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Safety and Efficacy of Itacitinib in Combination With Corticosteroids for Treatment of Graft-Versus-Host Disease in Pediatric Subjects

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ClinicalTrials.gov Identifier: NCT03721965
Recruitment Status : Recruiting
First Posted : October 26, 2018
Last Update Posted : November 7, 2019
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

Brief Summary:
The purpose of this study is to evaluate itacitinib in combination with corticosteroids for the treatment of Grades II to IV acute graft-versus-host disease (aGVHD) in steroid-naive pediatric participants.

Condition or disease Intervention/treatment Phase
Acute Graft-versus-host Disease Drug: Itacitinib Drug: Corticosteroids Phase 1 Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Single-Arm, Phase 1/2 Study Evaluating the Safety and Efficacy of Itacitinib in Combination With Corticosteroids for the Treatment of Steroid-Naive Acute Graft-Versus-Host Disease in Pediatric Subjects
Actual Study Start Date : April 16, 2019
Estimated Primary Completion Date : November 10, 2022
Estimated Study Completion Date : November 10, 2022


Arm Intervention/treatment
Experimental: Itacitinib + Corticosteroids Drug: Itacitinib
Phase 1: Itacitinib administered orally once daily at the protocol-defined dose according to age cohort, with dose reductions or modifications based on safety assessments. Phase 2: Itacitinib administered orally once daily at the recommended dose from Phase 1.
Other Name: INCB039110

Drug: Corticosteroids
Phase 1 and 2: Methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of disease as outlined per local treatment guidelines as background treatment.
Other Name: prednisone, methylprednisolone




Primary Outcome Measures :
  1. Phase 1: Participants with treatment-emergent adverse events (TEAEs) [ Time Frame: Up to approximately 12 months ]
    Safety and tolerability.

  2. Phase 1: Cmax of itacitinib when administered with corticosteroids [ Time Frame: Up to 28 days ]
    Maximum observed plasma concentration.

  3. Phase 1: Cmin of itacitinib when administered with corticosteroids [ Time Frame: Up to 28 days ]
    Minimum observed plasma concentration.

  4. Phase 1: Tmax of itacitinib when administered with corticosteroids [ Time Frame: Up to 28 days ]
    Time to maximum concentration.

  5. Phase 1: AUC of itacitinib when administered with corticosteroids [ Time Frame: Up to 28 days ]
    Area under the plasma concentration-time curve.

  6. Phase 1: Cl/F of itacitinib when administered with corticosteroids [ Time Frame: Up to 28 days ]
    Apparent oral dose clearance.

  7. Phase 2: Overall response rate [ Time Frame: Day 28 ]
    Defined as the proportion of participants demonstrating a complete response (CR), very good partial response (VGPR), or partial response (PR).


Secondary Outcome Measures :
  1. Phase 1: Overall response rate [ Time Frame: Day 28 ]
    Defined as the proportion of participants demonstrating a CR, VGPR, or PR.

  2. Phase 2: Cmax of itacitinib when administered with corticosteroids [ Time Frame: Day 7 ]
    Maximum observed plasma concentration.

  3. Phase 2: Cmin of itacitinib when administered with corticosteroids [ Time Frame: Day 7 ]
    Minimum observed plasma concentration.

  4. Phase 2: Tmax of itacitinib when administered with corticosteroids [ Time Frame: Day 7 ]
    Time to maximum concentration.

  5. Phase 2: AUC of itacitinib when administered with corticosteroids [ Time Frame: Day 7 ]
    Area under the plasma concentration-time curve.

  6. Phase 2: Cl/F of itacitinib when administered with corticosteroids [ Time Frame: Day 7 ]
    Apparent oral dose clearance.

  7. Phase 1 and 2: Overall response rate [ Time Frame: Up to 100 days ]
    Defined as the proportion of participants demonstrating a CR, VGPR, or PR.

  8. Phase 1 and 2: Nonrelapse mortality [ Time Frame: Up to 24 months ]
    Defined as the proportion of participants who died due to causes other than underlying hematologic disorders relapse.

  9. Phase 1 and 2: Duration of response [ Time Frame: Up to approximately 12 months ]
    Defined as the time of the onset of response to loss of response.

  10. Phase 1 and 2: Time to response [ Time Frame: Up to approximately 12 months ]
    Defined as the interval from treatment initiation to first response.

  11. Phase 1 and 2: Relapse rate of malignant and nonmalignant disorders [ Time Frame: Up to approximately 12 months ]
    Defined as the proportion of participants whose underlying disease relapses.

  12. Phase 1 and 2: Malignant and nonmalignant disorders relapse-related mortality rate [ Time Frame: Up to approximately 12 months ]
    Defined as the proportion of participants whose underlying hematologic disorder relapses and has a fatal outcome.

  13. Phase 1 and 2: Failure-free survival [ Time Frame: Up to 6 months ]
    Defined as the proportion of participants who are still alive, have not relapsed, have not required additional therapy for aGVHD, and have not demonstrated signs or symptoms of chronic GVHD.

  14. Phase 1 and 2: Overall survival [ Time Frame: Up to approximately 12 months ]
    Defined as the interval from study enrollment to death due to any cause.

  15. Phase 1 and 2: Number of adverse events [ Time Frame: Up to approximately 12 months ]
  16. Phase 1 and 2: Incidence rate of secondary graft failure [ Time Frame: Up to approximately 12 months ]
    To assess the proportion of participants experiencing secondary graft failure.

  17. Phase 1 and 2: Average corticosteroid dose [ Time Frame: Up to 180 days ]
  18. Phase 1 and 2: Cumulative corticosteroid dose [ Time Frame: Up to 180 days ]
  19. Phase 1 and 2: Proportion of participants who discontinue corticosteroids [ Time Frame: Up to 100 days ]
  20. Phase 1 and 2: Proportion of participants who discontinue immunosuppressive medication [ Time Frame: Up to 100 days ]
  21. Phase 1 and 2: Incidence rate of aGVHD flares [ Time Frame: Day 100 ]
  22. Phase 1 and 2: Incidence rate of cGVHD [ Time Frame: Up to 365 days ]


Information from the National Library of Medicine

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Ages Eligible for Study:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female participants: 12 to < 18 years old (Cohort 1), 6 to < 12 years old (Cohort 2), 2 to < 6 years old (Cohort 3), Weighing > 8 kg to < 2 years old (Cohort 4), and 28 days old to weighing ≤ 8 kg (Cohort 5).
  • Undergone 1 allogeneic hematopoietic stem cell transplantation (allo-HSCT) from any donor and source for hematological malignancies or disorders. Recipients of myeloablative and reduced-intensity conditioning regimens are eligible.
  • Clinically suspected Grade II to IV aGVHD as per Mount Sinai Acute GVHD International Consortium (MAGIC) criteria, occurring after allo-HSCT and any GVHD prophylactic medication.
  • Evidence of myeloid engraftment.

Exclusion Criteria:

  • More than 1 allo-HSCT.
  • Received more than 2 days of systemic corticosteroids for aGVHD before the first study drug administration.
  • Presence of GVHD overlap syndrome.
  • Presence of an active uncontrolled infection.
  • Known HIV infection.
  • Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection that requires treatment or at risk for HBV reactivation.
  • Evidence of relapsed primary disease or have been treated for relapse after the allo-HSCT was performed.
  • Any corticosteroid therapy for indications other than GVHD at doses > 1 mg/kg once daily of methylprednisolone (or equivalent) within 7 days of the first study drug administration.
  • Receipt of live (including attenuated) vaccines or anticipation of need for such vaccines during the study.
  • Receipt of JAK inhibitor therapy after allo-HSCT for any indication.
  • Treatment with any other investigational agent, device, or procedure within 21 days (or 5 half-lives, whichever is greater) of enrollment.

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): NCT03721965


Contacts
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Contact: Incyte Corporation Call Center (US) 1.855.463.3463 medinfo@incyte.com
Contact: Incyte Corporation Call Center (ex-US) +800 00027423 globalmedinfo@incyte.com

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Sponsors and Collaborators
Incyte Corporation
Investigators
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Study Director: Rodica Morariu-Zamfir, MD Incyte Corporation

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Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT03721965     History of Changes
Other Study ID Numbers: INCB 39110-120
First Posted: October 26, 2018    Key Record Dates
Last Update Posted: November 7, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
Acute graft-versus-host disease
GVHD
pediatric
JAK1 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