Chronic Graft-versus-host DiseasePhase 2/3NCT03584516
GRAVITAS-309: Itacitinib and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease
A Phase 2/3 study testing Itacitinib, Methylprednisolone and Prednisone in people with Chronic Graft-versus-host Disease, run by Incyte Corporation at 133 sites in 16 countries.
Trial summary
The purpose of this study is to assess the efficacy and safety of itacitinib in combination with corticosteroids as first-line treatment for moderate or severe chronic graft-versus-host disease (cGVHD). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Graft-versus-host Disease
- What is being tested?
- Itacitinib, Methylprednisolone and Prednisone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 155 participants
- Where
- 133 sitesin 16 countries
- Study dates
- 17 Jan 2019to 3 Nov 2023
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Active, clinically diagnosed, moderate or severe cGVHD per NIH Consensus Criteria
- Underwent allogeneic stem cell transplantation (allo-HCT)
- Karnofsky Performance Status score ≥ 60%.
- Evidence of myeloid and platelet engraftment.
- Willingness to avoid pregnancy or fathering children based on protocol-defined criteria.
Who cannot join
- Has received more than 3 days/72 hours of systemic corticosteroid treatment for cGVHD.
- Has received any other systemic treatment for cGVHD, including extracorporeal photopheresis (ECP).
- Prior treatment with a Janus kinase (JAK) inhibitor for acute GVHD, unless the participant achieved complete or partial response and has been off JAK inhibitor treatment for at least 8 weeks before randomization.
- cGVHD occurring after a nonscheduled donor lymphocyte infusion (DLI) administered for pre-emptive treatment of malignancy recurrence.
- Evidence of relapsed primary malignancy.
Trial locations and contacts
133 sites in 16 countries.
133 sites in 16 countries
United States39 sites
University of Michigan
Ann Arbor, Michigan, 48109
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
Augusta University - Medical College of Georgia
Augusta, Georgia, 30912
St David'S South Austin Medical Center
Austin, Texas, 78704
University of Maryland - Greenebaum Cancer Center
Baltimore, Maryland, 21201
Tufts Medical Center
Boston, Massachusetts, 02111-1552
Massachusetts General Hospital
Boston, Massachusetts, 02114
Rush University Medical Center
Chicago, Illinois, 60612
Illinois Cancer Specialists
Chicago, Illinois, 60714
Oncology Hematology Care, Inc
Cincinnati, Ohio, 45236
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106-1716
Texas Oncology - Medical City Dallas
Dallas, Texas, 75230
Texas Oncology - Baylor Sammons Cancer Center
Dallas, Texas, 75246
Henry Ford Health System
Detroit, Michigan, 48202
City of Hope National Medical Center
Duarte, California, 91010
Duke University Medical Center
Durham, North Carolina, 27710
Spectrum Health
Grand Rapids, Michigan, 49503
Hackensack University Medical Center
Hackensack, New Jersey, 07601-8550
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202-5201
University of California San Diego Medical Center, Moores Cancer Center
La Jolla, California, 92093
University of Arkansas For Medical Sciences - Winthrop P Rockefeller Cancer Institute
Little Rock, Arkansas, 72205
Loyola University Medical Center
Maywood, Illinois, 60153-3328
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, 33136-1002
University of Minnesota, Masonic Cancer Center
Minneapolis, Minnesota, 55455
Tri Star Bone Marrow Transplant
Nashville, Tennessee, 37203
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
Tulane University
New Orleans, Louisiana, 70112-2618
Advocate Lutheran General Hospital - Oncology Specislists Sc
Park Ridge, Illinois, 60028
University of Pennsylvania Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
Jefferson University Hospitals
Philadelphia, Pennsylvania, 19107
Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, 15224
University of Pittsburgh
Pittsburgh, Pennsylvania, 15232-1309
University of Rochester, James P. Wilmot Cancer Center
Rochester, New York, 14642-0001
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
Avera Cancer Institute
Sioux Falls, South Dakota, 57105-2108
Saint Louis University Cancer Center
St Louis, Missouri, 63110
Stony Brook University Medical Center
Stony Brook, New York, 11794
University of Arizona Cancer Center - Out Pt.
Tucson, Arizona, 85724
University of Kansas Hospital Authority
Westwood, Kansas, 66160
Italy19 sites
CLINICA DI EMATOLOGIA, UNIVERSIT� POLITECNICA DELLE MARCHE
Ancona, 60126
Azienda Ospedaliera Papa Giovanni Xxiii
Bergamo, 24127
L AZIENDA OSPEDALIERO-UNIVERSITARIA DI BOLOGNA POLICLINICO S. ORSOLA � MALPIGHI
Bologna, 40138
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Brescia, 25123
Azienda Policlinico Vittorio Emanuele
Catania, 95123
Fondazione Irccs Ca Granda Ospedale Maggiore
Milan, 20122
Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele
Milan, 20132
A.O.U. Di Modena - Policlinico
Modena, 41124
A.O.U. Federico Ii
Naples, 80131
Azienda Ospedaliera Ospedali Riuniti "Villa Sofia - Cervello"
Palermo, 90100
Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo
Pavia, 27100
Azienda Ospedaliera Bianchi-Melacrino-Morelli Ospedali Riuniti
Reggio Calabria, 89133
Universita Degli Studi Di Roma La Sapienza - Umberto I Policlinico Di Roma - Centro Di Ematologia
Roma, 00161
Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore
Roma, 00168
Irrcs Instituto Clinico Humanitas
Rozzano, 20089
I.R.C.C.S. Casa Sollievo Della Sofferenza
San Giovanni Rotondo, 71013
Azienda Ospedaliero Universitaria Citta Della Salute E Della Scienza
Torino, 10126
Azienda Ospedaliero-Universitaria Santa Maria Della Misericordia
Udine, 33100
Centro Ricerche Cliniche Di Verona (Crc)
Verona, 37134
Germany16 sites
Charite Berlin
Berlin, 12200
Universitatsklinikum Bonn Aoer
Bonn, 00011
Universitatsklinikum Koln
Cologne, 50937
University Clinic Carl Gustav Carus Technical University Dresden
Dresden, 01307
Universitaetsklinikum Erlangen - Medizinische Klinik 5
Erlangen, 91054
Universitatsklinikum Essen
Essen, 45147
UNIVERSIT�TSKLINIKUM HALLE (SAALE)
Halle, D06120
University Medical Centre Hamburg-Eppendorf Centre of Oncology
Hamburg, 20246
Universitaetsklinikum Jena
Jena, 07740
Selbststandige Abteilung Fur Hamatologie Und Internistische Onkologie
Leipzig, 00341
Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii
Mainz, 55131
University Hospital Mannheim
Mannheim, 68167
Iii Medizinische Klinik Und Poliklinik Klinikum Rechts Der Isar Technische Universitat Munchen
Munich, 81675
Universitatsklinikum Munster
Münster, 48149
Universitaetsmedizin Rostock
Rostock, 18057
Universitaetsklinikum in Tubingen
Tübingen, 72076
Spain14 sites
Institut Catala D Oncologia
Badalona, 08916
Hospital de La Santa Creu I Sant Pau
Barcelona, 08041
Hospital Universitario Virgen de Las Nieves
Granada, 18014
Ico Institut Catala D Oncologia
L'Hospitalet de Llobregat, 08908
Hospital General Universitario Gregorio Maranon
Madrid, 28007
Hospital Universitario Ramon Y Cajal
Madrid, 28034
Hospital Regional Universitario de Malaga
Málaga, 29010
Son Espases University Hospital
Palma, 07120
Clinica Universidad de Navarra (Cun)
Pamplona, 31008
Hospital Clinico Universitario de Salamanca
Salamanca, 37007
Hospital Universitario Marques de Valdecilla
Santander, 39008
Hospital Clinico de Santiago de Compostela
Santiago de Compostela, 15706
Hospital Universitario Y Politcnico de La Fe
Valencia, 46009
Hospital Clinico Universitario de Valencia
Valencia, 46010
France10 sites
Chu Amiens Picardie - Hopital Sud
Amiens, 80054
Centre Hospitalier D'Angers
Angers, 49000
Chu de Grenoble - Hopital Albert Michallon
Grenoble, 38700
Institut Paoli-Calmettes
Marseille, 13273
Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu
Nantes, 44000
Chu de Nice - Hospital L Archet
Nice, 06800
Chu de Rennes - Hospital Pontchaillou
Rennes, 35033
Centre Henri Becquerel
Rouen, 76038
Chru Hopitaux de Tours Hospital Bretonneau
Tours, 37000
Hopitaux de Brabois
Vandœuvre-lès-Nancy, 54511
United Kingdom8 sites
Bristol Haematology & Oncology Centre
Bristol, BS2 8ED
University Hospital of Wales
Cardiff, CF14 4XW
Barts Health Nhs Trust - St Bartholomews Hospital
London, EC1A 7BE
King'S College Hospital (Nhs Foundation)
London, SE5 9RS
Imperial College Healthcare Nhs Trust - Hammersmith Hospital
London, W12 0HS
Nottingham University Hospitals Nhs Trust
Nottingham, NG5 1PB
The Royal Marsden Nhs Foundation Trust - Sutton
Sutton, SM2 5PT
St. George'S University Hospitals Nhs Foundation Trust
Tooting, SW17 0QT
Belgium7 sites
Zna Stuivenberg
Antwerp, 02060
Institut Jules Bordet
Brussels, 01000
Universitair Ziekenhuis Antwerpen (Uza)
Edegem, 02650
Universitair Ziekenhuis Gent
Ghent, 09000
Universitaire Ziekenhuis Leuven - Gasthuisberg
Leuven, 03000
CENTRE HOSPITALIER UNIVERSITAIRE DE LI�GE - SART TILMAN
Liège, 04000
AZ DELTA
Roeselare, 08800
Canada4 sites
University of Alberta
Edmonton, Alberta, T6G 2P4
Hospital Maisonneuve Rosemont
Montreal, Quebec, H1T 2M4
Saskatchewan Cancer
Saskatoon, Saskatchewan, S7N 4H4
University Health Network
Toronto, Ontario, M5G 2M9
Israel4 sites
Rambam Medical Center
Haifa, 3109601
Hadassah Hebrew University Medical Center Ein Karem Hadassah
Jerusalem, 91120
Rabin Medical Center - Beilinson Hospital
Petach Tiqwa, 49100
Tel Aviv Sourasky Medical Center
Tel Aviv, 64239
Poland4 sites
Uniwersyteckie Centrum Kliniczne
Gdansk, 80-592
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy Oddzial W Gliwi
Gliwice, 44-101
Szpital Kliniczny Przemienienia Panskiego
Poznan, 60-569
Mtz Clinical Research Sp. Zo.O.
Warsaw, 02-106
Greece2 sites
University Hospital of West Attica - Attikon
Chaïdári, 124 62
General Hospital of Thessaloniki G. Papanikolaou
Thessaloniki, 57010
Sweden2 sites
Karolinska University Hospital Huddinge
Huddinge, 141 86
Skane University Hospital Lund
Lund, 22185
About this study
Official title: GRAVITAS-309: A Phase 2/3 Study of Itacitinib and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease
The purpose of this study is to assess the efficacy and safety of itacitinib in combination with corticosteroids as first-line treatment for moderate or severe chronic graft-versus-host disease (cGVHD).
- Conditions
- Chronic Graft-versus-host Disease
- Being tested
- Itacitinib, Placebo, Methylprednisolone, Prednisone
- Keywords
- Graft-versus-host-disease, itacitinib, Janus kinase inhibitor, corticosteroids
- Medical subject headings
- Bronchiolitis Obliterans Syndrome, Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ItacitinibDrug
Also called INCB039110
In Part 1dose determination participants will receive itacitinib administered orally once daily at the protocol-defined dose according to cohort enrollment. In Part 1 expansion, participants will receive either itacitinib administered orally either once daily or twice a day or corticosteroid alone based on the assigned treatment regimen according to cohort enrollment. In Part 2, participants will receive the recommended dose from Part 1 expansion.
PlaceboDrug
In Part 2, participants will receive matching placebo.
Also called Medrol, Medrol Dosepak, Solu-Medrol
Administered in Parts 1 and 2 as background reference therapy at a dose level that is commensurate with institutional guidelines based on organ involvement and severity of disease.
PrednisoneDrug
Also called Deltasone, Prednicot, predniSONE Intensol, Rayos, Sterapred, Sterapred DS
Administered in Parts 1 and 2 as background reference therapy at a dose level that is commensurate with institutional guidelines based on organ involvement and severity of disease.
| Study group | Role | What they receive |
|---|---|---|
| Part 1 : Dose determination of itacitinib | Experimental | itacitinib administered in combination with corticosteroids. Receives: Drug: Itacitinib; Drug: Methylprednisolone; Drug: Prednisone |
| Part 1 : Dose expansion of itacitinib | Experimental | itacitinib administered in combination with corticosteroids or corticosteroids alone. Receives: Drug: Itacitinib; Drug: Placebo; Drug: Methylprednisolone; Drug: Prednisone |
| Part 2 : itacitinib recommended dose from part 1 | Placebo comparator | itacitinib or placebo administered in combination with corticosteroids Receives: Drug: Itacitinib; Drug: Methylprednisolone; Drug: Prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Number of Participants With Dose-limiting Toxicities (DLTs)
A DLT was defined as the occurrence of any protocol-defined toxicity with onset up to and including Day 28, except those with a clear alternative explanation. Participants who received at least 21 of 28 doses of study drug at the level assigned or had a DLT were considered evaluable for determining tolerability of the dose. Participants who did not achieve this duration of exposure and did not have a DLT were to be replaced for purposes of toxicity identification.
Measured: up to Day 28
Part 1 Expansion: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug.
Measured: until at least 30 days after the last dose of study treatment (up to 1103 days)
Part 2: Response Rate at Month 6
Response rate was defined as the percentage of participants that had complete response (CR) or partial response (PR), per National Institutes of Health (NIH) Consensus Criteria, as determined by the investigator, within 14 days of the post-Baseline visit date until new anti-GVHD therapy or overall response-progression or relapse/progression of underlying disease. CR was defined as the complete resolution of all signs and symptoms of cGvHD in all evaluable organs. PR was defined as an improvement in at least one organ without progression in other organs.
Measured: Month 6
Secondary outcomes (34)
Part 1 Expansion: Response Rate at Months 3 and 6
Response rate was defined as the percentage of participants that had CR or PR, per NIH Consensus Criteria, as determined by the investigator, within 14 days of the post-Baseline visit date until new anti-GVHD therapy or overall response-progression or relapse/progression of underlying disease. CR was defined as the complete resolution of all signs and symptoms of cGvHD in all evaluable organs. PR was defined as an improvement in at least one organ without progression in other organs.
Measured: Months 3 and 6
Parts 1 and 1 Expansion: Cmax of Itacitinib
Cmax was defined as the maximum observed concentration of itacitinib.
Measured: Days 1, 7, and 28: predose and 1, 2, and 5 hours post-dose
Parts 1 and 1 Expansion: Ctau of Itacitinib
Ctau was defined as the trough concentration of itacitinib over the dose interval. For pharmacokinetic steady state Day 7 and Day 28, for the calculation of NCA exposure estimates (as more than 3 PK data points are necessary for the estimation beyond Cmax) it was assumed, that PK concentration returns to the predose value (at 12 hours post-dose for BID dosing; at 24 hours post-dose for QD dosing). Predose PK samples were transposed to 24 hours post-dose for QD administration and to 12 hours post-dose for BID administration to allow the steady-state NCA PK estimates on Day 7 and Day 28.
Measured: Day 1: predose, and 1, 2, and 5 hours post-dose. Days 7 and 28: predose, and 1, 2, 5, 12 (for BID dosing), and 24 hours post-dose (for QD dosing)
Parts 1 and 1 Expansion: Tmax of Itacitinib
tmax was defined as the time to the maximum concentration of itacitinib. For pharmacokinetic steady state Day 7 and Day 28, for the calculation of NCA exposure estimates (as more than 3 PK data points are necessary for the estimation beyond Cmax) it was assumed, that PK concentration returns to the predose value (at 12 hours post-dose for BID dosing; at 24 hours post-dose for QD dosing). Predose PK samples were transposed to 24 hours post-dose for QD administration and to 12 hours post-dose for BID administration to allow the steady-state NCA PK estimates on Day 7 and Day 28.
Measured: Day 1: predose, and 1, 2, and 5 hours post-dose. Days 7 and 28: predose, and 1, 2, 5, 12 (for BID dosing), and 24 hours post-dose (for QD dosing)
Parts 1 and 1 Expansion: Cl/F of Itacitinib
Cl/F was defined as the apparent oral dose clearance of itacitinib. For pharmacokinetic steady state Day 7 and Day 28, for the calculation of NCA exposure estimates (as more than 3 PK data points are necessary for the estimation beyond Cmax) it was assumed, that PK concentration returns to the predose value (at 12 hours post-dose for BID dosing; at 24 hours post-dose for QD dosing). Predose PK samples were transposed to 24 hours post-dose for QD administration and to 12 hours post-dose for BID administration to allow the steady-state NCA PK estimates on Day 7 and Day 28.
Measured: Day 1: predose, and 1, 2, and 5 hours post-dose. Days 7 and 28: predose, and 1, 2, 5, 12 (for BID dosing), and 24 hours post-dose (for QD dosing)
Part 2: Cmax of Itacitinib
Cmax was defined as the maximum observed concentration of itacitinib.
Measured: Days 1, 7, and 28: predose and 1, 2, and 5 hours post-dose
Part 2: Cmin of Itacitinib
Cmin was defined as the minimum observed plasma or serum concentration of itacitinib over the dose interval.
Measured: Days 1, 7, and 28: predose and 1, 2, and 5 hours post-dose
Part 2: Tmax of Itacitinib
tmax was defined as the time to the maximum concentration of itacitinib.
Measured: Days 1, 7, and 28: predose and 1, 2, and 5 hours post-dose
Part 2: AUC0-t of Itacitinib
AUC0-t was defined as the area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t.
Measured: Days 1, 7, and 28: predose and 1, 2, and 5 hours post-dose
Part 2: Cl/F of Itacitinib
Cl/F was defined as the apparent oral dose clearance of itacitinib.
Measured: Days 1, 7, and 28: predose and 1, 2, and 5 hours post-dose
Part 1: Response Rate at Months 3, 6, and 12
Response rate was defined as the percentage of participants that had CR or PR, per NIH Consensus Criteria, as determined by the investigator, within 14 days of the post-Baseline visit date until new anti-GVHD therapy or overall response-progression or relapse/progression of underlying disease. CR was defined as the complete resolution of all signs and symptoms of cGvHD in all evaluable organs. PR was defined as an improvement in at least one organ without progression in other organs.
Measured: Months 3, 6, and 12
Part 1 Expansion: Response Rate at Month 12
Response rate was defined as the percentage of participants that had CR or PR, per NIH Consensus Criteria, as determined by the investigator, within 14 days of the post-Baseline visit date until new anti-GVHD therapy or overall response-progression or relapse/progression of underlying disease. CR was defined as the complete resolution of all signs and symptoms of cGvHD in all evaluable organs. PR was defined as an improvement in at least one organ without progression in other organs.
Measured: Month 12
Part 1 Expansion: Time to Response
Time to response was defined as the interval between randomization and the first response (CR or PR) before initiation of new therapy. CR was defined as the complete resolution of all signs and symptoms of cGvHD in all evaluable organs. PR was defined as an improvement in at least one organ without progression in other organs.
Measured: up to Month 12
Part 1 Expansion: Duration of Response
Duration to response was defined as the interval between the first response and cGVHD progression, death, or the initiation of a new systemic cGVHD therapy.
Measured: up to 24 months
Part 1 Expansion: Overall Survival
Overall survival was defined as the interval between the date of randomization and the date of death due to any cause.
Measured: up to 36 months
Part 1 Expansion: Nonrelapse Mortality (NRM) Rate
NRM was defined as the percentage of participants who died due to causes other than a relapse of their primary hematologic disease.
Measured: up to 24 months
Part 1 Expansion: Percentage of Participants With a ≥50% Reduction in Daily Corticosteroid Dose at Day 180 From the Corticosteroid Dose on Day 1
The corticosteroid dose at Day 180 was compared to the corticosteroid dose on Day 1 to assess reduction.
Measured: Day 1; Day 180
Part 1 Expansion: Percentage of Participants Successfully Tapered Off All Corticosteroids at Day 180
The percentage of participants who were not taking any corticosteroids at Day 180 was assessed.
Measured: Day 180
Part 1 Expansion: Relapse Rate of Malignant and Nonmalignant Hematologic Diseases
The relapse rate was defined as the percentage of participants whose underlying disease relapsed at any time during the course of the study.
Measured: up to 1073 days
Part 1 Expansion: Time to Primary Hematologic Disease Relapse
Time to primary hematologic disease relapse was defined as the interval between the date of randomization and the date of relapse.
Measured: up to 24 months
Part 2: Change From Baseline in Lee cGVHD Symptom Scale (LLS) Scores
The LSS consists of 30 items in 7 subscales (skin, eye, mouth, lung, nutrition, energy, and psychological). It was to be used to assess patient-reported changes in health status, symptoms, and well being.
Measured: Baseline; End of Treatment in Phase 2
Part 2: Change From Baseline in Quality of Life-Short Form-36 Version 2 (QOL-SF-36 v2) Scores
The QOL-SF-36 v2 is 36-item scale that captures changes in health status during the course of treatment. The SF-36 assesses 8 health concepts related to limitations in physical activities, social activities, bodily pain, general mental and physical health, and vitality. It was to be used to assess patient-reported changes in health status, symptoms, and well being.
Measured: Baseline; End of Treatment in Phase 2
Part 2: Change From Baseline in EQ-5D-3L Scores
The EQ-5D-3L is a descriptive classification consisting of 5 dimensions of health: mobility, self-care, usual activities, anxiety/depression, and pain/discomfort. It was to be used to assess patient-reported changes in health status, symptoms, and well being.
Measured: Baseline; End of Treatment in Phase 2
Part 2: Change From Baseline in Patient Global Impression of Change (PGIC) Responses
The PGIC is 1 question that captures the overall change in symptoms over the course of treatment. It was to be used to assess patient-reported changes in health status, symptoms, and well being.
Measured: Baseline; End of Treatment in Phase 2
Part 2: Change From Baseline in Patient Global Impression of Severity (PGIS) Responses
The PGIS is 1 question that captures the overall change in the severity of symptoms over the previous week. It was to be used to assess patient-reported changes in health status, symptoms, and well being.
Measured: Baseline; End of Treatment in Phase 2
Part 2: Response Rate at Months 3 and 12
Response rate was defined as the percentage of participants that had CR or PR, per NIH Consensus Criteria, as determined by the investigator, within 14 days of the post-Baseline visit date until new anti-GVHD therapy or overall response-progression or relapse/progression of underlying disease. CR was defined as the complete resolution of all signs and symptoms of cGvHD in all evaluable organs. PR was defined as an improvement in at least one organ without progression in other organs.
Measured: Months 3 and 12
Part 2: Duration of Response
Duration to response was defined as the interval between the first response and cGVHD progression, death, or the initiation of a new systemic cGVHD therapy.
Measured: up to 24 months
Part 2: Overall Survival
Overall survival was defined as the interval between the date of randomization and the date of death due to any cause.
Measured: up to 36 months
Part 2: NRM Rate
NRM was defined as the percentage of participants who died due to causes other than a relapse of their primary hematologic disease.
Measured: up to 24 months
Part 2: Percentage of Participants With a ≥50% Reduction in Daily Corticosteroid Dose at Day 180 From the Corticosteroid Dose on Day 1
The corticosteroid dose at Day 180 was compared to the corticosteroid dose on Day 1 to assess reduction.
Measured: Day 1; Day 180
Part 2: Percentage of Participants Successfully Tapered Off All Corticosteroids at Day 180
The percentage of participants who were not taking any corticosteroids at Day 180 was assessed.
Measured: Day 180
Part 2: Relapse Rate of Malignant and Nonmalignant Hematologic Diseases
The relapse rate was defined as the defined as the percentage of participants whose underlying disease relapsed at any time during the course of the study.
Measured: up to 24 months
Part 2: Time to Primary Hematologic Disease Relapse
Time to primary hematologic disease relapse was defined as the interval between the date of randomization and the date of relapse.
Measured: up to 24 months
Part 2: Number of Participants With Any TEAE
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug.
Measured: up to 30 days after the last dose in Phase 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2018
- Study start17 Jan 2019
- Primary completion3 Nov 2023
- Study completion3 Nov 2023
Why it stopped: The study was terminated due to insufficient efficacy to support moving into Part 2 of the study; there were no safety concerns that contributed to this decision.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Graft-versus-host DiseaseStudies of the same condition, open and under way.
- More trials run by Incyte CorporationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- In Part 2 of the study, participants in the placebo group will be allowed to cross over to the experimental group after completion of the primary analysis.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 155 participants (actual)
Sponsor and investigators
- Lead sponsor
- Incyte Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Rodica Morariu-Zamfir, MD, Study director, Incyte Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03584516
- Sponsor's protocol ID
- INCB 39110-309
- Other IDs
- 2018-001606-29, 2018
- Status last verified
- Oct 2025
- First submitted
- 29 Jun 2018
- Last updated
- 20 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- GRAVITAS-309: A Phase 2/3 Study of Itacitinib and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease
- ClinicalTrials.gov ID
- NCT03584516
- Acronym / sponsor ID
- INCB 39110-309
- Conditions
- Chronic Graft-versus-host Disease
- Keywords
- Graft-versus-host-disease, itacitinib, Janus kinase inhibitor, corticosteroids
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated due to insufficient efficacy to support moving into Part 2 of the study; there were no safety concerns that contributed to this decision.
- Enrolment
- 155 participants (actual)
- Lead sponsor
- Incyte CorporationIndustry (pharma, biotech, devices)
- Study start
- 17 Jan 2019 (actual)
- Primary completion
- 3 Nov 2023 (actual)
- Study completion
- 3 Nov 2023 (actual)
- First posted
- 12 Jul 2018 (actual)
- Results
- Posted 27 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the efficacy and safety of itacitinib in combination with corticosteroids as first-line treatment for moderate or severe chronic graft-versus-host disease (cGVHD).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
- Model description
- In Part 2 of the study, participants in the placebo group will be allowed to cross over to the experimental group after completion of the primary analysis.
| Arm | Type | Receives |
|---|---|---|
| Part 1 : Dose determination of itacitinib | Experimental | Drug: Itacitinib, Drug: Methylprednisolone, Drug: Prednisoneitacitinib administered in combination with corticosteroids. |
| Part 1 : Dose expansion of itacitinib | Experimental | Drug: Itacitinib, Drug: Placebo, Drug: Methylprednisolone, Drug: Prednisoneitacitinib administered in combination with corticosteroids or corticosteroids alone. |
| Part 2 : itacitinib recommended dose from part 1 | Placebo comparator | Drug: Itacitinib, Drug: Methylprednisolone, Drug: Prednisoneitacitinib or placebo administered in combination with corticosteroids |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Active, clinically diagnosed, moderate or severe cGVHD per NIH Consensus Criteria
- Underwent allogeneic stem cell transplantation (allo-HCT)
- Karnofsky Performance Status score ≥ 60%.
- Evidence of myeloid and platelet engraftment.
- Willingness to avoid pregnancy or fathering children based on protocol-defined criteria.
Key exclusion criteria (5 listed)
- Has received more than 3 days/72 hours of systemic corticosteroid treatment for cGVHD.
- Has received any other systemic treatment for cGVHD, including extracorporeal photopheresis (ECP).
- Prior treatment with a Janus kinase (JAK) inhibitor for acute GVHD, unless the participant achieved complete or partial response and has been off JAK inhibitor treatment for at least 8 weeks before randomization.
- cGVHD occurring after a nonscheduled donor lymphocyte infusion (DLI) administered for pre-emptive treatment of malignancy recurrence.
- Evidence of relapsed primary malignancy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ItacitinibAlso: INCB039110In Part 1dose determination participants will receive itacitinib administered orally once daily at the protocol-defined dose according to cohort enrollment. In Part 1 expansion, participants will receive either itacitinib administered orally either once daily or twice a day or corticosteroid alone based on the assigned treatment regimen according to cohort enrollment. In Part 2, participants will receive the recommended dose from Part 1 expansion. | Drug | Part 1 : Dose determination of itacitinib, Part 1 : Dose expansion of itacitinib, Part 2 : itacitinib recommended dose from part 1 |
| PlaceboIn Part 2, participants will receive matching placebo. | Drug | Part 1 : Dose expansion of itacitinib |
| MethylprednisoloneAlso: Medrol, Medrol Dosepak, Solu-MedrolAdministered in Parts 1 and 2 as background reference therapy at a dose level that is commensurate with institutional guidelines based on organ involvement and severity of disease. | Drug | Part 1 : Dose determination of itacitinib, Part 1 : Dose expansion of itacitinib, Part 2 : itacitinib recommended dose from part 1 |
| PrednisoneAlso: Deltasone, Prednicot, predniSONE Intensol, Rayos, Sterapred, Sterapred DSAdministered in Parts 1 and 2 as background reference therapy at a dose level that is commensurate with institutional guidelines based on organ involvement and severity of disease. | Drug | Part 1 : Dose determination of itacitinib, Part 1 : Dose expansion of itacitinib, Part 2 : itacitinib recommended dose from part 1 |
Primary outcome
Part 1: Number of Participants With Dose-limiting Toxicities (DLTs)
Time frame: up to Day 28
A DLT was defined as the occurrence of any protocol-defined toxicity with onset up to and including Day 28, except those with a clear alternative explanation. Participants who received at least 21 of 28 doses of study drug at the level assigned or had a DLT were considered evaluable for determining tolerability of the dose. Participants who did not achieve this duration of exposure and did not have a DLT were to be replaced for purposes of toxicity identification.
Part 1 Expansion: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
Time frame: until at least 30 days after the last dose of study treatment (up to 1103 days)
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug.
Part 2: Response Rate at Month 6
Time frame: Month 6
Response rate was defined as the percentage of participants that had complete response (CR) or partial response (PR), per National Institutes of Health (NIH) Consensus Criteria, as determined by the investigator, within 14 days of the post-Baseline visit date until new anti-GVHD therapy or overall response-progression or relapse/progression of underlying disease. CR was defined as the complete resolution of all signs and symptoms of cGvHD in all evaluable organs. PR was defined as an improvement in at least one organ without progression in other organs.
34 secondary outcomes
Part 1 Expansion: Response Rate at Months 3 and 6
Time frame: Months 3 and 6
Parts 1 and 1 Expansion: Cmax of Itacitinib
Time frame: Days 1, 7, and 28: predose and 1, 2, and 5 hours post-dose
Parts 1 and 1 Expansion: Ctau of Itacitinib
Time frame: Day 1: predose, and 1, 2, and 5 hours post-dose. Days 7 and 28: predose, and 1, 2, 5, 12 (for BID dosing), and 24 hours post-dose (for QD dosing)
Parts 1 and 1 Expansion: Tmax of Itacitinib
Time frame: Day 1: predose, and 1, 2, and 5 hours post-dose. Days 7 and 28: predose, and 1, 2, 5, 12 (for BID dosing), and 24 hours post-dose (for QD dosing)
Parts 1 and 1 Expansion: Cl/F of Itacitinib
Time frame: Day 1: predose, and 1, 2, and 5 hours post-dose. Days 7 and 28: predose, and 1, 2, 5, 12 (for BID dosing), and 24 hours post-dose (for QD dosing)
Part 2: Cmax of Itacitinib
Time frame: Days 1, 7, and 28: predose and 1, 2, and 5 hours post-dose
Part 2: Cmin of Itacitinib
Time frame: Days 1, 7, and 28: predose and 1, 2, and 5 hours post-dose
Part 2: Tmax of Itacitinib
Time frame: Days 1, 7, and 28: predose and 1, 2, and 5 hours post-dose
Part 2: AUC0-t of Itacitinib
Time frame: Days 1, 7, and 28: predose and 1, 2, and 5 hours post-dose
Part 2: Cl/F of Itacitinib
Time frame: Days 1, 7, and 28: predose and 1, 2, and 5 hours post-dose
Part 1: Response Rate at Months 3, 6, and 12
Time frame: Months 3, 6, and 12
Part 1 Expansion: Response Rate at Month 12
Time frame: Month 12
Part 1 Expansion: Time to Response
Time frame: up to Month 12
Part 1 Expansion: Duration of Response
Time frame: up to 24 months
Part 1 Expansion: Overall Survival
Time frame: up to 36 months
Part 1 Expansion: Nonrelapse Mortality (NRM) Rate
Time frame: up to 24 months
Part 1 Expansion: Percentage of Participants With a ≥50% Reduction in Daily Corticosteroid Dose at Day 180 From the Corticosteroid Dose on Day 1
Time frame: Day 1; Day 180
Part 1 Expansion: Percentage of Participants Successfully Tapered Off All Corticosteroids at Day 180
Time frame: Day 180
Part 1 Expansion: Relapse Rate of Malignant and Nonmalignant Hematologic Diseases
Time frame: up to 1073 days
Part 1 Expansion: Time to Primary Hematologic Disease Relapse
Time frame: up to 24 months
Part 2: Change From Baseline in Lee cGVHD Symptom Scale (LLS) Scores
Time frame: Baseline; End of Treatment in Phase 2
Part 2: Change From Baseline in Quality of Life-Short Form-36 Version 2 (QOL-SF-36 v2) Scores
Time frame: Baseline; End of Treatment in Phase 2
Part 2: Change From Baseline in EQ-5D-3L Scores
Time frame: Baseline; End of Treatment in Phase 2
Part 2: Change From Baseline in Patient Global Impression of Change (PGIC) Responses
Time frame: Baseline; End of Treatment in Phase 2
Part 2: Change From Baseline in Patient Global Impression of Severity (PGIS) Responses
Time frame: Baseline; End of Treatment in Phase 2
Part 2: Response Rate at Months 3 and 12
Time frame: Months 3 and 12
Part 2: Duration of Response
Time frame: up to 24 months
Part 2: Overall Survival
Time frame: up to 36 months
Part 2: NRM Rate
Time frame: up to 24 months
Part 2: Percentage of Participants With a ≥50% Reduction in Daily Corticosteroid Dose at Day 180 From the Corticosteroid Dose on Day 1
Time frame: Day 1; Day 180
Part 2: Percentage of Participants Successfully Tapered Off All Corticosteroids at Day 180
Time frame: Day 180
Part 2: Relapse Rate of Malignant and Nonmalignant Hematologic Diseases
Time frame: up to 24 months
Part 2: Time to Primary Hematologic Disease Relapse
Time frame: up to 24 months
Part 2: Number of Participants With Any TEAE
Time frame: up to 30 days after the last dose in Phase 2
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rodica Morariu-Zamfir, MD study director
Incyte Corporation
133 sites in 16 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Itacitinib, Methylprednisolone and Prednisone in people with Chronic Graft-versus-host Disease, run by Incyte Corporation at 133 sites in 16 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 133 sites in United States, Italy, Germany, Spain, France and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1: Number of Participants With Dose-limiting Toxicities (DLTs) (time frame: up to Day 28). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2025.