Efficacy and Safety Study of Ontamalimab as Induction Therapy in Participants With Moderate to Severe Crohn's Disease (CARMEN CD 305)

• Register: ClinicalTrials.gov
• Last refreshed on: 22 March 2021
• Main ID: NCT03559517
• Date of registration: 09/05/2018
• Prospective Registration: Yes
• Primary sponsor: Shire
• Public title: Efficacy and Safety Study of Ontamalimab as Induction Therapy in Participants With Moderate to Severe Crohn's Disease (CARMEN CD 305) CARMEN CD 305
• Scientific title: A Phase 3 Randomized, Double-blind, Placebo-controlled, Parallel-group Efficacy and Safety Study of SHP647 as Induction Therapy in Subjects With Moderate to Severe Crohn's Disease (CARMEN CD 305)
• Date of first enrolment: June 25, 2018
• Target sample size: 30
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT03559517
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Australia, Austria, Croatia, Germany, Israel, Italy, Japan, Lithuania, Netherlands, Poland, Romania, Russian Federation, Serbia, South Africa, United Kingdom, United States

Contacts

• Name: Study Director
• Affiliation: Shire

Key inclusion & exclusion criteria

Inclusion Criteria:

- Participants must be between greater than or equal to (> =) 16 and less than or equal
to (<=) 80 years of age; participants less than (<) 18 years of age must weigh >=40 kg
and must have body mass index >=16.5 kilogram per meter square (kg/m^2)

- Participants must have active moderate to severe ileal (terminal ileum), ileocolic, or
colonic CD at baseline (Visit 2) as defined by:

1. CDAI score between 220 and 450 (inclusive) AND

2. Meeting the following subscores in the 2 item PRO:

i. Abdominal pain subscore >= 5 (average worst daily pain on the 11 point NRS) and
abdominal pain subscore >= 2 (average daily pain on the 4-point abdominal pain
variable of CDAI) over the 7 most recent days out of the 10 days before colonoscopy
preparation (may or may not be contiguous) AND/OR ii. Average of the daily stool
frequency subscore >=4 of type 6/7 (very soft stools/liquid stools) as shown in the
BSFS over the 7 most recent days out of the 10 days before colonoscopy preparation
(may or may not be contiguous) c. Presence of ulcerations that are characteristic to
CD, as determined by a colonoscopy performed during screening, and as defined by the
SES-CD >6 (SES CD >=4 for isolated ileitis) Note that the participant must be
confirmed as meeting the CDAI score and PRO subscore requirements before a colonoscopy
is done

- Participants must have a documented diagnosis (endoscopic with histology) of CD for
>=3 months before screening. Documented diagnosis is defined as:

1. A biopsy report in which the description of the histological findings is
consistent with the CD diagnosis AND

2. A report documenting disease duration based upon prior colonoscopy Note: If a
biopsy report is not available in the source document at the time of screening, a
biopsy must be performed during the screening colonoscopy and the histology
report should be consistent with the CD diagnosis. If the histology description
does not support the CD diagnosis at this time point, the participant should not
be randomized

- Participants must be willing and able to undergo a colonoscopy during screening after
all other inclusion criteria have been met

- Participants must have had an inadequate response to, or lost response to, or had an
intolerance to at least 1 conventional treatment such as sulfasalazine or mesalamine
(5-aminosalicylic acid [5-ASA]), glucocorticoids, or immunosuppressants (azathioprine
[AZA], 6-mercaptopurine [6-MP] or methotrexate [MTX]) or anti-tumor necrosis factor
(anti-TNF). Participants who have had an inadequate response to sulfasalazine or
mesalamine should have also failed at least 1 other conventional treatment such as
glucocorticoids

- Participants receiving any treatment(s) for CD are eligible provided they have been,
and are anticipated to be, on a stable dose for the designated period of time

- Participants are males or nonpregnant, nonlactating females who, if sexually active,
agree to comply with the contraceptive requirements of the protocol, or females of
nonchildbearing potential. Males and females of reproductive potential who are
sexually active must agree to use appropriate contraception (ie, highly effective
methods for female and medically appropriate methods for male study participants, for
the duration of the study

Exclusion criteria:

- Participants with indeterminate colitis, microscopic colitis, nonsteroidal
anti-inflammatory drug-induced colitis, ischemic colitis, infectious colitis, or
clinical/histologic findings suggestive of UC

- Participants with colonic dysplasia or neoplasia. (Participants with prior history of
adenomatous polyps will be eligible if the polyps have been completely removed)

- Participants with past medical history or presence of toxic megacolon

- Participants with presence of enterovesical (ie, between the bowel and urinary
bladder) or enterovaginal fistulae

- Participants with current symptomatic diverticulitis or diverticulosis

- Participants with clinically significant obstructive colonic stricture, or who have a
history of bowel surgery within 6 months before screening, or who are likely to
require surgery for CD during the treatment period. Participants who have undergone
previous colonic resection or ileocolectomy more than 6 months before screening must
have at least 25 cm of colon remaining

- Participants with past medical history of multiple small bowel resections resulting in
clinically significant short bowel syndrome

- Participants requiring total parenteral nutrition

- Participants with past medical history of bowel surgery resulting in an existing or
current stoma. Participants who had a j-pouch are excluded as a j-pouch could result
in a stoma

- Participants have had prior treatment with ontamalimab (formerly PF-00547659; SHP647)

- Participants with known or suspected intolerance or hypersensitivity to the
investigational product(s), closely related compounds, or any of the stated
ingredients

- Participants have received any nonbiologic treatment with immunomodulatory properties
(other than AZA, 6-MP, or MTX) or continuous antibiotics (>2 weeks) for the treatment
of CD within 30 days before baseline (Visit 2)

- Participants have received anti-TNF treatment within 60 days before baseline (Visit 2)

- Participants have received any biologic with immunomodulatory properties (other than
anti-TNFs) within 90 days before baseline (Visit 2)

- Participants have ever received anti-integrin/adhesion molecule treatment (eg,
natalizumab,vedolizumab, efalizumab, etrolizumab, or any other investigational
anti-integrin/adhesion molecule)

- Participants have received lymphocytes apheresis or selective monocyte granulocytes
apheresis within 60 days before baseline (Visit 2)

- Participants have received enteral nutrition treatment within 30 days before baseline
(Visit 2)

- Participants have received parenteral or rectal glucocorticoids or rectal 5-ASA within
14 days before screening colonoscopy

- Participants have taken >20 milligram per day(mg/day) of prednisone, >9 mg/day of
budesonide, or equivalent oral systemic corticosteroid dose within 14 days before
baseline (Visit 2) or have taken >=40 mg/day of prednisone or equivalent oral systemic
corticosteroid dose within 6 weeks before baseline (Visit 2)

- Participants have participated in other investigational stud


Age minimum: 16 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Crohn's Disease

Intervention(s)

Biological: Ontamalimab

Other: Placebo

Primary Outcome(s)

Number of Participants With Endoscopic Response at Week 16 [Time Frame: Week 16]

Number of Participants With Clinical Remission at Week 16 [Time Frame: Week 16]

Secondary Outcome(s)

Change From Baseline in Individual and Total Sign/Symptom Score Based on Participant Daily e-Diary Entries at Week 16 [Time Frame: Baseline, Week 16]

Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total (Absolute) Score [Time Frame: Baseline, Week 8, Week 12, up to Week 16, or early termination]

Change From Baseline in Short Form (SF)-36 at Week 16 [Time Frame: Baseline, Week 16]

Number of Participants With Clinical Remission and Endoscopic Response at Week 16 [Time Frame: Week 16]

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

Number of Participants With Clinical Remission by 2-item Patient Reported Outcome (PRO) at Week 16 [Time Frame: Week 16]

Number of Participants With Clinical Remission as Measured by Crohn's Disease Activity Index (CDAI) at Week 16 [Time Frame: Week 16]

Incidence of Hospitalizations [Time Frame: Baseline up to Week 32]

Number of Participants With Enhanced Endoscopic Response at Week 16 [Time Frame: Week 16]

Incidence of Crohn's Disease (CD)-related and Other Surgeries [Time Frame: Baseline up to Week 32]

Number of Participants With Clinical Remission Over Time [Time Frame: Baseline up to Week 16]

Number of Participants With Clinical Response as Measured by Crohn's Disease Activity Index (CDAI) -100 at Week 16 [Time Frame: Week 16]

Number of Participants With Endoscopic Healing at Week 16 [Time Frame: Week 16]

Number of Participants With Clinical Response as Measured by Crohn's Disease Activity Index (CDAI) -70 at Week 16 [Time Frame: Week 16]

Number of Participants With Clinical Response at Week 16 [Time Frame: Week 16]

Number of Participants With Complete Endoscopic Healing at Week 16 [Time Frame: Week 16]

Secondary ID(s)

SHP647-305

Source(s) of Monetary Support

Please refer to primary and secondary sponsors