SOAR Trial: Eltrombopag combined with cyclosporine as first line therapy in patients with severe acquired aplastic anemia with follow-up up to 60-months.

• Register: EUCTR
• Last refreshed on: 12 July 2021
• Main ID: EUCTR2016-002814-29-ES
• Date of registration: 16/12/2016
• Prospective Registration: Yes
• Primary sponsor: Novartis Farmacéutica, S.A
• Public title: SOAR Trial: Eltrombopag combined with cyclosporine as first line therapy in patients with severe acquired aplastic anemia with follow-up up to 60-months.
• 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. - SOAR
• Date of first enrolment: 21/03/2017
• Target sample size: 50
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002814-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: Departamento Médico (GMO)
• Affiliation: Novartis Farmacéutica, S.A

• Name: Departamento Médico (GMO)
• Affiliation: Novartis Farmacéutica, S.A

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/female =6 years old at the time of informed consent and able to swallow a tablet.
3.Patient has SAA characterized by:
a.Bone marrow cellularity <30% (excluding lymphocytes) and
b.At least two of the following (peripheral blood):
•Absolute neutrophil count <500/ µL
•Platelet count <20,000/ µL
•Absolute reticulocyte count <60,000/ µL
4.Normal ECG defined as the following as determined via the mean of a triplicate ECG
• Resting heart rate
6-<12 years: 60-130 bpm
12-<18 years: 60-120 bpm
=18 years: 50-90 bpm
•QTcF at screening <450 msec (male patients), 460 msec (female patients)
Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
1.Diagnosis of Fanconi anemia.
2.Evidence of a clonal hematologic bone marrow disorder on cytogenetics. Patients with very severe neutropenia (ANC < 200 /µL) 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 >3 x ULN.
6.Creatinine, total bilirubin, and alkaline phosphatase >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 patient’s 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.
In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.
13.Not able to understand the investigation nature of the study or to give informed consent.
14.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.
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:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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

First-line severe aplastic anaemia
MedDRA version: 19.0 Level: PT Classification code 10002967 Term: Aplastic anaemia System Organ Class: 10005329 - Blood and lymphatic system disorders

Intervention(s)

Trade Name: REVOLADE
Product Name: Eltrombopag
Product Code: ETB115
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ELTROMBOPAG
CAS Number: 496775-61-2
Current Sponsor code: ETB115
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Trade Name: REVOLADE
Product Name: Eltrombopag
Product Code: ETB115
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ELTROMBOPAG
CAS Number: 496775-61-2
Current Sponsor code: ETB115
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Primary end point(s): Primary analysis will be done after all the patients enrolled have completed 6 months of treatment with eltrombopag+cyclosporine or discontinued treatment with eltrombopag prior to 6 months for evaluating the primary endpoint.

Timepoint(s) of evaluation of this end point: The primary objective of the study is to evaluate the eltrombopag + cyclosporine as first-line therapy as assessed by the overall hematologic response rate by 6 months. Bayesian approach will be used for analysis of the primary endpoint. The primary analysis will be based on the calculation of observed overall hematologic response rate by 6 months and its posterior distribution using a beta-binomial model. Combination therapy of eltrombopag + cyclosporine will be declared efficacious if the following criteria are met:
a. Observed hematologic ORR = “clinically meaningful” threshold (30%)
b. Probability of true ORR “not being clinically meaningful (response = 20%) is less than 10%.

Main Objective: To evaluate the efficacy of eltrombopag + cyclosporine as first-line therapy on overall hematologic response (neutrophil, platelet, hemoglobin) by 6 months

Secondary Objective: Obj. 1: Evaluate the effect of ETB + CsA on overall hematologic response (neutrophil, platelet, hemoglobin) by 3 and 12 months
All of the following secondary objectives will be assessed by 6 months, 30 months and 60 months as appropriate and will be reported in a cumulative basis
Obj. 2: Evaluate the duration of hematologic response
Obj. 3: Evaluate disease relapse rate
Obj. 4: Evaluate the clonal evolution to myelodysplasia, paroxysmal nocturnal hemoglobinuria (PNH), and leukemia
Obj. 5: Evaluate the need for blood transfusion
Obj. 6: Evaluate the need for platelet transfusion
Obj. 7: Evaluate the duration of platelet and blood transfusion independence
Obj. 8: Evaluate overall survival (OS)
Obj. 9: Evaluate the effect of ETB and CsA on patient symptoms and health related quality of life
Obj. 10: Evaluate the safety and tolerability of ETB + CsA
Obj. 11: Characterize the PK of ETB when combined to CsA

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: The primary analysis will be conducted and the primary CSR will be written 6 M (months) after all the patients enrolled have completed 6 M of treatment with eltrombopag+cyclosporine or discontinued treatment with eltrombopag prior to 6 M.
The second CSR will be written based on the cumulative data obtained after all the patients enrolled have completed 30 M tapering of cyclosporine or discontinued treatment with cyclosporine prior to 30 M.
The final analysis will be done after all the patients enrolled completed 60 M in the study or discontinued the study prior to 60 M, based on which the final CSR will be written.
Overall survival will be reported by 6 months (EOT with Eltrombopag), by 30 M (EOT with Cyclosporine) and by the completion of 60 M (end of study).

Secondary end point(s): Second analysis will be done after all the patients enrolled have completed 30 months of treatment with cyclosporine or discontinued treatment with cyclosporine prior to 30 months.

Secondary ID(s)

CETB115E2403

Source(s) of Monetary Support

Novartis Pharma AG

Ethics review

Status: Approved
Approval date: 18/01/2017
Contact: