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

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2017/06/008898
• Date of registration: 22-06-2017
• Prospective Registration: Yes
• Primary sponsor: Novartis Healthcare Pvt Ltd
• Public title: Eltrombopag Combined With Cyclosporine (antibiotic) as First Line Therapy in Patients With Severe Acquired Aplastic Anemia
• Scientific title: SOAR Trial, A two-part study: Interventional phase II single-arm trial to assess efficacy and safety of Eltrombopag combined with cyclosporine as first line therapy in patients with severe acquired aplastic anemia, and an extension with up to 60-months follow-up
• Date of first enrolment: 17-07-2017
• Target sample size: 50
• Recruitment status: Closed to Recruitment of Participants
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=17320
• Study type: Interventional
• Study design: Single Arm Trial; Method of generating randomization sequence:Not Applicable Method of allocation concealment:Not Applicable Blinding and masking:Open Label
• Phase: Phase 2

Countries of recruitment

Brazil, Canada, France, Hong Kong, Hungary, India, Italy, Mexico, Qatar, Republic of Korea, Spain, Turkey

Contacts

• Name: Murugananthan K
• Affiliation: Novartis Healthcare Pvt Limited

• Name: Murugananthan K
• Affiliation: Novartis Healthcare Pvt Limited

Key inclusion & exclusion criteria

Inclusion criteria: 1. Patient has signed the Informed Consent (ICF) prior to any screening procedures being performed

2. Patient is male or female more than 6 years old at the time of informed consent and able to swallow a tablet

3.Patient has SAA characterized by

Bone marrow cellularity less than 30% (excluding lymphocytes) and At least two of the following (peripheral blood):

Absolute neutrophil count less than 500 per microliter

Platelet count less than 20000 per microliter

Absolute reticulocyte count less than 60000 per microliter



4.Normal ECG defined as the following as determined via the mean of a triplicate ECG

Resting heart rate 6 to 12 years is 60 to 130 bpm 12 to 18 years is 60 to 120 bpm 18 years and above is 50 to 90 bpm

QTcF at screening less than 450 msec (male patients) 460 msec (female patients)




Exclusion criteria: 1.Diagnosis of Fanconi anemia.

2.Evidence of a clonal hematologic bone marrow disorder on cytogenetics. Patients with very severe neutropenia (ANC less than 200 per microliter) will not be excluded initially if cytogenetics are not available or pending. If a clonal disorder is identified the patient will be excluded.

3.Prior immunosuppressive therapy with cyclosporine alemtuzumab rabbit or horse ATG and thrombopoietin receptor (TPO-R) agonists.

4.Hypersensitivity to eltrombopag or its components.

5.AST or ALT more than 3 x ULN.

6.Creatinine total bilirubin and alkaline phosphatase more than 3 x ULN .

7.Patient with liver cirrhosis.

8.Infection not adequately controlled with appropriate therapy.

9.Moribund status or concurrent hepatic renal cardiac neurologic pulmonary infectious or metabolic disease of such severity that it would preclude the patients ability to consent be compliant with study procedures tolerate protocol therapy or that death within 30 days is likely.

10.Patients with cancer who are not considered cure are on active chemotherapeutic treatment or who take drugs with hematological effects.

11.Administration of an investigational drug within 30 days or 5 half lives whichever is longer preceding the first dose of study treatment.

12.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 are using highly effective methods of contraception during dosing and for 3 months after stopping medication.

13.Not able to understand the investigation nature of the study or to give informed consent.

14.Clinically significant ECG abnormality including cardiac arrhythmias (ventricular tachycardia) complete left bundle branch block high grade atrioventricular block or inability to determine the QTcF interval on the ECG.

15.Presence of cardiac disease or family history of idiopathic sudden death or congenital long QT syndrome.

16.Risk factors for Torsades de Pointe including uncorrected hypokalemia or hypomagnesemia or use of concomitant medication(s) with a known risk to prolong the QT interval that cannot be discontinued.



Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- Patients with severe acquired aplastic anemia

Intervention(s)

Intervention1: Eltrombopag along with Cyclosporine: Eltrombopag Film-coated tablets 12.5 mg, 25 mg, 50 mg and 75 mg administered orally once daily. Dosing is done according to age and ethnicity
Cyclosporine Supplied in oral soft gel capsules or oral solution and dosage is based on body weight and administered every 12 hours. Dosing is titrated individually according to therapeutic trough level for 6 months.
Control Intervention1: NA: NA

Primary Outcome(s)

Overall hematologic response (CR plus PR) rateTimepoint: 6 months

Secondary Outcome(s)

Percentage of patients who received platelet transfusionTimepoint: up to 60 months

Duration of platelet and blood transfusion independenceTimepoint: 6 30 and 60 months

Overall survival of participantsTimepoint: 6 30 and 60 months

Overall hematologic response (CR plus PR) rateTimepoint: 3 and 12 months

Percentage of patients who received a blood transfusionTimepoint: up to 60 months

Pharmacokinetic parameter- Cmax of eltrombopag when combined with cyclosporineTimepoint: Week 2:hour 0,2,4,6,8 Week 4,8,12,26: hour 0

Duration of hematologic responseTimepoint: upto 60 months

Pharmacokinetic parameter- AUCtau of eltrombopag when combined with cyclosporineTimepoint: Week 2:hour 0,2,4,6,8 Week 4,8,12,26: hour 0

Pharmacokinetic parameter- CLss/F of eltrombopag when combined with cyclosporineTimepoint: Week 2:hour 0,2,4,6,8 Week 4,8,12,26: hour 0

Change in scores of FACT-TH18 Patient Reported OutcomeTimepoint: Baseline 6 and 30 months

Pharmacokinetic parameter- Ctrough of eltrombopag when combined with cyclosporineTimepoint: Time Frame: Week 2:hour 0,2,4,6,8 Week 4,8,12,26: hour 0

Change in scores of FACIT-Fatigue Patient Reported OutcomeTimepoint: Baseline 6 and 30 months

Percentage of patients with clonal evolution to myelodysplasia, PNH, acute leukemiaTimepoint: 6 30 and 60 months

Pharmacokinetic parameter- Tmax of eltrombopag when combined with cyclosporineTimepoint: Week 2:hour 0,2,4,6,8 Week 4,8,12,26: hour 0

Pharmacokinetic parameter-AUClast of eltrombopag when combined with cyclosporineTimepoint: Week 2:hour 0,2,4,6,8 Week 4,8,12,26: hour 0

Percentage of patients treated with immunosuppressive therapy (IST)Timepoint: 6 30 and 60 months

Secondary ID(s)

CETB115E2403-Protocol Version 01 dated 17-May-2017

NCT02998645

Source(s) of Monetary Support

Novartis Pharma AG, Basel, Switzerland.

Ethics review

Status: Approved
Approval date: 10/06/2017
Contact:

Institutional Review Board

Status: Approved
Approval date: 28/09/2018
Contact:

Institutional Ethics Committee, Yashoda Academy of Medical Education and Research