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

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ClinicalTrials.gov Identifier: NCT04700449
Recruitment Status : Recruiting
First Posted : January 7, 2021
Last Update Posted : May 12, 2021
Sponsor:
Information provided by (Responsible Party):
Suzhou Connect Biopharmaceuticals, Ltd.

Tracking Information
First Submitted Date  ICMJE October 22, 2020
First Posted Date  ICMJE January 7, 2021
Last Update Posted Date May 12, 2021
Actual Study Start Date  ICMJE February 27, 2019
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 9, 2021)
Adapted Mayo score [ Time Frame: at Week 12 ]
Change in adapted Mayo score from baseline at week 12 compared between CBP-307 and placebo
Original Primary Outcome Measures  ICMJE
 (submitted: January 6, 2021)
Clinical response rate [ Time Frame: at Week 12 ]
Compare clinical efficacy by evaluating the clinical response rate between 0.2mg and placebo at week 12. Clinical response is defined as a decrease of ≥ 3 points and at least 30% from baseline in the complete Mayo score, accompanied with a decrease of ≥ 1 point from baseline in the rectal bleeding subscore or an absolute rectal bleeding subscore of ≤ 1 point.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 9, 2021)
  • Change in complete Mayo score [ Time Frame: at Week 12 ]
    Change in complete Mayo score from baseline at week 12 after treatment
  • Comparison of clinical response rate by adapted Mayo score [ Time Frame: 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 response rate by complete Mayo score [ Time Frame: 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 adapted Mayo score [ Time Frame: 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]).
  • Comparison of clinical remission rate by complete Mayo score [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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)
Original Secondary Outcome Measures  ICMJE
 (submitted: January 6, 2021)
  • Clinical remission [ Time Frame: at Week 12 ]
    Clinical remission rate at week 12 after treatment (clinical remission is defined as a complete Mayo score of ≤ 2 points with no individual subscore > 1 point)
  • Clinical response rate [ Time Frame: at Week 12 ]
    Comparison of clinical response rate at week 12 between the 0.1 mg CBP-307 group and the placebo group
  • Complete Mayo score [ Time Frame: at Week 12 ]
    Change in complete Mayo score from baseline at week 12 after treatment
  • Adapted Mayo score [ Time Frame: at Week 12 ]
    Change in adapted Mayo score from baseline at week 12 after treatment
  • Mucosal healing rate [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 and skin examinations)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Assessing the Efficacy and Safety of CBP-307 in Subjects With Moderate to Severe Ulcerative Colitis (UC)
Official Title  ICMJE A Multicenter, 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)
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. After screening, subjects will enter the randomized, double-blind, placebo-controlled induction therapy for 12 weeks, i.e., the study stage 1. All subjects who complete 12 weeks of induction therapy (with CBP-307 or placebo) in the study stage 1 and complete all examinations (including colonoscopy) at the week 12 visit can choose to enter the study stage 2 of a total of 40 weeks, including 36 weeks of continuous administration and 4 weeks of safety follow-up after the last dose.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Moderate to Severe Ulcerative Colitis
Intervention  ICMJE
  • Drug: CBP-307
    CBP-307 capsules oral administration
  • Drug: Placebo
    Placebo capsules oral administration
Study Arms  ICMJE
  • Experimental: CBP-307 capsules
    CBP-307 capsules oral administration.
    Intervention: Drug: CBP-307
  • Placebo Comparator: Placebo capsules
    Placebo capsules oral administration.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 9, 2021)
134
Original Estimated Enrollment  ICMJE
 (submitted: January 6, 2021)
195
Estimated Study Completion Date  ICMJE September 2022
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

-

For the stage 1:

  1. Male or female subjects aged 18-75 years (inclusive).
  2. Female subjects of childbearing potential and male subjects who have not undergone vasectomy should use at least one highly effective methods of contraception during the entire study and 4 weeks after the last dose of investigational products after signing the informed consent form.
  3. The subject has a diagnosis of UC established at least 3 months prior to screening by clinical and endoscopic evidence corroborated by a histopathology report. Subjects are confirmed to have moderate to severe active UC within 14 days prior to the first dose of the investigational product, which is based on an adapted Mayo score of 4-9, and an endoscopic subscore of ≥ 2. Endoscopy must be performed during the screening period (day -14 to day -3, allowing centralized reading and evaluation before the first dose at week 0).
  4. The subject has evidence of UC extending to the rectum with ≥15 cm involvement on endoscopy.
  5. Subjects must be UC patients who are receiving treatment. They can be enrolled if they meet any items below.

    1. Prior to the randomization visit, subjects have received oral 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 have received oral or 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.
  6. If oral 5-ASA or corticosteroid for treatment of UC have been recently discontinued, they must have been stopped for at least 2 weeks prior to the screening endoscopy examination which is used for Mayo score assessment.
  7. If subjects use non-prohibited concomitant medications, a stable dosing regimen must be used, that is, within 7 days prior to first dose of investigational product or within 5 half lives of the drug (whichever is longer), there's no new concomitant medications started or changes in the dose of existing non-prohibited concomitant medications.
  8. The subject who has extensive colitis or pancolitis of >8 years duration or limited colitis of >12 years duration must have documented evidence that a surveillance colonoscopy was performed within 12 months prior to initial screening visit (can be performed during Screening if not performed in previous 12 months).

For subjects' entry into the study stage 2 from the stage 1:

  1. Subjects must be those with UC who participate in the study of CBP-307CN002 and have completed 12 weeks of treatment with CBP-307 or placebo in the stage 1 and have completed all the assessments (including colonoscopy) at study visit of week 12 in study stage 1.
  2. Female subjects of childbearing potential and male subjects who have not undergone vasectomy should use at least one highly effective methods of contraception during the entire study and 4 weeks after the last dose of investigational products after signing the informed consent form.

Exclusion Criteria:

-

UC-related exclusion criteria:

  1. At the screening visit, subjects have evidence of toxic megacolon.
  2. The subject has had, subtotal or total colectomy.
  3. The subject has an existing ileostomy, colostomy (a history of ileostomy or colostomy that has been reversed may be acceptable), or known symptomatic stenosis of the intestine.
  4. Investigator judges the subject currently requires or is anticipated to require surgical intervention for UC during the study.
  5. The subject has a history or evidence of adenomatous colonic polyps that have not been removed.
  6. Subjects were previously exposure to the following treatments:

    • Lymphocyte-depleting therapies (e.g., alemtuzumab, anti-CD4 antibody, cladribine, rituximab, ocrelizumab, cyclophosphamide, mitoxantrone, total body irradiation, bone marrow transplantation and daclizumab).
    • Previous treatment with D-penicillamine, leflunomide.
  7. Within 60 days prior to the screening visit, the subject has received any of the following for the treatment of UC:

    1. Intravenous immunoglobulin;
    2. Therapeutic plasma exchange (TPE).
  8. Within 30 days prior to randomization visit, the subject has received any of the following for the treatment of UC:

    1. Immunosuppressants (such as cyclosporine, tacrolimus, sirolimus or mycophenolate mofetil), thalidomide or traditional Chinese medicine;
    2. Approved non-biologic agents or traditional Chinese medicine treatment.
  9. Patients who plan to concurrently use an immunosuppressant (such as azathioprine, 6 mercaptopurine or methotrexate) after randomization. Patients treated with azathioprine, 6-mercaptopurine or methotrexate at screening are required to discontinue it prior to the first dose of the study drug.
  10. The subject has 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 is longer).

    Exclusion criteria for general conditions:

  11. History of uveitis or macular oedema.
  12. Clinically relevant cardiovascular conditions, including history or presence of any one of below:

    1. Ischemic heart disease or myocardial infarction; Unstable angina; History of angina pectoris caused by coronary artery spasm, or raynaud's phenomenon (Raynauds);
    2. Congestive heart failure (NYHA class III-IV), cardiac arrest;
    3. Stroke, transient ischemic attack;
    4. History of recurrent syncope or positive result of vasovagal syncope tilt test;
    5. Symptomatic bradycardia, sick sinus syndrome, sinoatrial block, second degree atrioventricular block (e.g., Mobitz type 2 atrioventricular block) or third degree atrioventricular block;
    6. Congenital long QT syndrome (LQTS), or prolonged QT interval corrected using Fridericia's formula (QTcF) in screening ECG (QTcF >450 ms in men, QTcF > 470 ms in women);
    7. Subjects at increased risk for QT prolongation due to hypokalemia or hypomagnesemia; or subjects who currently tacking medications to prolong QT interval (e.g., citalopram, chlorpromazine, haloperidol, methadone, and erythromycin) which result in risk for torsades de pointes;
    8. Under treatment or expected to taking treatment during the study with medications with a known impact on the cardiac conduction system (e.g., beta blockers, calcium channel blockers, Class Ia or Class III anti-arrhythmic drugs. [amiodarone, bromobenzylamine, sotalol, ibutilide, azimilide, dofetilide]);
    9. Hypertension (except well-controlled hypertension after pharmacotherapy); systolic blood pressure < 95 mm Hg or >140 mm Hg and diastolic blood pressure ≤ 50 mm Hg or ≥ 95 mm Hg at the screening visit;
    10. Resting heart rate < 55 times/min or ventricular rate < 55 times/min in 12-lead ECG at screening visit;
    11. Investigator deems that the 12-lead ECG at screening visit is clinically significant abnormal, such as, myocardial ischemia, any significant cardiac conduction abnormalities (such as the left bundle branch block), that would put the subject at risk or interfere with the study results;
    12. Any other significant heart disease that the investigator judges would put the subject at risk or interfere with the study results.
    13. Subjects have a family history of premature coronary heart disease.
  13. History of type 1 diabetes, uncontrolled type 2 diabetes (HbA1c > 7%) judged by investigator, patients with diabetes accompanied with significant complications, e.g., retinopathy or kidney disease.
  14. Pulmonary function test (including examinations of lung ventilation function and pulmonary gas exchange) at the screening visit shows one of the following abnormalities: forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) < 70% of normal expected value.
  15. During screening period, any of the following laboratory abnormalities:

    1. HGB < 8 g/dL;
    2. WBC count < 3.5 × 10E9/L;
    3. Neutrophils count < 1.5 × 10E9/L;
    4. Lymphocyte count < 0.8 × 10E9/L;
    5. Platelet count < 100 × 10E9/L or >1200 × 10E9/L;
    6. Serum creatinine > 124 μmol/L for female or > 141 μmol/L for male;
  16. Abnormal liver function test druring the screening period, such as abonormalities in alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (γ-GT), alkaline phosphatase (ALK) or serum total bilirubin, which suggests liver diseases or liver function impairment.
  17. If female, the subject is intending to become pregnant before, during, or within 4 weeks after participating in the study or intending to donate ova during such period.
  18. If male, the subject intends to donate sperm during the study or for 4 weeks thereafter.

    Exclusion criteria for infectious diseases:

  19. The subject has evidence of known active infection during the screening period.
  20. The subject has evidence of treatment for Clostridioides difficile (C. difficile) infection or other intestinal pathogen with 28 days prior to first dose of study drug.
  21. Active or latent tuberculosis (TB) evidenced.
  22. Chronic hepatitis B virus (HBV) infection* or chronic hepatitis C virus (HCV) infection**.
  23. The subject has any identified congenital or acquired immunodeficiency (e.g., common variable immunodeficiency, human immunodeficiency virus [HIV] infection, organ transplantation).
  24. The subject has received any live vaccine within 30 days prior to screening, or subjects are scheduled for immunization with any live vaccine during the study or within 1 month after the last dose of the investigational product.
  25. Positive syphilis antibody at screening.
  26. Subjects with a history of more than one episode of herpes zoster, or a history of disseminated herpes zoster or disseminated herpes simplex.

For subjects' entry into the study stage 2 from the stage 1:

  1. Subjects currently have evidence of active or untreated latent tuberculosis.
  2. Subjects currently have active or chronic recurrent infections, and in the opinion of the investigator subjects are not appropriate to participate in the stage 2 of the study.
  3. History of uveitis or macular oedema.
  4. Subjects had received any of the following treatments after administration of the first dose in the stage 1 of the study:

    • Biological product;
    • Prednisone>30 mg/day, budesonide>9 mg/day, methylprednisolone>24 mg/day or equivalent dose of steroid treatment;
    • Immunosuppressant (such as azathioprine and 6-mercaptopurine or methotrexate).
  5. Investigator deems that the 12-lead ECG results at the study visit of week 12 during study stage 1 is clinically significant abnormal, such as myocardial ischemia, any significant cardiac conduction abnormalities (such as the left bundle branch block), any abnormality that would put the subject at risk or interfere with the study results.
  6. Pulmonary function test (including examinations of lung ventilation function and pulmonary gas exchange) of subjects at the study visit of week 12 during the study stage 1 shows 1 of the following abnormalities: forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) < 50% of normal predicted value.
  7. Subjects' laboratory measurements at week 12 visit during the study stage 1 meet any of the following criteria:

    • AST or ALT> 3 ULN;
    • Absolute lymphocyte count < 0.2×10E9/L;
    • Serum creatinine > 124 μmol/L (in females) or > 141 μmol/L (in males)
  8. Any other reason that in the opinion of the investigator may interfere with subject compliance or evaluation of the results of the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: John Guo (+86)0512-53577866 jwguo@connectpharm.com
Contact: Amber Li (+86)0512-53577866 xwli@connectpharm.com
Listed Location Countries  ICMJE China,   Pakistan,   Ukraine,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04700449
Other Study ID Numbers  ICMJE CBP-307CN002
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Suzhou Connect Biopharmaceuticals, Ltd.
Study Sponsor  ICMJE Suzhou Connect Biopharmaceuticals, Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Suzhou Connect Suzhou Connect Biopharmaceuticals, Ltd.
PRS Account Suzhou Connect Biopharmaceuticals, Ltd.
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP