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

Chronic Graft Versus Host Disease Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02701634
• Other study ID #: GS-US-406-1840
• Secondary ID: 2015-004572-30
• Status: Terminated
• Phase: Phase 2
• Start date: May 27, 2016
• Est. completion date: March 6, 2018

Study information

• Verified date: December 2018
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 66
• Est. completion date: March 6, 2018
• Est. primary completion date: December 19, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Graft Versus Host Disease
• Graft vs Host Disease

Intervention

Drug:
• ENTO
Tablets administered orally
• Placebo
Tablets administered orally

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Korea, Republic of,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Best Overall Response Rate	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	Change From Baseline in the Skin Domain of the Lee Symptom Scale (LSS) at 24 Weeks	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
Secondary	Change From Baseline in the Mouth Domain of the LSS at 24 Weeks	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
Secondary	Change From Baseline in the Eyes Domain of the LSS at 24 Weeks	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
Secondary	Change From Baseline in the Total Score of the LSS at 24 Weeks	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
Secondary	Duration of Response	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
Secondary	Percentage of Participants Who Achieve at Least 50% Reduction in Systemic Corticosteroid Dose Relative to Baseline	The percentage reduction was calculated as (systemic corticosteroid dose post baseline - baseline systemic corticosteroid dose) / baseline systemic corticosteroid dose.	Baseline; Up to 48 weeks
Secondary	Percentage of Participants Who Initiate Second-Line Therapy for cGVHD	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
Secondary	Failure-Free Survival	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
Secondary	Percentage of Participants Who Experience Any Treatment-Emergent Adverse Events (AEs)	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
Secondary	Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event		Up to 48 weeks plus 30 days
Secondary	Percentage of Participants Who Experienced Treatment-Emergent Graded Laboratory Abnormalities		Up to 48 weeks plus 30 days