Clinical Trials Register

Summary
EudraCT Number:	2018-003296-35
Sponsor's Protocol Code Number:	CINC424G12201
National Competent Authority:	Greece - EOF
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2019-10-21
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

Greece - EOF

A.2

EudraCT number

2018-003296-35

A.3

Full title of the trial

A Phase II open-label, single-arm, multi-center study of ruxolitinib added to corticosteroids in pediatric subjects with moderate and severe chronic graft vs. host disease after allogeneic stem cell transplantation

A.3.1

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

Activity, safety and pharmacokinetics in pediatric subjects with moderate and severe chronic graft vs. host disease after allogeneic stem cell transplant

A.4.1

Sponsor's protocol code number

CINC424G12201

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/061/2018

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 (Hellas) S.A.C.I.
B.5.2	Functional name of contact point	Medical Information Desk
B.5.3	Address:
B.5.3.1	Street Address	National Road No 1 (12th km)
B.5.3.2	Town/ city	Metamorphosis, Athens
B.5.3.3	Post code	GR-144 51
B.5.3.4	Country	Greece
B.5.4	Telephone number	+30 2 102816415
B.5.5	Fax number	+30 2 102850590
B.5.6	E-mail	medinfo.gr@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	Jakavi
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
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	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.3.9.4	EV Substance Code	SUB32897
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.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

chronic graft versus host disease

E.1.1.1

Medical condition in easily understood language

graft versus host disease

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10064677
E.1.2	Term	Graft versus host disease in intestine
E.1.2	System Organ Class	100000004870

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10075161
E.1.2	Term	Graft versus host disease in GI tract
E.1.2	System Organ Class	100000004870

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the activity of ruxolitinib added to standard dose corticosteroids +/- CNI in pediatric subjects with moderate or severe treatment naivecGvHD or SR-cGvHD measured by overall response rate (ORR) at Cycle 7 Day 1 based on all subjects in the study

E.2.2

Secondary objectives of the trial

- To assess pharmacokinetics (PK) of
ruxolitinib in treatment-naïve cGvHD
and SR-cGvHD pediatric subjects
- To evaluate the safety of ruxolitinib  
- To assess duration of response (DOR)
- To estimate ORR at end of Cycle 3
- To assess best overall response (BOR)
- To estimate the failure free survival (FFS)
- To assess cumulative incidence of malignancy relapse/recurrence (MR)
- To assess non-relapse mortality (NRM)
- To assess overall survival (OS)
- To assess a reduction of at least ≥ 50% in daily corticosteroid use at Cycle 7 Day 1
- To assess a reduction to a low dose corticosteroid dose at Cycle 7 Day 1
- To assess graft failure

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Male or female subjects age ≥28 days and <18
years at the time of informed consent.
• Subjects who have undergone alloSCT from any
donor source (matched unrelated donor, sibling, haploidentical) using bone marrow, peripheral blood stem cells, or cord blood. Recipients of myeloablative or reduced intensity conditioning are eligible.
• Subjects with diagnosed moderate to severe
cGvHD according to NIH 2014 Consensus Criteria
(Section 16.2) prior to Cycle 1 Day 1. Other possible
diagnoses for clinical symptoms supporting cGvHD
diagnoses must be excluded (e.g., infection, drug side effects, malignancy). Subjects must be either:
o Treatment-naive cGvHD subjects that have not
received any prior systemic treatment for cGvHD
except for a maximum 72h of prior systemic
corticosteroid therapy of methylprednisolone or
equivalent after the onset of chronic GvHD. Subjects
are allowed to have received prior systemic treatment for cGvHD prophylaxis (as long as the prophylaxis was started prior to the diagnosis of cGvHD).
OR
o Steroid-refractory moderate to severe cGvHD as
per institutional criteria, and still receiving systemic
corticosteroids for the treatment of cGvHD for a
duration of <18 months prior to Cycle 1 Day 1. In case the corticosteroids were interrupted due to response,
the duration of < 18 months applies to the last period of corticosteroid use.

Additional inclusion criteria as per fulll protocol may apply.

E.4

Principal exclusion criteria

• SR-cGvHD subjects with a prior cGvHD
treatment with a JAK1- or a JAK2- or a JAK1/2-inhibitor, except when the subject achieved
complete or partial response and has been off JAK
inhibitor treatment for at least 4 weeks prior to Cycle Day 1 or up to 5 times the half-life of the prior JAK inhibitor, whichever is longer.
* Subjects who initiated systemic calcineurin
inhibitors (CNI; cyclosporine or tacrolimus) within 3
weeks prior to start of ruxolitinib on Cycle 1 Day 1.
Note: systemic CNI are allowed when initiated > 3
weeks from start of ruxolitinib.
• Failed prior alloSCT within the past 6 months
• Significant respiratory disease including subjects
who are on mechanical ventilation or who have a
resting oxygen saturation < 90% by pulse-oximetry on room-air.
• Impairment of gastrointestinal (GI) function
(unrelated to GvHD) or GI disease (unrelated to
GvHD) that may significantly alter the absorption of
oral ruxolitinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection),
• Cholestatic disorders, or unresolved sinusoidal
obstructive syndrome/veno-occlusive disease of the
liver (defined as persistent bilirubin abnormalities not attributable to cGvHD and ongoing organ dysfunction)
• Presence of clinically active uncontrolled
infection including significant bacterial, fungal, viral or parasitic infection requiring treatment.
• Known human immunodeficiency virus (HIV)
infection.
• Evidence of uncontrolled hepatitis B virus (HBV)
or hepatitis C virus (HCV) based on assessment done
by Investigator or delegate.
• Known allergies, hypersensitivity, or intolerance
to any of the study medications, excipients, or similar compounds.
• History of bone disorders such as osteogenesis
imperfecta, rickets, renal osteodystrophy,
osteomyelitis, osteopenia, fibrous dysplasia,
osteomalacia etc. prior to the underlying diagnosis
which resulted in the alloSCT.
• History of endocrine or kidney related growth
retardation prior to the underlying diagnosis which
resulted in the alloSCT.
• Evidence of clinically active tuberculosis (clinical
diagnosis per local practice)
• Any corticosteroid therapy for indications other
than cGvHD at doses > 1 mg/kg/day methylprednisolone (or equivalent prednisone dose 1.25 mg/kg/day) within 7 days of the screening visit.
• History of progressive multifocal leukoencephalopathy (PML).
• Presence of severely impaired renal function

Other protocol-defined inclusion/exclusion criteria may apply.

E.5 End points

E.5.1

Primary end point(s)

Overall Response Rate ORR defined as the
proportion of subjects demonstrating a complete
response (CR) or partial response (PR) without the
requirement of additional systemic therapies for an
earlier progression, mixed response or non-response

E.5.1.1

Timepoint(s) of evaluation of this end point

Cycle 7 Day 1 (Day 168)

E.5.2

Secondary end point(s)

1. Ruxolitinib concentrations by timepoint
2. Duration of response (DOR) assessed for
responders only. DOR is defined as the time from first response until cGvHD progression, death, or the date of addition of systemic therapies for cGvHD
3. Proportion of subjects who achieve OR (CR+PR)
at Cycle 4 Day 1
4. Proportion of subjects who achieved OR (CR+PR) at any time point
5. Composite time to event endpoint incorporating the following FFS events: i) relapse or recurrence of
underlying disease or death due to underlying disease, ii) non-relapse mortality, or iii) addition or initiation of another systemic therapy for cGvHD
6. Malignancy relapse/recurrence (MR) is defined
as the time from date of treatment assignment to
hematologic malignancy relapse/recurrence.
Calculated for subjects with underlying hematologic malignant disease
7. Non-relapse mortality (NRM), defined as the time
from date of treatment assignment to date of
death not preceded by underlying disease
relapse/recurrence.
8. Overall survival, defined as the time from the
date of treatment assignment to the date of death due to any cause
9. Proportion of subjects with ≥ 50% reduction from
baseline in daily corticosteroid dose at Cycle 7 Day 1
10. Proportion of subjects with reduction from
baseline in daily corticosteroid dose to ≤ 0.2
mg/kg/day methylprednisolone (or equivalent
dose of ≤ 0.25 mg/kg/day prednisone or
prednisolone) at Cycle 7 Day 1

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Cycle 7 Day 1 (from baseline to Day 168)
2. From baseline up to endof study treatment, up to
36 months
3. Cycle 4 Day 1 (Day 84)
4. Until Cycle 7 Day 1 (Day 168) or the start of
additional systemic therapy for cGvHD
5. From baseline up to 35 days after end of study
treatment, up to 37 months
6. Cycle 7 Day 1 (Day 168)
7. From baseline up to 35 days after end of study
treatment, up to 37 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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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)

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.8.3

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

Argentina

Brazil

Canada

Chile

Czech Republic

Germany

Greece

India

Italy

Japan

Korea, Republic of

Lithuania

Russian Federation

Saudi Arabia

Slovakia

Slovenia

Spain

Switzerland

Taiwan

Thailand

Turkey

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

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

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)

Yes

F.1.1.3.1

Number of subjects for this age range:

F.1.1.4

Infants and toddlers (28 days-23 months)

Yes

F.1.1.4.1

Number of subjects for this age range:

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)

F.1.3

Elderly (>=65 years)

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)

subjects who are still receiving ruxolitinib at their end of study, and deriving clinical benefit from ruxolitinib as assessed by the Investigator, will also be given the possibility to continue ruxolitinib outside the study as part of the Novartis post-trial access program, as permitted by and in accordance to local laws and regulations

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

2020-01-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-12-20

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2024-08-26

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