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

NCT03497273 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: INCB 39110-118
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 17

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).

Conditions

Acute Graft-versus-host Disease

Keywords

JAK1 inhibitor; GVHD; acute GVHD; Japan; corticosteroids

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Cmax of INCB039110

  Up to approximately 1 month

• Cl/F of INCB039110

  Up to approximately 1 month

• Objective response rate

  Up to 100 days

• Nonrelapse mortality

  Up to approximately 12 months

• Duration of response

  Up to approximately 12 months

Study Arms (1)

Itacitinib + corticosteroids

EXPERIMENTAL

Itacitinib administered in combination with corticosteroids.

Drug: Itacitinib; Drug: Corticosteroid

Interventions

Itacitinib DRUG

Itacitinib administered orally once daily at the protocol-defined dose.

Also known as: INCB039110

Itacitinib + corticosteroids

Corticosteroid DRUG

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

Itacitinib + corticosteroids

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (17)

JA-Aichi Anjo Kosei Hospital

Anjo-Shi, Aichi-ken, 446-8602, Japan

Location

Nagoya University Hospital

Nagoya, Aichi-ken, 466-8560, Japan

Location

Hokuyukai Sapporo Hokuyu Hospital

Sapporo, Hokkaido, 003-0006, Japan

Location

Hokkaido University Hospital

Sapporo, Hokkaido, 060-8648, Japan

Location

Hyogo College of Medicine Hospital

Nishinomiya-Shi, Hyōgo, 663-8501, Japan

Location

University of Tsukuba Hospital

Tsukuba, Ibaraki, 305-8576, Japan

Location

Jiaikai Imamura General Hospital

Kagoshima, Kagoshima-ken, 890-0064, Japan

Location

Tokai University Hospital

Isehara-Shi, Kanagawa, 259-1193, Japan

Location

Kanagawa Cancer Center

Yokohama, Kanagawa, 241-8515, Japan

Location

NHO Kumamoto Medical Center

Kumamoto, Kumamoto, 860-0008, Japan

Location

Tohoku University Hospital

Sendai, Miyagi, 980-8574, Japan

Location

Okayama University Hospital

Okayama, Okayama-ken, 700-8558, Japan

Location

Osaka City University Hospital

Osaka, Osaka, 545-8586, Japan

Location

Shizuoka Cancer Center

Nagaizumi-cho, Shizuoka, 411-8777, Japan

Location

Jichi Medical University Hospital

Shimotsuke-shi, Tochigi, 329-0498, Japan

Location

St. Luke's International Hospital

Chūōku, Tokyo-To, 104-8560, Japan

Location

Jikei University Hospital

Minatoku, Tokyo-To, 105-8471, Japan

Location

MeSH Terms

Interventions

itacitinib; INCB039110; Adrenal Cortex Hormones

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Rodica Morariu-Zamfir, MD

  Incyte Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2018
• First Posted: April 13, 2018
• Study Start: March 20, 2018
• Primary Completion: November 30, 2019
• Study Completion: February 17, 2020
• Last Updated: March 3, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

JP (17)