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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03139604
Ethics application status
Date submitted
2/05/2017
Date registered
4/05/2017
Date last updated
6/05/2019

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(has expanded access)
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 - Defined as the percentage of participants demonstrating a complete response (CR), very good partial response (VGPR), or partial response (PR).
Timepoint [1] 0 0
Day 28
Secondary outcome [1] 0 0
Nonrelapse mortality - Defined as the percentage of participants who died due to causes other than malignancy relapse.
Timepoint [1] 0 0
Month 6
Secondary outcome [2] 0 0
Duration of response - Defined as the interval from first response until GVHD progression or death.
Timepoint [2] 0 0
Baseline through 30-35 days after end of treatment, expected to average approximately 6 months
Secondary outcome [3] 0 0
Cmax of itacitinib when administered in combination with corticosteroids - Defined as maximum observed plasma concentration.
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 - Defined as minimum observed plasma concentration.
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 - Defined as time to maximum plasma concentration.
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 - Defined as area under the concentration-time curve.
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 - Defined as oral dose clearance.
Timepoint [7] 0 0
Protocol-defined timepoints up to Day 28

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
Gender
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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Icon Cancer Care - Auchenflower
Recruitment hospital [2] 0 0
St Vincents Hospital Sydney Limited - Darlinghurst
Recruitment postcode(s) [1] 0 0
4066 - Auchenflower
Recruitment postcode(s) [2] 0 0
NSW 2010 - Darlinghurst
Recruitment outside Australia
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Virginia
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Graz
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Catania
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Geneve
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Taoyuan City
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United Kingdom
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Manchester
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Surrey
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Cambridge
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Cardiff
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London
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United Kingdom
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Nottingham

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

Ethics approval
Ethics application status

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).
Trial website
https://clinicaltrials.gov/show/NCT03139604
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

Summary results
Other publications