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Efficacy and Tolerability of Entospletinib in Combination With Systemic Corticosteroids as First-Line Therapy in Adults With Chronic Graft Versus Host Disease (cGVHD)
Phase 2 trial testing ENTO in Chronic Graft Versus Host Disease in 66 participants. Terminated before completion.
| Lead sponsor | Gilead Sciences |
|---|---|
| Phase | Phase 2 |
| Status | Terminated |
| Study type | INTERVENTIONAL |
| Allocation | randomized |
| Design | parallel |
| Masking | double |
| Primary purpose | treatment |
| Enrollment | 66 |
| Start date | 27 May 2016 |
| Primary completion | 19 December 2017 |
| Estimated completion | 6 March 2018 |
| Sites | 30 locations across France, United Kingdom, Germany, South Korea, Canada, United States, Spain |
Gilead Sciences — full company profile →
Adults 18 to 75, any sex, with Chronic Graft Versus Host Disease. Patients with the condition only — healthy volunteers not accepted.
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
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.
| Group | Value | 95% CI |
|---|---|---|
| ENTO | 72.7 | |
| Placebo | 72.7 |
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.
| Group | Value | 95% CI |
|---|---|---|
| ENTO | 15.0 | ± 21.92 |
| Placebo | 19.8 | ± 22.34 |
| Group | Value | 95% CI |
|---|---|---|
| ENTO | -3.3 | ± 10.31 |
| Placebo | -9.4 | ± 14.24 |
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.
| Group | Value | 95% CI |
|---|---|---|
| ENTO | 15.2 | ± 18.17 |
| Placebo | 16.8 | ± 21.21 |
| Group | Value | 95% CI |
|---|---|---|
| ENTO | -4.2 | ± 16.54 |
| Placebo | -1.4 | ± 25.34 |
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.
| Group | Value | 95% CI |
|---|---|---|
| ENTO | 29.4 | ± 27.52 |
| Placebo | 21.4 | ± 24.22 |
| Group | Value | 95% CI |
|---|---|---|
| ENTO | 10.2 | ± 21.56 |
| Placebo | -1.4 | ± 31.32 |
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.
| Group | Value | 95% CI |
|---|---|---|
| ENTO | 16.0 | ± 9.74 |
| Placebo | 14.7 | ± 8.51 |
| Group | Value | 95% CI |
|---|---|---|
| ENTO | -0.5 | ± 8.35 |
| Placebo | -5.4 | ± 8.54 |
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.
| Group | Value | 95% CI |
|---|---|---|
| ENTO | 26.3 | 9.1 – 44.3 |
| Placebo | 32.0 | 8.1 – NA |
The percentage reduction was calculated as (systemic corticosteroid dose post baseline - baseline systemic corticosteroid dose) / baseline systemic corticosteroid dose.
| Group | Value | 95% CI |
|---|---|---|
| ENTO | 72.7 | |
| Placebo | 63.6 |
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.
| Group | Value | 95% CI |
|---|---|---|
| ENTO | 9.1 | |
| Placebo | 15.2 |
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.
| Group | Value | 95% CI |
|---|---|---|
| ENTO | 99.0 | 57.0 – 214.0 |
| Placebo | 85.0 | 56.0 – 254.0 |
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.
| Group | Value | 95% CI |
|---|---|---|
| ENTO | 96.9 | |
| Placebo | 97.0 |
| Group | Value | 95% CI |
|---|---|---|
| ENTO | 12.5 | |
| Placebo | 12.1 |
| Group | Value | 95% CI |
|---|---|---|
| ENTO | 100.0 | |
| Placebo | 100.0 |
Time frame: Baseline up to the last dose date plus 30 days (average exposure: ENTO = 18 weeks; Placebo = 17 weeks). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.
| Reaction | System | ENTO | Placebo |
|---|---|---|---|
| Pneumonia | Infections and infestations | — | — |
| Diarrhoea | Gastrointestinal disorders | — | — |
| Neutropenia | Blood and lymphatic system disorders | — | — |
| Coronary artery disease | Cardiac disorders | — | — |
| Abdominal pain | Gastrointestinal disorders | — | — |
| Colitis | Gastrointestinal disorders | — | — |
| Nausea | Gastrointestinal disorders | — | — |
| Small intestinal haemorrhage | Gastrointestinal disorders | — | — |
| Disease recurrence | General disorders | — | — |
| Pain | General disorders | — | — |
| Pyrexia | General disorders | — | — |
| Anal abscess | Infections and infestations | — | — |
| Bacteraemia | Infections and infestations | — | — |
| Cellulitis | Infections and infestations | — | — |
| H1N1 influenza | Infections and infestations | — | — |
| Infection | Infections and infestations | — | — |
| Listeriosis | Infections and infestations | — | — |
| Otitis media acute | Infections and infestations | — | — |
| Pneumonia bacterial | Infections and infestations | — | — |
| Pyelonephritis acute | Infections and infestations | — | — |
| Septic shock | Infections and infestations | — | — |
| Staphylococcal bacteraemia | Infections and infestations | — | — |
| Upper respiratory tract infection | Infections and infestations | — | — |
| Wound dehiscence | Injury, poisoning and procedural complications | — | — |
| Gamma-glutamyltransferase increased | Investigations | — | — |
| Reaction | System | ENTO | Placebo |
|---|---|---|---|
| Fatigue | General disorders | — | — |
| Cough | Respiratory, thoracic and mediastinal disorders | — | — |
| Oedema peripheral | General disorders | — | — |
| Abdominal pain | Gastrointestinal disorders | — | — |
| Diarrhoea | Gastrointestinal disorders | — | — |
| Pyrexia | General disorders | — | — |
| Alanine aminotransferase increased | Investigations | — | — |
| Gamma-glutamyltransferase increased | Investigations | — | — |
| Hyperglycaemia | Metabolism and nutrition disorders | — | — |
| Hypokalaemia | Metabolism and nutrition disorders | — | — |
| Anaemia | Blood and lymphatic system disorders | — | — |
| Dry eye | Eye disorders | — | — |
| Nausea | Gastrointestinal disorders | — | — |
| Vomiting | Gastrointestinal disorders | — | — |
| Cytomegalovirus infection | Infections and infestations | — | — |
| Respiratory tract infection | Infections and infestations | — | — |
| Aspartate aminotransferase increased | Investigations | — | — |
| Platelet count decreased | Investigations | — | — |
| Hypertriglyceridaemia | Metabolism and nutrition disorders | — | — |
| Thrombocytopenia | Blood and lymphatic system disorders | — | — |
| Abdominal pain upper | Gastrointestinal disorders | — | — |
| Constipation | Gastrointestinal disorders | — | — |
| Asthenia | General disorders | — | — |
| Candida infection | Infections and infestations | — | — |
| Influenza | Infections and infestations | — | — |
| Nasopharyngitis | Infections and infestations | — | — |
| Oral candidiasis | Infections and infestations | — | — |
| Sinusitis | Infections and infestations | — | — |
| Upper respiratory tract infection | Infections and infestations | — | — |
| Blood alkaline phosphatase increased | Investigations | — | — |
| Decreased appetite | Metabolism and nutrition disorders | — | — |
| Arthralgia | Musculoskeletal and connective tissue disorders | — | — |
| Back pain | Musculoskeletal and connective tissue disorders | — | — |
| Muscular weakness | Musculoskeletal and connective tissue disorders | — | — |
| Dry skin | Skin and subcutaneous tissue disorders | — | — |
| Hypertension | Vascular disorders | — | — |
| Lymphopenia | Blood and lymphatic system disorders | — | — |
| Neutropenia | Blood and lymphatic system disorders | — | — |
| Tachycardia | Cardiac disorders | — | — |
| Keratitis | Eye disorders | — | — |
Most-reported serious reactions: Pneumonia, Diarrhoea, Neutropenia, Coronary artery disease, Abdominal pain, Colitis, Nausea, Small intestinal haemorrhage.
Data from ClinicalTrials.gov NCT02701634 adverse events section.
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.
8 peer-reviewed publications reference this trial (live from Europe PMC):
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