Clinical Trials List
Protocol NumberINCB 39110-301
2017-12-01 - 2020-12-31
Phase III
Terminated3
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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Trial Applicant
MEDPACE TAIWAN LIMITED
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Sponsor
Incyte Corporation
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 賴冠銘 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Tung-Liang Lin Division of Hematology & Oncology
- Ming-Chung Kao Division of Hematology & Oncology
- 洪玉馨 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
- Ching-Chan Lin Division of Hematology & Oncology
- Ming-Yu Lien Division of Hematology & Oncology
- Che-Hung Lin Division of Hematology & Oncology
- Tzu-Ting Chen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
1 Terminated
Audit
None
Condition/Disease
Acute Graft Versus Host Disease
Objectives
Primary Objective:
Compare the efficacy of itacitinib in combination with corticosteroids versus placebo in combination with corticosteroids in terms of ORR at Day 28 in subjects with aGVHD.
Secondary Objectives:
*Compare additional response and longer-term efficacy outcomes between treatment cohorts.
*Assess the incidence and severity of AEs and SAEs.
*Evaluate the PK of itacitinib when administered in combination with corticosteroids.
*Evaluate the incidence of secondary graft failure.
*Evaluate the use and discontinuation of corticosteroids.
*Evaluate the use and discontinuation of immunosuppressive medications.
*Evaluate the incidence of aGVHD flares.
*Evaluate the incidence of cGVHD.
Exploratory Objectives
*Assess the efficacy of study treatment by aGVHD risk status and organ involvement
*Assess and compare the changes in healthcare utilization between treatment cohorts from screening through EOT.
*Assess the QOL impact between treatment cohorts.
*Evaluate changes in T-cell populations, cytokine expression, and other relevant biomarkers.
Test Drug
Itacitinib
Active Ingredient
Itacitinib adipate
Dosage Form
Tablet
Dosage
100 mg/tablet
Endpoints
Primary Endpoint:
ORR at Day 28, defined as the proportion of subjects demonstrating a CR, VGPR, or PR.
Key Secondary Endpoint
NRM at Month 6, defined as the proportion of subjects who died due to causes other than malignancy relapse at Month 6.
Exploratory Endpoints
1. ORR at Day 28 in standard-risk aGVHD, in high-risk aGVHD and by involved organ system.
2. Incident rate of unplanned ambulatory care, hospitalization(s), or emergency room visits; time for length of stay for any hospital visits
3. Changes in parameters collected using the QOL-SF-36 from screening until EOT.
4. Results will be summarized and correlated to efficacy and safety outcomes as appropriate.
ORR at Day 28, defined as the proportion of subjects demonstrating a CR, VGPR, or PR.
Key Secondary Endpoint
NRM at Month 6, defined as the proportion of subjects who died due to causes other than malignancy relapse at Month 6.
Exploratory Endpoints
1. ORR at Day 28 in standard-risk aGVHD, in high-risk aGVHD and by involved organ system.
2. Incident rate of unplanned ambulatory care, hospitalization(s), or emergency room visits; time for length of stay for any hospital visits
3. Changes in parameters collected using the QOL-SF-36 from screening until EOT.
4. Results will be summarized and correlated to efficacy and safety outcomes as appropriate.
Inclution Criteria
A subject who meets all of the following criteria may be included in the study:
1. Male or female, 18 years of age or older; outside the European Union, an older limit could apply depending on local regulation (eg, 20 years and older for Taiwan and Japan).
2. 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.
3. Clinically suspected Grade II to IV aGVHD as per MAGIC criteria, occurring after allo-HSCT and any GVHD prophylaxis regimen. Biopsies should be obtained to pathologically confirm aGVHD; in cases where a biopsy is negative, is unable to be obtained, or is clinically contraindicated, clinical suspicion of aGVHD by the treating physician is sufficient, provided that alternative diagnoses of drug effects or infection are adequately ruled out.
4. Evidence of myeloid engraftment (eg, ANC ≥ 0.5 × 109/L for 3 consecutive assessments if ablative therapy was previously used). Use of growth factor supplementation is allowed.
5. Be willing to avoid pregnancy or fathering children based on 1 of the following criteria:
a. Women of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR ≥ 12 months of amenorrhea).
b. Woman of childbearing potential who has a negative serum pregnancy test at screening and who agrees to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow-up. Permitted methods that are at least 99% effective in preventing pregnancy (see Appendix A) should be communicated to the subject and their understanding confirmed.
c. Man who agrees to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through safety follow-up. Permitted methods that are at least 99% effective in preventing pregnancy (see Appendix A) should be communicated to the subject and their understanding confirmed.
6. Able to give written informed consent and comply with all study visits and procedures.
7. Able to swallow and retain oral medication.
1. Male or female, 18 years of age or older; outside the European Union, an older limit could apply depending on local regulation (eg, 20 years and older for Taiwan and Japan).
2. 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.
3. Clinically suspected Grade II to IV aGVHD as per MAGIC criteria, occurring after allo-HSCT and any GVHD prophylaxis regimen. Biopsies should be obtained to pathologically confirm aGVHD; in cases where a biopsy is negative, is unable to be obtained, or is clinically contraindicated, clinical suspicion of aGVHD by the treating physician is sufficient, provided that alternative diagnoses of drug effects or infection are adequately ruled out.
4. Evidence of myeloid engraftment (eg, ANC ≥ 0.5 × 109/L for 3 consecutive assessments if ablative therapy was previously used). Use of growth factor supplementation is allowed.
5. Be willing to avoid pregnancy or fathering children based on 1 of the following criteria:
a. Women of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR ≥ 12 months of amenorrhea).
b. Woman of childbearing potential who has a negative serum pregnancy test at screening and who agrees to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow-up. Permitted methods that are at least 99% effective in preventing pregnancy (see Appendix A) should be communicated to the subject and their understanding confirmed.
c. Man who agrees to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through safety follow-up. Permitted methods that are at least 99% effective in preventing pregnancy (see Appendix A) should be communicated to the subject and their understanding confirmed.
6. Able to give written informed consent and comply with all study visits and procedures.
7. Able to swallow and retain oral medication.
Exclusion Criteria
1. Has received more than 1 allo-HSCT.
2. Has received more than 2 days of systemic corticosteroids for acute-GVHD.
3. Presence of GVHD overlap syndrome.
4. Presence of an active uncontrolled infection. An active uncontrolled infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs, or radiographic findings attributable to infection. Persisting fever without signs or symptoms will not be interpreted as an active uncontrolled infection.
5. Known human immunodeficiency virus infection.
6. Active HBV or HCV infection that requires treatment, or at risk for HBV
HBV DNA is undetectable
for HCV antibody polymerase chain
reaction . Subjects whose immune status is unknown or uncertain must have results confirming immune status before enrollment. Prior serology results are acceptable for determining eligibility.
7. Subjects with evidence of relapsed primary disease, or subjects who have been treated for relapse after the allo-HSCT was performed.
8. Any corticosteroid therapy for indications other than GVHD at doses > 1 mg/kg per day methylprednisolone (or prednisone equivalent) within 7 days of randomization.
9. Severe organ dysfunction unrelated to underlying GVHD, including:
a. Cholestatic disorders or unresolved veno-occlusive disease of the liver (defined as persistent bilirubin abnormalities not attributable to GVHD and ongoing organ dysfunction).
b. Clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months of enrollment, New York Heart Association Class III or IV congestive heart failure, circulatory collapse requiring vasopressor or inotropic support, or arrhythmia that requires therapy.
c. Clinically significant respiratory disease that requires mechanical ventilation support or 50% oxygen.
10. Serum creatinine > 2.0 mg/dL or creatinine clearance < 40 mL/min measured or calculated by Cockroft-Gault equation.
11. Currently breast feeding.
12. Receipt of live (including attenuated) vaccines or anticipation of need for such a vaccine during the study.
13. Received JAK inhibitor therapy after allo-HSCT for any indication. Treatment with a JAK inhibitor before allo-HSCT is permitted.
14. Treatment with any other investigational agent, device, or procedure, within 21 days (or 5 half-lives, whichever is greater) of enrollment. Subjects participating in a GVHD prophylaxis study or conditioning regimen should be discussed with the sponsor's medical monitor before enrollment.
15. 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 subject; or interfere with interpretation of study data.
16. Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.
2. Has received more than 2 days of systemic corticosteroids for acute-GVHD.
3. Presence of GVHD overlap syndrome.
4. Presence of an active uncontrolled infection. An active uncontrolled infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs, or radiographic findings attributable to infection. Persisting fever without signs or symptoms will not be interpreted as an active uncontrolled infection.
5. Known human immunodeficiency virus infection.
6. Active HBV or HCV infection that requires treatment, or at risk for HBV
HBV DNA is undetectable
for HCV antibody polymerase chain
reaction . Subjects whose immune status is unknown or uncertain must have results confirming immune status before enrollment. Prior serology results are acceptable for determining eligibility.
7. Subjects with evidence of relapsed primary disease, or subjects who have been treated for relapse after the allo-HSCT was performed.
8. Any corticosteroid therapy for indications other than GVHD at doses > 1 mg/kg per day methylprednisolone (or prednisone equivalent) within 7 days of randomization.
9. Severe organ dysfunction unrelated to underlying GVHD, including:
a. Cholestatic disorders or unresolved veno-occlusive disease of the liver (defined as persistent bilirubin abnormalities not attributable to GVHD and ongoing organ dysfunction).
b. Clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months of enrollment, New York Heart Association Class III or IV congestive heart failure, circulatory collapse requiring vasopressor or inotropic support, or arrhythmia that requires therapy.
c. Clinically significant respiratory disease that requires mechanical ventilation support or 50% oxygen.
10. Serum creatinine > 2.0 mg/dL or creatinine clearance < 40 mL/min measured or calculated by Cockroft-Gault equation.
11. Currently breast feeding.
12. Receipt of live (including attenuated) vaccines or anticipation of need for such a vaccine during the study.
13. Received JAK inhibitor therapy after allo-HSCT for any indication. Treatment with a JAK inhibitor before allo-HSCT is permitted.
14. Treatment with any other investigational agent, device, or procedure, within 21 days (or 5 half-lives, whichever is greater) of enrollment. Subjects participating in a GVHD prophylaxis study or conditioning regimen should be discussed with the sponsor's medical monitor before enrollment.
15. 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 subject; or interfere with interpretation of study data.
16. Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.
The Estimated Number of Participants
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Taiwan
18 participants
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Global
436 participants
