Crohn's Disease
Conditions
Keywords
Crohn's disease
Brief 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).
Interventions
DRUGOntamalimab
SC injection of 25 mg or 75 mg ontamalimab will be administered using a prefilled syringe.
OTHERPlacebo
SC injection of placebo matched with ontamalimab will be administered using a prefilled syringe.
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
16 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Remission at Week 52 | At Week 52 | Clinical remission was defined by 2-item PRO sub-scores of average worst daily abdominal pain less than or equal to (\<=) 3 (based on 11 point numerical rating scale \[NRS\] ranging from 0 \[no pain\] to 10 \[worst imaginable pain\]); and average daily stool frequency \<=2 of type 6/7 (very soft stools/liquid stools) as per the Bristol Stool Form Scale (BSFS) over the 7 most recent days. BSFS ranges from 1 (separate hard lumps, hard to pass), 2 (sausage-shaped, but lumpy), 3 (like a sausage but with cracks on the surface), 4 (like a sausage or snake, smooth and soft), 5 (soft blobs with clear-cut edges), 6 (fluffy pieces with ragged edges, a mushy stool), 7 (watery, no solid pieces, entirely liquid). Participants with missing data at Week 52 or discontinuation before Week 52 were considered failures. Number of participants with clinical remission at Week 52 were reported. |
| Number of Participants With Enhanced Endoscopic Response at Week 52 | At Week 52 | Enhanced endoscopic response was defined as a decrease in Simple Endoscopic Score for Crohn's disease (SES-CD) of at least 50 percent (%) from induction study (either SHP647-305 \[NCT03559517\] or SHP647-306 \[NCT03566823\] baseline. The SES-CD considers ileum, right colon, transverse colon, left colon, rectum in terms of: size of ulcers, ulcerated surface, affected surface and presence of narrowing. Each graded from 0-3. Scale ranges from 0-56 with a higher score indicating greater severity of disease. Participants with missing data at Week 52 or who discontinued before Week 52 were considered non responders. Number of participants with enhanced endoscopic response at Week 52 were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Remission Defined by Crohn's Disease (CD) E-diary Sub-scores- at Week 52 | At Week 52 | Clinical remission was defined by CD daily e-diary 2-item PRO subscores of average daily abdominal pain \<=1 (based on the 4 point scale, with scores ranging from 0 \[none\] to 3 \[severe\]) over the 7 most recent days and average daily stool frequency \<=3 of type 6/7 (very soft stools/liquid stools) as per the BSFS over the 7 most recent days. BSFS ranges from 1 (separate hard lumps, hard to pass), 2 (sausage-shaped, but lumpy), 3 (like a sausage but with cracks on the surface), 4 (like a sausage or snake, smooth and soft), 5 (soft blobs with clear-cut edges), 6 (fluffy pieces with ragged edges, a mushy stool), 7 (watery, no solid pieces, entirely liquid). Participants with missing data at Week 52 or who discontinued before Week 52 were considered failures. Number of participants with clinical remission based on Crohn's Disease (CD) e-diary Sub-scores for abdominal pain was was reported. |
| Number of Participants With Sustained Clinical Remission at Week 52 | At Week 52 | Sustained clinical remission was defined as clinical remission by 2-item PRO at both Week 52 visit and the maintenance baseline in this Study. Clinical remission was defined by 2-item PRO sub-scores of average worst daily abdominal pain less than or equal to (\<=) 3 (based on 11 point NRS ranging from 0 \[no pain\] to 10 \[worst imaginable pain\]); and average daily stool frequency \<=2 of type 6/7 (very soft stools/liquid stools) as per the BSFS over the 7 most recent days. BSFS ranges from 1 (separate hard lumps, hard to pass), 2 (sausage-shaped, but lumpy), 3 (like a sausage but with cracks on the surface), 4 (like a sausage or snake, smooth and soft), 5 (soft blobs with clear-cut edges), 6 (fluffy pieces with ragged edges, a mushy stool), 7 (watery, no solid pieces, entirely liquid). Number of participants with sustained clinical remission at Week 52 were reported. |
| Number of Participants With Clinical Remission Based on Crohn's Disease Activity Index (CDAI) Score at Week 52 | At Week 52 | Clinical remission was defined as a CDAI score of \<150. CDAI assessed CD based on clinical signs/symptoms such as number of liquid stools, intensity of abdominal pain, general well-being (subjective), and presence of complications, use of antidiarrheal, presence of abdominal mass, physical examination and hematocrit (objective). CDAI score is equal to sum of weighted scores for subjective and objective items which range from 0-149 points: asymptomatic remission, 150-220 points: mild to moderate active CD, 221-450 points: moderate to severe active CD, \>451 points: severely active to fulminant disease. Higher score indicating more severity. Participants with missing data at Week 52 or who discontinued before Week 52 were considered failures. Number of participants with clinical remission as measured by CDAI at Week 52 were reported. |
| Number of Participants With Clinical Remission Based on 2-item PRO With Enhanced Endoscopic Response at Week 52 | At Week 52 | Clinical remission was defined by 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 frequency \<= 2 of Type 6/7 (very soft stools/liquid stools) as shown in the BSFS over the 7 most recent days. Participants with missing data at Week 52 or who discontinued before Week 52 were considered failures. Enhanced endoscopic response was defined as a decrease in SES-CD of at least 50% from induction study (either SHP647-305 \[NCT03559517\] or SHP647-306 \[NCT03566823\]) baseline. Participants with missing data at Week 52 or who discontinued before Week 52 were considered non-responders. |
| Number of Participants With Complete Endoscopic Healing at Week 52 | At Week 52 | Complete endoscopic healing was defined as SES-CD scale score from 0-2. The SES-CD considers ileum, right colon, transverse colon, left colon, rectum in terms of: size of ulcers, ulcerated surface, affected surface and presence of narrowing. Each graded from 0-3. Scale ranges from 0-56 with a higher score indicating greater severity of disease. Participants with missing data at Week 52 or who discontinued before Week 52 were considered failures. Number of participants with complete endoscopic healing at Week 52 were reported. |
| Number of Participants With Sustained Enhanced Endoscopic Response at Week 52 | At Week 52 | Sustained enhanced endoscopic response was defined as enhanced endoscopic response at both Week 52 visit and the maintenance baseline in this study. Enhanced endoscopic response was defined as a decrease in SES-CD of at least 50 % from induction study (either SHP647-305 \[NCT03559517\] or SHP647-306 \[NCT03566823\]) baseline. The SES-CD considers ileum, right colon, transverse colon, left colon, rectum in terms of: size of ulcers, ulcerated surface, affected surface and presence of narrowing. Each graded from 0-3. Scale ranges from 0-56 with a higher score indicating greater severity of disease. Number of participants with sustained enhanced endoscopic response at Week 52 were reported. |
| Number of Participants With Glucocorticoid-free Clinical Remission at Week 52 | At Week 52 | Glucocorticoid-free clinical remission defined as clinical remission by 2-item PRO not requiring any treatment with glucocorticoids for at least 12 weeks prior to Week 52 visit. Clinical remission defined by 2-item PRO sub-scores of average worst daily abdominal pain \<=3 (based on 11 point NRS ranging from 0 \[no pain\] to 10 \[worst imaginable pain\]); and average daily stool frequency\<=2 of type 6/7 (very soft stools/liquid stools) as per the BSFS over the 7 most recent days. BSFS ranges from 1 (separate hard lumps, hard to pass), 2 (sausage-shaped, but lumpy), 3 (like a sausage but with cracks on the surface), 4 (like sausage or snake, smooth and soft), 5 (soft blobs with clear-cut edges), 6 (fluffy pieces with ragged edges, mushy stool), 7 (watery, no solid pieces, entirely liquid). Participants with missing data at Week 52 or who discontinued before Week 52 were non-responders. Number of participants with glucocorticoid-free clinical remission response at Week 52 were reported. |
Countries
Argentina, Australia, Austria, Belgium, Bosnia and Herzegovina, Bulgaria, Colombia, Croatia, Estonia, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Lebanon, Lithuania, Mexico, Netherlands, New Zealand, Poland, Portugal, Romania, Russia, Serbia, Slovakia, South Africa, South Korea, Spain, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 33 sites between 06 February 2019 (first participant first visit) and 13 September 2021 (last participant last visit). 278 sites were initiated in this study, but only 33 sites had enrolled participants.
Pre-assignment details
A total of 40 participants with moderate to severe Crohn's disease (CD) who completed their participation in an induction study (either SHP647-305 \[NCT03559517\] or SHP647-306 \[NCT03566823\]) and fulfilled the efficacy entry criteria of this study, including achieving endoscopic and/or clinical response were enrolled and received study treatment in this study. The study was closed early due to discontinuation of the ontamalimab clinical trial program.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received matched placebo of ontamalimab subcutaneous (SC) injection using prefilled syringe on Day 1 Baseline Visit (Week 16 of the SHP647-305 \[NCT03559517\] or SHP647-306 \[NCT03566823\]) once every 4 weeks for up to 52 weeks. | 19 |
| Ontamalimab 25 mg Participants received 25 mg ontamalimab SC injection, using prefilled syringe on Day 1 Baseline Visit (Week 16 of the SHP647-305 \[NCT03559517\] or SHP647-306 \[NCT03566823\]) once every 4 weeks for up to 52 weeks. | 10 |
| Experimental: Ontamalimab 75 mg Participants received 75 mg ontamalimab SC injection, using prefilled syringe on Day 1 Baseline Visit (Week 16 of the SHP647-305 \[NCT03559517\] or SHP647-306 \[NCT03566823\]) once every 4 weeks for up to 52 weeks. | 11 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 2 |
| Overall Study | Disease relapse | 7 | 5 | 1 |
| Overall Study | Other | 1 | 0 | 0 |
| Overall Study | Physician Decision | 2 | 0 | 0 |
| Overall Study | Site terminated by sponsor | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 2 |
Baseline characteristics
| Characteristic | Placebo | Ontamalimab 25 mg | Experimental: Ontamalimab 75 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 37.7 Years STANDARD_DEVIATION 14.26 | 38.4 Years STANDARD_DEVIATION 7.18 | 45.8 Years STANDARD_DEVIATION 14.85 | 40.1 Years STANDARD_DEVIATION 13.23 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 8 Participants | 10 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 17 Participants | 8 Participants | 10 Participants | 35 Participants |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 5 Participants | 18 Participants |
| Sex: Female, Male Male | 12 Participants | 4 Participants | 6 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 10 | 0 / 11 |
| other Total, other adverse events | 9 / 19 | 5 / 10 | 8 / 11 |
| serious Total, serious adverse events | 1 / 19 | 0 / 10 | 2 / 11 |
Outcome results
Primary
Number of Participants With Clinical Remission at Week 52
Clinical remission was defined by 2-item PRO sub-scores of average worst daily abdominal pain less than or equal to (\<=) 3 (based on 11 point numerical rating scale \[NRS\] ranging from 0 \[no pain\] to 10 \[worst imaginable pain\]); and average daily stool frequency \<=2 of type 6/7 (very soft stools/liquid stools) as per the Bristol Stool Form Scale (BSFS) over the 7 most recent days. BSFS ranges from 1 (separate hard lumps, hard to pass), 2 (sausage-shaped, but lumpy), 3 (like a sausage but with cracks on the surface), 4 (like a sausage or snake, smooth and soft), 5 (soft blobs with clear-cut edges), 6 (fluffy pieces with ragged edges, a mushy stool), 7 (watery, no solid pieces, entirely liquid). Participants with missing data at Week 52 or discontinuation before Week 52 were considered failures. Number of participants with clinical remission at Week 52 were reported.
Time frame: At Week 52
Population: The full analysis set (FAS) consisted of all participants in the randomized set who had received at least 1 dose of investigational product (IP) in the SHP647-307 study regardless of treatment received during the induction studies (either SHP647-305 \[NCT03559517\] or SHP647-306 \[NCT03566823\]).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinical Remission at Week 52 | 2 Participants |
| Ontamalimab 25 mg | Number of Participants With Clinical Remission at Week 52 | 3 Participants |
| Ontamalimab 75 mg | Number of Participants With Clinical Remission at Week 52 | 5 Participants |
Primary
Number of Participants With Enhanced Endoscopic Response at Week 52
Enhanced endoscopic response was defined as a decrease in Simple Endoscopic Score for Crohn's disease (SES-CD) of at least 50 percent (%) from induction study (either SHP647-305 \[NCT03559517\] or SHP647-306 \[NCT03566823\] baseline. The SES-CD considers ileum, right colon, transverse colon, left colon, rectum in terms of: size of ulcers, ulcerated surface, affected surface and presence of narrowing. Each graded from 0-3. Scale ranges from 0-56 with a higher score indicating greater severity of disease. Participants with missing data at Week 52 or who discontinued before Week 52 were considered non responders. Number of participants with enhanced endoscopic response at Week 52 were reported.
Time frame: At Week 52
Population: The FAS consisted of all participants in the randomized set who had received at least 1 dose of IP in the SHP647-307 study regardless of treatment received during the induction studies (either SHP647-305 \[NCT03559517\] or SHP647-306 \[NCT03566823\]).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Enhanced Endoscopic Response at Week 52 | 2 Participants |
| Ontamalimab 25 mg | Number of Participants With Enhanced Endoscopic Response at Week 52 | 4 Participants |
| Ontamalimab 75 mg | Number of Participants With Enhanced Endoscopic Response at Week 52 | 6 Participants |
Secondary
Number of Participants With Clinical Remission Based on 2-item PRO With Enhanced Endoscopic Response at Week 52
Clinical remission was defined by 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 frequency \<= 2 of Type 6/7 (very soft stools/liquid stools) as shown in the BSFS over the 7 most recent days. Participants with missing data at Week 52 or who discontinued before Week 52 were considered failures. Enhanced endoscopic response was defined as a decrease in SES-CD of at least 50% from induction study (either SHP647-305 \[NCT03559517\] or SHP647-306 \[NCT03566823\]) baseline. Participants with missing data at Week 52 or who discontinued before Week 52 were considered non-responders.
Time frame: At Week 52
Population: The FAS consisted of all participants in the randomized set who had received at least 1 dose of IP in the SHP647-307 study regardless of treatment received during the induction studies (either SHP647-305 \[NCT03559517\] or SHP647-306 \[NCT03566823\]).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinical Remission Based on 2-item PRO With Enhanced Endoscopic Response at Week 52 | 0 Participants |
| Ontamalimab 25 mg | Number of Participants With Clinical Remission Based on 2-item PRO With Enhanced Endoscopic Response at Week 52 | 3 Participants |
| Ontamalimab 75 mg | Number of Participants With Clinical Remission Based on 2-item PRO With Enhanced Endoscopic Response at Week 52 | 4 Participants |
Secondary
Number of Participants With Clinical Remission Based on Crohn's Disease Activity Index (CDAI) Score at Week 52
Clinical remission was defined as a CDAI score of \<150. CDAI assessed CD based on clinical signs/symptoms such as number of liquid stools, intensity of abdominal pain, general well-being (subjective), and presence of complications, use of antidiarrheal, presence of abdominal mass, physical examination and hematocrit (objective). CDAI score is equal to sum of weighted scores for subjective and objective items which range from 0-149 points: asymptomatic remission, 150-220 points: mild to moderate active CD, 221-450 points: moderate to severe active CD, \>451 points: severely active to fulminant disease. Higher score indicating more severity. Participants with missing data at Week 52 or who discontinued before Week 52 were considered failures. Number of participants with clinical remission as measured by CDAI at Week 52 were reported.
Time frame: At Week 52
Population: The FAS consisted of all participants in the randomized set who had received at least 1 dose of IP in the SHP647-307 study regardless of treatment received during the induction studies (either SHP647-305 \[NCT03559517\] or SHP647-306 \[NCT03566823\]).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinical Remission Based on Crohn's Disease Activity Index (CDAI) Score at Week 52 | 8 Participants |
| Ontamalimab 25 mg | Number of Participants With Clinical Remission Based on Crohn's Disease Activity Index (CDAI) Score at Week 52 | 4 Participants |
| Ontamalimab 75 mg | Number of Participants With Clinical Remission Based on Crohn's Disease Activity Index (CDAI) Score at Week 52 | 7 Participants |
Secondary
Number of Participants With Clinical Remission Defined by Crohn's Disease (CD) E-diary Sub-scores- at Week 52
Clinical remission was defined by CD daily e-diary 2-item PRO subscores of average daily abdominal pain \<=1 (based on the 4 point scale, with scores ranging from 0 \[none\] to 3 \[severe\]) over the 7 most recent days and average daily stool frequency \<=3 of type 6/7 (very soft stools/liquid stools) as per the BSFS over the 7 most recent days. BSFS ranges from 1 (separate hard lumps, hard to pass), 2 (sausage-shaped, but lumpy), 3 (like a sausage but with cracks on the surface), 4 (like a sausage or snake, smooth and soft), 5 (soft blobs with clear-cut edges), 6 (fluffy pieces with ragged edges, a mushy stool), 7 (watery, no solid pieces, entirely liquid). Participants with missing data at Week 52 or who discontinued before Week 52 were considered failures. Number of participants with clinical remission based on Crohn's Disease (CD) e-diary Sub-scores for abdominal pain was was reported.
Time frame: At Week 52
Population: The FAS consisted of all participants in the randomized set who had received at least 1 dose of IP in the SHP647-307 study regardless of treatment received during the induction studies (either SHP647-305 \[NCT03559517\] or SHP647-306 \[NCT03566823\]).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinical Remission Defined by Crohn's Disease (CD) E-diary Sub-scores- at Week 52 | 2 Participants |
| Ontamalimab 25 mg | Number of Participants With Clinical Remission Defined by Crohn's Disease (CD) E-diary Sub-scores- at Week 52 | 3 Participants |
| Ontamalimab 75 mg | Number of Participants With Clinical Remission Defined by Crohn's Disease (CD) E-diary Sub-scores- at Week 52 | 7 Participants |
Secondary
Number of Participants With Complete Endoscopic Healing at Week 52
Complete endoscopic healing was defined as SES-CD scale score from 0-2. The SES-CD considers ileum, right colon, transverse colon, left colon, rectum in terms of: size of ulcers, ulcerated surface, affected surface and presence of narrowing. Each graded from 0-3. Scale ranges from 0-56 with a higher score indicating greater severity of disease. Participants with missing data at Week 52 or who discontinued before Week 52 were considered failures. Number of participants with complete endoscopic healing at Week 52 were reported.
Time frame: At Week 52
Population: The FAS consisted of all participants in the randomized set who had received at least 1 dose of IP in the SHP647-307 study regardless of treatment received during the induction studies (either SHP647-305 \[NCT03559517\] or SHP647-306 \[NCT03566823\]).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Complete Endoscopic Healing at Week 52 | 0 Participants |
| Ontamalimab 25 mg | Number of Participants With Complete Endoscopic Healing at Week 52 | 3 Participants |
| Ontamalimab 75 mg | Number of Participants With Complete Endoscopic Healing at Week 52 | 3 Participants |
Secondary
Number of Participants With Glucocorticoid-free Clinical Remission at Week 52
Glucocorticoid-free clinical remission defined as clinical remission by 2-item PRO not requiring any treatment with glucocorticoids for at least 12 weeks prior to Week 52 visit. Clinical remission defined by 2-item PRO sub-scores of average worst daily abdominal pain \<=3 (based on 11 point NRS ranging from 0 \[no pain\] to 10 \[worst imaginable pain\]); and average daily stool frequency\<=2 of type 6/7 (very soft stools/liquid stools) as per the BSFS over the 7 most recent days. BSFS ranges from 1 (separate hard lumps, hard to pass), 2 (sausage-shaped, but lumpy), 3 (like a sausage but with cracks on the surface), 4 (like sausage or snake, smooth and soft), 5 (soft blobs with clear-cut edges), 6 (fluffy pieces with ragged edges, mushy stool), 7 (watery, no solid pieces, entirely liquid). Participants with missing data at Week 52 or who discontinued before Week 52 were non-responders. Number of participants with glucocorticoid-free clinical remission response at Week 52 were reported.
Time frame: At Week 52
Population: The FAS consisted of all participants in the randomized set who had received at least 1 dose of IP in the SHP647-307 study regardless of treatment received during the induction studies (either SHP647-305 \[NCT03559517\] or SHP647-306 \[NCT03566823\]).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Glucocorticoid-free Clinical Remission at Week 52 | 2 Participants |
| Ontamalimab 25 mg | Number of Participants With Glucocorticoid-free Clinical Remission at Week 52 | 1 Participants |
| Ontamalimab 75 mg | Number of Participants With Glucocorticoid-free Clinical Remission at Week 52 | 3 Participants |
Secondary
Number of Participants With Sustained Clinical Remission at Week 52
Sustained clinical remission was defined as clinical remission by 2-item PRO at both Week 52 visit and the maintenance baseline in this Study. Clinical remission was defined by 2-item PRO sub-scores of average worst daily abdominal pain less than or equal to (\<=) 3 (based on 11 point NRS ranging from 0 \[no pain\] to 10 \[worst imaginable pain\]); and average daily stool frequency \<=2 of type 6/7 (very soft stools/liquid stools) as per the BSFS over the 7 most recent days. BSFS ranges from 1 (separate hard lumps, hard to pass), 2 (sausage-shaped, but lumpy), 3 (like a sausage but with cracks on the surface), 4 (like a sausage or snake, smooth and soft), 5 (soft blobs with clear-cut edges), 6 (fluffy pieces with ragged edges, a mushy stool), 7 (watery, no solid pieces, entirely liquid). Number of participants with sustained clinical remission at Week 52 were reported.
Time frame: At Week 52
Population: The FAS consisted of all participants in the randomized set who had received at least 1 dose of IP in the SHP647-307 study regardless of treatment received during the induction studies (either SHP647-305 \[NCT03559517\] or SHP647-306 \[NCT03566823\]).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Sustained Clinical Remission at Week 52 | 2 Participants |
| Ontamalimab 25 mg | Number of Participants With Sustained Clinical Remission at Week 52 | 1 Participants |
| Ontamalimab 75 mg | Number of Participants With Sustained Clinical Remission at Week 52 | 2 Participants |
Secondary
Number of Participants With Sustained Enhanced Endoscopic Response at Week 52
Sustained enhanced endoscopic response was defined as enhanced endoscopic response at both Week 52 visit and the maintenance baseline in this study. Enhanced endoscopic response was defined as a decrease in SES-CD of at least 50 % from induction study (either SHP647-305 \[NCT03559517\] or SHP647-306 \[NCT03566823\]) baseline. The SES-CD considers ileum, right colon, transverse colon, left colon, rectum in terms of: size of ulcers, ulcerated surface, affected surface and presence of narrowing. Each graded from 0-3. Scale ranges from 0-56 with a higher score indicating greater severity of disease. Number of participants with sustained enhanced endoscopic response at Week 52 were reported.
Time frame: At Week 52
Population: The FAS consisted of all participants in the randomized set who had received at least 1 dose of IP in the SHP647-307 study regardless of treatment received during the induction studies (either SHP647-305 \[NCT03559517\] or SHP647-306 \[NCT03566823\]).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Sustained Enhanced Endoscopic Response at Week 52 | 1 Participants |
| Ontamalimab 25 mg | Number of Participants With Sustained Enhanced Endoscopic Response at Week 52 | 2 Participants |
| Ontamalimab 75 mg | Number of Participants With Sustained Enhanced Endoscopic Response at Week 52 | 3 Participants |