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

NCT03721965 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: INCB 39110-1202018-002253-30
• Study Type: interventional
• Target: 2
• Locations: 6 countries
• Sites: 38

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.

Conditions

Acute Graft-versus-host Disease

Keywords

Acute graft-versus-host disease; GVHD; pediatric; JAK1 inhibitor; corticosteroids

Outcome Measures

Primary Outcomes (7)

• Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  A TEAE was defined as an AE that began or worsened from Baseline after the first administration of study drug.

  up to 45 days

• Phase 1: Cmax of Itacitinib When Administered With Corticosteroids

  Cmax was defined as the maximum observed plasma concentration.

  Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose

• Phase 1: Cmin of Itacitinib When Administered With Corticosteroids

  Cmin was defined as the minimum observed plasma concentration.

  Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose

• Phase 1: Tmax of Itacitinib When Administered With Corticosteroids

  Tmax was defined as the time to the maximum concentration.

  Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose

• Phase 1: AUC of Itacitinib When Administered With Corticosteroids

  AUC was defined as the area under the plasma concentration-time curve.

  Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose

• Phase 1: Cl/F of Itacitinib When Administered With Corticosteroids

  Cl/F was defined as the apparent oral dose clearance.

  Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose

• Phase 2: Overall Response Rate up to Day 28

  Overall response rate was defined as the number of participants demonstrating a complete response (CR), a very good partial response (VGPR), or a partial response (PR).

  up to Day 28

Secondary Outcomes (22)

• Phase 2: Number of Participants With TEAEs

  up to 12 months

• Phase 2: Cmax of Itacitinib When Administered With Corticosteroids

  Day 7: predose; 1, 2, and 4 hours post-dose

• Phase 2: Cmin of Itacitinib When Administered With Corticosteroids

  Day 7: predose; 1, 2, and 4 hours post-dose

• Phase 2: Tmax of Itacitinib When Administered With Corticosteroids

  Day 7: predose; 1, 2, and 4 hours post-dose

• Phase 2: AUC of Itacitinib When Administered With Corticosteroids

  Day 7: predose; 1, 2, and 4 hours post-dose

Study Arms (1)

Itacitinib + Corticosteroids

EXPERIMENTAL

Drug: Itacitinib; Drug: Corticosteroids

Interventions

Itacitinib DRUG

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.

Also known as: INCB039110

Itacitinib + Corticosteroids

Corticosteroids DRUG

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.

Also known as: prednisone, methylprednisolone

Itacitinib + Corticosteroids

Eligibility Criteria

• Age: 28 Days - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (38)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Childrens Hospital of Orange County

Orange, California, 92868, United States

Location

Children's Hospital Colorado - Center for Cancer and Blood Disorders

Aurora, Colorado, 80045, United States

Location

Nemours/A.I. duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

Location

University of Minnesota Medical Center

Minneapolis, Minnesota, 55454, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University Hospitals Cleveland Medical Center - Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Doernbecher Children's Hospital - Division of Pediatric Hematology

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia - Center for Childhood Cancer Research

Philadelphia, Pennsylvania, 19104, United States

Location

Sarah Cannon Research Institute, LLC

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-6868, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-1024, United States

Location

Centre Hospitalier Universitaire de Rennes

Rennes, Cedex 2, 35203, France

Location

Hopitaux Universitaires De Strasbourg

Strasbourg, Cedex, 67098, France

Location

CHU de Grenoble

Grenoble, 38043, France

Location

CHU de Grenoble

Grenoble, 38403, France

Location

Robert Debre Hospital

Paris, 75019, France

Location

Hopitaux Universitaires De Strasbourg

Strasbourg, 67098, France

Location

CHRU Nancy

Vandœuvre-lès-Nancy, 54500, France

Location

CHU Nancy

Vandœuvre-lès-Nancy, 54500, France

Location

Universitaetsklinikum Aachen, AoeR

Aachen, 52074, Germany

Location

Universitatsklinikum Jena, Klinik fur Kinder und Jugendmedizin

Jena, 07747, Germany

Location

Policlinico S. Orsola-Malpighi

Bologna, 40138, Italy

Location

Azienda Ospedaliero Unversitatia Policlinico - Vittorio Emanuele - Presido Ospedaliero G. Rodolico

Catania, 95123, Italy

Location

Fondazione MBBM

Monza, 20900, Italy

Location

Ospedale Pediatrico Bambino Gesu

Roma, 00165, Italy

Location

AOU Citta della Salute e della Scienza di Torino - Ospedale Regina Margherita

Torino, 10126, Italy

Location

Hospital Vall D Hebron

Barcelona, 08035, Spain

Location

Hospital Clinico de Santiago de Compostela

Santiago de Compostela, 15706, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Birmingham Childrens Hospital

Birmingham, B4 6NH, United Kingdom

Location

Bristol Royal Hospital for Children

Bristol, BS2 8BJ, United Kingdom

Location

Leeds Teaching Hospitals NHS Trust

Leeds, LS13EX, United Kingdom

Location

Great Ormond Street Hospital for Children

London, WC1N 3JH, United Kingdom

Location

Central Manchester University Hospital - Royal Manchester Children's Hospital

Manchester, M13 9WL, United Kingdom

Location

Royal Marsden Hospital - Surrey

Surrey Quays, SM2 5PT, United Kingdom

Location

MeSH Terms

Interventions

itacitinib; INCB039110; Adrenal Cortex Hormones; Prednisone; Methylprednisolone

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Prednisolone; Pregnadienetriols

Results Point of Contact

• Title: Incyte Corporation Call Center
• Organization: Incyte Corporation

globalmedinfo@incyte.com

(0)330 100 3677

Study Officials

• Rodica Morariu-Zamfir, MD

  Incyte Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: October 25, 2018
• First Posted: October 26, 2018
• Study Start: December 31, 2019
• Primary Completion: February 17, 2020
• Study Completion: February 17, 2020
• Last Updated: November 4, 2025
• Results First Posted: February 21, 2023

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (14); FR (8); GB (6); ES (3); IT (5); DE (2)