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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
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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
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Secondary ID [1]
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INCB 39110-301
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Graft-versus-host Disease (GVHD)
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Condition category
Condition code
Inflammatory and Immune System
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0
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Other inflammatory or immune system disorders
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Intervention/exposure
Study type
Interventional
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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.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Overall Response Rate Based on Center for International Blood and Marrow Transplant Research (CIBMTR) Response Index
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Assessment method [1]
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Defined as the percentage of participants demonstrating a complete response (CR), very good partial response (VGPR), or partial response (PR).
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Timepoint [1]
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Day 28
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Secondary outcome [1]
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Nonrelapse Mortality
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Assessment method [1]
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Defined as the percentage of participants who died due to causes other than malignancy relapse.
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Timepoint [1]
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Month 6,9,12 and 24
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Secondary outcome [2]
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Duration of Response
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Assessment method [2]
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Defined as the interval from first response until GVHD progression or death.
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Timepoint [2]
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Baseline through 30-35 days after end of treatment, total particpation expected to average 24 months
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Secondary outcome [3]
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Cmax of Itacitinib When Administered in Combination With Corticosteroids
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Assessment method [3]
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Defined as maximum observed plasma concentration.
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Timepoint [3]
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Protocol-defined timepoints up to Day 28
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Secondary outcome [4]
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Cmin of Itacitinib When Administered in Combination With Corticosteroids
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Assessment method [4]
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Defined as minimum observed plasma concentration.
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Timepoint [4]
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Protocol-defined timepoints up to Day 28
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Secondary outcome [5]
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Tmax of Itacitinib When Administered in Combination With Corticosteroids
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Assessment method [5]
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Defined as time to maximum plasma concentration.
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Timepoint [5]
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Protocol-defined timepoints up to Day 28
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Secondary outcome [6]
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AUC of Itacitinib When Administered in Combination With Corticosteroids
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Assessment method [6]
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Defined as area under the concentration-time curve.
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Timepoint [6]
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Protocol-defined timepoints up to Day 28
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Secondary outcome [7]
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CL/F of Itacitinib When Administered in Combination With Corticosteroids
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Assessment method [7]
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Defined as oral dose clearance.
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Timepoint [7]
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Protocol-defined timepoints up to Day 28
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Secondary outcome [8]
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Time to Response
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Assessment method [8]
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Defined as the interval from treatment initiation to first response
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Timepoint [8]
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End of Study, total particpation expected to average 24 months
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Secondary outcome [9]
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Relapse Rate of Malignant and Nonmalignant Hematologic Disease
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Assessment method [9]
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Defined as the proportion of subjects whose underlying hematologic disease relapses
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Timepoint [9]
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Randomization through end of Study, study duration expected to average 24 months
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Secondary outcome [10]
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Malignancy Relapse-related Mortality Rate
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Assessment method [10]
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Defined as the proportion of subjects whose malignancy relapses and has a fatal outcome.
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Timepoint [10]
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Randomization through end of Study, study duration expected to average 24 months
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Secondary outcome [11]
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Failure-free Survival
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Assessment method [11]
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Defined as the proportion of subjects who are still alive, have not relapsed, have not required additional therapy for aGVHD, and have not demonstrated signs or symptoms of chronic graft-versus-host disease (cGVHD)
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Timepoint [11]
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6 months from randomization
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Secondary outcome [12]
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Overall Survival (OS)
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Assessment method [12]
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Defined as the interval from study enrollment to death due to any cause.
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Timepoint [12]
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End of Study up to approximately 24 months
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Secondary outcome [13]
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Number of Treatment-emergent Adverse Events With INCB39110
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Assessment method [13]
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Adverse events reported for the first time or worsening of a pre-existing event after the first dose of study treatment
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Timepoint [13]
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30-35 days after end of treatment, approximately 24 months
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Secondary outcome [14]
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Incidence Rate of Secondary Graft Failure
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Assessment method [14]
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Defined as \> 95% recipient cells any time after engraftment with no signs of relapse, OR retransplantation because of secondary neutropenia (\< 0.5 × 109/L) and/or thrombocytopenia (\< 20 × 109/L) within 2 months of transplantion
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Timepoint [14]
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Randomization through end of Study, study duration expected to average 24 months
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Secondary outcome [15]
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Proportion of Subjects Who Discontinue Corticosteroids
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Assessment method [15]
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Average and cumulative corticosteroid dose usage will be calculated and proportion of subjects discontinuing corticosteroids will be tabulated
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Timepoint [15]
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Days 28, 56, 100, and 180
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Secondary outcome [16]
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Proportion of Subjects Who Discontinue Immunosuppressive Medications
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Assessment method [16]
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Summary statistics of subjects discontinuing immunosuppressive medications will be calculated
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Timepoint [16]
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Days 56 and 100
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Secondary outcome [17]
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Incidence Rate of aGVHD Flares
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Assessment method [17]
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Timepoint [17]
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up to day 100
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Secondary outcome [18]
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Incidence Rate of cGVHD
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Assessment method [18]
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Timepoint [18]
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Days 180 and 365
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Secondary outcome [19]
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Objective Response Rate
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Assessment method [19]
0
0
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Timepoint [19]
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Days 14, 56 and 100
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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.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
19/07/2017
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
13/07/2020
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Sample size
Target
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Accrual to date
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Final
439
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Recruitment in Australia
Recruitment state(s)
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Recruitment hospital [1]
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St Vincents Hospital Sydney Limited - Darlinghurst
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Recruitment postcode(s) [1]
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NSW 2010 - Darlinghurst
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Taichung
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Cambridge
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Cardiff
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London
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Nottingham
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Incyte Corporation
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Address
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Ethics approval
Ethics application status
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Summary
Brief summary
The purpose of this study is to evaluate itacitinib or placebo in combination with corticosteroids as first-line treatment of participants with Grade II to IV acute graft-versus-host disease (aGVHD).
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Trial website
https://clinicaltrials.gov/study/NCT03139604
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Trial related presentations / publications
Pratta M, Paczesny S, Socie G, Barkey N, Liu H, Owens S, Arbushites MC, Schroeder MA, Howell MD. A biomarker signature to predict complete response to itacitinib and corticosteroids in acute graft-versus-host disease. Br J Haematol. 2022 Aug;198(4):729-739. doi: 10.1111/bjh.18300. Epub 2022 Jun 11. Zeiser R, Socie G, Schroeder MA, Abhyankar S, Vaz CP, Kwon M, Clausen J, Volodin L, Giebel S, Chacon MJ, Meyers G, Ghosh M, Deeren D, Sanz J, Morariu-Zamfir R, Arbushites M, Lakshminarayanan M, Barbour AM, Chen YB. Efficacy and safety of itacitinib versus placebo in combination with corticosteroids for initial treatment of acute graft-versus-host disease (GRAVITAS-301): a randomised, multicentre, double-blind, phase 3 trial. Lancet Haematol. 2022 Jan;9(1):e14-e25. doi: 10.1016/S2352-3026(21)00367-7.
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Public notes
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Contacts
Principal investigator
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Rodica Morariu-Zamfir, MD
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Incyte Corporation
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Contact person for public queries
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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No/undecided IPD sharing reason/comment
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What supporting documents are/will be available?
No Supporting Document Provided
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Other Details
Attachment
Study protocol
https://cdn.clinicaltrials.gov/large-docs/04/NCT03139604/Prot_000.pdf
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/04/NCT03139604/SAP_001.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT03139604