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)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 366
- 试验地点
- 395
- 主要终点
- Number of Participants With Remission Based on Composite Score at Week 52
研究概览
简要总结
The purpose of this study is to evaluate the efficacy of ontamalimab as maintenance therapy treatment of remission, based on composite score of patient-reported symptoms and centrally read endoscopy, in participants with moderate to severe ulcerative colitis (UC).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 16 Years 至 81 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 completed the 12-week induction treatment period (SHP647-301 [NCT03259334] and SHP647-302 [NCT03259308]).
- •Participants must have achieved clinical response in induction study (SHP647-301 [NCT03259334] and SHP647-302 [NCT03259308]). Clinical response is defined as:
- •i) A decrease from the induction study (SHP647-301 [NCT03259334] and SHP647-302 [NCT03259308]) 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 percent (%), with an accompanying decrease in the sub score for rectal bleeding greater than or equal to (>=) 1 point or a sub score for rectal bleeding less than or equal to (<=) 1 OR ii) A decrease from the induction study (SHP647-301 [NCT03259334] and SHP647-302 [NCT03259308]) baseline in total Mayo score of at least 3 points and at least 30%, with an accompanying decrease in the rectal bleeding sub score of at least 1 point or an absolute rectal bleeding sub score of 0 or
- •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 [NCT03259334] and SHP647-302 [NCT03259308]).
- •Participants receiving any treatment(s) for ulcerative colitis (UC) are eligible provided they have been, and are anticipated to be, on a stable dose for the designated period of time.
排除标准
- •Participants who had major protocol deviation(s) (as determined by the sponsor) in induction study (SHP647-301 [NCT03259334] and SHP647-302 [NCT03259308]).
- •Participants who permanently discontinued investigational product because of an adverse event (AE), regardless of relatedness to investigational product, in induction study (SHP647-301 [NCT03259334] and SHP647-302 [NCT03259308]).
- •Participants who are likely to require surgery for UC during the study period.
- •Participants are females who became pregnant during induction study (SHP647-301 [NCT03259334] and SHP647-302 [NCT03259308]), 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 (that is [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 [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 electrocardiogram (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 study (SHP647-301 [NCT03259334] and SHP647-302 [NCT03259308]) and 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 or plan to participate in other investigational studies (other than induction study SHP647- 301 [NCT03259334] and SHP647-302 [NCT03259308]) during study SHP647-303 [NCT03290781].
研究组 & 干预措施
Ontamalimab 25 mg
Participants will receive 25 milligram (mg) of ontamalimab or placebo and achieved a clinical response in one of the induction studies (SHP647-301 [NCT03259334] and SHP647-302 [NCT03259308]) will receive 25 mg of ontamalimab as maintenance treatment subcutaneously using a prefilled syringe once in every 4 weeks (Q4W) up to Week 52.
干预措施: Ontamalimab (Drug)
Ontamalimab 75 mg
Participants will receive 75 mg of ontamalimab or placebo and achieved a clinical response in one of the induction studies (SHP647-301 [NCT03259334] and SHP647-302 [NCT03259308]) will receive 75 mg of ontamalimab as maintenance treatment subcutaneously using a prefilled syringe Q4W up to Week 52.
干预措施: Ontamalimab (Drug)
Placebo
Participants will receive 25 mg or 75 mg ontamalimab or placebo matched to ontamalimab in the induction studies (SHP647-301 [NCT03259334] and SHP647-302 [NCT03259308]) will receive placebo matched to ontamalimab as maintenance treatment subcutaneously using a prefilled syringe Q4W up to Week 52.
干预措施: Placebo (Other)
结局指标
主要结局
Number of Participants With Remission Based on Composite Score at Week 52
时间窗: At Week 52
Remission: a composite score of participant reported symptoms using daily e-diary and centrally read endoscopy as follows: stool frequency sub-score 0 or 1 with at least a 1-point change from induction study baseline; and rectal bleeding sub-score of 0; and endoscopic sub-score 0 or 1 (modified, excludes friability). The composite score was a recommended measure consisted of Mayo score without the Physician global assessment (PGA) sub-score and ranges from 0-9 points. The Mayo score was a measure of UC disease activity ranged from 0-12 points and consisted of 4 sub-scores, each graded from 0-3 with higher scores indicating more severe disease. Sub-scores were rectal bleeding (range: 0-3, where 0= no blood \& 3=blood alone passes), stool frequency (range: 0-3, where 0= normal number of stools and 3=at least 5 stools more than normal), PGA sub-score (range: 0-3- higher score= severe disease), and an endoscopic sub-score (range: 0-3, where 0= normal/inactive disease; 3= severe disease).
次要结局
- Number of Participants With Clinical Response Based on Composite Score at Week 52(At Week 52)
- Number of Participants With Sustained Endoscopic Remission at Week 52(At Week 52)
- Number of Participants With Glucocorticoid-free Clinical Remission at Week 52(At Week 52)
- Number of Participants With Remission Based on Total Mayo Score at Week 52(At Week 52)
- Number of Participants With Clinical Remission at Week 52(At Week 52)
- Number of Participants With Mucosal Healing Based on Endoscopic and Histologic Assessment at Week 52(At Week 52)
- Number of Participants With Clinical Remission Based on Both Rectal Bleeding and Stool Frequency Sub-scores of 0(At Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52)
- Number of Participants Who Developed Positive Antidrug Antibodies to Ontamalimab(At Week 12, 24, 36 and 52)
- Number of Participants With Endoscopic Remission at Week 52(At Week 52)
- Number of Participants With Glucocorticoid-free Remission at Week 52(At Week 52)
- Number of Participants With Sustained Remission at Week 52(At Week 52)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)(From start of study drug administration up to follow-up (Week 64))