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

Sponsor

Incyte Corporation (Industry)

Overall Status

Completed

CT.gov ID

NCT03497273

Collaborator

(none)

Enrollment

Locations

Arm

Actual Duration (Months)

0.8

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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

Study Design

Study Type:

Interventional

Actual Enrollment :

14 participants

Allocation:

N/A

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 :

Mar 20, 2018

Actual Primary Completion Date :

Nov 30, 2019

Actual Study Completion Date :

Feb 17, 2020

Arms and Interventions

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 Names: INCB039110 Drug: Corticosteroid Either oral prednisolone or intravenous methylprednisolone at the investigator's discretion.

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 Names:

INCB039110

Drug: Corticosteroid

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

Outcome Measures

Primary Outcome Measures

Number of treatment-emergent adverse events [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

Cmax of INCB039110 [Up to approximately 1 month]
Maximum observed plasma concentration.
Cl/F of INCB039110 [Up to approximately 1 month]
Apparent oral dose clearance.
Objective response rate [Up to 100 days]
Defined as the proportion of participants demonstrating a complete response, very good partial response, or partial response.
Nonrelapse mortality [Up to approximately 12 months]
Defined as the proportion of participants who died due to causes other than malignancy.
Duration of response [Up to approximately 12 months]
Defined as the interval from first response until GVHD progression or death.
Time to response [Up to approximately 12 months]
Defined as the interval from treatment initiation to first response.
Malignancy relapse rate [Up to approximately 12 months]
Defined as the proportion of participants whose underlying malignancy relapses.
Failure-free survival [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).
Overall survival [Up to approximately 12 months]
Defined as the interval from study enrollment to death due to any cause.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	JA-Aichi Anjo Kosei Hospital	Anjo-Shi	Aichi	Japan	446-8602
2	Nagoya University Hospital	Nagoya-Shi	Aichi	Japan	466-8560
3	Hokuyukai Sapporo Hokuyu Hospital	Sapporo-Shi	Hokkaido	Japan	003-0006
4	Hokkaido University Hospital	Sapporo-shi	Hokkaido	Japan	060-8648
5	Hyogo College of Medicine Hospital	Nishinomiya-Shi	Hyogo	Japan	663-8501
6	University of Tsukuba Hospital	Tsukuba-shi	Ibaraki-Ken	Japan	305-8576
7	Jiaikai Imamura General Hospital	Kagoshima-Shi	Kagoshima	Japan	890-0064
8	Kanagawa Cancer Center	Yokohama-shi	Kanagawa-Ken	Japan	241-8515
9	Tokai University Hospital	Isehara-Shi	Kanagawa	Japan	259-1193
10	NHO Kumamoto Medical Center	Kumamoto-shi	Kumamoto-Ken	Japan	860-0008
11	Tohoku University Hospital	Sendai-shi	Miyagi-Ken	Japan	980-8574
12	Okayama University Hospital	Okayama-shi	Okayama-Ken	Japan	700-8558
13	Osaka City University Hospital	Osaka-Shi	Osaka	Japan	545-8586
14	Shizuoka Cancer Center	Nagaizumi-cho	Shizuoka-Ken	Japan	411-8777
15	Jichi Medical University Hospital	Shimotsuke-shi	Tochigi-Ken	Japan	329-0498
16	St. Luke's International Hospital	Chuo Ku	Tokyo-To	Japan	104-8560
17	Jikei University Hospital	Minato-ku	Tokyo-To	Japan	105-8471