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Anemia, AplasticPhase 2/3EMAANCT02773225

Efficacy and Safety of Eltrombopag + CSA in Patients With Moderate Aplastic Anemia (EMAA)

A Phase 2/3 study testing Eltrombopag in people with Anemia, Aplastic, run by B. Höchsmann at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The aim of this study 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 therapy requiring MAA. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Anemia, Aplastic
What is being tested?
Eltrombopag
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
93 participants
Where
1 siteGermany
Study dates
27 Jan 2015to 30 Jan 2025
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • absolute neutrophil count (ANC) < 1.2 G/L and > 0.5 G/l
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  • platelet count < 70 G/L
  • absolute reticulocyte count < 60 G/L
  • 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)
  • In this study need for treatment with CSA is defined as:
  • 2a) 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)
  • 2b) transfusion-dependent moderate aplastic anemia
  • 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 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.

Who cannot join

  • Age < 18 years
  • Severe or Very Severe Aplastic Anemia (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)
  • Constitutional aplastic anemia (Fanconi anemia or Dyskeratosis congenita)
  • 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.
  • Bone marrow reticulin fibrosis of grade 3 or greater
  • Severe concurrent diseases precluding the patient's ability to tolerate protocol therapy
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  • ALT > 3 times the upper limit of normal if this elevation is progressive, or persistent for 4 weeks, or accompanied by increased direct bilirubin, or accompanied by clinical symptoms of liver injury or evidence for hepatic decompensation
  • Infection not adequately responding to appropriate therapy
  • HIV-positivity (patients with Hepatitis B or Hepatits C-positivity are only in combination with hepatic failure (see criteria 7) excluded)
  • Moribund status with a likely death within 3 months
  • 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...).
  • Prior specific treatment of Aplastic Anemia with immunosuppression or androgens or interleukin2-receptor-antibodies. The use of these drugs in context of other disorders before diagnosis of aplastic anemia is not an exclusion criteria if these treatments were finished longer than 6 months before study entry.
  • Treatment with other hematological effective drugs (including erythropoetin) within 3 months before study entry as well as treatment with corticosteroids and G-CSF within 3 weeks before enrollment
  • Known hypersensitivity to Eltrombopag or its components
  • Known hypersensitivity to Ciclosporin
  • 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 with childbearing potential during the course of this study.
  • Inability to understand the investigational nature of the study or to give informed consent.
  • Renal failure with creatinine > 2× upper limit of normal.
  • Uncontrolled hypertension
  • Participation in any study using an investigational drug or treatment with an investigational drug within 30 days preceding the first dose of study medication

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • University Hospital Ulm

    Ulm, 89081

Other trials in Germany

About this study

Official title: Efficacy and Safety of Thrombopoetin-Receptor Agonist Eltrombopag in in Combination With Ciclosporin A in Moderate Aplastic Anemia (EMAA): Prospective Randomized Multicenter Study

The aim of this study 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 therapy requiring MAA.

Read the detailed description

After enrollment (see detailed inclusion and exclusion criteria below) the patients are randomized either to the Placebo or Eltrombopag arm. The randomization is double blinded. Randomization will take in account patient's age and disease severity by stratifying into 4 block combinations to ensure homogeneity between treatment arms. All patients receive background therapy with CSA, regardless of randomisation group, to treat MAA according to current standard of care.

Eltrombopag (or Placebo) is given at a daily starting dose of 150 mg orally as 75 mg tablets once daily (2 tablets Eltrombopag or placebo per day), (Olnes et al NEJM 2012).

In Asian patients Eltrombopag (or Placebo) is given at a daily starting dose of 75 mg orally (1 tablet Eltrombopag or placebo per day). In Asian-Caucasian patients no dose reduction of the starting dose is carried out, but cautious observation of the liver function due to the possibility of altered Eltrombopag metabolism is recommended.

Dose reduction:

In patients without history of thromboembolism or known risk factors for thrombembolism dose reduction (the possibility of an alternating dose schedule is given) is recommended if the platelet count is increasing > 150 G/L.

  • Dosage should be decreased to achieve a platelet count between 100 and 150 G/L after reaching a sufficient erythrocyte and granulocyte response (see 10.1).
  • If the platelet count decreases below 100 G/L the Eltrombopag dose should be escalated again.
  • Eltrombopag should be discontinued if the platelet count exceeds 450 G/L and could be restarted with a lower dose after decrease of the platelet count below 150 G/L.

In patients with history of thromboembolism or known risk factors for thromboembolism (e. g. Factor V Leiden, ATIII deficiency, antiphospholipid syndrome, PNH with GPI-deficient granulocyte population > 50 %, prolonged periods of immobilization, contraceptives and hormone replacement therapy or surgery) dose reduction is recommended if the platelet count is increasing > 100 G/L

  • The target platelet count will be 70-120 G/L after reaching a sufficient erythrocyte and granulocyte response (see 10.1).
  • If the platelet count decreases below 70 G/L the Eltrombopag dose should be escalated again.
  • Eltrombopag should be discontinued in patients with history of and risk factors for thromboembolism if the platelet count exceeds 150 G/L.

Duration of follow up: Last Follow up 24 months after end of study treatment. Patients will receive Eltrombopag or placebo within the study for a minimum of 6 months. Exceptions are patients with disease progression in Severe or Very Severe AA or patients with inacceptable adverse events within the first 6 months.

Eltrombopag will be administered for a maximum period of 12 months within the protocol. Recent data show that the response of hematopoiesis in refractory severe aplastic anemia can be sustained on discontinuation of Eltrombopag25.

As long-term effects of investigational treatments are an objective of the study, the follow-up of patients will cover 24 months after the end of the study treatment according to the protocol

Being tested
Eltrombopag, Placebo (for Eltrombopag)
Keywords
non severe Aplastic Anemia,
Medical subject headings
Anemia, Aplastic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EltrombopagDrug

    Also called Experimental arm

    • CSA + Eltrombopag, evaluation after three month therapy start regarding dose escalation
    • 6 month after therapy start --> evaluation and report of remission status of the study office --> unblinding by study office --> partial or complete remission Eltrombopag and slow tapering of CSA
    • 12 month after therapy start --> evaluation and report of remission status --> complete and partial remission --> tapering/end of study treatment

  • Placebo (for Eltrombopag)Drug

    Also called control

    • CSA + Placebo, evaluation after three month therapy start regarding dose escalation
    • 6 month after therapy start --> evaluation and report of remission status of the study office --> unblinding by study office --> no complete remission: CSA + Eltrombopag and evaluation 3 months after therapy start --> dose escalation
    • 12 month after start of eltrombopag --> evaluation and report of remission status --> complete and partial remission --> tapering/end of study treatment
Study groups in NCT02773225
Study groupRoleWhat they receive
Eltrombopag + Ciclosporin AExperimentalEltrombopag, 75 mg film tablets, starting dose: 2 tablets (150 mg per day), daily, per os + According to European guidelines CSA is administered orally with an initial daily dose of 5 mg/kg/day divided into two doses. Then dosage should be adjusted with the aim of a trough CSA blood level of 200-400 ng/mL (using a polyclonal assay) or 150-250 ng/mL (using a monoclonal assay).
Receives: Drug: Eltrombopag
Placebo + Ciclosporin APlacebo comparatorPlacebo for Eltrombopag 75 mg film tablets, 2 tablets, daily, per os + According to European guidelines CSA is administered orally with an initial daily dose of 5 mg/kg/day divided into two doses. Then dosage should be adjusted with the aim of a trough CSA blood level of 200-400 ng/mL (using a polyclonal assay) or 150-250 ng/mL (using a monoclonal assay).
Receives: Drug: Placebo (for Eltrombopag)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Trilineage hematologic response rate (CR + PR)

    The primary objective of this trial is to investigate whether Eltrombopag added to standard immunosuppressive treatment increases the rate of hematologic responses (complete and partial response) in untreated AA patient at six months after treatment start.

    A complete response (according to Marsh et al Blood 1992):

    A peripheral blood count with an ANC > 2.0 G/L and a platelet count > 100 G/L and transfusion independence.

    A partial response (according to Marsh et al Blood 1992):

    A peripheral blood count with an ANC >1.0 G/L and a platelet count >30 G/L and transfusion independence Transfusion independence is defined as No need for platelet transfusions in the last 4 weeks prior to evaluation and no need for packed red blood cell concentrates (PRBC) in the last 6 weeks prior to evaluation.

    Patients who remain transfusion-dependent will be classified as non-responders regardless of the ANC and platelet count.

    Measured: 6 months after treatment start

Secondary outcomes (4)

  1. Trilineage hematological response rate (CR and PR, detailed definition => primary endpoint) at 3, 12 and 18

    Increase of the platelet count by 20 G/L or hemoglobin by > 1.5 g/dL above baseline in patients without prior transfusion dependence or an absolute increase in ANC of > 0.5 G/L respectively at least a 100 percent increase over the baseline ANC in those with pre-treatment absolute ANC of ≤ 0.5 G/L or transfusion independence for a minimum of 8 weeks or a reduction of transfused units during the last 8 weeks compared with the 8 weeks previous to study entry in patients with prior transfusion dependency

    Measured: 3, 12 and 18 months

  2. single hematological response rate (CR and PR, detailed definition => primary endpoint) at 3, 12 and 18

    Increase of the platelet count by 20 G/L or hemoglobin by > 1.5 g/dL above baseline in patients without prior transfusion dependence or an absolute increase in ANC of > 0.5 G/L respectively at least a 100 percent increase over the baseline ANC in those with pre-treatment absolute ANC of ≤ 0.5 G/L

    Measured: 3, 12 and 18 months

  3. cumulative incidence of response

    proportion of patients with need for transfusions and number of units transfused (PRBC and platelet concentrates) since start of treatment cumulative incidence of progress to SAA/VSAA or intensive immunosuppressive treatment with ATG

    Measured: 3, 6, 12 and 18 months

  4. Comparison of number of SAEs between the two arms (CSA + Placebo versus CSA + Eltrombopag

    using the CTCAE criteria and the study specific criteria (developing of a ALT > 3.0 × ULN combined with an elevation of bilirubine > 2.0 × ULN, thrombotic/thromboembolic complications, clonal evolution)

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 May 2016 (estimated)
  2. Study start27 Jan 2015
  3. Primary completion30 Jan 2025
  4. Study completion30 Jan 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
93 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02773225
Sponsor's protocol ID
9345
Acronym
EMAA
Status last verified
Jun 2025
First submitted
29 Feb 2016
Last updated
10 Jun 2025
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Yes

Publications

  • Hochsmann B, Schafhausen P, Beier F, Heuser M, Westermann J, Drexler B, Roth A, Herbst RT, Hanel M, Schwarz M, Sicre de Fontbrune F, Peffault de Latour R, Marx-Hofmann A, Beitzen-Heineke A, Panse JP, Thol FR, Korper S, Brummendorf TH, Schrezenmeier H. Eltrombopag plus cyclosporine A for moderate aplastic anemia (EMAA): a placebo-controlled, double-blind, phase 3 trial. Blood. 2026 Aug 18:blood.2025032682. doi: 10.1182/blood.2025032682. Online ahead of print.

    PubMed 42611779

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Eltrombopag in people with Anemia, Aplastic, run by B. Höchsmann at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Trilineage hematologic response rate (CR + PR) (time frame: 6 months after treatment start). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02773225, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2025.

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