Clinical Trials Register

Summary
EudraCT Number:	2016-002814-29
Sponsor's Protocol Code Number:	CETB115E2403
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-07-05
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2016-002814-29

A.3

Full title of the trial

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 vizsgálat, mely két részből áll: II. fázisú, beavatkozással járó, egykaros vizsgálat az első vonalbeli kezelésként adott eltrombopag + ciklosporin kombináció hatásosságának és biztonságosságának felmérésére súlyos szerzett aplasticus anaemiás betegeknél, legfeljebb a 60. hónapig tartó követéssel.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

SOAR vizsgálat: Eltrombopag + ciklosporin kombináció mint a súlyos szerzett aplasticus anaemiás betegek első vonalbeli kezelése legfeljebb a 60. hónapig tartó követéssel

A.3.2

Name or abbreviated title of the trial where available

SOAR

A.4.1

Sponsor's protocol code number

CETB115E2403

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novartis Pharma AG
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Novartis Pharma AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Pharma AG
B.5.2	Functional name of contact point	Clinical Trial Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Forum 1, Novartis Campus
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4056
B.5.3.4	Country	Switzerland
B.5.6	E-mail	clinicaltrial.enquiries@novartis.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	REVOLADE
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Ltd
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Eltrombopag
D.3.2	Product code	ETB115
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ELTROMBOPAG
D.3.9.1	CAS number	496775-61-2
D.3.9.2	Current sponsor code	ETB115
D.3.9.4	EV Substance Code	SUB30140
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	12.5 to 75
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

First-line severe aplastic anaemia

E.1.1.1

Medical condition in easily understood language

First-line severe aplastic anaemia

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10002967
E.1.2	Term	Aplastic anaemia
E.1.2	System Organ Class	10005329 - Blood and lymphatic system disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

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

E.2.2

Secondary objectives of the trial

Obj. 1: Evaluate the effect of ETB + CsA on overall hematologic response (neutrophil, platelet, hemoglobin) by 6 Mon (months) and evaluate the overall hematologic response by 3 Mon and at Mon 12 for responders.
All of the following secondary objectives will be assessed by 6 Mon, 30 Mon and 60 Mon 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 blood transfusion need
Obj. 6: Evaluate the platelet transfusion need
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

E.2.3

Trial contains a sub-study

E.3

Principal 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 (for male patients), 460 msec (for female patients)

E.4

Principal 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. a. Hypersensitivity to eltrombopag or cyclopsorine or their components.
b. Contraindications to cyclosporine
5.AST or ALT >3 x ULN.
6.Serum creatinine, total bilirubin, and alkaline phosphatase >1.5 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 or replaced by safe alternative medication per www.qtdrugs.org.

E.5 End points

E.5.1

Primary end point(s)

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%.

E.5.1.1

Timepoint(s) of evaluation of this end point

Overall hematologic response rate by 6 months

E.5.2

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.

E.5.2.1

Timepoint(s) of evaluation of this end point

hematologic response rate by 3 months and at 12 months

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Biomarkers

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Brazil

France

Hong Kong

Hungary

India

Italy

Korea, Republic of

Mexico

Netherlands

Spain

Turkey

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Second treatment line for SAA

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-09-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-09-06

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-05-30

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials