Colitis, UlcerativePhase 2NCT01658605
A Study to Investigate the Efficacy and Safety of GSK1605786 for Treatment of Patients With Active Ulcerative Colitis
A Phase 2 study testing GSK1605786 in people with Colitis, Ulcerative, run by GlaxoSmithKline at 5 sites in 3 countries.
Trial summary
GSK1605786 is an oral antagonist specific for the chemokine receptor CCR9 in development for treatment of small bowel and colonic Crohn's disease (CD). The purpose of this Phase II proof of concept study is to investigate the efficacy and safety of GSK1605786 (500 mg twice daily) administered orally for 16 weeks for… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colitis, Ulcerative
- What is being tested?
- GSK1605786
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 5 sitesin 3 countries
- Study dates
- Feb 2013to Dec 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female aged 18 and over at the time of signing the informed consent.
- A female subject of child-bearing potential is eligible to participate if she agrees to use one of the contraception methods listed in Section 8.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until completion of the follow-up visit.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form, prior to any of the screening procedures including discontinuation of prohibited medication.
- At screening (visit 1): patients with a clinical history and examination suggestive of active UC for at least 3 months despite at least 2 weeks treatment with oral >2.4g/day mesalazine / mesalamine or equivalent.
- At screening/randomization (visit 2):
- Presence of active UC spread beyond the rectum (inflammation extending ≥ 15cm from anal verge) as evidenced by flexible sigmoidoscopy or colonoscopy during the screening window.
- AND MAYO score of 5 - 10 inclusive.
- AST and ALT < 2xULN; alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN
Who cannot join
- If female, is pregnant, has a positive pregnancy test or is breast-feeding.
- Confirmed diagnosis of celiac disease, those who follow a gluten-free diet to manage symptoms of suspected celiac disease and subjects with positive serologic test for Tissue transglutaminase, tTG.
- Subjects who have received immunisation with a live vaccine e.g. measles, mumps, rubella (each as in MMR vaccine), oral polio, varicella, yellow fever, within 4 weeks of screening and throughout the study, with the exception of influenza vaccine.
- Known or suspicion of CD, indeterminate colitis, microscopic colitis, ischaemic colitis or radiation-induced colitis, based on medical history, endoscopy and/or histological findings.
- Subjects with imminent need for surgery for UC in the opinion of the investigator.
- Subjects where assessment of MAYO score is likely to be confounded by previous surgery (for example colectomy, ileostomies, colostomies or rectal pouches).
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- Subjects requiring enteral or parenteral feeding.
- Use of prohibited medications within their specified timeframes (see Section 9).
- 5-Aminosalicylic acid enema: within 2 weeks of screening and throughout study
- Topical (suppository) 5-Aminosalicylic acid: at screening and throughout study
- Biologic use: within 12 weeks of screening and throughout study
- Corticosteroids use: Oral, rectal or parenteral corticosteroids within 4 weeks of screening and throughout study
- Antibiotics: Intravenous antibiotics within 8 weeks of screening and throughout study (oral antibiotics are permitted where they have been used for >4 weeks with stable dose for ≥2 weeks prior to screening)
- Probiotics: within 4 weeks of screening (patients who initiated probiotics or prebiotics more than 4 weeks prior to screening should continue use throughout study)
- NSAIDs: Within 7 days of screening and throughout the study (except low dose aspirin (≤325 mg/day) which may be continued for cardioprotection)
- Digoxin: or related cardiac glycoside (e.g. digitoxin, deslanoside, lanatoside C, metildigoxin) use at any time during screening and throughout the study.
- Known HIV infection
- A positive HBsAg, Anti-HBc, or Hepatitis C antibody result at screening or documented positive result within 3 months of screening.
- Known varicella, herpes zoster, or other severe viral infection within 6 weeks of screening.
- Active or latent tuberculosis (TB) infection:
- The subject has a history of TB disease or latent TB infection, in the absence of documented adequate therapy for same.
- Suspicion of current TB disease (including extra pulmonary TB disease such as tuberculosis enteritis) or latent tuberculosis infection, as evidenced by positive QuantiFERON-TB Gold test, or T-SPOT.TB test.
- Current or chronic history of liver disease or known hepatic or biliary abnormalities including primary sclerosing cholangitis (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- QTc ≥450 msec (≥480msec for those with Bundle Branch Block).
- either QTcb or QTcf, machine or manual overread, males or females. The QT correction formula used to determine exclusion and discontinuation should be the same throughout the study.
- based on single QTc value of ECG obtained over a brief recording period.
- The subject has a concurrent illness or disability that may affect the interpretation of clinical data, or otherwise contraindicates participation in this clinical study (e.g., an unstable cardiovascular, autoimmune, congenital or acquired immunodeficiency, renal, hepatic, pulmonary, endocrine, metabolic, gastrointestinal, haematologic, or neurological condition or mental impairment).
- The subject has current evidence of, or has been treated for a malignancy within the past 5 years (other than localised basal cell, squamous cell skin cancer, cervical dysplasia, or cancer in situ that has been resected).
- Use of any investigational drug within 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) prior to screening
- Medical history of sensitivity to any of the components of GSK1605786 (microcrystalline cellulose, colloidal silicon dioxide, crospovidone, magnesium stearate, gelatin).
- Prior exposure to GSK1605786: Any previous exposure to GSK1605786 (formerly ChemoCentryx compound CCX282-B).
- Known positive stool culture for enteric pathogens
- Positive immunoassay for C. difficile.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period (with the exception of subjects involved in the optional scintigraphy sub-study, where no more than 700 mL of blood will be collected over the duration of the study, including any extra assessments that may be required).
Trial locations and contacts
5 sites in 3 countries.
5 sites in 3 countries
United Kingdom3 sites
GSK Investigational Site
Cambridge, Cambridgeshire, CB2 0QQ
GSK Investigational Site
Oxford, Oxfordshire, OX3 9DU
GSK Investigational Site
Southampton, Hampshire, SO16 6YD
About this study
Official title: A Phase II, 20-week, Multi-centre, Randomised, Double-blind, Placebo-controlled, Parallel Group Proof of Concept Study to Investigate the Efficacy and Safety of GSK1605786 for Treatment of Patients With Active Ulcerative Colitis
GSK1605786 is an oral antagonist specific for the chemokine receptor CCR9 in development for treatment of small bowel and colonic Crohn's disease (CD). The purpose of this Phase II proof of concept study is to investigate the efficacy and safety of GSK1605786 (500 mg twice daily) administered orally for 16 weeks for the treatment of patients with active ulcerative colitis (UC). A key secondary objective is to understand the mechanism by which GSK1605786 is acting and to this end samples will be collected to confirm the degree of inhibition of CCR9 on T lymphocytes in the blood of patients, and to explore the relationship between concentration of drug and changes in lymphocyte and antigen presenting cell populations in the peripheral circulation and in the colon. Patients recruited at specified investigational sites will be invited to participate in an optional sub-study to explore the effects of GSK1605786 on trafficking of technetium labelled T cells using Single Photon Emission Computerized Tomography (SPECT). Specifically, the technique will be used to follow trafficking to large intestine and thymus and findings linked to pharmacokinetics of GSK1605786, receptor occupancy and clinical efficacy outcomes
- Conditions
- Colitis, Ulcerative
- Being tested
- GSK1605786, Placebo
- Keywords
- GSK1605786, ulcerative colitis, CCR9 antagonist, proof of concept
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK1605786Drug
500 mg twice daily administered orally
PlaceboOther
500 mg twice daily administered orally
| Study group | Role | What they receive |
|---|---|---|
| GSK1605786 | Experimental | Administered orally for 16 weeks in a 2:1 ratio Receives: Other: Placebo |
| Placebo | Placebo comparator | Administered orally for 16 weeks in a 2:1 ratio Receives: Drug: GSK1605786 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of GSK1605786 at week 12 following twice daily administration at 500 mg in patients with active UC.
Ordinal response (remission, response, or no response) to treatment as assessed by the MAYO score at week 12.
Measured: 12 weeks
Secondary outcomes (6)
safety and tolerability of GSK1605786 in patients with active UC following repeat dosing continued for up to 16 weeks
Adverse events (AEs), Treatment effects on blood pressure, heart rate, electrocardiography (ECG) parameters and haematology, clinical chemistry and urinalysis findings
Measured: 16 weeks
The time course of the efficacy of GSK1605786
Incidence of remission (MAYO score ≤ 2 with no individual subscale exceeding 1) at Week 12, incidence of response (MAYO score decreased for ≥ 3 points in comparison with baseline) at Week 12, change in partial MAYO score compared to baseline through week 16, change in SCCAI score compared to baseline through week 16, incidence of endoscopic remission (mucosal healing) rate at Week 12 (defined as proportion of patients with endoscopy score of 0 or 1 on the MAYO endoscopic sub-scale) and time to withdrawal and/or use of rescue medication
Measured: 16 Weeks
The anti-inflammatory activity of GSK1605786 in patients with active UC
Circulating soluble biomarkers (CRP, CXL10), faecal calprotectin levels, receptor occupancy (CCR9 internalization).
Measured: 16 Weeks
The effects of GSK1605786 on quality of life in patients with UC
Quality of Life (IBDQ) Questionnaire.
Measured: Baseline, week 12, week 16
The systemic pharmacokinetics (PK) of GSK1605786 following twice daily administration at 500 mg in patients with active UC.
The maximum observed concentration (Cmax) on Day 28; Trough concentration (Cτ) on Day 28; Plasma clearance and volume of distribution estimated based on population pharmacokinetic analysis of healthy volunteers (historical data) and patient data, if possible
Measured: DaysBaseline, week 4, week 8, week 12, week 16
CCR9 occupancy (RO) in peripheral blood
TECK/CCL25 and CCR9 expression in colon biopsy at baseline and at 12 weeks
Measured: 12 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2012 (estimated)
- Study startFeb 2013
- Primary completionFeb 2013
- Study completionDec 2014 (estimated)
Why it stopped: Study CCX115383 has been terminated prior to enrolment of any patients. A decision was made by GSK to delay pursuit of this indication as the biology evolves.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colitis, UlcerativeStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01658605
- Sponsor's protocol ID
- 115393
- Status last verified
- Jun 2013
- First submitted
- 24 May 2012
- Last updated
- 24 Jun 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, 20-week, Multi-centre, Randomised, Double-blind, Placebo-controlled, Parallel Group Proof of Concept Study to Investigate the Efficacy and Safety of GSK1605786 for Treatment of Patients With Active Ulcerative Colitis
- ClinicalTrials.gov ID
- NCT01658605
- Acronym / sponsor ID
- 115393
- Conditions
- Colitis, Ulcerative
- Keywords
- GSK1605786, ulcerative colitis, CCR9 antagonist, proof of concept
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study CCX115383 has been terminated prior to enrolment of any patients. A decision was made by GSK to delay pursuit of this indication as the biology evolves.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Feb 2013
- Primary completion
- Feb 2013 (actual)
- Study completion
- Dec 2014 (estimated)
- First posted
- 7 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
GSK1605786 is an oral antagonist specific for the chemokine receptor CCR9 in development for treatment of small bowel and colonic Crohn's disease (CD). The purpose of this Phase II proof of concept study is to investigate the efficacy and safety of GSK1605786 (500 mg twice daily) administered orally for 16 weeks for the treatment of patients with active ulcerative colitis (UC). A key secondary objective is to understand the mechanism by which GSK1605786 is acting and to this end samples will be collected to confirm the degree of inhibition of CCR9 on T lymphocytes in the blood of patients, and to explore the relationship between concentration of drug and changes in lymphocyte and antigen presenting cell populations in the peripheral circulation and in the colon. Patients recruited at specified investigational sites will be invited to participate in an optional sub-study to explore the effects of GSK1605786 on trafficking of technetium labelled T cells using Single Photon Emission Computerized Tomography (SPECT). Specifically, the technique will be used to follow trafficking to large intestine and thymus and findings linked to pharmacokinetics of GSK1605786, receptor occupancy and clinical efficacy outcomes
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GSK1605786 | Experimental | Other: PlaceboAdministered orally for 16 weeks in a 2:1 ratio |
| Placebo | Placebo comparator | Drug: GSK1605786Administered orally for 16 weeks in a 2:1 ratio |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female aged 18 and over at the time of signing the informed consent.
- A female subject of child-bearing potential is eligible to participate if she agrees to use one of the contraception methods listed in Section 8.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until completion of the follow-up visit.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form, prior to any of the screening procedures including discontinuation of prohibited medication.
- At screening (visit 1): patients with a clinical history and examination suggestive of active UC for at least 3 months despite at least 2 weeks treatment with oral >2.4g/day mesalazine / mesalamine or equivalent.
- At screening/randomization (visit 2):
Key exclusion criteria (34 listed)
- If female, is pregnant, has a positive pregnancy test or is breast-feeding.
- Confirmed diagnosis of celiac disease, those who follow a gluten-free diet to manage symptoms of suspected celiac disease and subjects with positive serologic test for Tissue transglutaminase, tTG.
- Subjects who have received immunisation with a live vaccine e.g. measles, mumps, rubella (each as in MMR vaccine), oral polio, varicella, yellow fever, within 4 weeks of screening and throughout the study, with the exception of influenza vaccine.
- Known or suspicion of CD, indeterminate colitis, microscopic colitis, ischaemic colitis or radiation-induced colitis, based on medical history, endoscopy and/or histological findings.
- Subjects with imminent need for surgery for UC in the opinion of the investigator.
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 |
|---|---|---|
| GSK1605786500 mg twice daily administered orally | Drug | Placebo |
| Placebo500 mg twice daily administered orally | Other | GSK1605786 |
Primary outcome
Efficacy of GSK1605786 at week 12 following twice daily administration at 500 mg in patients with active UC.
Time frame: 12 weeks
Ordinal response (remission, response, or no response) to treatment as assessed by the MAYO score at week 12.
6 secondary outcomes
safety and tolerability of GSK1605786 in patients with active UC following repeat dosing continued for up to 16 weeks
Time frame: 16 weeks
The time course of the efficacy of GSK1605786
Time frame: 16 Weeks
The anti-inflammatory activity of GSK1605786 in patients with active UC
Time frame: 16 Weeks
The effects of GSK1605786 on quality of life in patients with UC
Time frame: Baseline, week 12, week 16
The systemic pharmacokinetics (PK) of GSK1605786 following twice daily administration at 500 mg in patients with active UC.
Time frame: DaysBaseline, week 4, week 8, week 12, week 16
CCR9 occupancy (RO) in peripheral blood
Time frame: 12 Weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2013.
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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.
GSK Clinical Trials study director
GlaxoSmithKline
5 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GSK1605786 in people with Colitis, Ulcerative, run by GlaxoSmithKline at 5 sites in 3 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 34 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: withdrawn, as of the sponsor's last update on 24 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United Kingdom, Belgium, Netherlands. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Efficacy of GSK1605786 at week 12 following twice daily administration at 500 mg in patients with active UC. (time frame: 12 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 24 Jun 2013.