A Study Assessing the Efficacy and Safety of CBP-307 in Subjects With Moderate to Severe Ulcerative Colitis (UC)

NCT ID: NCT04700449

Last Updated: 2024-05-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 145 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-27
• Study Completion Date: 2022-11-10

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.

Conditions

Moderate to Severe Ulcerative Colitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Double-Blind 0.2mg CBP-307

0.2 mg CBP-307 capsules oral administration.

Group Type: EXPERIMENTAL

Double-Blind 0.2mg CBP-307

Intervention Type: DRUG

0.2 mg capsule oral administration

Double-Blind Placebo

Placebo capsules oral administration.

Group Type: PLACEBO_COMPARATOR

Double-Blind Placebo

Intervention Type: DRUG

Placebo capsule oral administration

Open-Label CBP-307

0.2 mg CBP-307 capsules oral administration.

Group Type: EXPERIMENTAL

Open-label CBP-307

Intervention Type: DRUG

0.2 mg capsule oral administration

Double-Blind 0.1mg CBP-307

0.1 mg CBP-307 capsules oral administration.

Group Type: EXPERIMENTAL

Double-Blind 0.1mg CBP-307

Intervention Type: DRUG

0.1 mg capsule oral administration

Interventions

Double-Blind 0.2mg CBP-307

0.2 mg capsule oral administration

Intervention Type: DRUG

Double-Blind Placebo

Placebo capsule oral administration

Intervention Type: DRUG

Open-label CBP-307

0.2 mg capsule oral administration

Intervention Type: DRUG

Double-Blind 0.1mg CBP-307

0.1 mg capsule oral administration

Intervention Type: DRUG

Eligibility Criteria

Exclusion Criteria

Subjects were eligible to be included in the study only if all the following criteria applied:

• Male or female subjects aged 18 to 75 years (inclusive) with a diagnosis of UC established at least 3 months prior to screening by clinical and endoscopic evidence corroborated by a histopathology report;
• Confirmed to have moderately to severely active UC within 14 days prior to the first dose of the investigational product, based on an adapted Mayo score of 4 to 9, and an endoscopic subscore of ≥2;
• Had evidence of UC extending to the rectum with ≥15 cm involvement on endoscopy;
• UC patients who were receiving treatment. Subjects could be enrolled if they met any items below:

1. Prior to the randomization visit, subjects had received oral 5-aminosalicylic acid (5-ASA) (e.g., mesalazine, sulfasalazine, olsalazine, balsalazide) for at least 4 weeks with the dose stable for at least 2 weeks;

2. Prior to the randomization visit, subjects had received oral or intravenous (IV) corticosteroids e.g. prednisone (daily doses ≤30 mg), budesonide (daily doses ≤9 mg), methylprednisolone (daily doses ≤24 mg), or equivalent dose of corticosteroids for at least 4 weeks, with the dose stable for at least 2 weeks;

• Oral 5-ASA or corticosteroid for treatment of UC had been stopped for at least 2 weeks prior to the screening endoscopy examination which was used for Mayo score assessment;
• A stable dosing regimen had to be used if non-prohibited concomitant medications were used.

Subjects who met any of the following criteria were excluded:

• Subjects had evidence of toxic megacolon;
• Had subtotal or total colectomy;
• An existing ileostomy, colostomy, or known symptomatic stenosis of the intestine; a history or evidence of adenomatous colonic polyps that had not been removed; a history or evidence of colonic mucosal dysplasia including low or high grade of dysplasia, as well as indeterminate for dysplasia; a suspected or confirmed diagnosis of Crohn's enterocolitis, undiagnosed types of colitis, ischemic colitis, or radiation colitis;
• Previous exposure to lymphocyte-depleting therapies or D-penicillamine, leflunomide; prior exposure to approved or investigational products that inhibited the lymphocyte trafficking;
• Received immunosuppressants within 30 days prior to randomization; received any investigational biologic or non-biologic agent, or approved biologic agent or biosimilars within 60 days or 5 half lives prior to screening (whichever was longer);
• Known active infection during the screening period; treatment for Clostridioides difficile (C. difficile) infection or other intestinal pathogen with 28 days prior to first dose of investigational product; active or latent tuberculosis (TB); Chronic hepatitis B virus (HBV) infection or chronic hepatitis C virus (HCV) infection; any identified congenital or acquired immunodeficiency;
• Received any live vaccine within 30 days prior to screening.

Subjects who met all the following criteria entered into the study Stage 2:

• subjects with UC who completed 12 weeks of treatment with CBP-307 or placebo in Stage 1 and completed all the assessments (including colonoscopy) at study visit of Week 12 in study Stage 1;
• Good compliance in Stage 1;
• Subjects or their legal representatives voluntarily signed the ICF for study Stage 2.

Subjects who met any of the following criteria were excluded from the study Stage 2:

• subjects had any unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, or other medical disorder that, in the opinion of the investigator, were to confound the study results or compromise subject safety;
• Allergic to CBP 307 or its excipients, experience of significant adverse events related to the study drug during Stage 1, and not appropriate to participate in Stage 2 assessed by the investigator;
• Active or chronic recurrent infections;
• A history of uveitis or macular oedema.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Connect Biopharm LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Suzhou Connect

Role: STUDY_DIRECTOR

Connect Biopharm LLC

Locations

Connect Investigative Site 2316

Phoenix, Arizona, United States

Connect Investigative Site 2308

Mission Hills, California, United States

Connect Investigative Site 2314

Hialeah, Florida, United States

Connect Investigative Site 2309

Homestead, Florida, United States

Connect Investigative Site 2320

Kissimmee, Florida, United States

Connect Investigative Site 2318

Miami, Florida, United States

Connect Investigative Site 2302

Orlando, Florida, United States

Connect Investigative Site 2304

Orlando, Florida, United States

Connect Investigative Site 2306

Orlando, Florida, United States

Connect Investigative Site 2307

Atlanta, Georgia, United States

Connect Investigative Site 2315

Cincinnati, Ohio, United States

Connect Investigative Site 2321

Oklahoma City, Oklahoma, United States

Connect Investigative Site 2311

Cypress, Texas, United States

Connect Investigative Site 2319

San Antonio, Texas, United States

Connect Investigative Site 2018

Hefei, Anhui, China

Connect Investigative Site 2004

Hefei, Anhui, China

Connect Investigative Site 2008

Beijing, Beijing Municipality, China

Connect Investigative Site 2001

Beijing, Beijing Municipality, China

Connect Investigative Site 2015

Jilin, Changchun, China

Connect Investigative Site 2006

Fuzhou, Fujian, China

Connect Investigative Site 2012

Xiamen, Fujian, China

Connect Investigative Site 2003

Guangzhou, Guangdong, China

Connect Investigative Site 2009

Guangzhou, Guangdong, China

Connect Investigative Site 2017

Shenzhen, Guangdong, China

Connect Investigative Site 2021

Shenzhen, Guangdong, China

Connect Investigative Site 2030

Nanning, Guangxi, China

Connect Investigative Site 2034

Haikou, Hainan, China

Connect Investigative Site 2026

Shijiazhuang, Hebei, China

Connect Investigative Site 2041

Shijiazhuang, Hebei, China

Connect Investigative Site 2022

Zhengzhou, Henan, China

Connect Investigative Site 2016

Wuhan, Hubei, China

Connect Investigative Site 2005

Wuhan, Hubei, China

Connect Investigative Site 2027

Nanjing, Jiangsu, China

Connect Investigative Site 2031

Nanjing, Jiangsu, China

Connect Investigative Site 2023

Nanjing, Jiangsu, China

Connect Investigative Site 2033

Suzhou, Jiangsu, China

Connect Investigative Site 2046

Nanchang, Jiangxi, 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 Municipality, China

Connect Investigative Site 2007

Shanghai, Shanghai Municipality, China

Connect Investigative Site 2019

Shanghai, Shanghai Municipality, China

Connect Investigative Site 2035

Shanghai, Shanghai Municipality, China

Connect Investigative Site 2038

Shanghai, Shanghai Municipality, China

Connect Investigative Site 2020

Taiyuan, Shanxi, China

Connect Investigative Site 2013

Chengdu, Sichuan, China

Connect Investigative Site 2043

Chongqing, Sichuan, China

Connect Investigative Site 2047

Hangzhou, Zhejiang, China

Connect Investigative Site 2032

Hangzhou, Zhejiang, China

Connect Investigative Site 2045

Wenzhou, Zhejiang, China

Connect Investigative Site 2151

Karachi, Sindh, Pakistan

Connect Investigative Site 2152

Karachi, Sindh, Pakistan

Connect Investigative Site 2211

Dnipro, , Ukraine

Connect Investigative Site 2217

Ivano-Frankivsk, , Ukraine

Connect Investigative Site 2202

Kharkiv, , Ukraine

Connect Investigative Site 2208

Kharkiv, , Ukraine

Connect Investigative Site 2205

Kyiv, , Ukraine

Connect Investigative Site 2220

Kyiv, , Ukraine

Connect Investigative Site 2215

Lviv, , Ukraine

Connect Investigative Site 2216

Lviv, , Ukraine

Connect Investigative Site 2218

Uzhhorod, , Ukraine

Connect Investigative Site 2209

Vinnytsia, , Ukraine

Connect Investigative Site 2214

Zaporizhzhia, , Ukraine

Countries

United States; China; Pakistan; Ukraine

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CBP-307CN002

Identifier Type: -

Identifier Source: org_study_id