1005378 / A UK Collaborative Study to Determine the Genetic Basis of Primary Sclerosing Cholangitis (UK-PSC)
A UK Collaborative Study to Determine the Genetic Basis of Primary Sclerosing Cholangitis (UK-PSC) (Study due to close 01/07/2023)
1206654 / PRED 4 – Predicting Serious Drug Side Effects in Gastroenterology
A Phase 3b, Multi-center, Open-label Trial to Evaluate the Long Term Safety of a Titrated Immediate-release selective arginine vasopressin type 2 receptor antagonist (30 mg to 120 mg/day, Split dose) in Subjects with Autosomal Dominant Polycystic Kidney Disease (protocol 156-13-211) (Study due to close 31/12/2019)
1307805 / Personalised Anti-TNF in Crohns Disease
Investigation of the clinical, serological and genetic factors that determine primary non-response, loss of response and adverse drug reactions to anti-tnf drugs in patients with active luminal crohn’s disease
1507119 / Study of immune related drug side effects underlying adverse drug reactions in gastroenterology
Study of immune related drug side effects underlying adverse drug reactions in gastroenterology (Study due to close 01/09/2018)
1508131 / Phase III, Randomized, Multicenter Double-Blind, Double Dummy Study To Evaluate The Efficacy And Safety Of Etrolizumab Compared With Infliximab In Patients With Moderate To Severe Active Ulcerative Colitis Who Are Naive To TNF Inhibitors
Phase III, randomised, multicenter, double-blind, double-dummy study to evaluate the efficacy and safety of Etrolizumab compared with Infliximab in patients with moderate to severe active ulcerative colitis who are naive to TNF inhibitors.
Protocol Number – GA29103 (Study due to close 09/05/2019)
1511170 / An Open-Label Extension And Safety Monitoring Study Of Moderate To Severe Ulcerative Colitis Patients Previously Enrolled In Etrolizumab Phase III Studies
This is an openlabel extension study and safety monitoring study open to eligible patients who were enrolled in studies GA28950 or GA29103. Patients can enter either or both parts of this study.
The study is divided in two parts. Part 1 (open-label extension; OLE) will assess the long term safety and efficacy of etrolizumab via subcutaneous injections (SC). Patients will receive etrolizumab every 4 weeks until the patient enters Safety monitoring (SM) (Part 2). As a substantial proportion of patients enrolling in this study may be receiving etrolizumab for the first time, all patients will be required to receive their first four doses (Week 0, 4, 8 and Week 12) of etrolizumab in the clinic setting and be monitored for 60 minutes following each dose. After this and if they are happy to do so, patients can continue to self administer the medication themselves at home.
Part 1 (OLE) will continue for up to 7 years after the first patient is enrolled into the study or until commercial availability, whichever is the earlier, or until the Sponsor’s decision to terminate the study. Patients who withdraw from Part 1 (OLE) should complete the 12week safety followup and then enter Part 2 (SM) for PML monitoring.
Part 2 (safety monitoringSM), will assess the longterm safety of etrolizumab.
Patients will not receive etrolizumab and will be followed up until 2 years after their last dose of etrolizumab. Part 2 will consist of telephone calls from the study doctor or study personnel approximately every 6 months to assess patients for any signs or symptoms of PML. (Study due to close 13/03/2024)
1511174 / A phase III, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of etrolizumab as an induction and maintenance treatment for patients with moderately to severely active crohn’s disease
The purpose of this study is to determine whether etrolizumab compared to a placebo, is a safe, effective and tolerable treatment for patients with moderately to severely active Crohns Disease (CD).
Etrolizumab is designed to work by blocking the binding of certain white blood cells to the lining of the stomach and intestines. This is thought to reduce inflammation caused by Crohns Disease. Etrolizumab is an experimental drug which means it has not been approved by the health authorities for treatment of Crohns Disease.
The screening period is up to 28 days during which patient eligibility will be determined. After screening the study will be divided into 3 Cohorts. Cohort 1 subjects will receive either placebo, a low dose of etrolizumab or a high dose of etrolizumab. Cohort 2 subjects will receive either a low dose of etrolizumab or a high dose of etrolizumab. Cohort 3 subjects will receive either placebo, a low dose of etrolizumab or a high dose of etrolizumab but at a different patient ratio to Cohort 1.
The study duration, from screening to end of study participation for a given eligible patient, will be up to 90 weeks (4-week screening period + 14-week Induction Phase + 60-week Maintenance Phase + 12-week Safety Follow-up Phase). The total length of the treatment period will be 74 weeks (14-weeks Induction Phase + 60-week
Maintenance Phase).
If eligible patients can opt to go into a 2 part Open Label Safety Monitoring study between weeks 10 and 14 or after Week 74. The study is completed after all patients have either completed the treatment and safety follow up period or discontinued early from the study.
Etrolizumab and placebo are administered via prefilled syringe.
Overall approximately 1250 patients will take part in this study in approximately 380 sites worldwide. (Study due to close 01/04/2019)
1511175 / An open-label extension and safety monitoring study of patients with moderately to severely active crohn’s disease previously enrolledin the etrolizumab phase III protocol GA29144
An open-label extension and safety monitoring study of patients with moderately to severely active crohn’s disease previously enrolled in the etrolizumab phase iii protocol GA29144 (Study due to close 02/07/2022)
1607270 / A Phase 3, Multicenter, Open-Label Extension Trial of Oral RPC1063 as Therapy for Moderate to Severe Ulcerative Colitis
A Phase 3, Multicenter, Open-Label Extension Trial of Oral RPC1063 as Therapy for Moderate to Severe Ulcerative Colitis (Study due to close 30/09/2021)
1607279 / A proSpective randomized controlled trial comParing infliximAbantimetabolites combination therapy to antimetabolites monotheRapy and infliximab monothErapy in Crohn’s disease patients in sustained steroid-free remission on combination therapy (SPARE)
A proSpective randomized controlled trial comParing infliximAbantimetabolites combination therapy to antimetabolites monotheRapy and infliximab monothErapy in Crohn’s disease patients in sustained steroid-free remission on combination therapy (SPARE) (Study due to close 31/12/2018)
1608299 / The UK Inflammatory Bowel Disease Bioresource: Progressing from Genetics to Function and Clinical Translation in Crohn’s Disease & Ulcerative Colitis
Working with the NIHR Bioresource, we are proposing to develop a centralised national recallable bioresource of 25,000 patients with Crohn’s disease or ulcerative colitis (collectively inflammatory bowel disease / IBD) to support scientific and clinical IBD research. Key features of IBD Bioresource:1. DNA and serum + clinical and genetic data from 25,000 IBD patients recruited UKwide stored in a central biorepository funded by NIHR Bioresource 2. 1000 newly diagnosed IBD patients. Detailed samples unconfounded by treatment or surgery, plus followup samples + clinical data 3.
Recallability run by the NIHR Bioresource office, allowing patients stratified by clinical subtype or carriage of specific IBD genetic risk variants to be recruited for stratified ‘stage 2’ scientific studies or clinical trials (each stage 2 study would require separate funding and new consent for each subject).IBD affects 4 per 1000 Europeans, peaking in young adults. Despite intensive medical therapies ~50% of patients require major surgery +/colostomy for treatment failure or complications. There is a pressing need to understand the causes of IBD and develop better treatments.
Since 2007 we and others have identified >160 distinct genetic risk factors for IBD. The next steps require additional sequencing for rare variants and functional analysis, to understand how associated variants disturb cell function to cause IBD; and translation of this knowledge for clinical benefit. These require access to a large Bioresource of patients of known or ascertainable genotype, to obtain fresh samples for analysis or to recruit patients to stratified clinical trials.
‘Recallability’ is a key novel feature for our disease area. The ethical framework for this has been established by the NIHR Cambridge Bioresource which since 2007 has run a programme of ‘recallability-by-genotype’ for healthy individuals. Our IBD Bioresource will be part of the NIHR Bioresource, and will extend recallable functionality to IBD allowing translation of recent genetic advances. (Study due to close 01/10/2020)
1609302 / I-CARE – IBD Cancer and Serious Infections in Europe
Inflammatory bowel disease (IBD), encompassing Crohn’s Disease (CD) and ulcerative Colitis (UC), is a chronic, disabling, incurable condition affecting 3 million Europeans. Current therapeutic options are limited immunosuppressant and biologics therapies such as antiTNF therapy in IBD patients are now used both earlier in patient treatment journeys and in a larger proportion of IBD patients. Such treatments can reduce the need for major bowel surgery in many patients whose IBD cannot be brought into remission by less potent medications.
However, antiTNF treatments (Adalimumab, Infliximab, Vedolizumab) with or without additional immunosuppressive therapies such Azathiopurine, Mercaptapurine or Methotrexate, place patients at greater risk of developing cancer (particularly lymphoma). The extent to which this risk exists is not clearly defined because no large scale prospective cohort studies have been conducted. ICARE is a Europeanwide, prospective, longitudinal, observational, multicentre cohort study designed to answer the question of risk of developing cancer or serious infection in IBD patients using immunosuppressive and biologic therapies.
A total of 16 countries will participate, including: Belgium, Denmark, France, Germany, Hungary, Ireland, Israel, Italy, Netherlands, Poland, Portugal, Russia, Spain, Sweden, Switzerland, and UK. The study aims to recruit a total of 17,600 patients across Europe, of which 1,100 people will be recruited in England. As an observational study there will no change to routine care for patients and the patients’ gastroenterologist can continue their regular care without affecting the study protocol.
The only patient interventions will be annual equestionnaires and monthly ediaries used to record disease activity. Patients will be followed up for 3 years after recruitment and medical information about their disease status and demographic data will be collected from their medical notes. Potential patients will be identified based on their IBD diagnosis and medication regime at the time of consent. Patients therefore will be identified by their Gastroenterologist in secondary care facilities. (Study due to close 31/12/2018)
1609306 / A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study, with a Vedolizumab IV Reference Arm, to Evaluate the Efficacy and Safety of Vedolizumab Subcutaneous as Maintenance Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis Who Achieved Clinical Response Following Open-Label Vedolizumab Intravenous Therapy
A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study, with a Vedolizumab IV Reference Arm, to Evaluate the Efficacy and Safety of Vedolizumab Subcutaneous as Maintenance Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis Who Achieved Clinical Response Following Open-Label Vedolizumab Intravenous Therapy (Study due to close 11/08/2018)
1609307 / A Phase 3b Open-label Study to Determine the Long-term Safety and Efficacy of Vedolizumab Subcutaneous in Subjects with Ulcerative Colitis and Crohn’s Disease
A Phase 3b Open-label Study to Determine the Long-term Safety and Efficacy of Vedolizumab Subcutaneous in Subjects with Ulcerative Colitis and Crohn’s Disease (Study due to close 30/06/2021)
1707456 / Combined Phase 3, Double-blind, Randomized, Placebo-Controlled Studies Evaluating the Efficacy and Safety of Fligotinib in the Induction and Maintenance of Remission in Subjects with Moderately to Severely Active Crohn’s Disease
Combined Phase 3, Double-Blind, Randomized, Placebo-Controlled Studies Evaluating the Efficacy and Safety of Filgotinib in the Induction and Maintenance of Remission in Subjects with Moderately to Severely Active Crohn’s Disease (Study due to close 30/09/2018)
1708482 / A Phase 3 Multicenter, Open-Label Extension (OLE) Study to Evaluate the Long-Term Safety and Efficacy of ABT-494 in Subjects with Ulcerative Colitis (UC)
A Phase 3 Multicenter, Open-Label Extension (OLE) Study to Evaluate the Long-Term Safety and Efficacy of ABT-494 in Subjects with Ulcerative Colitis (UC) (Study due to close 20/04/2020)
1708483 / A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of ABT-494 for Induction and Maintenance Therapy in Subjects with Moderately to Severely Active Ulcerative Colitis
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of ABT-494 for Induction and Maintenance Therapy in Subjects with Moderately to Severely Active Ulcerative Colitis (Study due to close 28/04/2020)
1708486 / A Long-Term Extension Study to Evaluate the Safety of Filgotinib in Subjects with Crohn’s Disease
A Long-Term Extension Study to Evaluate the Safety of Filgotinib in Subjects with Crohn’s Disease (Study due to close 30/11/2019)
1711527 / A Phase 2, double-blind, randomized, placebo-controlled study evaluating the efficacy and safety of Filgotinib in the treatment of Perianal Fistulizing Crohn’s Disease.
A randomized, double-blind, placebo controlled study to evaluate the efficacy and safety of Filgotinib in treating perianal fistulising Crohn’s disease. (Study due to close 30/11/2018)
1712550 / PROFILE
This study aims to demonstrate that a new ‘biomarker’ test will allow patients with Crohn’s disease to the receive the most appropriate treatment from the time of diagnosis.
Crohn’s disease is a chronic, debilitating intestinal condition, which typically occurs in young adults.
Once a patient is diagnosed, there is no way to predict how the disease will behave over their lifetime. Some patients may have frequent flare-ups and require treatment that involves hospital admission, toxic drugs and even surgery to remove severely damaged intestine, whereas others may have very few problems. Ideally, patients would receive treatment that is the most appropriate for them from diagnosis – using the most aggressive therapies for patients destined to experience aggressive disease, while avoiding drug toxicity and healthcare costs in those destined for mild disease. Unfortunately such “personalised therapy” will not be possible until doctors can reliably predict how an individual’s disease will behave in the future.
We have developed and validated a specialised ‘biomarker’ test, which by measuring expression of specific genes in a blood sample, can identify those patients who will experience aggressive disease and those who will experience much milder disease. The PROFILE trial aims to test whether this biomarker can deliver personalised medicine and improve outcomes in patients newly diagnosed with Crohn’s disease. (Study due to close 28/02/2020)
1802586 / Molecular biomarkers in pancreatic cyst fluid to improve diagnostic accuracy and malignancy risk assessment.
Asymptomatic pancreatic cysts are increasingly being detected due to the widespread use of high quality imaging modalities. Pancreatic cyst evaluation and management present a clinical conundrum as there are currently no broadly accepted guidelines, and the risk of malignancy from cysts remains uncertain. Cyst evaluation, which has implications on further management, focuses primarily on differentiating between nonmucinous benign cysts and mucinous premalignant ones which are most prevalent. Currently, making this differentiation definitively remains difficult.
Additionally, the natural history of these indolent yet premalignant mucinous cysts remains unclear. Therefore, the only currently available treatment is pancreatic resection, which is problematic given its associated morbidity. Given the current difficulties in diagnosis of malignant cysts, there is a need for better characterisation and understanding of cysts to improve management.
The goal of this study is to identify biomarkers of disease from cyst fluid collected by fine needle aspiration to improve diagnostic accuracy. (Study due to close 31/03/2019)
1804569 / Prospective cohort study to identify causes of depression and how depression leads to relapse in people with ulcerative colitis
Depression is common among people with Ulcerative Colitis (UC) and is associated with worse health outcomes e.g. more physical symptoms, worse health-related quality of life and relapse in UC activity. It remains unclear which factors predict depression among people with UC, and how depression impacts on UC outcomes. Recent research indicates levels of inflammatory activity may influence who gets depression and may also determine physical health outcomes. The role of inflammation in explaining the links between depression and disease activity in people with UC has not been investigated.
Our study will investigate among people with UC:
(i) The main factors that predict the development of depression.
(ii) How depression predicts UC outcomes.
We will recruit 250 patients with UC registered with the gastroenterology services at the Royal Devon and Exeter Hospital. Paper and computerised assessments will be conducted over 12 months at 6 monthly intervals. We will collect details of the person, their medical condition, social circumstances and psychological well-being. Key clinical data will be extracted from medical records.
We will conduct computerised assessments of the way individuals process emotionally important information (i.e. their emotional processing, such as how they perceive/remember emotions, how they respond to rewarding/threatening situations), which has been shown to determine the effects of inflammation on depression among healthy individuals. We will also collect blood samples to assess levels of inflammation.
Statistical techniques will identify:
(i) The most important predictors of depression in people with UC.
(ii) The extent to which depression predicts UC disease activity.
(iii) The roles of inflammation, emotional processing and other disease-related factors in contributing to depression.
This research is important as it could help identify those at highest risk of depression and worse UC outcomes. Understanding the mechanisms leading to worse UC outcomes could provide new treatment targets to improve UC outcomes. (Study due to close 01/08/2018)
1807651 / A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Efficacy and Safety of Filgotinib in the Treatment of Small Bowel Crohn’s Disease (SBCD)
A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Efficacy and Safety of Filgotinib in the Treatment of Small Bowel Crohn’s Disease (SBCD) (Study due to close 23/10/2018)
1808667 / A Randomized, Double-blind, Placebo-controlled Phase 2 Study to Evaluate the Testicular Safety of Filgotinib in Adult Males with Moderately to Severely Active Ulcerative Colitis
A Randomized, Double-blind, Placebo-controlled Phase 2 Study to evaluate the Testicular Safety of Filgotinib in Adult Males with Moderately to Severely Active Ulcerative Colitis (Study due to close 30/04/2019)
1808675 / perianal Crohn’s disease & Patient informational preferences
Patient informational preferences in surgical therapies of perianal Crohn’s disease
Patient informational preferences in surgical therapies of perianal Crohn’s disease (Study due to close 30/04/2018)
906278 / Characterising the Genetic Determinants of Inflammatory Bowel Disease
Characterising the Genetic Determinants of Inflammatory Bowel Disease (Study due to close 10/11/2018)