancy, or unwillingness to take oral contraceptives or use a barrier method of birth
control to refrain from pregnancy as well as a missing or positive pregnancy test within the last 14 days before inclusion for women of childbearing potential during the course of this study.
16. Inability to understand the investigational nature of the study or to give informed consent.
17. Renal failure with creatinine > 2× upper limit of normal.
18. Uncontrolled hypertension.
19. Participation in any study using an investigational drug or treatment with an investigational drug within 30 days preceding the first dose of study medication.



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

Health Condition(s) or Problem(s) studied

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

Moderate Aplastic Anemia (MAA)

Intervention(s)

Trade Name: Revolade 75 mg
Product Name: Eltrombopag
Product Code: SB497115
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Eltrombopag
CAS Number: 496775-62-3
Current Sponsor code: SB497115
Other descriptive name: ELTROMBOPAG OLAMINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 75-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 6 months

Main Objective: The aim of this trial is to improve treatment of Moderate Aplastic Anemia (MAA) by evaluating the safety and efficiency
of Eltrombopag as a new treatment option in patients with MAA requiring therapy.

The primary objective of this trial is the evaluation of the superiority of Eltrombopag on top of background treatment
with Ciclosporin (CSA) regarding hematologic response (PR +CR) at 6 months in comparison with treatment with CSA alone in untreated MAA patient.

Primary end point(s): The primary endpoint of the study is the hematologic response rate (CR + PR) at 6 months.

Secondary Objective: The secondary objective of this trial is to investigate the impact of Eltrombopag added to background therapy with
CSA on all outcome measures, safety and quality of life in untreated MAA patients. As well as the evaluation of telomere
lengths and telomerase mutations as biomarkers for response to Eltrombopag therapy in MAA and the evaluation of the new Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria (PNH) specific quality of life questionnaire QLQ-AA/PNH.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: • Trilineage hematological response rate (CR and PR) at 3, 6, 12 and 18 months.
• single lineage response at 3, 6, 12 and 18 months
• relapse rate at 6, 12 and 18 months

Secondary end point(s): Secondary endpoints are:
• Trilineage (CR and PR) and single lineage hematological response rate at 3, 6, 12 and 18 months.
• cumulative incidence of response
• time to best hematological trilineage and single lineage response
• Proportion of patients with need for transfusions and number of units transfused (PRBC and PC) since start of treatment
• cumulative incidence of progress to SAA/VSAA or intensive immunosuppressive treatment with ATG
• toxicity profile as measured using the CTCAE criteria
• relapse rate at 6, 12 and 18 months
• cumulative incidence of relapse (from best trilineage hematological response)
• overall survival
• failure-free survival
• telomere lengths and presence of telomerase mutations as biomarkers for response.
• quality of life as assessed by quality of life instruments (FACIT-F SCALE and EORTC QLQ-C30, QLQAA/PNH)

Pharmacokinetic studies for assessment of dose dependency regarding efficiency and safety in a subgroup of patients.

Secondary ID(s)

9345

Source(s) of Monetary Support

Novartis Pharma GmbH

Ethics review

Status: Approved
Approval date: 10/11/2014
Contact: