A Phase 3 Randomized, Double-blind, Placebo-controlled, Parallel-group Efficacy and Safety Study of SHP647 as Maintenance Therapy in Subjects With Moderate to Severe Crohn's Disease (CARMEN CD 307)
A Phase 3 Randomized, Double-blind, Placebo-controlled, Parallel-group Efficacy and Safety Study of SHP647 as Maintenance Therapy in Subjects With Moderate to Severe Crohn's Disease (CARMEN CD 307)
The purpose of this study is to evaluate the efficacy and safety of ontamalimab as maintenance treatment in participants with moderate to severe Crohn's disease (CD).
Inclusion Criteria:
Participants and/or their parent or legally authorized representative (LAR) must have an understanding, ability, and willingness to fully comply with study procedures and restrictions.
Participants must be able to voluntarily provide written, signed, and dated (personally or via a LAR) informed consent and/or assent, as applicable, to participate in the study.
Participants must have completed the 16-week induction treatment period from study SHP647-305 (NCT03559517) or SHP647-306 (NCT03566823) and met the following criteria at baseline in maintenance study SHP647-307:
Achieving clinical remission as determined by meeting the criteria for clinical remission using the 2-item PRO, that is, 2-item PRO sub scores of average worst daily abdominal pain <=3 (based on 11-point 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 Bristol Stool Form Scale (BSFS) over the 7 most recent days*.
A decrease of at least 100 points in CDAI score (CDAI-100) from induction studies baseline.
A decrease of >=30% and at least 2 points from induction studies 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 studies baseline and/or (ii) meeting the criteria for clinical remission, that is, 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*.
A decrease of >=30% from induction studies SHP647-305 (NCT03559517) or SHP647-306 (NCT03566823) 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 studies SHP647-305 (NCT03559517) or SHP647-306 (NCT03566823) baseline and/or (ii) meeting the criteria for clinical remission, that is, 2-item PRO sub score 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.
Participants receiving any treatments for CD are eligible provided they have been, and are anticipated to be, on a stable dose for the designated period of time.
Exclusion Criteria:
Participants who had major protocol deviations (as determined by the sponsor) in induction studies SHP647-305 (NCT03559517) or SHP647-306 (NCT03566823).
Participants who permanently discontinued investigational product because of an AE, regardless of relatedness to investigational product, in induction studies SHP647-305 (NCT03559517) or SHP647-306 (NCT03566823).
Participants who are likely to require surgery for CD during the study period, except minor interventions (eg, seton placement for anal fistulas).
Participants are females who became pregnant during induction studies SHP647-305 (NCT03559517) or SHP647-306 (NCT03566823), females who are lactating, females who are planning to become pregnant during the study period, or males or females of childbearing potential not agreeing to continue acceptable contraception methods (ie, highly effective methods for female participants and medically appropriate methods for male participants) through the conclusion of study participation.
Participants who do not agree to postpone donation of any organ or tissue, including male participants who are planning to bank or donate sperm and female participants who are planning to harvest or donate eggs, for the duration of the study and through 16 weeks after last dose of investigational product.
Participants who, in the opinion of the investigator or the sponsor, will be uncooperative or unable to comply with study procedures.
Participants who have developed obstructive colonic stricture, or enterovesical or enterovaginal fistulae during the induction study SHP647-305 (NCT03559517) or SHP647-306 (NCT03566823).
Participants 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).
Participants who have developed any major illness/condition or evidence of an unstable clinical condition (example [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 participant if he or she participates in the study.
Participants with any other severe acute or chronic medical or psychiatric condition or laboratory or 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 participant inappropriate for entry into this study.
Participants with known exposure to Mycobacterium tuberculosis (TB) since testing at screening in induction studies SHP647-305 (NCT03559517) or SHP647-306 (NCT03566823) and who have been advised to require treatment for latent or active disease but who are without a generally accepted course of treatment.
Participants with any of the following abnormalities in hematology and/or serum chemistry profiles during the evaluation of the last visit in the induction studies SHP647-305 (NCT03559517) or SHP647-306 (NCT03566823). If the results are considered by the investigator to be transient and inconsistent with the participant's clinical condition, may be repeated once prior to enrollment in Study SHP647-307.
Alanine aminotransferase (ALT) and aspartate aminotransferase levels >= 3.0 × the upper limit of normal (ULN).
Total bilirubin level >=1.5 × ULN or >2.0 × ULN if the participant has a known documented history of Gilbert's syndrome.
Hemoglobin level <=80 gram per liter (g/L) (8.0 gram per deciliter [g/dL]).
Platelet count <=100 × 10^9/L (100,000 cells per cubic millimeter [mm^3]) or >=1000 × 10^9/L (1,000,000 cells/mm^3).
White blood cell count <=3.5 × 10^9/L (3500 cells/mm^3).
Absolute neutrophil count<2 × 10^9/L (<2000 cells/mm^3)
Serum creatinine level >1.5 × ULN or estimated glomerular filtration rate <30 milliliter per minute (mL/min)/1.73 m^2 based on the abbreviated Modification of Diet in Renal Disease Study Equation.
Participants who are investigational site staff members or relatives of those site staff members or participants who are sponsor employees directly involved in the conduct of the study.
Participants who are participating in other investigational studies (other than induction studies SHP647-305 [NCT03559517] or SHP647-306 [NCT03566823]) or plan to participate in other investigational studies during this study.
Garland, Texas 75044, United States
Webster, Texas 77598, United States
Sofia, Sofia-Grad 1784, Bulgaria
Sofia, 1527, Bulgaria
Berlin-Zehlendorf, 14163, Germany
Paliao Faliro, 17562, Greece
Nishinomiya-shi, Hyôgo 663-8501, Japan
Minato-ku, Tokyo 105-8471, Japan
Kurume-shi, 839-0809, Japan
Shimotsuga-gun, 321-0293, Japan
Torun, Kuyavian-Pomeranian Voivodeship 87-100, Poland
Włocławek, Kuyavian-Pomeranian Voivodeship 87-800, Poland
Lódz, Lódzkie 90-302, Poland
Lódz, Lódzkie 90-647, Poland
Warsaw, Masovian Voivodeship 02-781, Poland
Szczecin, West Pomeranian Voivodeship 71-434, Poland
Poznan, 60-848, Poland
Gmina Końskie, Świętokrzyskie Voivodeship 26-200, Poland
Chernivtsi, Chernivtsi Oblast 58001, Ukraine
Kharkiv, Kharkiv Oblast 61037, Ukraine
Kyiv, Kyïv 04107, Ukraine
Kharkiv, 61058, Ukraine
Kherson, 73000, Ukraine