A Study Assessing the Efficacy and Safety of CBP-307 in Subjects With Moderate to Severe Ulcerative Colitis (UC)
- Conditions
- Moderate to Severe Ulcerative Colitis
- Interventions
- Drug: Open-label CBP-307Drug: Double-Blind 0.2mg CBP-307Drug: Double-Blind PlaceboDrug: Double-Blind 0.1mg CBP-307
- Registration Number
- NCT04700449
- Lead Sponsor
- Suzhou Connect Biopharmaceuticals, Ltd.
- Brief Summary
This study will evaluate the efficacy and safety of CBP-307 in subjects with moderate to severe ulcerative colitis (UC).
- Detailed Description
This is a multicenter, multicountry, randomized, double-blind, placebo-controlled phase II clinical trial to evaluate the efficacy and safety of CBP-307 in subjects with moderate to severe ulcerative colitis (UC). CBP-307 capsules are administered orally. This study includes stage 1 and stage 2.
Study Stage 1 After screening, subjects entered the randomized, double-blind, placebo-controlled induction therapy for 12 weeks.
Subjects were screened at 1 to 21 days prior to the baseline visit. The eligible subjects were enrolled and randomized at the baseline visit. As per study protocol (version 5.0 or earlier), subjects received CBP 307 0.1 mg, CBP-307 0.2 mg, and placebo at a ratio of 1:1:1. The subjects enrolled under protocol (version 6.0) were randomized to CBP-307 0.2 mg and placebo at a ratio of 1:1 into the 2 groups (approximately 52 subjects in each group) and stratified according to whether the subject failed a previous tumor necrosis factor (TNF)-α antagonist therapy. Subjects assigned were blinded to their treatment assignment (CBP-307 or placebo) in the 12-week double-blinded placebo-controlled treatment period.
Subjects randomized to CBP-307 group underwent dose titration for 1 week, while those in placebo group underwent simulated titration. Both CBP-307 and placebo were administered through the oral route. For subjects in the CBP-307 0.1 mg QD group, a daily dose of 0.05 mg CBP-307 was given from Day 1 to Day 4; then a daily dose of 0.1 mg CBP-307 was given for 3 days from Day 5 to Day 7; from Day 8, a daily target dose of 0.1 mg was administered. For subjects in the group of CBP-307 0.2 mg QD, a daily dose of 0.05 mg CBP-307 was given from Day 1 to Day 4; then, a dose of 0.1 mg CBP-307 was given daily for 3 days from Day 5 to Day 7; from Day 8, a daily target dose of 0.2 mg was administered.
For the subjects already enrolled as per study protocol version 5.0 or earlier, they continued the treatment in the Stage 1 according to the previous planned schedule.
Eligible subjects completing 12 weeks of induction therapy in Stage 1 were permitted to enter Stage 2 to be evaluated for the long-term maintenance administration of CBP-307. Subjects who withdrew early from the study or completed the Stage 1, but did not enter Stage 2, entered a 4-week safety follow-up period.
Study stage 2 All subjects who completed 12 weeks of induction therapy in the study Stage 1 and completed all examinations (including colonoscopy) at Week 12 (visit 11) could choose to enter the study Stage 2 of a total length of 40 weeks, including 36 weeks of continuous treatment and 4 weeks of safety follow up after the last dose. Subjects who chose to enter the Stage 2 signed an updated informed consent form (ICF) and screened for eligibility.
The study Stage 2 contained sub-study 1 and sub-study 2. Subjects entered 1 of sub-studies based on their results of efficacy evaluation in the study Stage 1.
Sub-study 1 (subjects who achieved clinical response by adapted Mayo score): Subjects who achieved clinical response at Week 12 in the study Stage 1 and met the eligibility criteria for Stage 2 entered sub study 1 of the study Stage 2 to receive double-blind maintenance treatment for 36 weeks (Week 13 to 48), i.e., the therapeutic regimen for them in Stage 1 was continually maintained. Safety follow-up was completed at 4 weeks after the last dose. Subjects who presented with recurrent UC during maintenance treatment were terminated from the treatment and withdrew from the study.
For the subjects already enrolled as per study protocol version 5.0 or earlier, they followed the previous planned treatment in the sub-study 1 of Stage 2 study.
Sub-study 2 (subjects who did not achieve clinical response by adapted Mayo score): Subjects who did not achieve clinical response at Week 12 in study Stage 1 and met the eligibility criteria for Stage 2 entered open-label treatment with CBP-307 0.2 mg. Subjects received CBP-307 QD at an oral dose of 0.2 mg in sub study 2 regardless of whether they received CBP-307 or placebo in the study Stage 1.
For subjects who entered sub-study 2 of study Stage 2, 1-week dose titration was performed at Week 13. Dose titration involved administration of CBP 0.05 mg for 4 consecutive days from Titration Day 1 to Day 4, followed by administration of CBP-307 0.1 mg for 3 days from Titration Day 5 to Day 7, and administration of CBP-307 at a target dose of 0.2 mg initiated on Titration Day 8. After dose titration was completed, subjects received oral treatment with CBP-307 0.2 mg QD, for 36 weeks. Safety follow-up was completed at 4 weeks after the last dose. If the subjects did not achieve clinical response by the efficacy evaluation including colonoscopy at Week 24, the treatment was to be discontinued and the subjects were to withdraw from the study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 145
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Open-Label CBP-307 Open-label CBP-307 0.2 mg CBP-307 capsules oral administration. Double-Blind 0.2mg CBP-307 Double-Blind 0.2mg CBP-307 0.2 mg CBP-307 capsules oral administration. Double-Blind Placebo Double-Blind Placebo Placebo capsules oral administration. Double-Blind 0.1mg CBP-307 Double-Blind 0.1mg CBP-307 0.1 mg CBP-307 capsules oral administration.
- Primary Outcome Measures
Name Time Method Change From Baseline for Adapted Mayo Score: 0.2 mg Versus Placebo The adapted Mayo score was evaluated at screening and Week 12 (or early termination visit) during the study Stage 1 as well as at Week 24 (only for the sub-study 2) and Week 48 (or early termination visit) during the study Stage 2. Change in adapted Mayo score from baseline at week 12 compared between CBP-307 0.2 mg and placebo in the Full Analysis Set by Multiple Imputation. Adapted Mayo scores were calculated based on data in stool frequency, rectal bleeding, and endoscopic findings. The Mayo scores range from 0 to 9 and consist of 3 subscores, each ranging from 0 to 3. The higher the score is, the more severe the disease is.
- Secondary Outcome Measures
Name Time Method Comparison of Clinical Response Rate by Adapted Mayo Score at Week 12 Comparison of clinical response rate at week 12 by adapted Mayo score (defined as a decrease of ≥ 2 points and at least 30% from baseline, accompanied with a decrease of ≥ 1 point from baseline in the rectal bleeding subscore or an absolute rectal bleeding subscore of ≤ 1 point).
Comparison of Clinical Remission Rate by Adapted Mayo Score at Week 12 Comparison of clinical remission rate at week 12 by adapted Mayo score (defined as a rectal bleeding subscore = 0 and a stool frequency subscore ≤ 1, with an Endoscopy subscore ≤ 1 \[excluding friability\]).
Change in Complete Mayo Score From Baseline at Week 12 Change in complete Mayo score from baseline at week 12 after treatment. Complete Mayo scores were calculated based on data in stool frequency, rectal bleeding, endoscopic findings, and physician's global assessment. The Mayo scores range from 0 to 12 and consist of 4 subscores, each ranging from 0 to 3. The higher the score is, the more severe the disease is.
Comparison of Clinical Response Rate by Complete Mayo Score at Week 12 Comparison of clinical response rate at week 12 by complete Mayo score (defined as a decrease of ≥ 3 points and at least 30% from baseline, accompanied with a decrease of ≥ 1 point from baseline in the rectal bleeding subscore or an absolute rectal bleeding subscore of ≤ 1 point).
Comparison of Clinical Remission Rate by Complete Mayo Score at Week 12 Comparison of clinical remission rate at week 12 by complete Mayo score (defined as a total Mayo score of ≤ 2 points with no individual subscore \> 1 point).
Mucosal Healing Rate at Week 12 Mucosal healing rate at week 12 after treatment (mucosal healing is defined as Mayo endoscopic subscore ≤ 1)
Incidence, Type and Severity of Treatment Emergent Adverse Event (TEAE) for 12 consecutive weeks The safety and tolerability will be assessed on basis of incidence, type and severity of TEAEs as well as their relations with the investigational product .
Incidence, Type and Severity of Serious Adverse Event (SAE) for 12 consecutive weeks The safety and tolerability will be assessed on basis of incidence, type and severity of SAEs as well as their relations with the investigational product and SAEs that lead to discontinuation of study.
Incidence, Type and Severity of Adverse Events (AE) for 12 consecutive weeks The safety and tolerability will be assessed on basis of AEs that lead to discontinuation of study, and AEs of special interest (cardiac events as well as pulmonary function tests, ophthalmologic examinations, skin examinations, and nervous system physical examinations)
Change From Baseline in Adapted Mayo Score: 0.1 mg Versus Placebo at Week 12 Change from baseline in adapted Mayo score at Week 12 between CBP-307 0.1 mg and placebo in the Full Analysis Set by Multiple Imputation. Adapted Mayo scores were calculated based on data in stool frequency, rectal bleeding, and endoscopic findings. The Mayo scores range from 0 to 9 and consist of 3 subscores, each ranging from 0 to 3. The higher the score is, the more severe the disease is.
Trial Locations
- Locations (66)
Connect Investigative Site 2314
🇺🇸Hialeah, Florida, United States
Connect Investigative Site 2320
🇺🇸Kissimmee, Florida, United States
Connect Investigative Site 2015
🇨🇳Jilin, Changchun, China
Connect Investigative Site 2017
🇨🇳Shenzhen, Guangdong, China
Connect Investigative Site 2021
🇨🇳Shenzhen, Guangdong, China
Connect Investigative Site 2033
🇨🇳Suzhou, Jiangsu, China
Connect Investigative Site 2020
🇨🇳Taiyuan, Shanxi, China
Connect Investigative Site 2309
🇺🇸Homestead, Florida, United States
Connect Investigative Site 2308
🇺🇸Mission Hills, California, United States
Connect Investigative Site 2307
🇺🇸Atlanta, Georgia, United States
Connect Investigative Site 2315
🇺🇸Cincinnati, Ohio, United States
Connect Investigative Site 2018
🇨🇳Hefei, Anhui, China
Connect Investigative Site 2311
🇺🇸Cypress, Texas, United States
Connect Investigative Site 2004
🇨🇳Hefei, Anhui, China
Connect Investigative Site 2008
🇨🇳Beijing, Beijing, China
Connect Investigative Site 2001
🇨🇳Beijing, Beijing, China
Connect Investigative Site 2012
🇨🇳Xiamen, Fujian, China
Connect Investigative Site 2006
🇨🇳Fuzhou, Fujian, China
Connect Investigative Site 2003
🇨🇳Guangzhou, Guangdong, China
Connect Investigative Site 2009
🇨🇳Guangzhou, Guangdong, China
Connect Investigative Site 2030
🇨🇳Nanning, Guangxi, China
Connect Investigative Site 2041
🇨🇳Shijiazhuang, Hebei, China
Connect Investigative Site 2026
🇨🇳Shijiazhuang, Hebei, China
Connect Investigative Site 2034
🇨🇳Haikou, Hainan, China
Connect Investigative Site 2022
🇨🇳Zhengzhou, Henan, China
Connect Investigative Site 2016
🇨🇳Wuhan, Hubei, China
Connect Investigative Site 2027
🇨🇳Nanjing, Jiangsu, China
Connect Investigative Site 2005
🇨🇳Wuhan, Hubei, China
Connect Investigative Site 2046
🇨🇳Nanchang, Jiangxi, China
Connect Investigative Site 2031
🇨🇳Nanjing, Jiangsu, China
Connect Investigative Site 2023
🇨🇳Nanjing, Jiangsu, China
Connect Investigative Site 2025
🇨🇳Dalian, Liaoning, China
Connect Investigative Site 2040
🇨🇳Shenyang, Liaoning, China
Connect Investigative Site 2028
🇨🇳Jinan, Shandong, China
Connect Investigative Site 2044
🇨🇳Jinan, Shandong, China
Connect Investigative Site 2024
🇨🇳Qingdao, Shandong, China
Connect Investigative Site 2011
🇨🇳Shanghai, Shanghai, China
Connect Investigative Site 2007
🇨🇳Shanghai, Shanghai, China
Connect Investigative Site 2019
🇨🇳Shanghai, Shanghai, China
Connect Investigative Site 2038
🇨🇳Shanghai, Shanghai, China
Connect Investigative Site 2035
🇨🇳Shanghai, Shanghai, China
Connect Investigative Site 2013
🇨🇳Chengdu, Sichuan, China
Connect Investigative Site 2208
🇺🇦Kharkiv, Ukraine
Connect Investigative Site 2047
🇨🇳Hangzhou, Zhejiang, China
Connect Investigative Site 2043
🇨🇳Chongqing, Sichuan, China
Connect Investigative Site 2032
🇨🇳Hangzhou, Zhejiang, China
Connect Investigative Site 2045
🇨🇳Wenzhou, Zhejiang, China
Connect Investigative Site 2211
🇺🇦Dnipro, Ukraine
Connect Investigative Site 2205
🇺🇦Kyiv, Ukraine
Connect Investigative Site 2209
🇺🇦Vinnytsia, Ukraine
Connect Investigative Site 2220
🇺🇦Kyiv, Ukraine
Connect Investigative Site 2151
🇵🇰Karachi, Sindh Province, Pakistan
Connect Investigative Site 2152
🇵🇰Karachi, Sindh Province, Pakistan
Connect Investigative Site 2217
🇺🇦Ivano-Frankivsk, Ukraine
Connect Investigative Site 2202
🇺🇦Kharkiv, Ukraine
Connect Investigative Site 2216
🇺🇦Lviv, Ukraine
Connect Investigative Site 2215
🇺🇦Lviv, Ukraine
Connect Investigative Site 2218
🇺🇦Uzhhorod, Ukraine
Connect Investigative Site 2214
🇺🇦Zaporizhzhia, Ukraine
Connect Investigative Site 2318
🇺🇸Miami, Florida, United States
Connect Investigative Site 2316
🇺🇸Phoenix, Arizona, United States
Connect Investigative Site 2302
🇺🇸Orlando, Florida, United States
Connect Investigative Site 2321
🇺🇸Oklahoma City, Oklahoma, United States
Connect Investigative Site 2304
🇺🇸Orlando, Florida, United States
Connect Investigative Site 2306
🇺🇸Orlando, Florida, United States
Connect Investigative Site 2319
🇺🇸San Antonio, Texas, United States