Clinical Trials Register

Summary
EudraCT Number:	2018-001606-29
Sponsor's Protocol Code Number:	INCB39110-309
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2019-01-11
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

Sweden - MPA

A.2

EudraCT number

2018-001606-29

A.3

Full title of the trial

GRAVITAS-309: A Phase 2/3 Study of Itacitinib and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease

A.3.1

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

A study evaluating safety and efficacy of Itacitinib or Placebo in combination with corticosteroids as initial treatment of chronic graft versus-host disease

A.3.2

Name or abbreviated title of the trial where available

GRAVITAS-309

A.4.1

Sponsor's protocol code number

INCB39110-309

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	Clinical Trial Information
B.5.3	Address:
B.5.3.1	Street Address	1801 Augustine Cut-Off
B.5.3.2	Town/ city	Wilmington
B.5.3.3	Post code	DE 19803
B.5.3.4	Country	United States
B.5.4	Telephone number	+1 302498 5670
B.5.5	Fax number	+13024252734
B.5.6	E-mail	RA@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	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/3/17/1964
D.3 Description of the IMP
D.3.1	Product name	Itacitinib
D.3.2	Product code	INCB039110
D.3.4	Pharmaceutical form	Prolonged-release 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	itacitinib
D.3.9.1	CAS number	1334302-63-4
D.3.9.2	Current sponsor code	INCB039110 adipate
D.3.9.3	Other descriptive name	itacitinib adipate
D.3.9.4	EV Substance Code	SUB184194
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	100
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Moderate or severe cGVHD

E.1.1.1

Medical condition in easily understood language

Moderate or severe chronic Graft Versus Host Disease

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10066261
E.1.2	Term	Chronic graft versus host disease
E.1.2	System Organ Class	10021428 - Immune system disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10072160
E.1.2	Term	Chronic graft versus host disease in liver
E.1.2	System Organ Class	10021428 - Immune system disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10072158
E.1.2	Term	Chronic graft versus host disease in intestine
E.1.2	System Organ Class	10021428 - Immune system disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10072159
E.1.2	Term	Chronic graft versus host disease in skin
E.1.2	System Organ Class	10021428 - Immune 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

Part 1 and Part 1 expansion: to identify an appropriate dose of itacitinib in combination with corticosteroids as initial treatment for moderate or severe cGVHD.

Part 2: To compare the efficacy of itacitinib versus placebo in combination with corticosteroids as initial treatment for moderate or
severe cGVHD.

E.2.2

Secondary objectives of the trial

* Part 1:
- To evaluate the PK of itacitinib when administered in combination with corticosteroids in the study population.
- To estimate efficacy outcomes.

*Part 1 Expansion:
- To evaluate preliminary activity across treatment cohorts with respect to response rate at Month 3 and Month 6 (Key secondary objective)
- To evaluate the PK of itacitinib when administered in combination with corticosteroids in the study population.
- To estimate efficacy outcomes for each dose cohort.

*Part 2:
- To compare changes in health-related quality of life.
- To compare additional efficacy outcomes between treatment groups.
- To evaluate the PK of itacitinib in combination with corticosteroids in 1L cGVHD.
- To evaluate the safety and tolerability of study treatment across the 2 treatment cohorts.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female, aged 18 years or older inclusive at the time of signing the ICF.

2. Active, clinically diagnosed, moderate or severe cGVHD per NIH Consensus Criteria :
a. Moderate cGVHD: At least 1 organ (except lung) with a score of 2, 3 or more organs involved with a score of 1 in each organ, or lung score of 1.
b. Severe cGVHD: At least 1 organ with a score of 3, or lung score of 2 or 3
Note: Candidates who transition from active aGVHD to cGVHD without tapering off of corticosteroids (< 0.25 mg/kg per day methylprednisolone or equivalent) ± CNI are also eligible.

3. Underwent allo-HCT from any donor HLA type (related or unrelated donor with any degree of HLA matching) using any graft source (bone marrow, peripheral blood stem cells, or cord blood). Recipients of myeloablative, nonmyeloablative, or reduced intensity conditioning are eligible.

4. KPS score ≥ 60%.

5. Evidence of myeloid and platelet engraftment, that is, ANC ≥ 1.0 × 10E9/L and platelet count ≥ 50 × 10E9/L. Note: Use of growth factor supplementation and transfusion support is allowed during the study; however, transfusion to reach a minimum platelet count for inclusion is not allowed within the 7 days before the screening laboratory assessment.

E.4

Principal exclusion criteria

1. Has received more than 1 prior allo-HCT. Prior autologous HCT is allowed.

2. Has received more than 3 days/72 hours of systemic corticosteroid treatment for cGVHD.

3. Has received any other systemic treatment for cGVHD, including ECP. CNIs initiated before randomization may be continued at the same or lower dose; topical/inhaled steroids are acceptable.

4. Prior treatment with a JAK inhibitor within 8 weeks before randomization. Participants who received a JAK inhibitor for aGVHD are eligible only if they achieved CR or PR.

E.5 End points

E.5.1

Primary end point(s)

*Part 1: DLT data through Day 28 and additional data from clinical safety and laboratory assessments.

* Part 1 expansion: Incidence and severity of adverse events, across treatment cohorts.

*Part 2: Response rate at Month 6, defined as the proportion of participants demonstrating a CR or PR at Month 6.

E.5.1.1

Timepoint(s) of evaluation of this end point

Part 1: through Day 28

Part 1 Expansion: throughout Part 1 expansion duration

Part 2: at Month 6

E.5.2

Secondary end point(s)

* Part 1:
- Cmax, Cmin, Tmax, AUC0-t, and Cl/F.
- Response rate at Month 3, 6, and 12, defined as the proportion of participants who demonstrate either a CR or PR at each timepoint.
- Time to response, defined as the interval between randomization and first response.
- DoR, defined as the interval between first response and cGVHD progression, death, or initiation of new systemic cGVHD therapy.
- OS, defined as the interval between the date of randomization and the date of death due to any cause.
- NRM, defined as the proportion of participants who died due to causes other than a relapse of their primary hematologic disease.
- Proportion of participants with ≥ 50% reduction in daily corticosteroid dose at Day 180.
- Proportion of participants successfully tapered off all corticosteroids at Day 180.
- Relapse rate of malignant and non-malignant hematologic diseases, defined as the proportion of participants whose underlying disease relapses.
- Time to primary hematologic disease relapse, defined as the interval between the date of randomization and the date of relapse.

* Part 1 Expansion:
- for the Key secondary objective: response rate at Month 3 and Month 6, defined as the proportion of participants who demonstrate a CR or PR at each timepoint.
- Response rate at Month 12.
- Cmax, Cmin, Tmax, AUC0-t, and Cl/F;
- Response rate at Month 3, 6 and 12;
- Duration of response
- OS
- NMR
- Proportion of participants with ≥ 50% reduction in daily corticosteroid dose at Day 180.
- Proportion of participants successfully tapered off all corticosteroids at Day 180.
- Relapse rate of malignant and non-malignant hematologic diseases, defined as the proportion of participants whose underlying disease relapses.
- Time to primary hematologic disease relapse, defined as the interval between the date of randomization and the date of relapse.

* Part 2:
- Changes in symptom scores using the LSS, QOL-SF-36 v2, and EQ-5D-3L, PGIC and PGIS.
- Response rate at Month 3 and 12, defined as the proportion of participants who demonstrate either a CR or PR at each timepoint.
- DoR, defined as the interval between first response and cGVHD progression, death, or initiation of new systemic cGVHD therapy.
- OS, defined as the interval between the date of randomization and the date of death due to any cause.
- NRM, defined as the proportion of participants who died due to causes other than a relapse of their primary hematologic disease.
- Proportion of participants with ≥ 50% reduction in daily corticosteroid dose at Day 180.
- Proportion of participants successfully tapered off all corticosteroids at Day 180.
- Relapse rate of malignant and non-malignant hematologic diseases, defined as the proportion of participants whose underlying disease relapses.
- Time to primary hematologic disease relapse, defined as the interval between the date of randomization and the date of relapse.
- Cmin in all participants; Cmax, Tmax, AUC0-t, and Cl/F, data permitting.
- Data from clinical safety assessments (eg, AEs, infections) will be listed and tabulated.

E.5.2.1

Timepoint(s) of evaluation of this end point

* Part 1: Month 3, 6 and 12

*Part 1 Expansion:
Day 180
Month 3, 6, and 12

* Part 2: Month 3, 6, 12

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

Yes

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)

Yes

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

Yes

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Part 1 + Part 1 Expansion are open-label; Part 2 is double-blind, placebo-controlled

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

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

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

Austria

Belgium

Canada

Denmark

Finland

Germany

Greece

Israel

Italy

Poland

Spain

Sweden

Switzerland

United Kingdom

United States

France

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 study will end once all randomized patients have reached Month 36 or discontinued the study early due to any reason.

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:

294

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

107

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

230

F.4.2.2

In the whole clinical trial

401

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

2019-01-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-04-24

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-11-03

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