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

Phase 2TerminatedNCT02701634

Gilead Sciences66 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Chronic Graft Versus Host Disease

Interventions

ENTODRUG

Tablets administered orally

PlaceboDRUG

Tablets administered orally

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (30)

Outcomes

Primary Outcomes

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.

Time frame: Up to 24 weeks

Secondary Outcomes

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.

Time frame: Baseline; Week 24

Change From Baseline in the Mouth Domain of the LSS at 24 Weeks

Time frame: Baseline; Week 24

Change From Baseline in the Eyes Domain of the LSS at 24 Weeks

Time frame: Baseline; Week 24

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.

Data from ClinicalTrials.gov

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