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

This study is currently recruiting participants.
Verified September 2017 by Gilead Sciences
Sponsor:
ClinicalTrials.gov Identifier:
NCT02701634
First Posted: March 8, 2016
Last Update Posted: September 20, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Gilead Sciences
  Purpose
This study will evaluate the effect of entospletinib on the best overall response rate in adults with chronic graft versus host disease (cGVHD) who are currently receiving systemic corticosteroids as first-line therapy for cGVHD.

Condition Intervention Phase
Chronic Graft Versus Host Disease Drug: Entospletinib Drug: Placebo Drug: Systemic Corticosteroids Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Best Overall Response Rate [ Time Frame: Up to 24 weeks ]
    Best overall response rate by 24 weeks is defined as the proportion of participants who achieve 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.


Secondary Outcome Measures:
  • 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.

  • 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.

  • 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.

  • 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.

  • Duration of Response [ Time Frame: Up to 48 weeks ]
    Duration of response is defined as the time from the documentation of best overall response rate to the documentation of progressive disease.

  • Proportion of Participants who Achieve at Least 50% Reduction in Systemic Corticosteroid Dose Relative to Baseline [ Time Frame: Baseline; Week 24 ]
    The percentage reduction is calculated as (systemic corticosteroid dose at 24 weeks - baseline systemic corticosteroid dose) / baseline systemic corticosteroid dose.

  • Proportion of Participants who Initiate Second-Line Therapy for cGVHD [ Time Frame: Up to 48 weeks ]
    Second-line therapy for cGVHD is 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.

  • Failure-free survival [ Time Frame: Up to 48 weeks ]
    Failure-free survival is defined as the time from randomization to the earliest of first documentation of systemic therapy change, nonrelapse mortality, or recurrent malignancy.

  • Proportion of Participants who Experience Any Adverse Events [ Time Frame: Up to 48 weeks plus 30 days ]
  • Proportion of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event [ Time Frame: Up to 48 weeks ]
  • Proportion of Participants who Experienced Graded Laboratory Abnormalities [ Time Frame: Up to 48 weeks plus 30 days ]

Estimated Enrollment: 100
Actual Study Start Date: May 27, 2016
Estimated Study Completion Date: August 2019
Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Entospletinib
Entospletinib for 48 weeks in combination with systemic corticosteroids as first-line therapy
Drug: Entospletinib
Entospletinib tablet(s) administered orally twice daily under fasted conditions
Other Name: GS-9973
Drug: Systemic Corticosteroids
Systemic corticosteroids may include prednisone or prednisone equivalent.
Placebo Comparator: Placebo
Placebo to match entospletinib for 48 weeks in combination with systemic corticosteroids as first-line therapy
Drug: Placebo
Placebo to match entospletinib tablet(s) administered orally twice daily under fasted conditions
Drug: Systemic Corticosteroids
Systemic corticosteroids may include prednisone or prednisone equivalent.
Experimental: Open-Label Extension
After Week 48, all participants will have the option to receive entospletinib for an additional 96 weeks in the open-label extension phase, while continuing treatment with systemic corticosteroids as first-line therapy.
Drug: Entospletinib
Entospletinib tablet(s) administered orally twice daily under fasted conditions
Other Name: GS-9973
Drug: Systemic Corticosteroids
Systemic corticosteroids may include prednisone or prednisone equivalent.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02701634


Contacts
Contact: Gilead Study Team 406-1840@gilead.com

  Show 47 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Gilead Study Director Gilead Sciences
  More Information

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02701634     History of Changes
Other Study ID Numbers: GS-US-406-1840
2015-004572-30 ( EudraCT Number )
First Submitted: February 24, 2016
First Posted: March 8, 2016
Last Update Posted: September 20, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Gilead Sciences:
Chronic Graft Versus Host Disease (cGVHD)
newly diagnosed cGVHD
immune reconstitution
Immune System Diseases
allogeneic stem cell transplantation
SYK inhibitor

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases