We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Open-Label Extension Study of GSK1605786A (SHIELD-3)

This study has been terminated.
(This study was terminated due to the lack of efficacy of GSK1605786A in Crohn's disease based on the results of Study CCX114151.)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01318993
First Posted: March 21, 2011
Last Update Posted: September 14, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
March 3, 2011
March 21, 2011
July 5, 2017
September 14, 2017
September 14, 2017
April 1, 2011
September 1, 2013   (Final data collection date for primary outcome measure)
Number of Participants With Any Adverse Events (AE) and Any Serious Adverse Events (SAE) [ Time Frame: Up to Week 112 ]
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death; was life threatening; required hospitalization or prolongation of existing hospitalization; resulted in disability/incapacity; was a congenital anomaly/birth defect. The Safety population consisted of all participants who enrolled in the study except those who did not take >=1 dose of investigational product.
Number of subjects with adverse events and serious adverse events [ Time Frame: Over 112 weeks ]
Incidence of adverse events and serious adverse events
Complete list of historical versions of study NCT01318993 on ClinicalTrials.gov Archive Site
  • Change From Baseline (Week 0) in Systolic and Diastolic Blood Pressure (SBP and DBP) Over Period [ Time Frame: Baseline (Week 0) and up to Week 112 ]
    The SBP and DBP values were obtained as part of vital sign monitoring and measured after the participant was at rest in the supine position for at least 5 minutes. Baseline value was recorded at Week 0. Change from Baseline measurements in SBP and DBP were assessed at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 4 weeks post-treatment. The Baseline value is defined as the value at Week 0. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.
  • Change From Baseline (Week 0) in Heart Rate (HR) Over Period [ Time Frame: Baseline (week 0) and up to Week 112 ]
    The HR values were obtained as part of vital sign monitoring and measured after the participant was at rest in the supine position for at least 5 minutes. Change from Baseline in HR was assessed at Week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 4 weeks post-treatment. The Baseline value is defined as the value at Week 0. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.
  • Number of Participants With Shifts From Baseline (Week 0) for the Indicated Hematology Parameters [ Time Frame: Baseline (Week 0) and up to Week 112 ]
    Hematology parameters measured included platelets, neutrophils (NL), lymphocytes, monocytes, eosinophils, basophils, hematocrit, band cells, red blood cell (RBC) count, hemoglobin, white blood cell (WBC) count, and segmented (seg) NL. The Baseline value is defined as the value obtained at Week 0. The number of participants with the indicated hematology parameters data reference range shifts from Baseline (defined as shift to low, shift to normal or no change, shift to high) until 4 weeks post treatment are presented.
  • Number of Participants With Shifts From Baseline (Week 0) for the Indicated Clinical Chemistry Parameters [ Time Frame: Baseline (Week 0) and up to Week 112 ]
    Clinical chemistry parameters included platelets, total protein, phosphorous, albumin, sodium, potassium, chloride, calcium, glucose, gamma-glutamyl transferase, total bilirubin (TB), direct bilirubin (DB), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN)/urea, creatinine, uric acid, bicarbonate, lactate dehydrogenase, cholesterol, alkaline phosphatase (ALP), gamma glutamyl transferases (GGT), and creatine kinase. The Baseline value is defined as the value obtained at Week 0. The number of participants with the indicated clinical chemistry parameters' data reference range shifts from Baseline (defined as shift to low, shift to normal or no change, or shift to high) until 4 weeks post-treatment are presented.
  • Change From Baseline (Week 0) in ALT, AST, ALP, and GGT as a Function of Liver Function Test (LFT) [ Time Frame: Baseline (Week 0) and up to Week 112 ]
    Changes in Baseline in ALP, ALT, AST, and GGT were assessed to monitor liver function. Blood samples were taken at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72, 84, 96, 108, and 4 Weeks post-treatment. The last value on or prior to the treatment start date was considered the Baseline value. Change from Baseline was calculated as the post-Baseline value at the time point indicated minus the value at Baseline.
  • Change From Baseline (Week 0) in Total Bilirubin [ Time Frame: Baseline (Week 0) and up to Week 112 ]
    Changes from Baseline (Week 0) in total bilirubin (TB) was assessed to monitor liver function. Blood samples were taken at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72, 84, 96, 108, and 4 Weeks post-treatment. The last value on or prior to the treatment start date was considered the Baseline value. Change from Baseline was calculated as the post-Baseline value at the time point indicated minus the value at Baseline.
  • Change From Baseline (Week 0) in Albumin [ Time Frame: Baseline (Week 0) and up to Week 112 ]
    Change from Baseline in albumin was assessed to monitor liver function. Blood samples were taken at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 72, 84, 96, 108, and 4 Weeks post treatment. The last value on or prior to the treatment start date (Week 0) was considered the Baseline value. Change from Baseline was calculated as the post-Baseline value at the time point indicated minus the value at Baseline.
  • Number of Participants With the Indicated Change From Baseline (Week 0) in Corrected QT Interval (QTc) Value [ Time Frame: Baseline (week 0) and Weeks 24, 48, 72, 108, and 112 (4 weeks post treatment) ]
    QTc is the corrected QT interval as measured by the electrocardiogram (ECG). ECG parameters including the change from Baseline in the QTc interval values QTcF and QTcB were summarised. The QTcF is Fridericia's formula and defined as the QT interval/cubed root of the R-R interval. The QTcB is the Bazett's formula defined as the QT/squared root of the R-R interval. The number of participants with change from Baseline in the QTcF and QTcB intervals of >30, 30 to <60 and >=60 milliseconds were assessed at Week 24, 48, 72, 108, and Week 112. The last value on or prior to the treatment start date was considered the Baseline value (Week 0). Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.
  • Change From Baseline (Week 0) in Crohn's Disease Activity Index (CDAI) Score Over 108 Weeks [ Time Frame: Baseline (Week 0) and up to 108 weeks ]
    The CDAI score was determined by interactive voice response relationship (IVRS) based on the combination of participant,investigator entries, standardized weight determination, and Hematocrit values received from the central laboratory. The Baseline CDAI score was recorded pre-dose on Week 0. Change from Baseline is the value at indicated time point minus the Baseline value. Remissions are defined as participants with CDAI score of < 150 points. No imputation for missing data was performed. The assessment was based on questionnaire like number of liquid stool in past 7 days, abdominal pain, other symptoms, antidiarrheal use, abdominal mass, anemia, and body weight. The total score is summation of all individual sub-scores. CDAI scoring scale ranges from 0-500 and a score of 150 or below indicates remission and a score above 450 indicates extremely severe disease. A decrease in CDAI over time indicates improvement in disease activity.
  • Percentage of Participants in Clinical Remission (CDAI Score Less Than 150) for All Participants, for Participants in Remission at Baseline (Week 0), and for Participants Not in Remission at Baseline Over 108 Weeks [ Time Frame: Baseline (Week 0) and up to 108 weeks ]
    The CDAI score was determined by interactive voice response relationship (IVRS) based on the combination of participant and investigator entries and standardized weight determination. Haematocrit values received from the central laboratory on the day of the visit were to be utilized for calculation of the CDAI scores. The Baseline (Week 0) CDAI score was defined as the last evaluation prior to or on the date the first dose of investigational product is taken. The CDAI score was measured over 108 weeks although it was planned to be measured till 112 weeks. Remissions are defined as subjects with CDAI score of < 150 points. Percentages are based on the number of subjects with observed data. No imputation for missing data was performed. Combined data for participants with remission at Baseline and without remission at Baseline has been presented.
  • Percentage of Participants Achieving Response (CDAI Decrease of at Least 100 Points From Baseline ([Week 0] of Prior Induction Study) in the Sub-population of Non-responders at Study Entry Over 112 Weeks [ Time Frame: Baseline (Week 0) and up to 112 weeks ]
    The CDAI score was determined by interactive voice response relationship (IVRS) based on the combination of participant and investigator entries and standardized weight determination. Haematocrit values received from the central laboratory on the day of the visit were to be utilized for calculation of the CDAI scores. The Baseline (Week 0) CDAI score was defined as the last evaluation prior to or on the date the first dose of investigational product was taken. Remissions are defined as subjects with CDAI score of < 150 points. Percentages are based on the number of subjects with observed data. No imputation for missing data was performed.
  • Change From Baseline (Week 0) in Inflammatory Bowel Disease Questionnaire (IBDQ), Short Form Health Survey (SF-36) Version 2, EuroQol 5 Dimensional (EQ-5D), Work and Productivity Activity Impairment-Crohn's Disease (WPAI-CD) and Disability Over 112 Weeks [ Time Frame: Baseline (Week 0) and up to 112 weeks ]
    IBDQ, SF-36, EQ-5D, WPAI-CD, and disability scores were all health outcome related scores that were based on assessment of participants based on different questionnaire. Each scoring scale had different range and participants were planned to be rated separately based on each scale.
  • Change from baseline in vital signs, haematology and clinical chemistry parameters, electrocardiogram measurements [ Time Frame: Over 112 weeks ]
    Change from baseline in vital signs, haematology and clinical chemistry, electrocardiogram measurements
  • Change from baseline in CDAI score [ Time Frame: Over 112 weeks ]
    Change from baseline in CDAI score
  • Proportion of subjects in clinicalremission [ Time Frame: Over 112 weeks ]
    Proportion of subjects in clinical remission (CDAI score less than 150) for all subjects, for subjects in remission at baseline and for subjects not in remission at baseline
  • Proportion of subjects achieving clinical response [ Time Frame: Over 112 weeks ]
    Proportion of subjects achieving response (CDAI decrease of at least 100 points from baseline of prior induction study) in the sub-population of non-responders at study entry
  • Change from baseline in health outcome measures (IBDQ, SF-36v2, EQ-5D, Work and Productivity Activity Impairment-Crohn's disease and disability) [ Time Frame: Over 112 weeks ]
    Change from baseline in IBDQ, SF-36v2, EQ-5D, Work and Productivity Activity Impairment-Crohn's Disease (WPAI-CD) and disability
Not Provided
Not Provided
 
Open-Label Extension Study of GSK1605786A
An Open-Label Extension Study to Assess the Safety of GSK1605786A in Subjects With Crohn's Disease
An open-label study to evaluate the safety and effectiveness of GSK1605786A 500 mg twice daily over 108 weeks in adult subjects with Crohn's disease. Subjects completing previous GSK-sponsored studies with GSK1605786A or subjects who withdraw early from Study CCX114157 (maintenance study of GSK1605786A) due to worsening of Crohn's disease requiring a treatment change may be eligible to participate. The primary objective is to evaluate the safety of GSK1605786A, as assessed by recording of adverse events, clinical laboratory parameters, vital signs and electrocardiogram. Secondary objectives will include assessments of effectiveness of long-term treatment with GSK1605786A. Health outcomes assessments will include changes in Inflammatory Bowel Disease Questionnaire (IBDQ), SF-36v2, EQ-5D, Work and Productivity Activity Impairment-Crohn's Disease (WPAI-CD) and receipt of disability.

This is a multi-centre, open-label extension study to assess the long-term safety, tolerability and effectiveness of GSK1605786A in subjects with Crohn's disease. Subjects will enter the study via one of three routes:

  1. completion of the placebo-controlled induction study, CCX114151, without achieving clinical response (CDAI decrease of at least 100 points) or clinical remission (CDAI score less than 150) at Week 12 or completion of any other GSK-sponsored induction study as designated by the sponsor
  2. completion of maintenance study CCX114157 at Week 52
  3. withdrawal from maintenance study CCX114157 due to worsening of Crohn's disease and requiring a treatment change.

The primary objective is to evaluate the safety of GSK1605786A, as assessed by recording of adverse events, clinical laboratory parameters, vital signs and electrocardiogram. Secondary objectives will include assessments of effectiveness of long-term treatment with GSK1605786A. Health outcomes assessments will include changes in Inflammatory Bowel Disease Questionnaire (IBDQ), SF-36v2, EQ-5D, Work and Productivity Activity Impairment-Crohn's Disease (WPAI-CD) and disability.

It is estimated that approximately 800 subjects will be enrolled in total. All subjects will enter the study at baseline (Week 0) and commence oral treatment with GSK1605786A 500 mg twice daily.

The study will be conducted for 108 weeks. Once the results of the induction study CCX114151 are known, the risk-to-benefit ratio will be re-assessed and the study duration may be amended.

Study assessments for Crohn's disease will be performed every 12 weeks through Week 108. At week 12, the investigator will make a determination of whether the subject is receiving clinical benefit, and subjects who are not receiving clinical benefit must be withdrawn. More frequent blood draws are required for liver function testing only; every 2 weeks for the first 12 weeks, then every 4 weeks up to Week 52, and every 12 weeks after Week 60 for the duration of the study.

Interventional
Phase 3
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Crohn's Disease
Drug: GSK1605786A
500 milligrams twice daily
Experimental: GSK1605786A
500 milligrams twice daily
Intervention: Drug: GSK1605786A
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
399
October 29, 2013
September 1, 2013   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Previous participation in a GSK-sponsored study with GSK1605786A
  • Written informed consent prior to any study-specific procedures
  • Female subjects: To be eligible, females of child-bearing potential must be sexually inactive or commit to consistent and correct use of a contraceptive method of birth control with less than 1% failure rate

Exclusion Criteria:

  • If female, is pregnant, has a positive pregnancy test or is breast-feeding, or is planning to become pregnant
  • Subjects with known or suspected coeliac disease or a positive screening test for anti-tissue transglutaminase antibodies should have been excluded from enrolment into any induction study. Subjects in whom a diagnosis of coeliac disease is subsequently suspected should be tested for anti-tissue transglutaminase antibodies and excluded or withdrawn from the study upon positive test result
  • Fixed symptomatic stenoses or strictures of small bowel or colon
  • Enterocutaneous, abdominal or pelvic fistulae likely to require surgery during the study period
  • Current sepsis or infections requiring intravenous antibiotic therapy greater than 2 weeks
  • Evidence of hepatic dysfunction or viral hepatitis
  • Subjects who have demonstrated safety or tolerability issues during participation in a previous study with GSK1605786A which, in the opinion of the investigator, was possibly related to study treatment and poses an unacceptable risk to the subject.
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Australia,   Austria,   Belgium,   Bulgaria,   Canada,   Chile,   Czechia,   Denmark,   Estonia,   France,   Germany,   Hong Kong,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   New Zealand,   Poland,   Portugal,   Russian Federation,   Slovakia,   South Africa,   Spain,   Sweden,   Switzerland,   Taiwan,   Turkey,   Ukraine,   United Kingdom,   United States
Argentina,   Brazil,   Czech Republic,   Greece,   Ireland
 
NCT01318993
114644
2010-022384-35 ( EudraCT Number )
Yes
Not Provided
Not Provided
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
July 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP