A Safety Extension Study of Ontamalimab in Participants With Moderate to Severe Ulcerative Colitis or Crohn's Disease (AIDA)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of long-term treatment with ontamalimab in participants with moderate to severe Ulcerative Colitis (UC) or Crohn's disease (CD)

Official Title
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A Phase 3 Long-term Safety Extension Study of SHP647 in Subjects With Moderate to Severe Ulcerative Colitis or Crohn's Disease (AIDA)

Conditions
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Ulcerative Colitis, Crohn's Disease

Intervention / Treatment
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* Drug: 25 mg Ontamalimab
* Drug: 75 mg Ontamalimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with Ulcerative Colitis (UC): Participants and/or their parent or legally authorized representative 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 legally authorized representative) informed consent and/or assent, as applicable, to participate in the study. Participants must have been enrolled previously in study SHP647-301 (NCT03259334), SHP647-302 (NCT03259308), and are in the treatment period of Study SHP647-303, completed the early termination (ET) or Week 52 visit in maintenance study SHP647-303 (NCT03290781), had responded to ontamalimab treatment (in the induction and/or maintenance studies), and meet one of the following criteria: a. Participants are on placebo at the maintenance study ET or Week 52 visit: they received ontamalimab in the induction studies and fulfilled the maintenance study response criteria, OR b. Participants have received ontamalimab at the maintenance study ET or Week 52 visit: i) Clinical composite score that has decreased by >or=2 points and >or=30%, with an accompanying decrease in the subscore for RB >or=1 point or a subscore for RB <or=1, compared to the baseline value for induction studies, and/or ii) Composite score that has decreased by >or=30% and >or=3 points compared to the baseline value for induction studies. Participants receiving any treatment(s) for UC are eligible provided they have been on a stable dose for the designated period of time. Participants with Crohn's Disease: Participants and/or their parent or legally authorized representative 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 legally authorized representative) informed consent and/or assent, as applicable, to participate in the study. Participants must have been enrolled previously in Study SHP647-305 (NCT03559517) or SHP647-306 (NCT03566823) and are in the treament period of Study SHP647-307 (NCT03627091), completed the ET or Week 52 visit in maintenance study SHP647-307, had responded to ontamalimab treatment (in the induction or maintenance studies) and meet one of the following criteria: Participants are on placebo at the maintenance study ET or Week 52 visit: they received ontamalimab in the induction study and fulfilled the maintenance study response criteria, OR Participants have received ontamalimab at the maintenance study ET or Week 52 visit: i) CDAI score that has decreased by >or=100 points at EOT visit compared to the baseline value for induction studies, and/or ii) SES-CD that has decreased by >or=25% compared to the baseline value for induction studies. Participants receiving any treatment(s) for CD are eligible provided they have been on a stable dose for the designated period of time. Exclusion Criteria: Participants with UC: Participants who had major protocol deviation(s) (as determined by the sponsor) in study SHP647-301, SHP647-302, or SHP647-303. Participants who permanently discontinued investigational product because of an AE, regardless of relatedness to investigational product, in study SHP647-301, SHP647-302, or SHP647-303. Participants who are likely to require major surgery for UC. Participants are females who became pregnant during study SHP647-301, SHP647-302, or SHP647-303, 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 using appropriate contraception methods (i.e. highly effective methods for female and medically appropriate methods for male study 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 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 [e.g.], renal, hepatic, hematologic, gastrointestinal [except disease under study], endocrine, cardiovascular, pulmonary, immunologic [e.g. 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 study SHP647-301 (NCT03259334) or SHP647-302 (NCT03259308) and who have been advised to require treatment for latent or active disease, but who are without a generally accepted course of treatment. 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 SHP647-301, SHP647-302, or SHP647-303) or plan to participate in other investigational studies during long-term extension study SHP647-304. Participants with Crohn's Disease: Participants who had major protocol deviation(s) (as determined by the sponsor) in study SHP647-305, SHP647-306 or SHP647-307. Participants who permanently discontinued investigational product because of an adverse events (AE), regardless of relatedness to investigational product, in study SHP647-305, SHP647-306 or SHP647-307. Participants who are likely to require major surgery for CD or developed acute severe complications of CD (with or without fulfilling the treatment failure criteria in the maintenance study) that required immediate intervention (e.g. need for immediate biologic treatment with proven effect) and/or Crohn's Disease Activity Index (CDAI) score more than (>) 450. Participants are females who became pregnant during study SHP647-305, SHP647-306 or SHP647-307, 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 appropriate contraception methods (i.e. highly effective methods for female and medically appropriate methods for male study 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.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 25 mg Ontamalimab<br>Participants will be receiving 25 milligram (mg) of ontamalimab solution for injection subcutaneously (SC) every 4 weeks until the participant withdraws from the study, or the investigator or sponsor decide to withdraw the participant, or the sponsor decides to close the study, or the program is stopped. | Drug: 25 mg Ontamalimab<br>* Ontamalimab sterile aqueous buffered solution will be administered in dose of 25 mg subcutaneously.<br>* Other names: SHP647;|
| Experimental: 75 mg Ontamalimab<br>Participants will be receiving 75 mg of ontamalimab solution for injection SC every 4 weeks until the participant withdraws from the study, or the investigator or sponsor decide to withdraw the participant, or the sponsor decides to close the study, or the program is stopped. | Drug: 75 mg Ontamalimab<br>* Ontamalimab sterile aqueous buffered solution will be administered in dose of 75 mg subcutaneously.<br>* Other names: PF-00547659;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent AEs (TEAEs) are defined as AEs with start dates or worsening dates at the time of or following the first exposure to investigational product. The TEAEs will be further categorized based on severity as mild (may require only minimal treatment) to severe (may require intensive therapeutic intervention). | Baseline upto 12 weeks post end of treatment (EOT) (upto a maximum of 3 years) | 
| Number of Participants With Serious Infections | Number of participants with serious infections will be assessed. | Baseline upto 12 weeks post EOT (upto a maximum of 3 years) | 
| Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as an Adverse Event | Clinical laboratory assessments include hematology, serum chemistry and urinalysis. Any clinically significant change in the clinical laboratory value from baseline will be recorded as an AE. | Baseline upto 12 weeks post EOT (upto a maximum of 3 years) | 
| Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as an Adverse Event | 12-lead ECG will be recorded. Any clinically significant change in ECG will be recorded as an AE. | Baseline upto EOT (upto a maximum of 3 years) | 
| Number of Participants With Clinically Significant Change in Vital Signs Reported as an Adverse Event | Vital sign assessments include blood pressure, pulse, respiratory rate and temperature. Any clinically significant change in vital signs from baseline will be recorded as an AE. | Baseline upto 12 weeks post EOT (upto a maximum of 3 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Ulcerative Colitis with Treatment Response Over Time | Treatment response over time is defined as clinical composite score that has decreased by greater than or equal to (>or= 2) points and >or=30 percentage (%), with an accompanying decrease in the sub score for RB >or= 1 point or a subscore for rectal bleeding (RB) >or=1, and/or composite score that has decreased by >or= 30% and >or=3 points compared to the baseline value for induction studies. The clinical composite score is a measure consisting of sub scores RB (0-3) plus stool frequency (0-3) with higher scores indicating more severe disease. | Baseline upto 12 weeks post end of treatment (EOT) (upto a maximum of 3 years) | 
| Number of Participants with Crohn's Disease with Treatment Response Over Time | Treatment response over time defined as CDAI score that has decreased >or= 100 points compared to baseline value for induction studies and/or simple endoscopic score for Crohn's disease (SES-CD) that has decreased by >or= 25% compared to baseline value for induction studies. SES-CD is simple scoring system based on 4 endoscopic variables measured in same 5 ileocolonic segments as Crohn's disease index of severity. Overall values on SES-CD range from 0-56, with higher values indicating more severe disease. 4 endoscopic variables are scored from 0-3 in each bowel segment: ileum, right/transverse/left colon, rectum. Presence and size of ulcers (none= score 0; diameter 0.1-0.5centimetre(cm)= score 1; 0.5-2cm= score 2; diameter >2cm= score 3); extent of ulcerated surface (none= 0; <10%=1; 10%-30%= 2; >30%= 3); extent of affected surface (none= 0; <50%= 1; 50%-75%= 2; >75%= 3); Presence and type of narrowing (none=0; single can be passed=1; multiple can be passed=2; cannot be passed=3). | Baseline upto 12 weeks post EOT (upto a maximum of 3 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunosuppressants, Mesalamine, Ulcerative Colitis, Crohn's disease, Gastroenteritis