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Safety of Itacitinib in Combination With Corticosteroids for Treatment of Steroid-Naive Acute Graft-Versus-Host Disease in Japanese Subjects

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ClinicalTrials.gov Identifier: NCT03497273
Recruitment Status : Recruiting
First Posted : April 13, 2018
Last Update Posted : June 21, 2019
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

Brief Summary:
The purpose of this study is to assess the safety and tolerability of itacitinib in combination with corticosteroids in Japanese subjects with Grades II to IV acute graft-versus-host disease (aGVHD).

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Single-Arm Phase 1 Study Evaluating Safety of Itacitinib in Combination With Corticosteroids for the Treatment of Steroid-Naive Acute Graft-Versus-Host Disease in Japanese Subjects
Actual Study Start Date : March 20, 2018
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : February 2020


Arm Intervention/treatment
Experimental: Itacitinib + corticosteroids
Itacitinib administered in combination with corticosteroids.
Drug: Itacitinib
Itacitinib administered orally once daily at the protocol-defined dose.
Other Name: INCB039110

Drug: Corticosteroid
Either oral prednisolone or intravenous methylprednisolone at the investigator's discretion.




Primary Outcome Measures :
  1. Number of treatment-emergent adverse events [ Time Frame: Up to approximately 12 months ]
    Defined as any adverse event reported for the first time or worsening of a pre-existing event after first dose of study drug.


Secondary Outcome Measures :
  1. Cmax of INCB039110 [ Time Frame: Up to approximately 1 month ]
    Maximum observed plasma concentration.

  2. Cl/F of INCB039110 [ Time Frame: Up to approximately 1 month ]
    Apparent oral dose clearance.

  3. Objective response rate [ Time Frame: Up to 100 days ]
    Defined as the proportion of participants demonstrating a complete response, very good partial response, or partial response.

  4. Nonrelapse mortality [ Time Frame: Up to approximately 12 months ]
    Defined as the proportion of participants who died due to causes other than malignancy.

  5. Duration of response [ Time Frame: Up to approximately 12 months ]
    Defined as the interval from first response until GVHD progression or death.

  6. Time to response [ Time Frame: Up to approximately 12 months ]
    Defined as the interval from treatment initiation to first response.

  7. Malignancy relapse rate [ Time Frame: Up to approximately 12 months ]
    Defined as the proportion of participants whose underlying malignancy relapses.

  8. 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 (cGVHD).

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



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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Japanese; subject was born in Japan and has not lived outside of Japan for a total of > 10 years, and subject can trace maternal and paternal Japanese ancestry.
  • Has undergone 1 allo-hematopoietic stem cell transplant (HSCT) from any donor and source (unrelated, sibling, haploidentical donors with any matching) using bone marrow, peripheral blood or cord blood for hematologic malignancies. Recipients of myeloablative and reduced-intensity conditioning regimens are eligible.
  • Clinically suspected Grades II to IV aGVHD as per Mount Sinai Acute GVHD International Consortium (MAGIC) criteria, occurring after allo-HSCT and any anti-GVHD prophylactic medication.
  • Evidence of myeloid engraftment (eg, absolute neutrophil count [ANC] ≥ 0.5 × 10^9/L for 3 consecutive assessments if ablative therapy was previously used). Use of growth factor supplementation is allowed.
  • Female subjects should agree to use medically acceptable contraceptive measures, should not be breastfeeding, and must have a negative pregnancy test before the start of study drug administration if of childbearing potential or must have evidence of non-childbearing potential by fulfilling protocol-defined criteria at screening.

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 (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).
  • Known human immunodeficiency virus infection.
  • Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection that requires treatment or at risk for HBV reactivation. For subjects with negative HBsAg and positive total hepatitis B core antibody and for subjects who are positive for HCV antibody, HBV DNA and HCV RNA must be undetectable upon testing.
  • Evidence of relapsed primary disease or having been treated for relapse after the allo-HSCT was performed.
  • Any corticosteroid therapy (for indication other than GVHD) at doses > 1 mg/kg per day methylprednisolone or equivalent within 7 days of enrollment.
  • Severe organ dysfunction unrelated to underlying GVHD, including the following:

    • 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.
  • Serum creatinine > 2.0 mg/dL or creatinine clearance < 40 mL/min measured or calculated by Cockroft-Gault equation
  • Received Janus kinase (JAK) inhibitor therapy after allo-HSCT for any indication. Treatment with a JAK inhibitor before allo-HSCT is permitted.
  • Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.

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): NCT03497273


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

Locations
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Japan
JA-Aichi Anjo Kosei Hospital Active, not recruiting
Anjo-Shi, Aichi, Japan, 446-8602
Nagoya University Hospital Recruiting
Nagoya-Shi, Aichi, Japan, 466-8560
Principal Investigator: Makoto Murata         
Hokuyukai Sapporo Hokuyu Hospital Recruiting
Sapporo-Shi, Hokkaido, Japan, 003-0006
Principal Investigator: Shuichi Ota         
Hokkaido University Hospital Recruiting
Sapporo-shi, Hokkaido, Japan, 060-8648
Principal Investigator: Takanori Teshima         
Hyogo College of Medicine Hospital Active, not recruiting
Nishinomiya-Shi, Hyogo, Japan, 663-8501
University of Tsukuba Hospital Recruiting
Tsukuba-shi, Ibaraki-Ken, Japan, 305-8576
Principal Investigator: Yuichi Hasegawa         
Jiaikai Imamura General Hospital Recruiting
Kagoshima-Shi, Kagoshima, Japan, 890-0064
Principal Investigator: Nobuaki Nakano         
Kanagawa Cancer Center Recruiting
Yokohama-shi, Kanagawa-Ken, Japan, 241-8515
Principal Investigator: Heiwa Kanamori         
Tokai University Hospital Recruiting
Isehara-Shi, Kanagawa, Japan, 259-1193
Principal Investigator: Kiyoshi Ando         
NHO Kumamoto Medical Center Recruiting
Kumamoto-shi, Kumamoto-Ken, Japan, 860-0008
Principal Investigator: Michihiro Hidaka         
Tohoku University Hospital Recruiting
Sendai-shi, Miyagi-Ken, Japan, 980-8574
Principal Investigator: Yasushi Onishi         
Okayama University Hospital Recruiting
Okayama-shi, Okayama-Ken, Japan, 700-8558
Principal Investigator: Yoshinobu Maeda         
Osaka City University Hospital Recruiting
Osaka-Shi, Osaka, Japan, 545-8586
Principal Investigator: Hideo Koh         
Shizuoka Cancer Center Recruiting
Nagaizumi-cho, Shizuoka-Ken, Japan, 411-8777
Principal Investigator: Takashi Ikeda         
Jichi Medical University Hospital Recruiting
Shimotsuke-shi, Tochigi-Ken, Japan, 329-0498
Principal Investigator: Masahiro Ashizawa         
St. Luke's International Hospital Recruiting
Chuo Ku, Tokyo-To, Japan, 104-8560
Principal Investigator: Shinichiro Mori         
Jikei University Hospital Recruiting
Minato-ku, Tokyo-To, Japan, 105-8471
Principal Investigator: Takeshi Saito         
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: NCT03497273     History of Changes
Other Study ID Numbers: INCB 39110-118
First Posted: April 13, 2018    Key Record Dates
Last Update Posted: June 21, 2019
Last Verified: June 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
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Incyte Corporation:
JAK1 inhibitor
GVHD
acute GVHD
Japan
corticosteroids
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases