Efficacy and Tolerability of Entospletinib in Combination With Systemic Corticosteroids as First-Line Therapy in Adults With Chronic Graft Versus Host Disease (cGVHD)

NCT ID: NCT02701634

Last Updated: 2018-12-26

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

66 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-05-27

Study Completion Date

2018-03-06

Brief Summary

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The primary objective of this study is to evaluate the effect of entospletinib (ENTO) on the best overall response rate in adults with chronic graft versus host disease (cGVHD) who are currently receiving systemic corticosteroids as part of first-line therapy for cGVHD.

Detailed Description

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Conditions

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Chronic Graft Versus Host Disease

Keywords

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Chronic Graft Versus Host Disease (cGVHD) newly diagnosed cGVHD immune reconstitution Immune System Diseases allogeneic stem cell transplantation SYK inhibitor

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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ENTO

ENTO 400 mg or 200 mg tablet twice daily for 48 weeks

Group Type EXPERIMENTAL

ENTO

Intervention Type DRUG

Tablets administered orally

Placebo

Placebo to match tablet twice daily for 48 weeks

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Tablets administered orally

Interventions

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ENTO

Tablets administered orally

Intervention Type DRUG

Placebo

Tablets administered orally

Intervention Type DRUG

Other Intervention Names

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GS-9973

Eligibility Criteria

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Inclusion Criteria

* Willing and able to provide written informed consent
* Male or non-pregnant, non-lactating, females
* Newly diagnosed cGVHD defined by:

* At least 100 days after receiving any allogeneic hematopoietic stem cell transplant AND
* Receiving a new course of systemic corticosteroids (≥ 0.5 mg/kg/day) as first-line cGVHD therapy at least 1 day and no more than 21 days prior to first dose of ENTO/Placebo AND
* Moderate to severe cGVHD as assessed by NIH cGVHD Diagnosis and Staging Criteria (NCDSC) with at least three organ systems involved OR one organ system with a score of 2 OR lung organ score = 1
* Individuals who have undergone transplant for hematologic malignancy are required to be in complete remission.
* Have either a normal ECG or one with abnormalities that are considered clinically insignificant by the investigator in consultation with the Sponsor

Exclusion Criteria

* Inability to begin systemic corticosteroids therapy at a dose of ≥ 0.5 mg/kg/day (or equivalent)
* Uncontrolled infection within 4 weeks prior to randomization
* History of the following therapies in the post-transplant period:

* B cell depleting biologic agents
* CD19 CAR-T cells based therapies
* BTK/SYK/JAK/PI3K inhibitors
* Phototherapy-unless administered for acute GVHD
* Treatment of cGVHD with anti-thymocyte globulins (ATG), or campath within 60 days of screening visit unless used for treatment of acute GVHD
* Severe organ dysfunction manifested during screening period:

* Requiring supplemental oxygen at more than 2 L/min
* Uncontrolled arrhythmia or heart failure
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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University of Miami

Miami, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

University of Kansas Cancer Center

Westwood, Kansas, United States

Site Status

Weill Cornell Medical Center

New York, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Taussig Cancer Institute

Cleveland, Ohio, United States

Site Status

Ohio State University, Wexner Medical Center

Columbus, Ohio, United States

Site Status

Vanderbilt University

Nashville, Tennessee, United States

Site Status

Princess Margaret

Toronto, Ontario, Canada

Site Status

Institut Paoli Calmettes

Marseille, , France

Site Status

Hopital Saint Louis

Paris, , France

Site Status

Institut Gustave Roussy

Villejuif, , France

Site Status

Universitätsklinikum Carl Gustav Carus

Dresden, , Germany

Site Status

Universitatsklinikum Frankfurt

Frankfurt am Main, , Germany

Site Status

Universitatsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Site Status

Klinikum der Universitaet Regensburg

Regensburg, , Germany

Site Status

Pusan National University Hospital

Busan, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Site Status

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Site Status

Hospital Universitario de Salamanca

Salamanca, , Spain

Site Status

Hospital Universitario Marques de Valdecilla

Santander, , Spain

Site Status

Hospital Universitario Virgen del Rocio

Seville, , Spain

Site Status

Hospital Universitario La Fe

Valencia, , Spain

Site Status

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Site Status

Kings College Hospital NHS Trust

London, , United Kingdom

Site Status

St Bartholomew's Hospital

London, , United Kingdom

Site Status

Manchester Royal Infirmary

Manchester, , United Kingdom

Site Status

Countries

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United States Canada France Germany South Korea Spain United Kingdom

Provided Documents

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Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol: Original

View Document

Document Type: Study Protocol: Amendment 1

View Document

Document Type: Study Protocol: Amendment 2

View Document

Document Type: Study Protocol: Amendment 3

View Document

Other Identifiers

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2015-004572-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-406-1840

Identifier Type: -

Identifier Source: org_study_id