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

Acute Graft-versus-host Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03497273
• Other study ID #: INCB 39110-118
• Status: Completed
• Phase: Phase 1
• Start date: March 20, 2018
• Est. completion date: February 17, 2020

Study information

• Verified date: March 2020
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: February 17, 2020
• Est. primary completion date: November 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Graft-versus-host Disease
• Graft vs Host Disease

Intervention

Drug:
• Itacitinib
Itacitinib administered orally once daily at the protocol-defined dose.
• Corticosteroid
Either oral prednisolone or intravenous methylprednisolone at the investigator's discretion.

Locations

Country	Name	City	State
Japan	JA-Aichi Anjo Kosei Hospital	Anjo-Shi	Aichi
Japan	St. Luke's International Hospital	Chuo Ku	Tokyo-To
Japan	Tokai University Hospital	Isehara-Shi	Kanagawa
Japan	Jiaikai Imamura General Hospital	Kagoshima-Shi	Kagoshima
Japan	NHO Kumamoto Medical Center	Kumamoto-shi	Kumamoto-Ken
Japan	Jikei University Hospital	Minato-ku	Tokyo-To
Japan	Shizuoka Cancer Center	Nagaizumi-cho	Shizuoka-Ken
Japan	Nagoya University Hospital	Nagoya-Shi	Aichi
Japan	Hyogo College of Medicine Hospital	Nishinomiya-Shi	Hyogo
Japan	Okayama University Hospital	Okayama-shi	Okayama-Ken
Japan	Osaka City University Hospital	Osaka-Shi	Osaka
Japan	Hokkaido University Hospital	Sapporo-shi	Hokkaido
Japan	Hokuyukai Sapporo Hokuyu Hospital	Sapporo-Shi	Hokkaido
Japan	Tohoku University Hospital	Sendai-shi	Miyagi-Ken
Japan	Jichi Medical University Hospital	Shimotsuke-shi	Tochigi-Ken
Japan	University of Tsukuba Hospital	Tsukuba-shi	Ibaraki-Ken
Japan	Kanagawa Cancer Center	Yokohama-shi	Kanagawa-Ken

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of treatment-emergent adverse events	Defined as any adverse event reported for the first time or worsening of a pre-existing event after first dose of study drug.	Up to approximately 12 months
Secondary	Cmax of INCB039110	Maximum observed plasma concentration.	Up to approximately 1 month
Secondary	Cl/F of INCB039110	Apparent oral dose clearance.	Up to approximately 1 month
Secondary	Objective response rate	Defined as the proportion of participants demonstrating a complete response, very good partial response, or partial response.	Up to 100 days
Secondary	Nonrelapse mortality	Defined as the proportion of participants who died due to causes other than malignancy.	Up to approximately 12 months
Secondary	Duration of response	Defined as the interval from first response until GVHD progression or death.	Up to approximately 12 months
Secondary	Time to response	Defined as the interval from treatment initiation to first response.	Up to approximately 12 months
Secondary	Malignancy relapse rate	Defined as the proportion of participants whose underlying malignancy relapses.	Up to approximately 12 months
Secondary	Failure-free survival	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).	Up to 6 months
Secondary	Overall survival	Defined as the interval from study enrollment to death due to any cause.	Up to approximately 12 months