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

NCT02701634 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: GS-US-406-18402015-004572-30
• Study Type: interventional
• Target: 66
• Locations: 7 countries
• Sites: 30

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Change From Baseline in the Skin Domain of the Lee Symptom Scale (LSS) at 24 Weeks

  Baseline; Week 24

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

  Baseline; Week 24

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

  Baseline; Week 24

• Change From Baseline in the Total Score of the LSS at 24 Weeks

  Baseline; Week 24

• Duration of Response

  Up to 48 weeks

Study Arms (2)

ENTO

EXPERIMENTAL

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

Drug: ENTO

Placebo

PLACEBO COMPARATOR

Placebo to match tablet twice daily for 48 weeks

Drug: Placebo

Interventions

ENTO DRUG

Tablets administered orally

Also known as: GS-9973

ENTO

Placebo DRUG

Tablets administered orally

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (30)

University of Miami

Miami, Florida, United States

Location

Emory University

Atlanta, Georgia, United States

Location

Loyola University Medical Center

Maywood, Illinois, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, United States

Location

Weill Cornell Medical Center

New York, New York, United States

Location

Duke University Medical Center

Durham, North Carolina, United States

Location

Taussig Cancer Institute

Cleveland, Ohio, United States

Location

Ohio State University, Wexner Medical Center

Columbus, Ohio, United States

Location

Vanderbilt University

Nashville, Tennessee, United States

Location

Princess Margaret

Toronto, Ontario, Canada

Location

Institut Paoli Calmettes

Marseille, France

Location

Hopital Saint Louis

Paris, France

Location

Institut Gustave Roussy

Villejuif, France

Location

Universitätsklinikum Carl Gustav Carus

Dresden, Germany

Location

Universitatsklinikum Frankfurt

Frankfurt am Main, 60590, Germany

Location

Universitatsklinikum Hamburg-Eppendorf

Hamburg, Germany

Location

Klinikum der Universitaet Regensburg

Regensburg, Germany

Location

Pusan National University Hospital

Busan, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, South Korea

Location

Hospital Universitario Vall d'Hebron

Barcelona, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, Spain

Location

Hospital Universitario de Salamanca

Salamanca, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, 39008, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, Spain

Location

Hospital Universitario La Fe

Valencia, 46009, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, Spain

Location

Kings College Hospital NHS Trust

London, United Kingdom

Location

St Bartholomew's Hospital

London, United Kingdom

Location

Manchester Royal Infirmary

Manchester, United Kingdom

Location

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome; Immune System Diseases

Interventions

6-(1H-indazol-6-yl)-N-(4-morpholinophenyl)imidazo(1,2-a)pyrazin-8-amine

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2016
• First Posted: March 8, 2016
• Study Start: May 27, 2016
• Primary Completion: December 19, 2017
• Study Completion: March 6, 2018
• Last Updated: December 26, 2018
• Results First Posted: December 26, 2018

Record last verified: 2018-12

Locations

CA (1); GB (3); US (9); FR (3); ES (7); DE (4); KR (3)