An Efficacy and Safety Study of SHP647 as Maintenance Therapy in Participants With Moderate to Severe Ulcerative Colitis

Clinical Trials.gov
13 May, 2019 ,

Shire is conducting a Randomized study in 772 participants in order to evaluate the efficacy of SHP647 as maintenance therapy treatment of remission, based on composite score of patient-reported symptoms and centrally read endoscopy, in participants with moderate to severe ulcerative colitis. 

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Primary Outcome Measures  :

  1. Remission at Week 52 [ Time Frame: Week 52 ]

    Remission is defined as a composite score of patient reported symptoms using daily e-diary and centrally read endoscopy as follows: stool frequency subscore of 0 or 1 with at least a 1-point change from induction baseline; and rectal bleeding subscore of 0; and endoscopic subscore of 0 or 1 (modified, excludes friability). The Mayo score is a measure of UC disease activity. It ranges from 0 to 12 points and consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease. The subscores are Stool frequency (0-3); Rectal bleeding (0-3); Findings of endoscopy (0-3); Physician global assessment (PGA, 0-3). The composite score is a recommended measure consisting of the Mayo score without the PGA subscore and ranges from 0 to 9 points.

 

Secondary Outcome Measures  :

  1. Endoscopic Remission at Week 52 [ Time Frame: Week 52 ]

    Endoscopic remission is defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability).The centrally read endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease.

  2. Clinical Remission at Week 52 [ Time Frame: Week 52 ]

    Clinical remission is defined by stool frequency subscore of 0 or 1 with at least a 1-point change from induction study baseline in stool frequency subscore, and rectal bleeding subscore of 0. The stool frequency subscores and rectal bleeding subscores of mayo score ranges from 0 to 3 with higher scores indicating more severe disease.

  3. Sustained Remission at Week 52 [ Time Frame: Week 52 ]

    Sustained remission that is (ie), participants in remission at Week 52, among participants who were in remission at the time of baseline. Remission is defined as a composite score of patient reported symptoms using daily e-diary and centrally read endoscopy as follows: stool frequency subscore of 0 or 1 with at least a 1-point change from induction baseline; and rectal bleeding subscore of 0; and endoscopic subscore of 0 or 1 (modified, excludes friability). The stool frequency subscores, rectal bleeding subscores and endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. The composite score is a recommended measure consisting of the Mayo score without the PGA subscore and ranges from 0 to 9 points.

  4. Clinical Response Based on Composite Score at Week 52 [ Time Frame: Week 52 ]

    Clinical response based on composite score is defined as a decrease from induction study baseline in the composite score of participant-reported symptoms using daily e-diary and centrally read endoscopy of at least 2 points and at least 30 percent (%), with an accompanying decrease in the subscore for rectal bleeding greater than or equal to (>=) 1 point or a subscore for rectal bleeding less than or equal to (<=) 1. The rectal bleeding subscores and centrally read endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. The composite score is a recommended measure consisting of the Mayo score without the PGA subscore and ranges from 0 to 9 points.

  5. Mucosal Healing Based on Endoscopic and Histologic Assessment at Week 52 [ Time Frame: Week 52 ]

    Mucosal healing is defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability) and centrally read Geboes score of <=2. The centrally read endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. Geboes score grading system, is a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher geboes score indicates more severe disease.

  6. Glucocorticoid-free Clinical Remission at Week 52 [ Time Frame: Week 52 ]

    Glucocorticoid-free clinical remission is defined as clinical remission in addition to not requiring any treatment with glucocorticoids for at least 4 weeks prior to the Week 52. Clinical remission is defined as stool frequency subscore of 0 or 1 with at least a 1-point change from induction study baseline in stool frequency subscore, and rectal bleeding subscore of 0, at the Week 52. The stool frequency subscore and rectal bleeding subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease.The composite score is a recommended measure consisting of the Mayo score without the PGA subscore and ranges from 0 to 9 points.

  7. Glucocorticoid-free Remission at Week 52 [ Time Frame: Week 52 ]

    Glucocorticoid-free remission is defined as remission in addition to not requiring any treatment with glucocorticoids for at least 4 weeks prior to the Week 52. Remission is defined as a composite score of participant-reported symptoms using daily e-diary and endoscopy, with stool frequency subscore of 0 or 1 with at least a 1-point change from induction study baseline, and rectal bleeding subscore of 0, and endoscopic subscore of 0 or 1 (modified, excludes friability). The stool frequency subscore, rectal bleeding subscore and endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. The composite score is a recommended measure consisting of the Mayo score without the PGA subscore and ranges from 0 to 9 points.

  8. Remission Based on Total Mayo Score at Week 52 [ Time Frame: Week 52 ]

    Remission defined as a total mayo score of less than or equal to <=2 with no individual subscore (stool frequency, rectal bleeding, endoscopy [modified, excludes friability], and physician's global assessment) exceeding 1, at Week 52. The total mayo score ranges from 0 to 12 points and consists of the following 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease: Stool frequency (0-3); Rectal bleeding (0-3); Findings of endoscopy (0-3); Physician global assessment (PGA; 0-3).

  9. Clinical Response Based on Total Mayo Score at Week 52 [ Time Frame: Week 52 ]

    Clinical response (Mayo) is defined as a decrease from induction study baseline in the total mayo score of at least 3 points and at least 30%, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. The total mayo score ranges from 0 to 12 points and consists of the following 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease: Stool frequency (0-3); Rectal bleeding (0-3); Findings of endoscopy (0-3); Physician global assessment (PGA; 0-3).

  10. Partial Mayo Score Over Time [ Time Frame: Baseline up to Week 52 ]

    The partial mayo score ranges from 0 to 9 points and consists of the following 3 subscores, each graded from 0 to 3 with higher scores indicating more severe disease: Stool frequency (0-3); Rectal bleeding (0-3); Physician global assessment (PGA; 0-3).

  11. Clinical Remission Over Time [ Time Frame: Baseline up to Week 52 ]

    Clinical remission is defined by stool frequency subscore of 0 or 1 with at least a 1-point change from induction study baseline in stool frequency subscore, and rectal bleeding subscore of 0. The stool frequency subscore and rectal bleeding subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease.The composite score is a recommended measure consisting of the Mayo score without the PGA subscore and ranges from 0 to 9 points.

  12. Endoscopic Remission at Week 52 With Endoscopic Subscore of 0 [ Time Frame: Week 52 ]

    Endoscopic remission at Week 52 with endoscopic subscore of 0 will be reported. The endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. The composite score is a recommended measure consisting of the Mayo score without the PGA subscore and ranges from 0 to 9 points.

  13. Clinical Remission Over Time With Both Rectal Bleeding and Stool Frequency Subscores of 0 [ Time Frame: Baseline up to Week 52 ]

    Clinical remission over time with both rectal bleeding and stool frequency subscores of 0 will be reported. The stool frequency subscore and rectal bleeding subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. The composite score is a recommended measure consisting of the Mayo score without the PGA subscore and ranges from 0 to 9 points.

  14. Deep Remission at Week 52 [ Time Frame: Week 52 ]

    Deep remission is defined as both endoscopic and rectal bleeding subscores of 0, and stool frequency subscore <=1 and a centrally read Geboes score of <=2.. The stool frequency subscore, rectal bleeding subscore and endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. The composite score is a recommended measure consisting of the Mayo score without the PGA subscore and ranges from 0 to 9 points. The Geboes score grading system, is a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher geboes score indicates more severe disease.

  15. Sustained Endoscopic Remission at Week 52 [ Time Frame: Baseline up to Week 52 ]

    Sustained endoscopic remission ie, participants in endoscopic remission at Week 52 among participants who were in remission at the time of baseline, as defined by a centrally read endoscopic subscore of 0 or 1 (modified, excludes friability). The centrally read endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. The composite score is a recommended measure consisting of the Mayo score without the PGA subscore and ranges from 0 to 9 points.

  16. Sustained Mucosal Healing at Week 52 [ Time Frame: Baseline up to Week 52 ]

    Sustained mucosal healing ie, participants with mucosal healing at Week 52 among participants who were in remission at the time of baseline, as defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability) and a centrally read Geboes score of <=2. The centrally read endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. Geboes score grading system, is a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher geboes score indicates more severe disease.

  17. Sustained Deep Remission at Week 52 [ Time Frame: Baseline up to Week 52 ]

    Sustained deep remission ie, participants in deep remission at Week 52 among participants who were in remission at the time of baseline, as defined as both endoscopic and rectal bleeding subscores of 0, and stool frequency subscore <=1 and a centrally read Geboes score of <=2. The stool frequency subscore, rectal bleeding subscore and endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. Geboes score grading system, is a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher geboes score indicates more sever.

  18. Sustained Clinical Remission Over Time [ Time Frame: Baseline up to Week 52 ]

    Sustained clinical remission over time ie, participants in clinical remission at baseline and each visit, as defined by stool frequency subscore of 0 or 1 with at least a 1-point change from induction study baseline in stool frequency subscore, and rectal bleeding subscore of 0. The stool frequency subscore and rectal bleeding subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease.

  19. Sustained Endoscopic Remission at Week 52 [ Time Frame: Baseline up to Week 52 ]

    Sustained endoscopic remission at Week 52 ie, endoscopic remission at Week 52 among participants who were in remission at the time of baseline, with a mayo endoscopic subscore of 0. The endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease.

  20. Sustained Remission at Week 52 [ Time Frame: Baseline up to Week 52 ]

    Sustained remission at Week 52 ie, remission at the SHP647-303 Week 52 among participants who were in remission at the time of baseline. Remission is defined as a total mayo score <=2 with no individual subscore (stool frequency, rectal bleeding, endoscopy [modified, excludes friability], and physician's global assessment) exceeding 1. The Mayo score is a measure of UC disease activity. It ranges from 0 to 12 points and consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease. The subscores are Stool frequency (0-3); Rectal bleeding (0-3); Findings of endoscopy (0-3); Physician global assessment (PGA, 0-3).

  21. Sustained Clinical Remission Over Time With Both Rectal Bleeding and Stool Frequency Subscores of 0 [ Time Frame: Baseline up to Week 52 ]

    Sustained clinical remission over time ie, clinical remission at study baseline and each visit with both rectal bleeding and stool frequency subscores of 0. The stool frequency subscore and rectal bleeding subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease.

  22. Glucocorticoid-free Clinical Remission Over Time [ Time Frame: Baseline, every 4 weeks up to EOS (Approximately 52 weeks) ]

    Glucocorticoid-free clinical remission is defined as clinical remission in addition to not requiring any treatment with glucocorticoids in participants who previously received glucocorticoids.

  23. Change From Induction Study Baseline in Abdominal Pain Score Based on Participant e-Diary [ Time Frame: Baseline, Week 12, 24 and 52 ]

    Change from induction study baseline in abdominal pain based on participant e-diary will be assessed. Participants will be asked to record the abdominal pain worst severity using 0-10 numeric rating scale, with 0 anchor at "No pain" and 10 at "Worst Imaginable Pain" as experienced over the previous 24 hours, in the e-diary.

  24. Change From Induction Study Baseline in Diarrhea Score Based on Participant e-Diary [ Time Frame: Baseline, Week 12, 24 and 52 ]

    Change from induction study baseline in diarrhea based on participant e-diary will be assessed. Participants will be asked to record the diarrhea frequency (enter number of loose or watery bowel movements) as experienced over the previous 24 hours, in the e-diary.

  25. Change From Induction Study Baseline in Urgency Score Based on Participant e-Diary [ Time Frame: Baseline, Week 12, 24 and 52 ]

    Change from induction study baseline in urgency based on participant e-diary will be assessed. Participants will be asked to record the urgency frequency (enter number of bowel movements with urgency) as experienced over the previous 24 hours, in the e-diary.

  26. Change From Induction Study Baseline in Absolute Stool Frequency Score Based on Participant e-Diary [ Time Frame: Baseline, Week 12, 24 and 52 ]

    Change from induction study baseline in absolute stool frequency based on participant e-diary will be assessed. Participants will be asked to record the stool frequency (enter number of bowel movements passed) as experienced over the previous 24 hours, in the e-diary.

  27. Change From Induction Study Baseline in Absolute Rectal Bleeding Score Based on Participant e-Diary [ Time Frame: Baseline, Week 12, 24 and 52 ]

    Change from induction study baseline in absolute rectal bleeding based on participant e-diary will be assessed. Participants will be asked to record the rectal bleeding severity and frequency (enter number of bowel movements with blood) as experienced over the previous 24 hours, in the e-diary.

  28. Change From Induction Study Baseline Total Sign/Symptom Score Based on Participant e-Diary [ Time Frame: Baseline, Week 12, 24 and 52 ]

    Change from induction study baseline total sign/symptom score based on participant e-diary will be assessed. The total sign/symptom score ranges from 0 to 10 with higher scores indicating higher severity.

  29. Change From Induction Study Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Domains and Total Absolute Scores in Inflammatory Bowel Disease Questionnaire (IBDQ) [ Time Frame: Baseline, Week 12, 24 and 52 ]

    The IBDQ is a psychometrically validated patient-reported outcome (PRO) instrument for measuring the disease-specific HRQL in participants with inflammatory bowel disease, including UC. The IBDQ consists of 32 items, which are grouped into 4 dimensions: bowel function, emotional status, systemic symptoms, and social function. The 4 domains are scored as follows: Bowel symptoms: 10 to 70; Systemic symptoms: 5 to 35; Emotional function: 12 to 84; Social function: 5 to 35. The total IBDQ score ranges from 32 to 224. For the total score and each domain, a higher score indicates better HRQL. A score of at least 170 corresponds to clinical remission and an increase of at least 16 points is considered to indicate a clinically meaningful improvement.

  30. Change From Induction Study Baseline in Short Form-36 Health Survey (SF-36), Version 2, Acute (Physical and Mental Component Summary Scores and Individual Domain Scores) [ Time Frame: Baseline, Week 12, 24 and 52 ]

    The SF-36 is a generic quality-of-life instrument that has been widely used to assess health-related quality of life (HRQL) of participants. Generic instruments are used in general populations to assess a wide range of domains applicable to a variety of health states, conditions, and diseases. The SF-36 consists of 36 items that are aggregated into 8 multi-item scales (physical functioning, role - physical, bodily pain, general health, vitality, social functioning, role - emotional, and mental health), with scores ranging from 0 to 100. Higher scores indicate better HRQL.

  31. Incidence of Hospitalizations [ Time Frame: Baseline up to Week 68 ]

    Incidence of hospitalizations during the entire study period will be reported.

  32. Incidence of Total Inpatient Days [ Time Frame: Baseline up to Week 68 ]

    Incidence of total inpatient days during the entire study period will be reported.

  33. Number of Participants With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: From start of study drug administration up to Week 68 ]

    An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. Treatment-emergent AEs (TEAEs) are defined as AEs with start dates at the time of or following the first exposure to investigational product.

  34. Number of Participants With Clinically Significant Change in Clinical Laboratory Results Reported as Adverse Event [ Time Frame: From start of study drug administration up to Week 68 ]

    Clinical laboratory assessments include serum chemistry, hematology and urinalysis. The investigator will assess out-of-range clinical laboratory values for clinical significance, to indicate whether or not the values are clinically significant.

  35. Number of Participants With Clinically Significant Findings in Physical Examinations Reported as Adverse Event [ Time Frame: From start of study drug administration up to Week 68 ]

    Complete physical examinations will be carried out which include review of the following body systems: general appearance, skin, head, eyes, ears, nose, and throat (HEENT), heart, lungs, confrontational visual fields (eyes), breast (optional), abdomen, external genitalia (optional), extremities, neurologic function, back, and lymph nodes. Any changes from the baseline in physical examination findings that are deemed clinically significant in the opinion of the investigator are to be recorded as an AE.

  36. Number of Participants With Clinically Significant Change in Vital Signs Reported as Adverse Event [ Time Frame: From start of study drug administration up to Week 68 ]

    Vital sign assessments include blood pressure, pulse, respiratory rate, and temperature. Any deviations from baseline that are deemed clinically significant in the opinion of the investigator are to be recorded as an AE.

  37. Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as Adverse Event [ Time Frame: From start of study drug administration up to Week 52 ]

    12-lead ECG will be recorded and a central ECG reader will be used in the study. Any abnormality in ECG assessed by an investigator considered as clinically significant will be reported as AE.

  38. Number of Participants who Develop Antidrug Antibodies to SHP647 [ Time Frame: Baseline, Week 12, 24, 36 and 52 ]

    Serum samples will be analysed for presence of antidrug antibodies to SHP647. Participants who showed positive results for SHP647 will be reported.