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

NCT02773225 | Completed Phase 2 DMC

• 1 other identifier: 9345
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Anemia, Aplastic

Keywords

non severe Aplastic Anemia,

Outcome Measures

Primary Outcomes (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.

  6 months after treatment start

Secondary Outcomes (4)

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

  3, 12 and 18 months

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

  3, 12 and 18 months

• cumulative incidence of response

  3, 6, 12 and 18 months

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

  2 years

Study Arms (2)

Eltrombopag + Ciclosporin A

EXPERIMENTAL

Eltrombopag, 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).

Drug: Eltrombopag

Placebo + Ciclosporin A

PLACEBO COMPARATOR

Placebo 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).

Drug: Placebo (for Eltrombopag)

Interventions

Eltrombopag DRUG

* 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

Also known as: Experimental arm

Eltrombopag + Ciclosporin A

Placebo (for Eltrombopag) DRUG

* 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

Also known as: control

Placebo + Ciclosporin A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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:
• 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)

You may not qualify if:

• 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
• 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...).
• 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
• Inability to understand the investigational nature of the study or to give informed consent.

Sponsors & Collaborators

• B. Höchsmann: lead

Study Sites (1)

University Hospital Ulm

Ulm, 89081, Germany

Location

MeSH Terms

Conditions

Anemia, Aplastic

Interventions

eltrombopag

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Study Officials

• Britta Höchsmann, MD

  Sponsor GmbH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr. med.

Study Record Dates

• First Submitted: February 29, 2016
• First Posted: May 16, 2016
• Study Start: January 27, 2015
• Primary Completion: January 30, 2025
• Study Completion: January 30, 2025
• Last Updated: June 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

DE (1)