Chronic Graft Versus Host DiseasePhase 2NCT02701634
Efficacy and Tolerability of Entospletinib in Combination With Systemic Corticosteroids as First-Line Therapy in Adults With Chronic Graft Versus Host Disease (cGVHD)
A Phase 2 study testing ENTO in people with Chronic Graft Versus Host Disease, run by Gilead Sciences at 30 sites in 7 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Chronic Graft Versus Host Disease
- What is being tested?
- ENTO
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 66 participants
- Where
- 30 sitesin 7 countries
- Study dates
- 27 May 2016to 6 Mar 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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 locations and contacts
30 sites in 7 countries.
30 sites in 7 countries
United States9 sites
Emory University
Atlanta, Georgia
Taussig Cancer Institute
Cleveland, Ohio
Ohio State University, Wexner Medical Center
Columbus, Ohio
Duke University Medical Center
Durham, North Carolina
Loyola University Medical Center
Maywood, Illinois
University of Miami
Miami, Florida
Vanderbilt University
Nashville, Tennessee
Weill Cornell Medical Center
New York, New York
University of Kansas Cancer Center
Westwood, Kansas
Spain7 sites
Hospital Universitario Vall d'Hebron
Barcelona
Hospital General Universitario Gregorio Marañon
Madrid
Hospital Universitario de Salamanca
Salamanca
Hospital Universitario Marques de Valdecilla
Santander, 39008
Hospital Universitario Virgen del Rocio
Seville
Hospital Universitario La Fe
Valencia, 46009
Hospital Clinico Universitario de Valencia
Valencia
Germany4 sites
Universitätsklinikum Carl Gustav Carus
Dresden
Universitatsklinikum Frankfurt
Frankfurt am Main, 60590
Universitatsklinikum Hamburg-Eppendorf
Hamburg
Klinikum der Universitaet Regensburg
Regensburg
France3 sites
Institut Paoli Calmettes
Marseille
Hopital Saint Louis
Paris
Institut Gustave Roussy
Villejuif
South Korea3 sites
Pusan National University Hospital
Busan
Samsung Medical Center
Seoul
Severance Hospital, Yonsei University Health System
Seoul
United Kingdom3 sites
Kings College Hospital NHS Trust
London
St Bartholomew's Hospital
London
Manchester Royal Infirmary
Manchester
About this study
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)
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
- Being tested
- ENTO, Placebo
- Keywords
- Chronic Graft Versus Host Disease (cGVHD), newly diagnosed cGVHD, immune reconstitution, Immune System Diseases, allogeneic stem cell transplantation, SYK inhibitor
- Medical subject headings
- Bronchiolitis Obliterans Syndrome, Immune System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ENTODrug
Also called GS-9973
Tablets administered orally
PlaceboDrug
Tablets administered orally
| Study group | Role | What they receive |
|---|---|---|
| ENTO | Experimental | ENTO 400 mg or 200 mg tablet twice daily for 48 weeks Receives: Drug: ENTO |
| Placebo | Placebo comparator | Placebo to match tablet twice daily for 48 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 24 weeks
Secondary outcomes (11)
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.
Measured: Baseline; Week 24
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.
Measured: Baseline; Week 24
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.
Measured: 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.
Measured: Baseline; Week 24
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.
Measured: Up to 48 weeks
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.
Measured: Baseline; Up to 48 weeks
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.
Measured: Up to 48 weeks
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.
Measured: Up to 48 weeks
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.
Measured: Up to 48 weeks plus 30 days
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
Measured: Up to 48 weeks plus 30 days
Percentage of Participants Who Experienced Treatment-Emergent Graded Laboratory Abnormalities
Measured: Up to 48 weeks plus 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2016 (estimated)
- Study start27 May 2016
- Primary completion19 Dec 2017
- Study completion6 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gilead Study Director, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02701634
- Sponsor's protocol ID
- GS-US-406-1840
- Other IDs
- 2015-004572-30, 2015
- Status last verified
- Dec 2018
- First submitted
- 24 Feb 2016
- Last updated
- 26 Dec 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02701634
- Acronym / sponsor ID
- GS-US-406-1840
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- 27 May 2016 (actual)
- Primary completion
- 19 Dec 2017 (actual)
- Study completion
- 6 Mar 2018 (actual)
- First posted
- 8 Mar 2016 (estimated)
- Results
- Posted 26 Dec 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ENTO | Experimental | Drug: ENTOENTO 400 mg or 200 mg tablet twice daily for 48 weeks |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo to match tablet twice daily for 48 weeks |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Willing and able to provide written informed consent
- Male or non-pregnant, non-lactating, females
- Newly diagnosed cGVHD defined by:
- 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 (12 listed)
- 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:
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ENTOAlso: GS-9973Tablets administered orally | Drug | ENTO |
| PlaceboTablets administered orally | Drug | Placebo |
Primary outcome
Best Overall Response Rate
Time frame: Up to 24 weeks
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.
11 secondary outcomes
Change From Baseline in the Skin Domain of the Lee Symptom Scale (LSS) at 24 Weeks
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
Time frame: Baseline; Week 24
Duration of Response
Time frame: Up to 48 weeks
Percentage of Participants Who Achieve at Least 50% Reduction in Systemic Corticosteroid Dose Relative to Baseline
Time frame: Baseline; Up to 48 weeks
Percentage of Participants Who Initiate Second-Line Therapy for cGVHD
Time frame: Up to 48 weeks
Failure-Free Survival
Time frame: Up to 48 weeks
Percentage of Participants Who Experience Any Treatment-Emergent Adverse Events (AEs)
Time frame: Up to 48 weeks plus 30 days
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
Time frame: Up to 48 weeks plus 30 days
Percentage of Participants Who Experienced Treatment-Emergent Graded Laboratory Abnormalities
Time frame: Up to 48 weeks plus 30 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Dec 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gilead Study Director study director
Gilead Sciences
30 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ENTO in people with Chronic Graft Versus Host Disease, run by Gilead Sciences at 30 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in United States, Spain, Germany, France, South Korea and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Best Overall Response Rate (time frame: Up to 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Dec 2018.