Clinical trial NCT02701634: Efficacy and Tolerability of Entospletinib in Combination With Systemic Corticosteroids as First-Line Therapy in Adults With Chronic Graft Versus Host Disease (cGVHD)
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Graft Versus Host Disease
Keywords: Chronic Graft Versus Host Disease (cGVHD)
newly diagnosed cGVHD
immune reconstitution
Immune System Diseases
allogeneic stem cell transplantation
SYK inhibitor
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2016-03-08
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Best Overall Response Rate
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Change From Baseline in the Skin Domain of the Lee Symptom Scale (LSS) at 24 Weeks
timeFrame: Baseline; Week 24
measure: Change From Baseline in the Mouth Domain of the LSS at 24 Weeks
timeFrame: Baseline; Week 24
measure: Change From Baseline in the Eyes Domain of the LSS at 24 Weeks
timeFrame: Baseline; Week 24
measure: Change From Baseline in the Total Score of the LSS at 24 Weeks
timeFrame: Baseline; Week 24
measure: Duration of Response
timeFrame: Up to 48 weeks
measure: Percentage of Participants Who Achieve at Least 50% Reduction in Systemic Corticosteroid Dose Relative to Baseline
timeFrame: Baseline; Up to 48 weeks
measure: Percentage of Participants Who Initiate Second-Line Therapy for cGVHD
timeFrame: Up to 48 weeks
measure: Failure-Free Survival
timeFrame: Up to 48 weeks
measure: Percentage of Participants Who Experience Any Treatment-Emergent Adverse Events (AEs)
timeFrame: Up to 48 weeks plus 30 days
measure: Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
timeFrame: Up to 48 weeks plus 30 days
measure: Percentage of Participants Who Experienced Treatment-Emergent Graded Laboratory Abnormalities
timeFrame: Up to 48 weeks plus 30 days
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: New York
country: United States
facility: Weill Cornell Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Taussig Cancer Institute
state: Ohio
city: Columbus
country: United States
facility: Ohio State University, Wexner Medical Center
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Toronto
country: Canada
facility: Princess Margaret
state: Ontario
city: Marseille, Cedex 9
country: France
facility: Institut Paoli Calmettes
city: Paris Cedex 10
country: France
facility: Hopital Saint Louis
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
city: Frankfurt am Main
country: Germany
facility: Universitatsklinikum Frankfurt
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg-Eppendorf
city: Regensburg
country: Germany
facility: Klinikum der Universitaet Regensburg
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: London
country: United Kingdom
facility: Kings College Hospital NHS Trust
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: