Register a trial

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03139604




Registration number
NCT03139604
Ethics application status
Date submitted
2/05/2017
Date registered
4/05/2017

Titles & IDs
Public title
GRAVITAS-301: A Study of Itacitinib or Placebo in Combination With Corticosteroids for Treatment of Acute Graft-Versus-Host Disease
Scientific title
GRAVITAS-301: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Itacitinib or Placebo in Combination With Corticosteroids for the Treatment of First-Line Acute Graft-Versus-Host Disease
Secondary ID [1] 0 0
INCB 39110-301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Graft-versus-host Disease (GVHD) 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Itacitinib
Treatment: Drugs - Placebo
Treatment: Drugs - Prednisone
Treatment: Drugs - Methylprednisolone

Experimental: Itacitinib - Itacitinib plus corticosteroids

Placebo comparator: Placebo - Matching placebo plus corticosteroids


Treatment: Drugs: Itacitinib
Itacitinib at the protocol-defined dose administered orally once daily (QD) plus corticosteroids.

Treatment: Drugs: Placebo
Matching placebo tablets administered orally once daily (QD) plus corticosteroids.

Treatment: Drugs: Prednisone
Oral prednisone may be used to begin standard corticosteroid background treatment at the investigator's discretion, at a dose equivalent to methylprednisolone 2 mg/kg per day.

Treatment: Drugs: Methylprednisolone
Methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose appropriate for the severity of disease as background treatment.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Response Rate Based on Center for International Blood and Marrow Transplant Research (CIBMTR) Response Index
Timepoint [1] 0 0
Day 28
Secondary outcome [1] 0 0
Nonrelapse Mortality
Timepoint [1] 0 0
Month 6,9,12 and 24
Secondary outcome [2] 0 0
Duration of Response
Timepoint [2] 0 0
Baseline through 30-35 days after end of treatment, total particpation expected to average 24 months
Secondary outcome [3] 0 0
Cmax of Itacitinib When Administered in Combination With Corticosteroids
Timepoint [3] 0 0
Protocol-defined timepoints up to Day 28
Secondary outcome [4] 0 0
Cmin of Itacitinib When Administered in Combination With Corticosteroids
Timepoint [4] 0 0
Protocol-defined timepoints up to Day 28
Secondary outcome [5] 0 0
Tmax of Itacitinib When Administered in Combination With Corticosteroids
Timepoint [5] 0 0
Protocol-defined timepoints up to Day 28
Secondary outcome [6] 0 0
AUC of Itacitinib When Administered in Combination With Corticosteroids
Timepoint [6] 0 0
Protocol-defined timepoints up to Day 28
Secondary outcome [7] 0 0
CL/F of Itacitinib When Administered in Combination With Corticosteroids
Timepoint [7] 0 0
Protocol-defined timepoints up to Day 28
Secondary outcome [8] 0 0
Time to Response
Timepoint [8] 0 0
End of Study, total particpation expected to average 24 months
Secondary outcome [9] 0 0
Relapse Rate of Malignant and Nonmalignant Hematologic Disease
Timepoint [9] 0 0
Randomization through end of Study, study duration expected to average 24 months
Secondary outcome [10] 0 0
Malignancy Relapse-related Mortality Rate
Timepoint [10] 0 0
Randomization through end of Study, study duration expected to average 24 months
Secondary outcome [11] 0 0
Failure-free Survival
Timepoint [11] 0 0
6 months from randomization
Secondary outcome [12] 0 0
Overall Survival (OS)
Timepoint [12] 0 0
End of Study up to approximately 24 months
Secondary outcome [13] 0 0
Number of Treatment-emergent Adverse Events With INCB39110
Timepoint [13] 0 0
30-35 days after end of treatment, approximately 24 months
Secondary outcome [14] 0 0
Incidence Rate of Secondary Graft Failure
Timepoint [14] 0 0
Randomization through end of Study, study duration expected to average 24 months
Secondary outcome [15] 0 0
Proportion of Subjects Who Discontinue Corticosteroids
Timepoint [15] 0 0
Days 28, 56, 100, and 180
Secondary outcome [16] 0 0
Proportion of Subjects Who Discontinue Immunosuppressive Medications
Timepoint [16] 0 0
Days 56 and 100
Secondary outcome [17] 0 0
Incidence Rate of aGVHD Flares
Timepoint [17] 0 0
up to day 100
Secondary outcome [18] 0 0
Incidence Rate of cGVHD
Timepoint [18] 0 0
Days 180 and 365
Secondary outcome [19] 0 0
Objective Response Rate
Timepoint [19] 0 0
Days 14, 56 and 100

Eligibility
Key inclusion criteria
* Has undergone 1 allo-HSCT from any donor (related or unrelated with any degree of HLA matching) and any donor source (bone marrow, peripheral blood stem cells, or cord blood) for a hematologic malignancy or disorder. Recipients of myeloablative and reduced-intensity conditioning regimens are eligible.
* Clinically suspected Grade II to IV aGVHD as per MAGIC criteria, occurring after allo-HSCT and any GVHD prophylaxis regimen.
* Evidence of myeloid engraftment. Use of growth factor supplementation is allowed.
* Serum creatinine = 2.0 mg/dL or creatinine clearance = 40 mL/min measured or calculated by Cockroft Gault equation.
* Willing to avoid pregnancy or fathering children.
* Able to give written informed consent and comply with all study visits and procedures.
* Able to swallow and retain oral medication.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Has received more than 1 allo-HSCT.
* Has received more than 2 days of systemic corticosteroids for aGVHD.
* Presence of GVHD overlap syndrome.
* Presence of an active uncontrolled infection.
* Known human immunodeficiency virus infection.
* Active hepatitis B virus (HBV) or hepatitis C virus infection that requires treatment or at risk for HBV reactivation.
* Participants with evidence of relapsed primary disease, or participants who have been treated for relapse after the allo-HSCT was performed.
* Any corticosteroid therapy for indications other than GVHD at doses > 1 mg/kg per day methylprednisolone (or prednisone equivalent) within 7 days of randomization.
* Severe organ dysfunction unrelated to underlying GVHD, including:

* Cholestatic disorders or unresolved veno-occlusive disease of the liver.
* Clinically significant or uncontrolled cardiac disease.
* Clinically significant respiratory disease that requires mechanical ventilation support or 50% oxygen.
* Currently breast feeding.
* Received JAK inhibitor therapy after allo-HSCT for any indication. Treatment with a JAK inhibitor before allo-HSCT is permitted.
* Treatment with any other investigational agent, device, or procedure within 21 days (or 5 half-lives, whichever is greater) of enrollment.
* Any medical complications or conditions that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
* Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/07/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
13/07/2020
Sample size
Target
Accrual to date
Final
439
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
St Vincents Hospital Sydney Limited - Darlinghurst
Recruitment postcode(s) [1] 0 0
NSW 2010 - Darlinghurst
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Iowa
Country [7] 0 0
United States of America
State/province [7] 0 0
Kansas
Country [8] 0 0
United States of America
State/province [8] 0 0
Louisiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
Mississippi
Country [13] 0 0
United States of America
State/province [13] 0 0
Missouri
Country [14] 0 0
United States of America
State/province [14] 0 0
Nebraska
Country [15] 0 0
United States of America
State/province [15] 0 0
New Hampshire
Country [16] 0 0
United States of America
State/province [16] 0 0
New Jersey
Country [17] 0 0
United States of America
State/province [17] 0 0
New York
Country [18] 0 0
United States of America
State/province [18] 0 0
North Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
Ohio
Country [20] 0 0
United States of America
State/province [20] 0 0
Oklahoma
Country [21] 0 0
United States of America
State/province [21] 0 0
Oregon
Country [22] 0 0
United States of America
State/province [22] 0 0
Pennsylvania
Country [23] 0 0
United States of America
State/province [23] 0 0
South Carolina
Country [24] 0 0
United States of America
State/province [24] 0 0
Tennessee
Country [25] 0 0
United States of America
State/province [25] 0 0
Texas
Country [26] 0 0
United States of America
State/province [26] 0 0
Virginia
Country [27] 0 0
Austria
State/province [27] 0 0
Linz
Country [28] 0 0
Belgium
State/province [28] 0 0
Antwerpen
Country [29] 0 0
Belgium
State/province [29] 0 0
Brugge
Country [30] 0 0
Belgium
State/province [30] 0 0
Brussels
Country [31] 0 0
Belgium
State/province [31] 0 0
Gent
Country [32] 0 0
Belgium
State/province [32] 0 0
Hasselt
Country [33] 0 0
Belgium
State/province [33] 0 0
Liege 1
Country [34] 0 0
Belgium
State/province [34] 0 0
Roeselare
Country [35] 0 0
Czechia
State/province [35] 0 0
Praha 2
Country [36] 0 0
Finland
State/province [36] 0 0
Helsinki
Country [37] 0 0
France
State/province [37] 0 0
Amiens
Country [38] 0 0
France
State/province [38] 0 0
LILLE Cedex
Country [39] 0 0
France
State/province [39] 0 0
Nantes
Country [40] 0 0
France
State/province [40] 0 0
Paris
Country [41] 0 0
France
State/province [41] 0 0
Pessac
Country [42] 0 0
France
State/province [42] 0 0
Strasbourg cedex
Country [43] 0 0
France
State/province [43] 0 0
Toulouse Cedex 9
Country [44] 0 0
France
State/province [44] 0 0
Vandoeuvre les Nancy
Country [45] 0 0
Germany
State/province [45] 0 0
Dresden
Country [46] 0 0
Germany
State/province [46] 0 0
Freiburg
Country [47] 0 0
Germany
State/province [47] 0 0
Hamburg
Country [48] 0 0
Germany
State/province [48] 0 0
Köln
Country [49] 0 0
Germany
State/province [49] 0 0
Leipzig
Country [50] 0 0
Germany
State/province [50] 0 0
Mainz
Country [51] 0 0
Germany
State/province [51] 0 0
Marburg
Country [52] 0 0
Greece
State/province [52] 0 0
Chortiátis
Country [53] 0 0
Israel
State/province [53] 0 0
Haifa
Country [54] 0 0
Israel
State/province [54] 0 0
Jerusalem
Country [55] 0 0
Israel
State/province [55] 0 0
Ramat Gan
Country [56] 0 0
Israel
State/province [56] 0 0
Tel Aviv
Country [57] 0 0
Italy
State/province [57] 0 0
Bergamo
Country [58] 0 0
Italy
State/province [58] 0 0
Cagliari
Country [59] 0 0
Italy
State/province [59] 0 0
Catania
Country [60] 0 0
Italy
State/province [60] 0 0
Firenze
Country [61] 0 0
Italy
State/province [61] 0 0
Milano
Country [62] 0 0
Italy
State/province [62] 0 0
Milan
Country [63] 0 0
Italy
State/province [63] 0 0
Monza
Country [64] 0 0
Italy
State/province [64] 0 0
Palermo
Country [65] 0 0
Italy
State/province [65] 0 0
Pavia
Country [66] 0 0
Italy
State/province [66] 0 0
Pescara
Country [67] 0 0
Italy
State/province [67] 0 0
Reggio Calabria
Country [68] 0 0
Italy
State/province [68] 0 0
Reggio Emilia
Country [69] 0 0
Italy
State/province [69] 0 0
Roma
Country [70] 0 0
Italy
State/province [70] 0 0
Rozzano
Country [71] 0 0
Italy
State/province [71] 0 0
Torino
Country [72] 0 0
Italy
State/province [72] 0 0
Udine
Country [73] 0 0
Korea, Republic of
State/province [73] 0 0
Seoul
Country [74] 0 0
New Zealand
State/province [74] 0 0
Auckland
Country [75] 0 0
Poland
State/province [75] 0 0
Gliwice
Country [76] 0 0
Poland
State/province [76] 0 0
Warsaw
Country [77] 0 0
Portugal
State/province [77] 0 0
Lisboa
Country [78] 0 0
Portugal
State/province [78] 0 0
Porto
Country [79] 0 0
Spain
State/province [79] 0 0
Barcelona
Country [80] 0 0
Spain
State/province [80] 0 0
Granada
Country [81] 0 0
Spain
State/province [81] 0 0
Madrid
Country [82] 0 0
Spain
State/province [82] 0 0
Salamanca
Country [83] 0 0
Spain
State/province [83] 0 0
San Sebastián
Country [84] 0 0
Spain
State/province [84] 0 0
Santander
Country [85] 0 0
Spain
State/province [85] 0 0
Santiago de Compostela
Country [86] 0 0
Spain
State/province [86] 0 0
Sevilla
Country [87] 0 0
Spain
State/province [87] 0 0
Valencia
Country [88] 0 0
Switzerland
State/province [88] 0 0
Basel
Country [89] 0 0
Switzerland
State/province [89] 0 0
Geneve
Country [90] 0 0
Switzerland
State/province [90] 0 0
Zuerich
Country [91] 0 0
Taiwan
State/province [91] 0 0
Taichung
Country [92] 0 0
United Kingdom
State/province [92] 0 0
Cambridge
Country [93] 0 0
United Kingdom
State/province [93] 0 0
Cardiff
Country [94] 0 0
United Kingdom
State/province [94] 0 0
London
Country [95] 0 0
United Kingdom
State/province [95] 0 0
Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Incyte Corporation
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Rodica Morariu-Zamfir, MD
Address 0 0
Incyte Corporation
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03139604