Eltrombopag Combined With Cyclosporine as First Line Therapy in Patients With Severe Acquired Aplastic Anemia

NCT02998645 | Completed Phase 2 Results

• 2 other identifiers: CETB115E24032016-002814-29
• Study Type: interventional
• Target: 54
• Locations: 9 countries
• Sites: 20

Brief Summary

The purpose of this study was to evaluate the efficacy and safety of eltrombopag in combination with cyclosporine alone as first-line therapy on overall hematologic response

Conditions

Severe Aplastic Anemia

Keywords

severe acquired aplastic anemia; SAA; first line; eltrombopag; cyclosporine; h-ATG; severe aplastic anemia; aplastic anemia

Outcome Measures

Primary Outcomes (1)

• Overall Hematologic Response Rate by 6 Months

  Overall hematologic response rate by 6 months was defined as the percentage of participants with complete response (CR) or partial response (PR) any time on or before 6 months. PR was defined as any two of the following parameters at two consecutive measurements at least 7 days apart and no platelet transfusion within 7 days of platelet measurement: * Absolute neutrophil count (ANC) \>500/μL * Platelet count \>20 000/μL * Reticulocyte count \>60 000/μL CR was defined as all three parameters meet the following criteria at two consecutive measurements at least 7 days apart and no platelet transfusions within 7 days of platelet measurement and no red blood cell transfusion with 14 days of the hemoglobin measurements: * ANC \> 1 000/μL * Platelet count \>100 000/μL * Hemoglobin \>10 g/L

  Up to 6 months

Secondary Outcomes (17)

• Overall Hematologic Response Rate by 3 Months

  Up to 3 months

• Overall Hematologic Response Rate at 12 and 24 Months

  12 and 24 months

• Duration of First Hematologic Response

  Up to 6 months (non-responders at Month 6) and up to 24 months (responders at Month 6)

• Relapse Rate by 6 and 24 Months

  Up to 6 months (non-responders at Month 6) and up to 24 months (responders at Month 6)

• Percentage of Participants With Evolution to Myelodysplasia, Paroxysmal Nocturnal Hemoglobinuria (PNH) and Leukemia

  Up to 6 months (non-responders at Month 6) and up to 24 months (responders at Month 6)

Study Arms (1)

Eltrombopag + cyclosporine

EXPERIMENTAL

Participants received eltrombopag (orally, 150 mg once daily for non-Asian participants / 100 mg once daily for participants of Asian ancestry) in combination with cyclosporine (orally, 10.0 mg/kg/day in divided doses every 12 hours) for up to 6 months. Thereafter, responders at Month 6 were treated with cyclosporine until Month 24

Drug: eltrombopag; Drug: Cyclosporine

Interventions

eltrombopag DRUG

Film-coated tablets (12.5 mg, 25 mg, 50 mg and 75 mg) administered orally, once daily for up to 6 months. East and Southeast Asian participants were treated with 100 mg once daily, to adjust for the lower apparent clearance of eltrombopag. All other participants were treated with 150 mg once daily.

Also known as: ETB115

Eltrombopag + cyclosporine

Cyclosporine DRUG

Supplied as oral soft gel capsules. The starting dose was based on body weight at 10.0 mg/kg/day (acceptable rounding range was from 9.5 to 10.5 mg/kg/day) in divided doses every 12 hours. After Day 1, dosing was titrated individually according to therapeutic trough level between 200 and 400 μg/L for 6 months. After 6 months (only for responders at Month 6), tapering of cyclosporine was done as follows: * 6-9 months: at the 6 months visit, the dose was reduced by 25% for 3 months * 9-12 months: at the 9 months visit, the dose was further reduced by 25% for another 3 months * 12-24 months: dose was maintained

Eltrombopag + cyclosporine

Eligibility Criteria

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

You may qualify if:

• Patient had signed the Informed Consent (ICF) prior to any screening procedures
• Patient was male/female ≥18 years old at the time of informed consent and able to swallow a tablet.
• Patient had SAA characterized by:
• Bone marrow cellularity \<30% (excluding lymphocytes) and
• At least two of the following (peripheral blood):
• Absolute neutrophil count \<500/µL
• Platelet count \<20,000/µL
• Absolute reticulocyte count \<60,000/µL
• Normal ECG defined as the following as determined via the mean of a triplicate ECG
• Resting heart rate: 50-90 bpm
• QTcF at screening \<450 msec (for male patients), ≤460 msec (for female patients)

You may not qualify if:

• Diagnosis of Fanconi anemia.
• Evidence of a clonal hematologic bone marrow disorder on cytogenetics by central review
• Prior immunosuppressive therapy with cyclosporine, alemtuzumab, rabbit or horse ATG and thrombopoietin receptor (TPO-R) agonists.
• Hypersensitivity to eltrombopag or cyclosporine or their components.
• AST or ALT \>3 x ULN.
• Serum creatinine, total bilirubin, or alkaline phosphatase \>1.5 x ULN.
• Patient with liver cirrhosis.
• Patients who were human immune deficiency virus (HIV), hepatitis C virus or hepatitis B surface antigen (HBsAg) positive. HCV-RNA negative patients were allowed to be enrolled.
• Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the patient's ability to consent, be compliant with study procedures, tolerate protocol therapy, or that death within 30 days is likely.
• Patients with cancer who were not considered cure, were on active chemotherapeutic treatment or who took drugs with hematological effects.
• Administration of an investigational drug within 30 days or 5 half-lives, whichever was longer, preceding the first dose of study treatment.
• Pregnancy statements and contraception requirements:
• Pregnancy or nursing (lactating) women Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant (or female partners of male patients), unless they were using highly effective methods of contraception during dosing and for 3 months after stopping medication.
• Not able to understand the investigation nature of the study or to give informed consent.
• Clinically significant ECG abnormality including cardiac arrhythmias (e. g. ventricular tachycardia) complete left bundle branch block, high grade atrioventricular block, or inability to determine the QTcF interval on the ECG.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (20)

Novartis Investigative Site

Ribeirão Preto, São Paulo, 14048-900, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 01323-900, Brazil

Location

Novartis Investigative Site

Hong Kong, Hong Kong

Location

Novartis Investigative Site

Hyderabad, Telangana, 500082, India

Location

Novartis Investigative Site

Vellore, India

Location

Novartis Investigative Site

Bologna, BO, 40138, Italy

Location

Novartis Investigative Site

Brescia, BR, 25123, Italy

Location

Novartis Investigative Site

Milan, MI, 20122, Italy

Location

Novartis Investigative Site

Mexico D F, Mexico City, 06726, Mexico

Location

Novartis Investigative Site

Monterrey, Nuevo León, 64460, Mexico

Location

Novartis Investigative Site

Puebla City, 72000, Mexico

Location

Novartis Investigative Site

Seoul, 03722, South Korea

Location

Novartis Investigative Site

Seoul, 06351, South Korea

Location

Novartis Investigative Site

Donostia / San Sebastian, Basque Country, 20080, Spain

Location

Novartis Investigative Site

Madrid, 28041, Spain

Location

Novartis Investigative Site

Bangkok, 10330, Thailand

Location

Novartis Investigative Site

Bangkok, 10700, Thailand

Location

Novartis Investigative Site

Chiang Mai, 50200, Thailand

Location

Novartis Investigative Site

Istanbul, 34890, Turkey (Türkiye)

Location

Novartis Investigative Site

Samsun, 55139, Turkey (Türkiye)

Location

Related Publications (1)

• Scheinberg P, Finelli C, Montano-Figueroa EH, Vallejo C, Norasetthada L, Calado RT, Turgut M, Peffault de Latour R, Kriemler-Krahn U, Haenig J, Clark J, Jang J. Activity and safety of eltrombopag in combination with cyclosporin A as first-line treatment of adults with severe aplastic anaemia (SOAR): a phase 2, single-arm study. Lancet Haematol. 2024 Mar;11(3):e206-e215. doi: 10.1016/S2352-3026(23)00395-2. Epub 2024 Feb 6.

  PMID: 38335978 DERIVED

MeSH Terms

Conditions

Anemia, Aplastic

Interventions

eltrombopag; Cyclosporine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Study director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2016
• First Posted: December 20, 2016
• Study Start: May 11, 2017
• Primary Completion: November 3, 2020
• Study Completion: May 30, 2022
• Last Updated: December 11, 2023
• Results First Posted: December 11, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

BR (2); ME (3); KR (2); IN (2); ES (2); HK (1); TH (3); TU (2); IT (3)