Clinical Trials Register

Summary
EudraCT Number:	2010-024473-39
Sponsor's Protocol Code Number:	CINC424A2401
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-06-30
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

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A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2010-024473-39

A.3

Full title of the trial

An open-label, multicenter, expanded access study of INC424 for patients with primary myelofibrosis (PMF) of post polycythemia vera myelofibrosis (PPV MF) or post-essential thrombocythemia myelofibrosis (PET-MF)

A.3.1

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

Safety and efficacy study of INC424 in patients with myelofibrosis

A.4.1

Sponsor's protocol code number

CINC424A2401

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 GmbH
B.5.2	Functional name of contact point	Medizinischer Infoservice
B.5.3	Address:
B.5.3.1	Street Address	Roonstr. 25
B.5.3.2	Town/ city	Nürnberg
B.5.3.3	Post code	90429
B.5.3.4	Country	Germany
B.5.4	Telephone number	+491802232300
B.5.5	Fax number	+49911273 12 160
B.5.6	E-mail	infoservice.novartis@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	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	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	RUXOLITINIB PHOSPHATE
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)	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.IMP: 2
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	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	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	Ruxolitinib Phosphate
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	10
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

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

Myelofibrosis

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

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 collect additional safety of INC424 in patients with PMF, PPV MF, or
PET MF, who have either received prior treatment with commercially
available agents or never received treatment

E.2.2

Secondary objectives of the trial

To access the best overall response rate of INC424 in patients with PMF,
PPV MF, or PET-MF as evaluated by the Investigator.
To collect (QoL) information in patients with PMF, PPV MF, or PET-MF
treated with INC424.
To document MRU in patients with PMF, PPV MF, or PET-MF treated with
INC424

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients must give written informed consent according to local
guidelines prior to any screening procedures.
2. Patients must not be eligible for another ongoing INC424 clinical trial.
3. Male or female patients aged ≥ 18 years of age.
4. Patients must be diagnosed with PMF, PPV-MF or PET-MF, according to
the 2008 revised International Standard Criteria , irrespective of JAK2
mutation status.
5. Patients with PMF requiring therapy must be classified as high risk (3 prognostic factors) OR intermediate risk level 2 (2 prognostic factors, no
more), OR intermediate risk level 1 with an enlarged spleen at the
screening visit (assessment to occur at the Screening Visit). The
prognostic factors, defined by the International Working Group
(Cervantes 2009) are described in Section 1.1 and Section 5.2 and
should be evaluated at the Screening Visit.
6. Patients with Intermediate-1 and splenomegaly, must have a palpable
spleen measuring 5 cm or greater from the costal margin to the point of
greatest splenic protrusion.
7. Patients with a peripheral blood blast percentage count of < 10%.
8. Patients with adequate liver function defined as total bilirubin or
direct bilirubin ≤ 2.0 x ULN, and ALT ≤ 2.5 x ULN.
9. Patients with adequate renal function defined as serum creatinine
≤ 2 x ULN.
10. Patients with an ECOG performance status of 0, 1, or 2
11. Women of childbearing potential must have had a negative serum
pregnancy test within 14 days prior to the administration of study drug.
12. Patients must have recovered or stabilized sufficiently from any
adverse drug reactions associated with prior treatments before
beginning treatment with INC424

E.4

Principal exclusion criteria

1. Patients eligible for hematopoietic stem cell transplantation (suitable candidate and a suitable donor is available).
2. Patients with a history of malignancy in the past 3 years, except for
treated early stage squamous or basal cell carcinoma in situ.
5. Patients receiving any medications listed in the "Prohibited
Medications" listing
6. Impairment of GI function or GI disease that may significantly alter
the absorption of INC424
7. Patients with cardiac disease which in the Investigator's opinion may
jeopardize the safety of the patient or the compliance with the protocol.
8. Patients with currently uncontrolled or unstable angina, rapid or
paroxysmal fibrillation or recent (approximately 6 months) myocardial
infarction or acute coronary syndrome.
9. Patients with clinically significant bacterial, fungal, parasitic or viral
infection that requires therapy. Patients with acute bacterial infections
requiring antibiotic use should delay screening/enrollment until the
course of antibiotic therapy has been completed.
10. Patients with known active hepatitis A, B, C or who are HIV-positive.
11. Patients with inadequate bone marrow reserve at baseline visit as demonstrated by:
(a) ANC that is ≤ 1000/μL.
(b) Platelet count that is <75,000/μL without the assistance of growth
factors, thrombopoietic factors or platelet transfusions.
12. Patients with any history of platelet counts < 50,000/μL or ANC
<500/μL except during treatment for a MPD or treatment with cytotoxic
therapy for any other reason.
13. Patients with coagulation parameters (PT, PTT, INR) >1.5 x ULN.
14. Patients with known hypersensitivity to INC424 or other JAK1/JAK2
inhibitors, or to its excipients.
15. Patients receiving ongoing treatment with another investigational
medication or having been treated with an investigational medication
within 30 days of study drug treatment.
16. Pregnant or nursing (lactating) women, where pregnancy is defined
as the state of a female after conception and until termination of
gestation, confirmed by a positive βHCG laboratory test (> 5 mIU/mL).
17. Women of child-bearing potential, defined as all women
physiologically capable of becoming pregnant, including women whose
career, lifestyle, or sexual orientation precludes intercourse with a male
partner and women whose partners have been sterilized by vasectomy
or other means, UNLESS they are using highly effective contraception
methods (see Appendix II) defined as:
- Total abstinence and
- Female sterilization
- Combination of any two of the following (a+b or a+c or b+c):
(a) Use of oral, injected or implanted hormonal methods of
contraception
(b) Placement of an intrauterine device (IUD) or intrauterine system
(IUS)
(c) Barrier methods of contraception: Condom or Occlusive cap
(diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/ vaginal suppository
18. Patients who are unable to comprehend or are unwilling to sign an
ICF.
19. Patients with active alcohol or drug addiction that would interfere
with their ability to comply with the study requirements.
20. Patients with any concurrent condition that, in the Investigator's
opinion, would jeopardize the safety of the patient or compliance with
the protocol.

E.5 End points

E.5.1

Primary end point(s)

Safety and tolerability will be collected by monitoring the frequency,
duration and severity of all grade AEs by the National Cancer Institute
CTCAE v. 3 0, performing physical exams (PE), and evaluating changes in
vital signs (VS), ECOG performance status (PS), electrocardiograms
(ECGs) and serum chemistry and hematology results.
Grade 3 and 4 AEs, Serious Adverse Events (SAEs).
Laboratory values from Baseline to End of Treatment (serum chemistry
and hematology).
Changes in weight from Baseline to each assessment point and at end of
treatment.
Cardiac function as assessed by electrocardiograms (ECGs).
Changes in vital signs.

E.5.1.1

Timepoint(s) of evaluation of this end point

Monthly for the first 3 months, then every 3 months and at study discontinuation

E.5.2

Secondary end point(s)

Quality of Life
- Change in ECOG PS from Baseline to each visit where measured.
-Change in Functional Assessment of Cancer Therapy for patients with
Lymphoma (FACT-Lym) version 4 from Baseline to each visit where
measured
- Change in Functional Assessment of Chronic Illness Therapy (FACIT)
Fatigue from baseline to each visit where measured
Medical resource utilization (MRU)
Medical resource utilization (MRU) will be assessed as follows:
- Frequency and duration of hospitalization from Baseline up to week 48
of therapy
- Frequency of emergency room visits from Baseline up to week 48 of
therapy.
- Frequency of general practitioner, specialist, and urgent care visits
from Baseline up to week 48 of therapy.
- Number of transfusions and transfusion dependency status end of
study.
- Splenectomy and use of splenic irradiation.
- Changes in use of concomitant medications for MPN symptom
management
Efficacy
- Best overall response to treatment as assessed by spleen palpation
(calculated as the percentage change in spleen length compared with
Baseline)
- Change in spleen length from Baseline to end of each visit.
- WBC and platelet count changes from Baseline will be summarized at
end of each visit/month of therapy and at end of treatment.
- Shift in fibrosis in the bone marrow from Baseline to worst/best value
on study (where bone marrow biopsies are performed – not mandatory).
- Progression free survival, acute myeloid leukemia free survival and overall survival.
- In patients without splenomegaly, efficacy assessments will only be
provided by the patient reported outcomes that measure symptoms of
the disease.

E.5.2.1

Timepoint(s) of evaluation of this end point

Monthly for the first 3 months, then every 3 months and at study discontinuation

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

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

Quality of Life
Medical resource utilization (MRU)

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

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

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

E.8.5.1

Number of sites anticipated in the EEA

252

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

Algeria

Argentina

Brazil

Canada

Colombia

Egypt

Israel

Korea, Republic of

Kuwait

Lebanon

Mexico

Morocco

Russian Federation

Saudi Arabia

Singapore

South Africa

Switzerland

Taiwan

Thailand

Tunisia

United Arab Emirates

Venezuela, Bolivarian Republic of

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

LPLV

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

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	180
F.4.2	For a multinational trial
F.4.2.1	In the EEA	900
F.4.2.2	In the whole clinical trial	1600

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	PPD
G.4.3.4	Network Country	United States

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2011-07-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-08-11

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-01-26

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