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GRAVITAS-309: Itacitinib and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease

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 evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03584516
Recruitment Status : Active, not recruiting
First Posted : July 12, 2018
Last Update Posted : October 19, 2022
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

Study Description
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Brief 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).

Condition or disease Intervention/treatment Phase
Chronic Graft-versus-host Disease Drug: Itacitinib Drug: Placebo Drug: Methylprednisolone Drug: Prednisone Phase 2 Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 155 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention 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 (Participant, Investigator)
Primary Purpose: Treatment
Official Title: GRAVITAS-309: A Phase 2/3 Study of Itacitinib and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease
Actual Study Start Date : January 17, 2019
Estimated Primary Completion Date : March 30, 2023
Estimated Study Completion Date : March 30, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Steroids

Arms and Interventions
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Arm Intervention/treatment
Experimental: Part 1 : Dose determination of itacitinib
itacitinib administered in combination with corticosteroids.
 Drug: Itacitinib
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.
Other Name: INCB039110

Drug: Methylprednisolone
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.
Other Name: Medrol, Medrol Dosepak, Solu-Medrol

Drug: Prednisone
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.
Other Name: Deltasone, Prednicot, predniSONE Intensol, Rayos, Sterapred, Sterapred DS
Experimental: Part 1 : Dose expansion of itacitinib
itacitinib administered in combination with corticosteroids or corticosteroids alone.
 Drug: Itacitinib
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.
Other Name: INCB039110

Drug: Placebo
In Part 2, participants will receive matching placebo.

Drug: Methylprednisolone
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.
Other Name: Medrol, Medrol Dosepak, Solu-Medrol

Drug: Prednisone
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.
Other Name: Deltasone, Prednicot, predniSONE Intensol, Rayos, Sterapred, Sterapred DS
Placebo Comparator: Part 2 : itacitinib recommended dose from part 1
itacitinib or placebo administered in combination with corticosteroids
 Drug: Itacitinib
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.
Other Name: INCB039110

Drug: Methylprednisolone
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.
Other Name: Medrol, Medrol Dosepak, Solu-Medrol

Drug: Prednisone
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.
Other Name: Deltasone, Prednicot, predniSONE Intensol, Rayos, Sterapred, Sterapred DS


Outcome Measures
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Primary Outcome Measures :
  1. Part 1 : Dose Determination: Number of dose-limiting toxicities [ Time Frame: 28 days ]
    To identify an appropriate dose of itacitinib in combination with corticosteroids as initial treatment for moderate or severe cGVHD.

  2. Part 2 : Response rate [ Time Frame: Month 6 ]
    Defined as the proportion of participants demonstrating a complete response (CR) or partial response (PR) per National Institutes of Health (NIH) consensus guideline.

  3. Part 1 : Dose Expansion: Number of dose-limiting toxicities [ Time Frame: 28 days ]
    To identify an appropriate dose of itacitinib in combination with corticosteroids as initial treatment for moderate or severe cGVHD.


Secondary Outcome Measures :
  1. Part 1, 1 expansion, and Part 2: Cmax of itacitinib when administered in combination with corticosteroids [ Time Frame: Up to 28 days ]
    Maximum observed concentration.

  2. Part 1, 1 expansion, and Part 2: Cmin of itacitinib when administered in combination with corticosteroids [ Time Frame: Up to 28 days ]
    Minimum observed plasma or serum concentration over the dose interval.


Other Outcome Measures:
  1. Part 1, 1 expansion, and Part 2: Response rate [ Time Frame: Up to 12 months ]
    Defined as the proportion of participants who demonstrate a CR or PR per NIH consensus guideline.

  2. Part 1: Time to response [ Time Frame: Up to 36 months ]
    Defined as the interval between randomization and first response.

  3. Part 1, 1 expansion, and Part 2: Duration of response [ Time Frame: Up to 36 months ]
    Defined as the interval between first response and cGVHD progression, death, malignancy relapse, or initiation of new systemic cGVHD therapy.

  4. Part 1, 1 expansion, and Part 2: Overall survival [ Time Frame: Up to 36 months ]
    Defined as the interval between the date of randomization and the date of death due to any cause.

  5. Part 1, 1 expansion, and Part 2: Nonrelapse mortality [ Time Frame: Up to 36 months ]
    Defined as the proportion of participants who died due to causes other than malignancy relapse.

  6. Part 2: Number of treatment-emergent adverse events [ Time Frame: Up to 36 months ]
    Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment).


Eligibility Criteria
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Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03584516


Locations
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Sponsors and Collaborators
Incyte Corporation
Investigators
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Study Director: Rodica Morariu-Zamfir, MD Incyte Corporation
More Information
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Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT03584516    
Other Study ID Numbers: INCB 39110-309
First Posted: July 12, 2018    Key Record Dates
Last Update Posted: October 19, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

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
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
URL: https://www.incyte.com/our-company/compliance-and-transparency

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Incyte Corporation:
Graft-versus-host-disease
itacitinib
Janus kinase inhibitor
corticosteroids
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases
Prednisone
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Glucocorticoids
 Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents