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 303).

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2017-000573-37-NL
• Date of registration: 02/11/2017
• 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 303).
• Scientific title: A Phase 3 Randomized, Double-blind, Placebo controlled, Parallel group Efficacy and Safety Study of SHP647 as Maintenance Therapy in Subjects With Moderate to Severe Ulcerative Colitis (FIGARO UC 303) - FIGARO UC 303
• Date of first enrolment: 15/03/2018
• Target sample size: 772
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-000573-37
• 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

Argentina, Australia, Austria, Belgium, Bosnia and Herzegovina, Brazil, Bulgaria, Canada, Colombia, Croatia, Czech Republic, Estonia, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Lebanon, Lithuania, Mexico, Netherlands, New Zealand, Poland, Portugal, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Switzerland, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Chantal L. Letourneau
• Affiliation: Shire Human Genetic Therapies, Inc.

• Name: Chantal L. Letourneau
• 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 and/or their parent or legally authorized representative must have an understanding, ability, and willingness to fully comply with study procedures and restrictions.
2. Subjects 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.
3. Subjects must have completed the 12 week induction treatment period from study SHP647 301 or SHP647-302.
4. Subjects must have achieved clinical response in induction study SHP647-301 or SHP647 302. Clinical response is defined as:
1) A decrease from the induction study (SHP647 301 or SHP647-302) 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
OR
2) A decrease from the induction study (SHP647 301 or SHP647-302) baseline in total Mayo score of at least 3 points and at least 30%, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1.
For eligibility assessment, clinical response will be determined based on the centrally read endoscopy performed during screening and at Week 12 of induction study SHP647 301 or SHP647 302.
5. Subjects receiving any treatment(s) for UC described in Section 5.2.1 are eligible provided they have been, and are anticipated to be, on a stable dose for the designated period of time.
Are the trial subjects under 18? yes
Number of subjects for this age range: 77
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 679
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 16

Exclusion criteria:
Subjects are excluded from the study if any of the following exclusion criteria are met:
1. Subjects who had major protocol deviation(s) (as determined by the sponsor) in induction study SHP647 301 or SHP647 302.
2. Subjects who permanently discontinued investigational product because of an adverse event, regardless of relatedness to investigational product, in induction study SHP647-301 or SHP647-302.
3. Subjects who are likely to require surgery for UC during the study period.
4. Subjects are females who became pregnant during induction study SHP647-301 or SHP647-302, 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 (ie, highly
effective methods for female and medically appropriate methods for male study subjects) through the conclusion of study participation.
5. Subjects who do not agree to postpone donation of any organ or tissue, including male subjects who are planning to bank or donate sperm, and female subjects who are planning to harvest or donate eggs, for the duration of the study and through 16 weeks after last dose of investigational product.
6. Subjects who, in the opinion of the investigator or the sponsor, will be uncooperative or unable to comply with study procedures.
7. Subjects 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).
8. Subjects who have developed any major illness/condition or evidence of an unstable clinical condition (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 subject if he or she participates in the study.
9. Subjects 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 subject inappropriate for entry into this study.
10. Subjects with known exposure to Mycobacterium tuberculosis (TB) since testing at screening in induction study SHP647-301 or SHP647-302 and who are without a generally accepted course of treatment.
11. Subjects who are investigational site staff members or relatives of those site staff members or subjects who are sponsor employees directly involved in the conduct of the study.
12. Subjects who are participating in or plan to participate in other investigational studies (other than induction study SHP647-301 or SHP647 302) during study SHP647-303.



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)

Timepoint(s) of evaluation of this end point: Week 52 visit

Main Objective: The primary objective of the study is to evaluate the efficacy of ontamalimab as maintenance treatment of remission, based on composite score of patient reported symptoms and centrally read endoscopy, in subjects with moderate to severe UC.

Primary end point(s): The primary efficacy endpoint is proportion of subjects in remission at the Week 52 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 induction (SHP647 301 or SHP647 302) baseline
AND
• rectal bleeding subscore of 0
AND
• endoscopic subscore of 0 or 1 (modified, excludes friability).

Secondary Objective: The key secondary objectives of the study are as follows:
• To evaluate the efficacy of ontamalimab on endoscopic remission, based on centrally read endoscopy.
• To evaluate the efficacy of ontamalimab on clinical remission, based on composite score of patient-reported symptoms.
• To evaluate the efficacy of ontamalimab on maintenance of remission among subjects in remission at baseline of the SHP647-303 study, based on composite score of patient-reported symptoms and centrally read endoscopy.
• To evaluate the efficacy of ontamalimab on clinical response, based on composite score of patient-reported symptoms and centrally read endoscopy.
• To evaluate the efficacy of ontamalimab on mucosal healing, based on a centrally read endoscopic and histological assessment using the Geboes Score grading system.
• To evaluate the efficacy of ontamalimab on glucocorticoid free clinical remission.
• To evaluate the efficacy of ontamalimab on glucocorticoid free remission.

Secondary Outcome(s)

Secondary end point(s): The key secondary efficacy endpoints are as follows:
• Endoscopic remission, as defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability), at the Week 52 visit.
• Clinical remission as defined by stool frequency subscore of 0 or 1 with at least a 1-point change from induction study (SHP647-301 or SHP647-302) baseline in stool frequency subscore, and rectal bleeding subscore of 0, at the Week 52 visit.
• Sustained remission, ie, in remission at the SHP647-303 Week 52 visit, among subjects who were in remission at the time of baseline in study SHP647 303. Remission is defined as a composite score of patient-reported symptoms using daily e-diary and centrally read endoscopy, with stool frequency subscore of 0 or 1 with at least a 1-point change from induction study (SHP647-301 or SHP647-302) baseline, and rectal bleeding subscore of 0, and endoscopic subscore of 0 or 1 (modified, excludes friability).
• Clinical response based on composite score at the Week 52 visit. Clinical response (composite) is defined as a decrease from induction study (SHP647-301 or SHP647 302) baseline in the composite score of subject-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 histologic assessment, at the Week 52 visit. Mucosal healing is defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability) and centrally read Geboes score of =2.
• Subjects achieving glucocorticoid-free clinical remission at Week 52, among subjects using glucocorticoids in study SHP647-303 baseline. Glucocorticoid-free clinical remission is defined as clinical remission in addition to not requiring any treatment with glucocorticoids for at least 4 weeks prior to the Week 52 visit. Clinical remission is defined as stool frequency subscore of 0 or 1 with at least a 1-point change from induction study (SHP647-301 or SHP647-302) baseline in stool frequency subscore, and rectal bleeding subscore of 0, at the Week 52 visit.
• Subjects achieving glucocorticoid-free remission at Week 52, among subjects using glucocorticoids in study SHP647-303 baseline. Glucocorticoid-free remission is defined as remission in addition to not requiring any treatment with glucocorticoids for at least 4 weeks prior to the Week 52 visit. Remission is defined as a composite score of subject-reported symptoms using daily e diary and endoscopy, with stool frequency subscore of 0 or 1 with at least a 1-point change from induction study (SHP647-301 or SHP647-302) baseline, and rectal bleeding subscore of 0, and endoscopic subscore of 0 or 1 (modified, excludes friability).

Timepoint(s) of evaluation of this end point: Week 52 visit

Secondary ID(s)

2017-000573-37-IE

NCT03290781

SHP647-303

Source(s) of Monetary Support

Shire Human Genetic Therapies, Inc.

Ethics review

Status: Approved
Approval date: 15/03/2018
Contact: