Efficacy and Tolerability of Entospletinib in Combination With Systemic Corticosteroids as First-Line Therapy in Adults With Chronic Graft Versus Host Disease (cGVHD)
Condition: Chronic Graft Versus Host Disease
MeSH terms: Bronchiolitis Obliterans Syndrome; Graft vs Host Disease
Intervention: ENTO; Placebo
Intervention description: Tablets administered orally; Tablets administered orally
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 66.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Chronic Graft Versus Host Disease (cGVHD); newly diagnosed cGVHD; immune reconstitution; Immune System Diseases; allogeneic stem cell transplantation; SYK inhibitor

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.