a type of IBD that may affect any part of the gastroinestinal tract from mouth to anus Crohn's Disease
Conditions
Interventions
Sponsors
Shire
Eligibility
Age
12 Years to 99 Years
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study: 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 305 or SHP647 306 and met the following criteria at baseline in maintenance Study SHP647 307: a) Meet endoscopic response criteria of a reduction in the Simple Endoscopic Score for CD (SES-CD) from induction study (SHP647 305 or SHP647 306) baseline by *25% at Week 16 of induction study (SHP647 305 or 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 305 or 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 305 or SHP647 306) baseline. iii. A decrease of *30% and at least 2 points from induction study (SHP647 305 or 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 305 or 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 305 or 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 305 or 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 of the protocol 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: Subjects are excluded from the study if any of the following exclusion criteria are met: 1. Subjects who had major protocol deviation(s) (as determined by the sponsor) in induction study SHP647 305 or SHP647 306. 2. Subjects who permanently discontinued investigational product because of an adverse event (AE), regardless of relatedness to investigational product, in induction study SHP647 305 or 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 SHP647-305 or SHP647 306, females who are lactating, females who are planning to become pregnant during the study period, and males or females of childbearing potential not agreeing to continue using appropriate contraception methods (ie, highly effective methods for female subjects and medically appropriate methods for males, as described in Section 4.4 of the protocol) through the conclusion of study participation. 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, and 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 305 or 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 SHP647-305 or 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 305 or SHP647 306 studies. If the results are considered by the investigator to be transient and inconsistent with the subject*s clinical condition, may be r
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Coprimary: The coprimary objectives of the study are to evaluate the efficacy of ontamalimab as maintenance treatment in subjects with moderate to severe Crohn*s disease (CD) based on: * Clinical remission based on 2 item patient-reported outcome (PRO) (abdominal pain severity and very soft stool/liquid stool frequency) * Enhanced endoscopic response based on centrally read colonoscopy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Key secondary: * To evaluate the efficacy of ontamalimab as maintenance treatment on clinical remission as measured by Crohn's Disease Activity Index (CDAI) * To evaluate the efficacy of ontamalimab as maintenance treatment on glucocorticoid free clinical remission based on patient-reported clinical signs and symptoms (as measured by 2-item PRO) * To evaluate the efficacy of ontamalimab as maintenance treatment on clinical remission based on abdominal pain severity and very soft stool/liquid stool frequency (alternate thresholds) * To evaluate the efficacy of ontamalimab on maintenance of clinical remission among subjects in clinical remission at baseline of the SHP647-307 study based on patient-reported clinical signs and symptoms (as measured by 2-item PRO) * To evaluate the efficacy of ontamalimab on maintenance of enhanced endoscopic response among subjects with enhanced endoscopic response at baseline of the SHP647-307 study based on centrally read colonoscopy * To evaluate the efficacy of ontamalimab as maintenance treatment based on achieving clinical remission as well as achieving enhanced endoscopic response in the same subject * To evaluate the effect of ontamalimab as maintenance treatment on complete endoscopic healing. Other secondary: * To evaluate the safety and tolerability of ontamalimab as maintenance treatment * To evaluate the effect of ontamalimab as maintenance treatment on other clinical outcomes (2 item PRO based clinical response over time, 2-item PRO based and CDAI based clinical remission over time, and 2 item PRO based and CDAI based sustained clinical remission over time) * To evaluate the effect of ontamalimab on abdominal pain, very soft stool/liquid stool frequency (as shown by type 6/7 on Bristol Stool Form Scale [BSFS]), total stool frequency, rectal urgency, rectal bleeding, nausea, vomiting, and rectal incontinence * To evaluate the efficacy of ontamalimab as maintenance treatment on different grade | — |
Countries
Netherlands
Outcome results
None listed