GRAVITAS-309: Itacitinib and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease
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ClinicalTrials.gov Identifier: NCT03584516 |
Recruitment Status :
Active, not recruiting
First Posted : July 12, 2018
Last Update Posted : October 19, 2022
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Condition or disease | Intervention/treatment | Phase |
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Chronic Graft-versus-host Disease | Drug: Itacitinib Drug: Placebo Drug: Methylprednisolone Drug: Prednisone | Phase 2 Phase 3 |
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 |

Arm | Intervention/treatment |
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Experimental: Part 1 : Dose determination of itacitinib
itacitinib administered in combination with corticosteroids.
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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.
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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
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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 |
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Part 1: Time to response [ Time Frame: Up to 36 months ]Defined as the interval between randomization and first response.
- 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.
- 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.
- 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.
- 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).

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

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

Study Director: | Rodica Morariu-Zamfir, MD | Incyte Corporation |
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 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Graft-versus-host-disease itacitinib Janus kinase inhibitor corticosteroids |
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 |