Moderate to Severe Crohn Disease CD
Conditions
Interventions
This study consists of a 52-week, double-blind treatment period, followed by a 16-week safety follow-up period for subjects who either discontinue treatment early or complete the treatment period and
subjects who received 25 mg SHP647 in one of the induction studies will be randomized (1:1) to receive either 25 mg SHP647 or placebo
subjects who received 75 mg SHP647 in one of the induction studies will be randomized (1:1) to receive either 75 mg SHP647 or placebo.
Subjects who fulfill all eligibility criteria and who received placebo in the induction study will be randomized in a 2:2:1 ratio to receive 1 of 3 treatments (25 mg SHP647, 75 mg SHP647, or placebo,
Sponsors
Shire Human Genetic Therapies, Inc. ("Shire")
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Subjects and/or their parent or legally authorized representative must have an understanding, ability, and willingness to fully comply with study procedures and restrictions. 2. Subjects must be able to voluntarily provide written, signed, and dated (personally or via a legally authorized representative) informed consent and/or assent, as applicable, to participate in the study. 3. Subjects must have completed the 16-week induction treatment period from study SHP647-306 and met the following criteria at baseline in maintenance Study SHP647-307: a) Meet endoscopic response criteria of a reduction in SES-CD from induction study SHP647-306 baseline by =25% at Week 16 of induction study SHP647-306 OR b) Meet at least 1 of the following 4 criteria at baseline in maintenance study SHP647-307, in addition to no worsening of endoscopic score as measured by SES-CD relative to induction study SHP647-306 baseline: i. Achieving clinical remission as determined by meeting the criteria for clinical remission using the 2-item PRO, ie, 2-item PRO subscores of average worst daily abdominal pain =3 (based on 11-point numerical rating scale [NRS]) over the 7 most recent days* and average daily stool type frequency =2 of type 6/7 (very soft stools/liquid stools) as shown in the BSFS over the 7 most recent days* ii. A decrease of at least 100 points in CDAI score (CDAI-100) from induction study SHP647-306 baseline. iii. A decrease of =30% and at least 2 points from induction study SHP647-306 baseline in the average daily worst abdominal pain over the 7 most recent days*, with the average daily stool frequency of type 6/7 (very soft stools/liquid stools) either: (i) not worsening from induction study SHP647-306 baseline and/or (ii) meeting the criteria for clinical remission, ie, 2-item PRO subscore of average daily stool frequency =2 of type 6/7 (very soft stools/liquid stools) as shown in the BSFS over the 7 most recent days* iv. A decrease of =30% from induction study SHP647-306 baseline in the average daily stool frequency of type 6/7 (very soft stools/liquid stools) as shown in the BSFS over the 7 most recent days*, with the average daily worst abdominal pain either: (i) not worsening from induction study SHP647-306 baseline and/or (ii) meeting the criteria for clinical remission, ie, 2-item PRO subscore of average worst daily abdominal pain =3 (based on 11-point NRS) over the 7 most recent days* *Note: The 7 days may or may not be contiguous during the 10 days of data collection before colonoscopy preparation, depending on days to be excluded because of missing data. If fewer than 7 days are available, the criterion will be calculated on all available most recent 6 or 5 days. If fewer than 5 days are available, the criterion will be treated as missing. 4. Subjects receiving any treatment(s) for CD described in Section 5.2.1 are eligible provided they have been, and are anticipated to be, on a stable dose for the designated period of time.
Exclusion criteria
Exclusion criteria: 1. Subjects who had major protocol deviation(s) (as determined by the sponsor) in induction study SHP647-306. 2. Subjects who permanently discontinued investigational product because of an AE, regardless of relatedness to investigational product, in induction study SHP647-306. 3. Subjects who are likely to require surgery for CD during the study period, except minor interventions (eg, seton placement for anal fistulas). 4. Subjects are females who became pregnant during induction study SHP647-306, females who are planning to become pregnant during the study period, or males or females of childbearing potential not agreeing to continue using appropriate contraception methods through the conclusion of study participation (Section 4.4). 5. Subjects who do not agree to postpone donation of any organ or tissue, including male subjects who are planning to bank or donate sperm, or female subjects who are planning to harvest or donate eggs, for the duration of the study and through 16 weeks after last dose of investigational product. 6. Subjects who, in the opinion of the investigator or the sponsor, will be uncooperative or unable to comply with study procedures. 7. Subjects who have developed obstructive colonic stricture, or enterovesical or enterovaginal fistulae during the induction study SHP647-306. 8. Subjects who have a newly diagnosed malignancy or recurrence of malignancy (other than resected cutaneous basal cell carcinoma, squamous cell carcinoma, or carcinoma in situ of the uterine cervix that has been treated with no evidence of recurrence). 9. Subjects who have developed any major illness/condition or evidence of an unstable clinical condition (eg, renal, hepatic, hematologic, gastrointestinal [except disease under study], endocrine, cardiovascular, pulmonary, immunologic [eg, Felty’s syndrome], or local active infection/infectious illness) that, in the investigator’s judgment, will substantially increase the risk to the subject if he or she participates in the study. 10. Subjects with any other severe acute or chronic medical or psychiatric condition or laboratory or electrocardiogram (ECG) abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. 11. Subjects with known exposure to Mycobacterium tuberculosis since testing at screening in induction study SHP647-306 and who have been advised to require treatment for latent or active disease but who are without a generally accepted course of treatment. 12. Subjects with any of the following abnormalities in hematology and/or serum chemistry profiles during the evaluation of the last visit in the SHP647-306 study. If the results are considered by the investigator to be transient and inconsistent with the subject’s clinical condition, may be repeated once prior to enrolment in Study SHP647-307. ? Alanine aminotransferase and aspartate aminotransferase levels > ou = 3 × the upper limit of normal (ULN) ? Total bilirubin level > ou =1.5 × ULN or >2 × ULN if the subject has a known documented history of Gilbert’s syndrome ? Hemoglobin level ou = 1000 × 109/L (1,000,000 cells/mm3)* ? White blood cell count < ou = 3.5 × 109/L (3500 cells/mm3) ? Absolute neutrophil
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Name: Clinical remission;Timepoints: week 52;Measure: Clinical remission, as measured by a decrease below prespecified thresholds in the 2-item PRO (abdominal pain severity and very soft stool/liquid stool frequency [as shown in the BSFS]).;Name: Enhanced endoscopic response;Timepoints: week 52;Measure: Enhanced endoscopic response, as measured by a decrease in SES-CD. | — |
Secondary
| Measure | Time frame |
|---|---|
| Name: Clinical Remission defined by CDAI score;Timepoints: week 52 ;Measure: Clinical Remission defined by CDAI score at week 52;Name: Glucocorticoid-free Clinical Remission Based on Patient-reported Clinical Signs and Symptoms (2-item PRO);Timepoints: Week 52;Measure: Glucocorticoid-free Clinical Remission at week 52;Name: Clinical Remission Defined by Average Daily Abdominal Pain =1 (Based on the 4-point Scale) and Average Daily Stool Frequency =3 of Type 6/7;Timepoints: Week 52 ;Measure: Clinical Remission at week 52 ;Name: Clinical Remission Among Subjects in Clinical Remission at Baseline of the SHP647-307 Study, Based on Patient-reported Clinical Signs and Symptoms (2-Item PRO);Timepoints: Week 52 ;Measure: Clinical Remission at week 52 ;Name: Enhanced Endoscopic Response Among Subjects with Enhanced Endoscopic Response at Baseline of the SHP647-307 Study;Timepoints: Week 52;Measure: Enhanced Endoscopic Response at week 52;Name: Clinical Remission as Well as Enhanced Endoscopic Response in the Same Subject;Timepoints: Week 52;Measure: Clinical Remission as Well as Enhanced Endoscopic Response at week 52;Name: Complete Endoscopic Healing;Timepoints: week 52;Measure: Complete Endoscopic Healing at week 52 | — |
Countries
Australia, Austria, Belgium, Bosnia and Herzegovina, Bulgaria, Canada, Colombia, Croatia, Czech Republic, Democratic People Republic of Korea, Estonia, Germany, Hungary, Ireland, Italy, Japan, Lebanon, Lithuania, Mexico, Netherlands, New Zealand, Poland, Portugal, Republic of Serbia, Russian Federation, Slovakia, South Africa, Spain, Ukraine, United Kingdom, United States of America
Contacts
Public ContactAziz Zoghbi
CRO
Outcome results
None listed