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

December 5, 2018 updated by: Gilead Sciences

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Tolerability of Entospletinib, a Selective SYK Inhibitor, in Combination With Systemic Corticosteroids as First-Line Therapy in Subjects With Chronic Graft Versus Host Disease (cGVHD)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
66

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada
        • Princess Margaret
  • France
      • Marseille, Cedex 9, France
        • Institut Paoli Calmettes
      • Paris Cedex 10, France
        • Hopital Saint Louis
      • Villejuif, France
        • Institut Gustave Roussy
  • Germany
      • Dresden, Germany
        • Universitätsklinikum Carl Gustav Carus
      • Frankfurt am Main, Germany, 60590
        • Universitätsklinikum Frankfurt
      • Hamburg, Germany
        • Universitätsklinikum Hamburg-Eppendorf
      • Regensburg, Germany
        • Klinikum der Universitaet Regensburg
  • Korea, Republic of
      • Busan, Korea, Republic of
        • Pusan National University Hospital
      • Seoul, Korea, Republic of
        • Samsung Medical Center
      • Seoul, Korea, Republic of
        • Severance Hospital, Yonsei University Health System
  • Spain
      • Barcelona, Spain
        • Hospital Universitario Vall d'Hebron
      • Madrid, Spain
        • Hospital General Universitario Gregorio Marañon
      • Salamanca, Spain
        • Hospital Universitario de Salamanca
      • Santander, Spain, 39008
        • Hospital Universitario Marques de Valdecilla
      • Sevilla, Spain
        • Hospital Universitario Virgen del Rocio
      • Valencia, Spain, 46009
        • Hospital Universitario La Fe
      • Valencia, Spain
        • Hospital Clinico Universitario de Valencia
  • United Kingdom
      • London, United Kingdom
        • St Bartholomew's Hospital
      • London, United Kingdom
        • Kings College Hospital NHS Trust
      • Manchester, United Kingdom
        • Manchester Royal Infirmary
  • United States
    • Florida
      • Miami, Florida, United States
        • University of Miami
    • Georgia
      • Atlanta, Georgia, United States
        • Emory University
    • Illinois
      • Maywood, Illinois, United States
        • Loyola University Medical Center
    • Kansas
      • Westwood, Kansas, United States
        • University of Kansas Cancer Center
    • New York
      • New York, New York, United States
        • Weill Cornell Medical Center
    • North Carolina
      • Durham, North Carolina, United States
        • Duke University Medical Center
    • Ohio
      • Cleveland, Ohio, United States
        • Taussig Cancer Institute
      • Columbus, Ohio, United States
        • Ohio State University, Wexner Medical Center
    • Tennessee
      • Nashville, Tennessee, United States
        • Vanderbilt University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Key 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

Key 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

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: ENTO
ENTO 400 mg or 200 mg tablet twice daily for 48 weeks
Drug: ENTO
Tablets administered orally
Other Names:
  • GS-9973
Placebo Comparator: Placebo
Placebo to match tablet twice daily for 48 weeks
Drug: Placebo
Tablets administered orally

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Best Overall Response Rate
Time Frame: Up to 24 weeks
Best overall response rate by 24 weeks was defined as the proportion of participants who achieved a complete or partial overall response as assessed by the NIH cGVHD Activity Assessment (NCAA) within 24 weeks, in the setting of add-on therapy to systemic corticosteroids as part of first-line therapy for cGVHD.
Up to 24 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in the Skin Domain of the Lee Symptom Scale (LSS) at 24 Weeks
Time Frame: Baseline; Week 24
The LSS is a patient-reported questionnaire used to measure symptom burden. Each of the LSS subscales ranged between 0 and 100, with higher scores indicating more severe symptoms. A decrease from baseline value correlates with improvement in clinical outcome.
Baseline; Week 24
Change From Baseline in the Mouth Domain of the LSS at 24 Weeks
Time Frame: Baseline; Week 24
The LSS is a patient-reported questionnaire used to measure symptom burden. Each of the LSS subscales ranged between 0 and 100, with higher scores indicating more severe symptoms. A decrease from baseline value correlates with improvement in clinical outcome.
Baseline; Week 24
Change From Baseline in the Eyes Domain of the LSS at 24 Weeks
Time Frame: Baseline; Week 24
The LSS is a patient-reported questionnaire used to measure symptom burden. Each of the LSS subscales ranged between 0 and 100, with higher scores indicating more severe symptoms. A decrease from baseline value correlates with improvement in clinical outcome.
Baseline; Week 24
Change From Baseline in the Total Score of the LSS at 24 Weeks
Time Frame: Baseline; Week 24
The LSS is a patient-reported questionnaire used to measure symptom burden. Each of the LSS subscales ranged between 0 and 100, with higher scores indicating more severe symptoms. The total score was calculated by taking the average of the subscale scores. A decrease from baseline value correlates with improvement in clinical outcome.
Baseline; Week 24
Duration of Response
Time Frame: Up to 48 weeks
Duration of response was defined as the time from the documentation of best overall response rate to the documentation of progressive disease. Note that flare was not considered as progressive disease in this analysis.
Up to 48 weeks
Percentage of Participants Who Achieve at Least 50% Reduction in Systemic Corticosteroid Dose Relative to Baseline
Time Frame: Baseline; Up to 48 weeks
The percentage reduction was calculated as (systemic corticosteroid dose post baseline - baseline systemic corticosteroid dose) / baseline systemic corticosteroid dose.
Baseline; Up to 48 weeks
Percentage of Participants Who Initiate Second-Line Therapy for cGVHD
Time Frame: Up to 48 weeks
Second-line therapy for cGVHD was defined as receiving any therapy besides systemic corticosteroids or study drug for the treatment of cGVHD. Inhaled and topical steroids are not considered second-line therapy.
Up to 48 weeks
Failure-Free Survival
Time Frame: Up to 48 weeks
Failure-free survival was defined as the time from randomization to the earliest of first documentation of systemic therapy change, nonrelapse mortality, or recurrent malignancy.
Up to 48 weeks
Percentage of Participants Who Experience Any Treatment-Emergent Adverse Events (AEs)
Time Frame: Up to 48 weeks plus 30 days
Treatment-emergent adverse events are defined as 1 or both of the following: 1) any AEs with an onset on or after study drug or placebo start date and no later than earlier of 30 days after permanent discontinuation of study drug or placebo, 2) any AEs leading to premature discontinuation of study drug or placebo.
Up to 48 weeks plus 30 days
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
Time Frame: Up to 48 weeks plus 30 days
Up to 48 weeks plus 30 days
Percentage of Participants Who Experienced Treatment-Emergent Graded Laboratory Abnormalities
Time Frame: Up to 48 weeks plus 30 days
Up to 48 weeks plus 30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Gilead Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 27, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 19, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 6, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 24, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 2, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 8, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 26, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 5, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GS-US-406-1840
  • 2015-004572-30 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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