Clinical Trials Register

Summary
EudraCT Number:	2009-009858-24
Sponsor's Protocol Code Number:	CINC424A2352
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-04-03
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2009-009858-24

A.3

Full title of the trial

COntrolled MyeloFibrosis Study with ORal JAK Inhibitor Treatment-II

A.3.1

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

A Randomized Study of the JAK Inhibitor INC424 Tablets Compared to Best Available Therapy in Subjects with Primary Myelofibrosis (PMF), Post-Polycythemia Vera-Myelofibrosis (PPV-MF) or Post-Essential
Thrombocythemia Myelofibrosis (PET-MF)

A.3.2

Name or abbreviated title of the trial where available

The COMFORT-II Trial

A.4.1

Sponsor's protocol code number

CINC424A2352

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 Services 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 Services 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	Belgium
B.5.4	Telephone number	+41613241111
B.5.5	Fax number	+41613248001
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	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/08/572 and EU/3/09/620
D.3 Description of the IMP
D.3.1	Product name	Ruxolitinib
D.3.2	Product code	INC424
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Ruxolitinib
D.3.9.1	CAS number	1092939-17-7
D.3.9.2	Current sponsor code	INC424
D.3.9.3	Other descriptive name	INCB018424
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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

Primary Myelofibrosis (PMF),
Post-Polycythemia Vera-Myelofibrosis (PPV-MF)
or
Post-Essential Thrombocythemia-Myelofibrosis (PET-MF)

E.1.1.1

Medical condition in easily understood language

Primary Myelofibrosis (PMF),
Post-Polycythemia Vera-Myelofibrosis (PPV-MF)
or
Post-Essential Thrombocythemia-Myelofibrosis (PET-MF)

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10028537
E.1.2	Term	Myelofibrosis
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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 compare the efficacy, safety and tolerability of INC424 given twice daily compared to the best-available therapy, in subjects with primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (PPV-MF) and post essential thrombocythemia myelofibrosis (PET-MF).

E.2.2

Secondary objectives of the trial

To evaluate the population pharmacokinetics of INC424.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

All subjects must meet the following inclusion criteria:
1.Subjects 18 years of age or older.
2.Subjects must be diagnosed with PMF, PPV-MF or PET-MF, according to the 2008 World Health Organization criteria, irrespective of JAK2 mutation status.
3.Subjects with myelofibrosis requiring therapy must be classified as high risk (3 or more prognostic factors) OR intermediate risk level 2 (2 or more prognostic factors). The prognostic factors, defined by the International Working Group (Cervantes et al, 2009) are:
•Age > 65 yrs
•Presence of constitutional symptoms (weight loss, fever, night sweats)
•Marked anemia (Hgb < 10g/dL)*
•Leukocytosis (history of WBC > 25 x10 E9/L)
•Circulating blasts ≥1%
* A hemoglobin value < 10 g/dL must be demonstrated during the Screening
Visit for subjects who are not transfusion dependent. Subjects receiving regular
transfusions of packed red blood cells will be considered to have hemoglobin
< 10 g/dL for the purpose of evaluation of risk factors.
4.Subjects with peripheral blood blast count of <10%.
5.Subjects with an ECOG performance status of 0, 1, 2 or 3
6.Subjects must have a palpable spleen measuring 5 cm or greater from the costal margin to the point of greatest splenic protrusion.
7.Subjects must have been on a stable therapeutic regimen for at least 2 weeks before Screening and no less than 4 weeks prior to Baseline.
8.Subjects who have not previously received treatment with a JAK inhibitor

E.4

Principal exclusion criteria

Any of the following are cause for exclusion from the study:
1.Subjects with a life expectancy of less than 6 months.
2.Females who are pregnant or are currently breastfeeding.
3.Subjects of childbearing potential who are unwilling to take appropriate precautions (from Screening through Follow-up) to avoid fathering a child or becoming pregnant.
•Females of non-childbearing potential are defined as postmenopausal if they have a history of amenorrhea for 1 year if over age 55, OR have been surgically sterile for at least 3 months
•For subjects of childbearing potential, appropriate precautions are those that are at least 99% effective in preventing the occurrence of pregnancy. These methods should be communicated to the subjects and their understanding confirmed.
4.Subjects with inadequate bone marrow reserve as demonstrated by:
a.Absolute neutrophil count (ANC) that is ≤ 1000/µL.
b.Platelet count that is < 100,000/µL without the assistance of growth factors, thrombopoietic factors or platelet transfusions.
5.Subjects with any history of platelet counts < 50,000/µL or ANC < 500/µL except during treatment for a myeloproliferative disorder or treatment with cytotoxic therapy for any other reason.
6.Subjects with inadequate liver or renal function as demonstrated by:
a.Direct bilirubin > 2.0x ULN.
b.Alanine aminotransferase (ALT) > 2.5x institutional upper limit of normal (ULN).
c.Creatinine >2.0 mg/dL.
7.Subjects with clinically significant bacterial, fungal, parasitic or viral infection which require therapy:
a.Subjects with acute bacterial infections requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed
b.Patients with known active hepatitis A, B, C or who are HIV-positive.
8.Subjects must not currently have the option of stem cell transplantation, either because they are not a candidate, or because a suitable donor is not available.
9.Subjects with history of malignancy in past 5 years except for treated, early-stage squamous or basal cell carcinoma of the skin.
10.Subjects with cardiac disease which in the Investigator’s opinion may jeopardize the safety of the subject or the compliance with the protocol.
11.Subjects with currently uncontrolled or unstable angina.
12. Subjects under ongoing treatment with another investigational medication or having been treated with an investigational medication within 14 days or 6 half-lives (whichever is longer) prior to enrollment.
13.Subjects for whom the dose or dose-regimen of any therapies used to treat MF has been modified at any time from 2 weeks prior to the start of Screening through the beginning of Baseline evaluations.
14.Subjects who have had splenic irradiation within 12 months prior to Screening.
15.Subjects with currently rapid or paroxysmal atrial fibrillation.
16.Subjects undergoing treatment with hematopoietic growth factor receptor agonists (ie, erythropoietin (Epo), granulocyte colony stimulating factor (GCSF), romiplostim, eltrombopag) at any time within 2 weeks prior to Screening or 4 weeks prior to Baseline.
17.Subjects with recent (approximately 6 months) myocardial infarction or acute coronary syndrome.
18.Resting heart rate > 110 beats per minute.
19.Resting systolic blood pressure > 160 mm Hg.
20.Resting diastolic blood pressure > 100 mm Hg.
21.Subjects who are unable to comprehend or are unwilling to sign an informed consent form (ICF).
22.Subjects with active alcohol or drug addiction which would interfere with their ability to comply with the study requirements.
23.Subjects with any concurrent condition that, in the Investigator’s opinion, would jeopardize the safety of the subject or compliance with the protocol.

E.5 End points

E.5.1

Primary end point(s)

Proportion of subjects achieving 35% reduction in spleen volume from
Baseline to Week 48 as measured by MRI (or by CT for subjects unable
to undergo MRI).

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 48

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

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

Yes

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Best available therapy as selected by Investigator

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

Yes

E.8.2.3.1

Comparator description

Best available therapy as selected by Investigator

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

100

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

Yes

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

The End of Study or Early Termination Visit constitutes the final study visit where study drug has been taken. An End of Study Visit may occur with a planned discontinuation for any reason (eg, at Week 20, it is determined that subject will participate in the study only 1 more month; therefore, the Week 24 Visit will become the End of Study Visit).

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

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

Information not present in EudraCT

F.1.1.2

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

Information not present in EudraCT

F.1.1.3

Newborns (0-27 days)

Information not present in EudraCT

F.1.1.4

Infants and toddlers (28 days-23 months)

Information not present in EudraCT

F.1.1.5

Children (2-11years)

Information not present in EudraCT

F.1.1.6

Adolescents (12-17 years)

Information not present in EudraCT

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

100

F.4.2.2

In the whole clinical trial

100

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)

Treatment & Follow-up: 48 weeks with indefinite extension for subjects receiving benefit; Follow-up occurs 1 month after discontinuing study medication.

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

2009-05-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-05-18

P. End of Trial
P.	End of Trial Status	Completed

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