An Active Treatment Study to Induce Clinical Response and/or Remission With GSK1605786A in Subjects With Crohn's Disease

NCT ID: NCT01536418

Last Updated: 2018-01-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 255 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-11
• Study Completion Date: 2013-10-17

Brief Summary

This is a multi-centre, randomised, double-blind, active treatment, parallel group induction study in subjects with moderately-to-severely active Crohn's disease. Subjects will receive one of two doses (500 milligrams once daily, 500 milligrams twice daily) of GSK1605786A for 12 weeks. The primary objective of the study is to induce clinical response (Crohn's Disease Activity Index [CDAI] decrease from baseline of at least 100 points) and/or remission (CDAI score less than 150) with GSK1605786A at Week 12 in subjects with active Crohn's disease to qualify subjects for enrolment into a 52 week maintenance study (CCX114157). Secondary objectives will include assessment of the safety and evaluation of the efficacy in induction of clinical response or remission. Safety will be assessed by recording of adverse events and assessment of changes in clinical laboratory parameters, vital signs and electrocardiogram. Population pharmacokinetics will evaluate the two doses of GSK1605786A. Health outcomes assessments will include changes in Inflammatory Bowel Disease Questionnaire, SF-36, EQ-5D, and Work Productivity and Activity Impairment-Crohn's Disease.

Detailed Description

This is a multi-centre, double-blind, randomised, active treatment, parallel group study designed to induce clinical response and/or clinical remission with two oral doses of GSK1605786A (500 milligrams once daily, 500 milligrams twice daily) over a 12-week treatment period in subjects with moderately-to-severely active Crohn's disease. The primary objective of this study is to qualify subjects for enrolment into a follow up 52 week maintenance study CCX114157. Subjects who achieve induction of clinical response (CDAI decrease from baseline of at least 100 points) or remission (CDAI score less than 150) at Week 12 following treatment with GSK1605786A will be eligible for enrolment into the maintenance study CCX114157. Secondary objectives will include assessment of the safety and evaluation of the efficacy in induction of clinical response or remission.

The study is planned to randomise approximately 900 subjects (450 subjects per group) with active Crohn's disease who have been diagnosed for at least 4 months, with documented history of disease in the small and/or large intestine, and characterised by a CDAI score between 220 to 450 (inclusive). Subjects will be required to have evidence of current active inflammation by elevated C-reactive protein (greater than the upper limit of normal of the highly sensitive C-reactive protein test) OR an elevated level of faecal calprotectin. Subjects will be allowed to participate in the study while continuing on stable doses of agents typically used to treat Crohn's disease. Inclusion of subjects who received prior treatment with an anti-tumor necrosis factor agent and discontinued due to loss or lack of efficacy will be limited to approximately 50 percent of the study population. Following a 3-week screening period, subjects will be randomised at baseline to receive blinded treatment with one of two doses of GSK1605786A (500 milligrams once daily or twice daily) for 12 weeks. All subjects meeting the definition of responder (CDAI decrease from baseline of at least 100 points) or who are in remission (CDAI score less than 150 points) at Week 12 will be eligible for randomisation into an ongoing maintenance study (CCX114157). Subjects who do not meet the definition of responder or who are not in remission at Week 12 will not be eligible to participate in study CCX114157.

For subjects who complete the study the minimum duration of participation is 15 weeks and the maximum duration is 19 weeks.

Conditions

Crohn's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

GSK1605786A, 500 milligrams, once daily

500 milligrams once daily, orally administered for 12 weeks

Group Type: EXPERIMENTAL

GSK1605786A

Intervention Type: DRUG

500 milligrams once daily, orally administered for 12 weeks

GSK1605786A, 500 milligrams twice daily

500 milligrams twice daily, orally administered for 12 weeks

Group Type: EXPERIMENTAL

GSK1605786A

Intervention Type: DRUG

500 milligrams twice daily, orally adminstered for 12 weeks

Interventions

GSK1605786A

500 milligrams once daily, orally administered for 12 weeks

Intervention Type: DRUG

GSK1605786A

500 milligrams twice daily, orally adminstered for 12 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female subjects aged 18 years or older
• Written informed consent prior to any of the screening procedures including discontinuation of prohibited medications
• Diagnosis of Crohn's disease for more than 4 months with small bowel and/or colonic involvement
• Current evidence of moderately-to-severely active disease defined by a baseline Crohn's Disease Activity Index (CDAI) score of 220 to 450, inclusive
• Confirmation of active disease by elevated CRP (greater than or equal to the upper limit of normal for the highly sensitive C-reactive protein test) or elevated levels of faecal calprotectin
• History of inadequate response and/or intolerance or adverse event leading to discontinuation of at least one of the following treatments for Crohn's disease: corticosteroids or immunosuppressants
• Stable doses of permitted concomitant medications or having previously received, but are not currently receiving, medications for Crohn's disease
• Demonstrated ability to comply with Crohn's disease symptom recording using the interactive voice response system
• Female subjects of child-bearing potential are eligible if not pregnant or nursing and committed to use of contraceptive methods with a failure rate of less than 1 percent per year

Exclusion Criteria

• Known coeliac disease, those who follow a gluten-free diet to manage symptoms of suspected coeliac disease and subjects with a positive screening test for coeliac disease (elevated anti-tissue transglutaminase antibodies)
• Diagnosis of ulcerative or indeterminate colitis
• Enterocutaneous, abdominal or pelvic fistulae with abscesses, or fistulae likely to require surgery during the course of the study period
• Bowel surgery, other than appendectomy, within 12 weeks prior to screening and/or has planned surgery or deemed likely to need surgery for Crohn's disease during the study period
• Extensive colonic resection, subtotal or total colectomy
• Presence of ileostomies, colostomies or rectal pouches
• Fixed symptomatic stenoses of small bowel or colon
• History of more than 3 small bowel resections or diagnosis of short bowel syndrome
• Chronic use of narcotics for chronic pain defined as daily use of one or more doses of narcotic containing medicaitons
• Use of prohibited medications, including enteral feeding or elemental diet, within their specified timeframes and throughout the study. Prohibited medications include the following:

1. Biologic use: Use of any TNF inhibitor (such as infliximab, adalimumab or certolizumab) or natalizumab within 10 weeks prior to Randomisation

2. Corticosteroid use: Use of parenteral glucocorticoids within 4 weeks prior to Screening

3. Immunospressant use: Use of cyclosporine, tacrolimus, sirolimus or mycophenolate mofetil within 4 weeks prior to Screening

4. Intravenous antibiotic use: Use of intravenous antibiotics for Crohn's disease within 4 weeks prior to Screening

5. Enteral feeding: Use of tube or enteral feeding, elemental diet within 2 weeks prior to Screening

6. Rectal Treatment: Use of 5-aminosalicylates or corticosteroid enemas or suppositories within 2 weeks prior to Screening

7. Leukocytapheresis or granulocytapheresis within 2 weeks prior to Screening

8. Paracetamol or acetaminophen greater than 2 grams per day

9. Opioid analgesics for worsening Crohn's disease pain are prohibited when used on a regular daily basis for more than 3 days

10. Digoxin or related cardiac glycosides: Use within 7 days prior to Screening

11. Any previous participation in a clinical study of GSK1605786A (formerly ChemoCentryx compound CCX282-B)

• Positive immunoassay for Clostridium difficile
• Known HIV infection
• Known varicella, herpes zoster, or other severe viral infection within 6 weeks of screening
• Immunization with a live vaccine within 4 weeks of Screening and throughout the study with the exception of the influenza vaccine
• Positive hepatitis B surface antigen or hepatitis B core antibody test or positive Hepatitis C test result at Screening
• Active or latent tuberculosis infection determined by results of QuantiFERON TB Gold test
• Current sepsis or infections requiring intravenous antibiotic therapy for more than 2 weeks
• Previous infections characterised by opportunistic pathogens, and/or dissemination suggestive of clinically significant immunocompromise
• Evidence of hepatic dysfunction, viral hepatitis, or abnormalities in liver function test results
• Corrected QT interval of ECG (electrocardiogram) greater than or equal to 450 milliseconds
• Congenital or acquired immunodeficiency or has evidence of immunocompromise manifested by current opportunistic infection
• Current evidence of, or has been treated for a malignancy within the past five years (other than localised basal cell, squamous cell skin cancer, cervical dysplasia, or any cancer in situ that has been resected)
• History of evidence of adenomatous colonic polyps that have not been removed.
• History of evidence of colonic mucosal dysplasia
• If female, is pregnant, has a positive pregnancy test or is breast-feeding
• Concurrent illness or disability that may affect the interpretation of clinical data, or otherwise contraindicates participation in this clinical study (such as an unstable cardiovascular, autoimmune, renal, hepatic, pulmonary, endocrine, metabolic, gastrointestinal, haematologic, or neurological condition or mental impairment)
• Medical history of sensitivity to any of the components of GSK1605786A (microcrystalline cellulose, crospovidone, sodium stearyl fumarate).
• Use of any investigational product within 30 days prior to screening

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Little Rock, Arizona, United States

GSK Investigational Site

Tucson, Arizona, United States

GSK Investigational Site

La Jolla, California, United States

GSK Investigational Site

Aurora, Colorado, United States

GSK Investigational Site

Denver, Colorado, United States

GSK Investigational Site

Littleton, Colorado, United States

GSK Investigational Site

Hamden, Connecticut, United States

GSK Investigational Site

New Haven, Connecticut, United States

GSK Investigational Site

Washington D.C., District of Columbia, United States

GSK Investigational Site

Jacksonville, Florida, United States

GSK Investigational Site

Port Orange, Florida, United States

GSK Investigational Site

Suwanee, Georgia, United States

GSK Investigational Site

Chicago, Illinois, United States

GSK Investigational Site

Chevy Chase, Maryland, United States

GSK Investigational Site

Towson, Maryland, United States

GSK Investigational Site

Towson, Maryland, United States

GSK Investigational Site

Boston, Massachusetts, United States

GSK Investigational Site

Chesterfield, Michigan, United States

GSK Investigational Site

Rochester, Minnesota, United States

GSK Investigational Site

Lee's Summit, Missouri, United States

GSK Investigational Site

Mexico, Missouri, United States

GSK Investigational Site

Brooklyn, New York, United States

GSK Investigational Site

Lake Success, New York, United States

GSK Investigational Site

Stony Brook, New York, United States

GSK Investigational Site

Chapel Hill, North Carolina, United States

GSK Investigational Site

Charlotte, North Carolina, United States

GSK Investigational Site

Charlotte, North Carolina, United States

GSK Investigational Site

Columbus, Ohio, United States

GSK Investigational Site

Tulsa, Oklahoma, United States

GSK Investigational Site

Portland, Oregon, United States

GSK Investigational Site

Pittsburgh, Pennsylvania, United States

GSK Investigational Site

Nashville, Tennessee, United States

GSK Investigational Site

Austin, Texas, United States

GSK Investigational Site

Ogden, Utah, United States

GSK Investigational Site

Christiansburg, Virginia, United States

GSK Investigational Site

Danville, Virginia, United States

GSK Investigational Site

Norfolk, Virginia, United States

GSK Investigational Site

Richmond, Virginia, United States

GSK Investigational Site

Madison, Wisconsin, United States

GSK Investigational Site

Milwaukee, Wisconsin, United States

GSK Investigational Site

Bankstown, New South Wales, Australia

GSK Investigational Site

Adelaide, South Australia, Australia

GSK Investigational Site

Box Hill, Victoria, Australia

GSK Investigational Site

Fitzroy, Victoria, Australia

GSK Investigational Site

Prahran, Victoria, Australia

GSK Investigational Site

Fremantle, Western Australia, Australia

GSK Investigational Site

Hall in Tirol, , Austria

GSK Investigational Site

Linz, , Austria

GSK Investigational Site

Oberpullendorf, , Austria

GSK Investigational Site

St.Veit/Glan, , Austria

GSK Investigational Site

Vienna, , Austria

GSK Investigational Site

Vienna, , Austria

GSK Investigational Site

Vienna, , Austria

GSK Investigational Site

Bonheiden, , Belgium

GSK Investigational Site

Edegem, , Belgium

GSK Investigational Site

Ghent, , Belgium

GSK Investigational Site

Kortrijk, , Belgium

GSK Investigational Site

Leuven, , Belgium

GSK Investigational Site

Roeselare, , Belgium

GSK Investigational Site

Plovdiv, , Bulgaria

GSK Investigational Site

Sofia, , Bulgaria

GSK Investigational Site

Sofia, , Bulgaria

GSK Investigational Site

Sofia, , Bulgaria

GSK Investigational Site

Varna, , Bulgaria

GSK Investigational Site

Kingston, Ontario, Canada

GSK Investigational Site

London, Ontario, Canada

GSK Investigational Site

London, Ontario, Canada

GSK Investigational Site

Viña del Mar, , Chile

GSK Investigational Site

Hradec Králové, , Czechia

GSK Investigational Site

Olomouc, , Czechia

GSK Investigational Site

Prague, , Czechia

GSK Investigational Site

Prague, , Czechia

GSK Investigational Site

Teplice, , Czechia

GSK Investigational Site

Ústí nad Orlicí, , Czechia

GSK Investigational Site

Aalborg, , Denmark

GSK Investigational Site

Aarhus, , Denmark

GSK Investigational Site

Herlev, , Denmark

GSK Investigational Site

Koebenhavn NV, , Denmark

GSK Investigational Site

Tallinn, , Estonia

GSK Investigational Site

Tallinn, , Estonia

GSK Investigational Site

Tartu, , Estonia

GSK Investigational Site

Clichy, , France

GSK Investigational Site

Lille, , France

GSK Investigational Site

Paris, , France

GSK Investigational Site

Saint-Priest-en-Jarez, , France

GSK Investigational Site

Heidelberg, Baden-Wurttemberg, Germany

GSK Investigational Site

Mannheim, Baden-Wurttemberg, Germany

GSK Investigational Site

Ulm, Baden-Wurttemberg, Germany

GSK Investigational Site

Weiden, Bavaria, Germany

GSK Investigational Site

Frankfurt am Main, Hesse, Germany

GSK Investigational Site

Brinkum/Stuhr, Lower Saxony, Germany

GSK Investigational Site

Hanover, Lower Saxony, Germany

GSK Investigational Site

Rostock, Mecklenburg-Vorpommern, Germany

GSK Investigational Site

Cologne, North Rhine-Westphalia, Germany

GSK Investigational Site

Minden, North Rhine-Westphalia, Germany

GSK Investigational Site

Dresden, Saxony, Germany

GSK Investigational Site

Halle, Saxony-Anhalt, Germany

GSK Investigational Site

Magdeburg, Saxony-Anhalt, Germany

GSK Investigational Site

Jena, Thuringia, Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

Athens, , Greece

GSK Investigational Site

Athens, , Greece

GSK Investigational Site

Athens, , Greece

GSK Investigational Site

Heraklion, Crete, , Greece

GSK Investigational Site

Ioannina, , Greece

GSK Investigational Site

Hong Kong, , Hong Kong

GSK Investigational Site

Shatin, New Territories, , Hong Kong

GSK Investigational Site

Békéscsaba, , Hungary

GSK Investigational Site

Budapest, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

GSK Investigational Site

Debrecen, , Hungary

GSK Investigational Site

Mosonmagyaróvár, , Hungary

GSK Investigational Site

Szekszárd, , Hungary

GSK Investigational Site

Vác, , Hungary

GSK Investigational Site

Afula, , Israel

GSK Investigational Site

Beersheba, , Israel

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Haifa, , Israel

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Holon, , Israel

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Jerusalem, , Israel

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Jerusalem, , Israel

GSK Investigational Site

Kfar Saba, , Israel

GSK Investigational Site

Petah Tikva, , Israel

GSK Investigational Site

Ramat Gan, , Israel

GSK Investigational Site

Tel Aviv, , Israel

GSK Investigational Site

Ẕerifin, , Israel

GSK Investigational Site

Genova, , Italy

GSK Investigational Site

Aichi, , Japan

GSK Investigational Site

Aichi, , Japan

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Aichi, , Japan

GSK Investigational Site

Fukuoka, , Japan

GSK Investigational Site

Fukuoka, , Japan

GSK Investigational Site

Fukuoka, , Japan

GSK Investigational Site

Hiroshima, , Japan

GSK Investigational Site

Hokkaido, , Japan

GSK Investigational Site

Hyōgo, , Japan

GSK Investigational Site

Kagoshima, , Japan

GSK Investigational Site

Kanagawa, , Japan

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Kanagawa, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Shizuoka, , Japan

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Tokyo, , Japan

GSK Investigational Site

Wakayama, , Japan

GSK Investigational Site

Amsterdam, , Netherlands

GSK Investigational Site

Amsterdam, , Netherlands

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Amsterdam, , Netherlands

GSK Investigational Site

Ede, , Netherlands

GSK Investigational Site

Eindhoven, , Netherlands

GSK Investigational Site

Rotterdam, , Netherlands

GSK Investigational Site

Canterbury, , New Zealand

GSK Investigational Site

Dunedin, , New Zealand

GSK Investigational Site

Hamilton, , New Zealand

GSK Investigational Site

Lower Hutt, , New Zealand

GSK Investigational Site

Otahuhu, , New Zealand

GSK Investigational Site

Takapuna, Auckland, , New Zealand

GSK Investigational Site

Tauranga, , New Zealand

GSK Investigational Site

Bydgoszcz, , Poland

GSK Investigational Site

Bydgoszcz, , Poland

GSK Investigational Site

Lublin, , Poland

GSK Investigational Site

Sopot, , Poland

GSK Investigational Site

Wroclaw, , Poland

GSK Investigational Site

Lisbon, , Portugal

GSK Investigational Site

Lisbon, , Portugal

GSK Investigational Site

Porto, , Portugal

GSK Investigational Site

Viseu, , Portugal

GSK Investigational Site

Irkutsk, , Russia

GSK Investigational Site

Kazan', , Russia

GSK Investigational Site

Lipetsk, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Nizhny Novgorod, , Russia

GSK Investigational Site

Rostov-on-Don, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Samara, , Russia

GSK Investigational Site

Tomsk, , Russia

GSK Investigational Site

Bratislava, , Slovakia

GSK Investigational Site

Bratislava, , Slovakia

GSK Investigational Site

Bratislava, , Slovakia

GSK Investigational Site

Nitra, , Slovakia

GSK Investigational Site

Nové Mesto nad Váhom, , Slovakia

GSK Investigational Site

Prešov, , Slovakia

GSK Investigational Site

Trnava, , Slovakia

GSK Investigational Site

Daegu, , South Korea

GSK Investigational Site

Pusan, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Wŏnju, , South Korea

GSK Investigational Site

Badalona, , Spain

GSK Investigational Site

Elche, , Spain

GSK Investigational Site

Fuenlabrada (Madrid), , Spain

GSK Investigational Site

Galdakao/Vizcaya, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Marbella, , Spain

GSK Investigational Site

Sabadell (Barcelona), , Spain

GSK Investigational Site

Santander, , Spain

GSK Investigational Site

Bern, , Switzerland

GSK Investigational Site

Zurich, , Switzerland

GSK Investigational Site

Taichung, , Taiwan

GSK Investigational Site

Taipei, , Taiwan

GSK Investigational Site

Taipei, , Taiwan

GSK Investigational Site

Taoyuan District, , Taiwan

GSK Investigational Site

Ankara, , Turkey (Türkiye)

GSK Investigational Site

Chernivtsi, , Ukraine

GSK Investigational Site

Dnipropetrovsk, , Ukraine

GSK Investigational Site

Donetsk, , Ukraine

GSK Investigational Site

Donetsk, , Ukraine

GSK Investigational Site

Kharkiv, , Ukraine

GSK Investigational Site

Kyiv, , Ukraine

GSK Investigational Site

Odesa, , Ukraine

GSK Investigational Site

Simferopol, , Ukraine

GSK Investigational Site

Vinnytsia, , Ukraine

GSK Investigational Site

Glasgow, Lanarkshire, United Kingdom

GSK Investigational Site

Harrow, Middlesex, United Kingdom

GSK Investigational Site

Birmingham, , United Kingdom

GSK Investigational Site

Dundee, , United Kingdom

GSK Investigational Site

Edinburgh, , United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

Manchester, , United Kingdom

GSK Investigational Site

Newcastle upon Tyne, , United Kingdom

GSK Investigational Site

Oxford, , United Kingdom

Countries

United States; Australia; Austria; Belgium; Bulgaria; Canada; Chile; Czechia; Denmark; Estonia; France; Germany; Greece; Hong Kong; Hungary; Israel; Italy; Japan; Netherlands; New Zealand; Poland; Portugal; Russia; Slovakia; South Korea; Spain; Switzerland; Taiwan; Turkey (Türkiye); Ukraine; United Kingdom

Other Identifiers

114643

Identifier Type: -

Identifier Source: org_study_id