Efficacy and Safety Study of Ontamalimab as Maintenance Treatment in Participants With Moderate to Severe Crohn's Disease (CARMEN CD 307)
Condition: Crohn's Disease
MeSH terms: Crohn Disease
Intervention: Ontamalimab; Placebo
Intervention description: SC injection of 25 mg or 75 mg ontamalimab will be administered using a prefilled syringe.; SC injection of placebo matched with ontamalimab will be administered using a prefilled syringe.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 40.0
Sex: All
Minimum age: 16 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Crohn's disease

Summary:

      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).
    

Eligibility criteria:

        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:

               1. Meet endoscopic response criteria of a reduction in SES-CD from induction studies
                  SHP647-305 (NCT03559517) or SHP647-306 (NCT03566823) baseline by greater than or
                  equal to >=25% at Week 16 of induction studies SHP647-305 (NCT03559517) or
                  SHP647-306 (NCT03566823) or

               2. 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 studies SHP647-305 (NCT03559517) or SHP647-306
                  (NCT03566823) baseline:

          -  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.

               1. Alanine aminotransferase (ALT) and aspartate aminotransferase levels >= 3.0 × the
                  upper limit of normal (ULN).

               2. Total bilirubin level >=1.5 × ULN or >2.0 × ULN if the participant has a known
                  documented history of Gilbert's syndrome.

               3. Hemoglobin level <=80 gram per liter (g/L) (8.0 gram per deciliter [g/dL]).

               4. 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).

               5. White blood cell count <=3.5 × 10^9/L (3500 cells/mm^3).

               6. Absolute neutrophil count<2 × 10^9/L (<2000 cells/mm^3)

               7. 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.

                    -  Note: If platelet count is <150,000 cells/mm^3, a further evaluation should
                       be performed to rule out cirrhosis, unless another etiology has already been
                       identified.

          -  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.