Research study to determine whether an investigational drug, SHP647, is safe and effective in the treatment of moderate to severe Ulcerative Colitis, compared with placebo (dummy treatment) – using a randomised and blinded study design (investigator and patients are not aware whether they receive study drug or placebo)(FIGARO UC 301).

• Register: EUCTR
• Last refreshed on: 5 April 2021
• Main ID: EUCTR2017-000599-27-LT
• Date of registration: 31/10/2017
• Prospective Registration: Yes
• Primary sponsor: Shire Human Genetic Therapies, Inc.
• Public title: Research study to determine whether an investigational drug, SHP647, is safe and effective in the treatment of moderate to severe Ulcerative Colitis, compared with placebo (dummy treatment) – using a randomised and blinded study design (investigator and patients are not aware whether they receive study drug or placebo)(FIGARO UC 301).
• 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 Ulcerative Colitis (FIGARO UC 301)
• Date of first enrolment: 30/01/2018
• Target sample size: 825
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-000599-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: yes; Other specify the comparator: 25 mg or 75 mg ontamalimab; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Brazil, Croatia, Czech Republic, Czechia, Germany, Greece, Israel, Italy, Japan, Lithuania, Netherlands, New Zealand, Poland, Romania, Russian Federation, Serbia, Slovakia, South Africa, United Kingdom, United States

Contacts

• Name: Holly Oakley
• Affiliation: Shire Human Genetic Therapies, Inc.

• Name: Holly Oakley
• Affiliation: Shire Human Genetic Therapies, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Subjects must be between =16 and =80 years of age at the time of the signing of the informed consent/assent form.
NOTE: Subjects <18 years of age must weigh =40 kg and must have body mass index (BMI) =16.5 kg/m2
2. Subjects must have a documented diagnosis (radiologic or endoscopic with histology) of UC for =3 months before screening. The following must be available in each subject’s source documentation:
• A biopsy report to confirm the histological diagnosis.
• A report documenting disease duration based upon prior colonoscopy.
NOTE: If this documentation is not available at the time of screening, a colonoscopy with biopsy to confirm the diagnosis is required during the screening period.
3. Subjects must be willing to undergo a flexible sigmoidoscopy or colonoscopy (if preferred), including biopsy sample collection, during screening after all other inclusion criteria have been met.
4. Subjects must have moderate to severe active UC, defined as a total Mayo score of =6, including a centrally read endoscopic subscore =2, rectal bleeding subscore =1, and stool frequency subscore =1 at baseline (Visit 2).
5. Subjects must have evidence of UC extending proximal to the rectum (ie, not limited to proctitis).
6. Subjects must have had an inadequate response to, or lost response to, at least 1 conventional treatment such as mesalamine (5 aminosalicylic acid [5-ASA]), glucocorticoids, immunosuppressants (azathioprine [AZA], 6 mercaptopurine [6 MP], or methotrexate [MTX]), or anti-TNF.
7. Subjects must have evidence of UC extending proximal to the rectum (ie, not limited to proctitis).
8. Subjects must have had an inadequate response to, or lost response to, or had an intolerance to at least 1
conventional treatment such as mesalamine (5-aminosalicylic acid [5-ASA]), glucocorticoids,
immunosuppressants (azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate [MTX]), or anti-TNF.
9. Subjects receiving any treatment(s) for UC described in Section 5.2.1 of the protocol are eligible provided they have been, and are anticipated to be, on a stable dose for the designated period of time.
10. Subjects 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 subjects) (as described in Section 4.4 of the protocol) for the
duration of the study.
Are the trial subjects under 18? yes
Number of subjects for this age range: 82
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 726
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 17

Exclusion criteria:
Subjects are excluded from the study if any of the following exclusion criteria are met:
1. Subjects with indeterminate colitis, microscopic colitis, non-steroidal anti-inflammatory drug-induced colitis, ischemic colitis, infectious colitis, or clinical/histologic findings suggestive of Crohn’s disease.
2. Subjects with colonic dysplasia or neoplasia.
3. Subjects with past medical history or presence of toxic megacolon.
4. Subjects with colonic stricture, past medical history of colonic resection, a history of bowel surgery within 6 months before screening, or who are likely to require surgery for UC during the treatment period.
5. Subjects at risk for colorectal cancer must have a colonoscopy performed during the screening period with
results available within 10 days before the baseline visit (Visit 2), unless the subject has had a surveillance
colonoscopy performed within 1 year prior to screening, and any adenomatous polyps found at that
examination have been excised. Colonoscopy report and pathology report (if biopsies are obtained) from the
colonoscopy performed during screening or in the prior year confirming no evidence of dysplasia and colon
cancer must be available in the source documents.
Subjects at risk for colorectal cancer include, but are not limited to:
? Subjects with extensive colitis for =8 years or disease limited to left side of colon (ie, distal to splenic
flexure) for =10 years before screening, regardless of age.
? Subjects =50 years of age at the time of signing of the informed consent form.
6. Subjects have had prior treatment with ontamalimab (formerly PF-00547659; SHP647).
7. Subjects with known or suspected intolerance or hypersensitivity to the investigational product(s), closely
related compounds, or any of the stated ingredients.
8. Subjects have received anti-TNF treatment within 60 days before baseline (Visit 2).
9. Subjects have received any biologic with immunomodulatory properties (other than anti-TNFs) within 90 days before baseline (Visit 2).
10. Subjects have received any nonbiologic treatment with immunomodulatory properties (other than their current background UC treatment) within 30 days before baseline (Visit 2).
11. Subjects have ever received anti-integrin/adhesion molecule treatment (eg, natalizumab, vedolizumab,
efalizumab, etrolizumab, or any other investigational anti-integrin/adhesion molecule).
12. Subjects have received parenteral or rectal glucocorticoids, or rectal 5-ASA, within 14 days before screening
endoscopic procedure.
13. Subjects have received leukocyte apheresis or selective lymphocyte, monocyte, or granulocyte apheresis or
plasma exchange within 30 days before baseline (Visit 2).
14. Subjects have participated in other investigational studies within either 30 days or 5 half-lives of
investigational product used in the study (whichever is longer) before baseline (Visit 2).
15. Subjects have received a live (attenuated) vaccine within 30 days before the baseline visit (Visit 2).
16. Subjects with active enteric infections (positive stool culture and sensitivity), Clostridium difficile infection or pseudomembranous colitis [subjects with C. difficile infection at screening may be allowed re-test after
treatment], evidence of active cytomegalovirus infection or Listeria monocytogenes, known active invasive
fungal infections such as histoplasmosis or parasitic infections, clinically significant underlying disease that
could predispose the subj

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Ulcerative colitis
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Code: SHP647
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ontamalimab
Current Sponsor code: SHP647
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 75-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Product Code: SHP647
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ontamalimab
Current Sponsor code: SHP647
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: The primary objective of the study is to evaluate the efficacy of ontamalimab in inducing remission, based on composite score of patient-reported symptoms and centrally read endoscopy, in subjects with moderate to severe ulcerative colitis (UC).

Timepoint(s) of evaluation of this end point: Week 12 visit

Primary end point(s): The primary efficacy endpoint is remission at the Week 12 visit. Remission is defined as a composite score of patient-reported symptoms using daily e-diary and centrally read endoscopy as follows:
• stool frequency subscore of 0 or 1 with at least a 1-point change from baseline
AND
• rectal bleeding subscore of 0
AND
• endoscopic subscore of 0 or 1 (modified, excludes friability).

Secondary Objective: • To evaluate the efficacy of ontamalimab in achieving endoscopic remission, based on centrally read endoscopy.
• To evaluate the efficacy of ontamalimab in achieving clinical remission, based on composite score of patient-reported symptoms.
• To evaluate the efficacy of ontamalimab in inducing clinical response, based on composite score of patient-reported symptoms and centrally read endoscopy.
• To evaluate the efficacy of ontamalimab in achieving mucosal healing, based on endoscopic and histological assessment using the Geboes Score grading system.

Secondary Outcome(s)

Secondary end point(s): • Endoscopic remission, as defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability), at the Week 12 visit.
• Clinical remission, as defined by stool frequency subscore of 0 or 1 with at least a 1-point change from baseline in stool frequency subscore, and rectal bleeding subscore of 0, at the Week 12 visit.
• Clinical response based on composite score at the Week 12 visit. Clinical response (composite) is defined as a decrease from baseline in the composite score of patient-reported symptoms using daily-e diary and centrally read endoscopy of at least 2 points and at least 30%, with an accompanying decrease in the subscore for rectal bleeding =1 point or a subscore for rectal bleeding =1.
• Mucosal healing based on endoscopic and histological assessment at the Week 12 visit. Mucosal healing is defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability) and centrally read Geboes score of =2.

Timepoint(s) of evaluation of this end point: Week 12 visit

Secondary ID(s)

NCT03259334

2017-000599-27-DE

SHP647-301

Source(s) of Monetary Support

Shire Human Genetic Therapies, Inc.

Ethics review

Status: Approved
Approval date: 23/01/2018
Contact: