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

Gilead Sciences

Status and phase: Terminated; Phase 2

Conditions: Chronic Graft Versus Host Disease

Treatments: Drug: ENTO; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02701634

GS-US-406-1840

2015-004572-30 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 66 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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66 participants in 2 patient groups, including a placebo group

ENTO

Experimental group

Description:

ENTO 400 mg or 200 mg tablet twice daily for 48 weeks

Treatment:

Drug: ENTO

Placebo

Placebo Comparator group

Description:

Placebo to match tablet twice daily for 48 weeks

Treatment:

Drug: Placebo