Clinical Trials Register

Summary
EudraCT Number:	2012-002318-37
Sponsor's Protocol Code Number:	INCB18424-357
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:	2012-09-27
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2012-002318-37

A.3

Full title of the trial

Polycythemia Vera Symptom Study Evaluating Ruxolitinib Versus Hydroxyurea in a Randomized, Multicenter, Double-Blind, Double-Dummy, Phase 3 Efficacy and Safety Study of Patient Reported Outcomes

A.3.1

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

Randomized Polycythemia Vera Symptom Study comparing the effectiveness and patient assessed effects of Ruxolitinib with Hydroxyurea in a Phase 3 trial

A.3.2

Name or abbreviated title of the trial where available

The RELIEF Study

A.4.1

Sponsor's protocol code number

INCB18424-357

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01632904

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	Incyte Corporation
B.1.3.4	Country	United States
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	Incyte Corporation
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Incyte Corporation
B.5.2	Functional name of contact point	Incyte Call Centre
B.5.3	Address:
B.5.3.1	Street Address	Rt 141 & Henry Clay Road
B.5.3.2	Town/ city	Wilmington
B.5.3.3	Post code	DE 19880
B.5.3.4	Country	United States
B.5.4	Telephone number	18554633463
B.5.5	Fax number	13024252734
B.5.6	E-mail	regaffairs@incyte.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	Jakafi
D.2.1.1.2	Name of the Marketing Authorisation holder	Incyte Corporation
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	ruxolitinib
D.3.2	Product code	INCB018424
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.3.9.3	Other descriptive name	RUXOLITINIB
D.3.9.4	EV Substance Code	SUB29286
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	Comparator
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	Par Hydroxyurea
D.2.1.1.2	Name of the Marketing Authorisation holder	Par Pharmaceutical Inc
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Hydroxyurea
D.3.4	Pharmaceutical form	Capsule, hard
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	HYDROXYCARBAMIDE
D.3.9.3	Other descriptive name	Hydroxyurea
D.3.9.4	EV Substance Code	SUB08076MIG
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	500
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Polycythemia Vera

E.1.1.1

Medical condition in easily understood language

Polycythemia Vera

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 compare the efficacy of ruxolitinib and HU for reducing the cluster of symptoms defined by tiredness, itching, muscle aches, night sweats, and sweats while awake in subjects with PV.

E.2.2

Secondary objectives of the trial

To compare the efficacy of ruxolitinib and HU for reducing the following individual symptoms:
− Tiredness
− Itching
− Muscle aches
− Night sweats
− Sweats while awake
• To evaluate the durability of symptomatic improvement in subjects experiencing relief from the cluster of symptoms that includes tiredness, itching, muscle aches, night sweats, and sweats while awake, and for each of these symptoms individually.
• To evaluate the safety of ruxolitinib and HU.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Men or women aged ≥ 18 years with a confirmed diagnosis of PV according to the revised World Health Organization criteria.
• Subjects must currently be reporting symptoms on a stable dose of HU monotherapy and be eligible to continue HU on study after randomization. Before screening, the subject must have been receiving HU for at least 12 weeks and on the same dose for the last 4 weeks.
• Subjects must have completed the modified MPN-SAF screening symptom form and have a screening total symptom score (TSS) of ≥ 8 for the cytokine-related symptoms, or symptom cluster C (TSS-C): tiredness, itching, muscle aches, night sweats, and sweats while awake.
• Subjects should meet at least one of the following criteria with respect to phlebotomy and splenomegaly:
− No more than 2 phlebotomies within the 6 months before screening OR
− No palpable splenomegaly
• Subjects must have a hematocrit that can be controlled within 35% to 48% (inclusive) before randomization. (A phlebotomy may be performed during the screening phase to achieve this target range.)
• Subjects must have recovered from all side effects associated with phlebotomy, and at least 1 week must have elapsed between the phlebotomy and the beginning of the baseline phase.
• Subjects with Eastern Cooperative Oncology Group performance status of 0, 1, or 2 at screening.

E.4

Principal exclusion criteria

• Subjects with inadequate liver or renal function at screening as demonstrated by:
− Encephalopathy ≥ Grade 2 as per Child-Pugh System
− Hepatocellular disease
− Total bilirubin > 2 × upper limit of normal (ULN), unless direct bilirubin is < 2 × ULN
− Alanine aminotransferase > 2.5 × ULN
− Modification of Diet in Renal Disease estimated glomerular filtration rate < 30 mL/min/1.73 m2 or on dialysis
• Subjects with platelet count < 100 × 10^9/L or an absolute neutrophil count of < 1 × 10^9/L
• Subjects with peripheral blood blast count of > 0% at screening.

E.5 End points

E.5.1

Primary end point(s)

Proportion of subjects with ≥ 50% reduction in the TSS-C (tiredness, itching, muscle aches, night sweats, and sweats while awake) at Week 16 compared to baseline, as measured by the modified MPN-SAF diary.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 16

E.5.2

Secondary end point(s)

• Proportion of subjects with ≥ 50% reduction in individual symptoms at Week 16 compared to baseline, as measured by the modified MPN-SAF diary for the following items:
− Tiredness
− Itching
− Muscle aches
− Night sweats
− Sweats while awake
Noncomparative Secondary Endpoints
• Proportion of subjects in Arm A who achieve a durable response, defined as a ≥ 50% reduction in TSS-C at Week 16 that is maintained at Week 48.
• Proportions of subjects in Arm A who achieve a durable response, defined as a ≥ 50% reduction in the individual symptoms in TSS-C (tiredness, itching, muscle aches, night sweats, and sweats while awake) at Week 16 that is maintained at Week 48.
• Safety of ruxolitinib and HU.

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 16 and 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

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

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

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)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Hydroxyurea

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

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

United States

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

Subjects who remain on study at the end of the formal data collection period (when all enrolled subjects have reached Week 48 on study or have been withdrawn) will be withdrawn from the study.

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

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)

F.1.1.6

Adolescents (12-17 years)

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

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)

None

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

2012-09-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-11-08

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-06-24

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