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  • Status : Approved
    • First Submitted Date : 2020/06/15
    • Registered Date : 2020/06/30
    • Last Updated Date : 2020/05/29
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1. Background

Background Information
CRIS
Registration Number
KCT0005185 
Unique Protocol ID 4-2020-0204 
Public/Brief Title A multicenter study to evaluate the efficacy and safety of Infliximab and Lactobacillus gasseri KBL697 in subjects with moderate to severe active ulcerative colitis patients. 
Scientific Title A multicenter, double-blind, randomized, placebo-controlled, IIT, exploratory human study to evaluate the efficacy and safety of Infliximab and Lactobacillus gasseri KBL697 in the induction of remission in subjects with moderate to severe active ulcerative colitis patients.  
Acronym  
MFDS Regulated Study No
IND/IDE Protocol No
Registered
at Other Registry
No
Healthcare Benefit
Approval Status
Submitted pending

2. Institutional Review Board/Ethics Committee

Institutional Review Board Information
Board Approval Status Submitted approval 
Board Approval Number 4-2020-0204 
Approval Date 2020-04-14 
Institutional Review Board  
Name Yonsei University Health system, Severance Hospital, Institutional Review Board  
Address 50-1, Yonsei-ro, Seodaemun-gu, Seoul 
Telephone 02-2228-0435 
Data Monitoring Committee No  

3. Contact Details

Contact Details Information
Contact Person for Principal Investigator / Scientific Queries  
Name JAE HEE CHEON 
Title Professor 
Telephone +82-2-2228-0435 
Affiliation Yonsei University Health System, Severance Hospital 
Address 50-1, Yonsei-ro, Seodaemun-gu, Seoul 
Contact Person for Public Queries
Name JOO YEON EUM 
Title study coordinator 
Telephone +82-2-2228-0535 
Affiliation Yonsei University Health System, Severance Hospital 
Address 50-1, Yonsei-ro, Seodaemun-gu, Seoul 
Contact Person for Updating Information
Name Yoonjeong Lee 
Title study coordinator 
Telephone +82-2-2228-0557 
Affiliation Yonsei University Health System, Severance Hospital 
Address 50-1, Yonsei-ro, Seodaemun-gu, Seoul 

4. Status

Status Information
Study Site Multi-center (Number of center : 5)
Overall Recruitment Status Not yet recruiting  
Date of First Enrollment 2020-07-27 , Anticipated
Target Number of Participant 80
Primary Completion Date 2022-04-13 , Anticipated
Study Completion Date 2022-04-13 , Anticipated
Recruitment Status by Participating Study Site 1
Name of Study Site Yonsei University Health System, Severance Hospital 
Recruitment Status Not yet recruiting  
Date of First Enrollment 2020-07-27 , Anticipated
Recruitment Status by Participating Study Site 2
Name of Study Site Yonsei University Health System, Gangnam Severance Hospital 
Recruitment Status Not yet recruiting  
Date of First Enrollment 2020-07-27 , Anticipated
Recruitment Status by Participating Study Site 3
Name of Study Site Seoul National University Hospital 
Recruitment Status Not yet recruiting  
Date of First Enrollment 2020-07-27 , Anticipated
Recruitment Status by Participating Study Site 4
Name of Study Site Seoul National University Bundang Hospital 
Recruitment Status Not yet recruiting  
Date of First Enrollment 2020-07-27 , Anticipated
Recruitment Status by Participating Study Site 5
Name of Study Site Korea University Anam Hospital 
Recruitment Status Not yet recruiting  
Date of First Enrollment 2020-07-27 , Anticipated

5. Source of Monetary / Material Support

Source of Monetary / Material Support Information
Source of Monetary/Material Support 1   
Organization Name Kobiolabs 
Organization Type Others  
Project ID  

6. Sponsor Organization

Sponsor Organization Information
Sponsor Organization 1   
Organization Name Yonsei University Health System, Severance Hospital 
Organization Type Medical Institute  

7. Study Summary

Study Summary Information
Lay Summary Ulcerative colitis(UC) is a chronic inflammatory bowel disease charaterized by inflammation of the mucous membrane limited to the colon, and even though pathogenesis mechanism has not been identified yet, the recent study about sensitive genes, known to be related to the barrier of intestinal epithelial cells or immune function, an imbalance in immune function triggered by changes in intestinal bacteria (or metabolites) or other infections caused by animal experimental models, help to understand inflammatory mechanism of bowel disease. In addition, inflammatory cytokines such as interleukin (IL)-6, IL-8, and IL-10 tumor necrosis factor (TNF)-α in colon tissue of ulcerative colitis patients increased compared to normal controls. Recently, studies have been published on the intake of probiotics as an additional food in addition to treatments for inflammatory bowel diseases. However, most of the research on the working mechanism of probiotics in ulcerative colitis has been done in non-living experiments or animal models. Although these effects are thought to be closely related to various clinical conditions, there are some differences in the results of basic studies and clinical studies, and are also discrepancies between basic studies.
We expect KBL697 induce remission of moderate to severe UC as an additional factor through non-human application studies. Currently, atopic dermatitis patients are being tested for human application test and KBL697 belonging to L.gasseri, a strain that is used as a raw material for various health functional foods as a kind of lactobacillus, has long proven empirical safety, minimizing risk factors in the early stages of food development.
Therefore, the overall risks and benefits of the KBL697 capsule are considered acceptable, and this human application test is intended to assess the effectiveness of the induction along with the stability of the KBL697 capsule in patients with moderate to severe UC.  

8. Study Design

Study Design Information
Study Type Interventional Study 
Study Purpose Treatment    
Phase Not applicable 
Intervention Model Parallel  
Blinding/Masking Double 
Blinded Subject Subject, Investigator 
Allocation RCT 
Intervention Type Others (Health/Functional Food)
Intervention Description The study is Randomized, double blinded, placebo controlled parallel assigned multi-center study. The number of total subjects are 80 for the study. Subjects will be equally asigned to active and placebo group, 40 for Active:40 for Placebo accordingly.
Those who meet the exclusion criteria shall take Lactobacillus gaseri KBL697 capsule or placebo daily for 14 weeks and inject Infliximab into IVF for three times (base line, V3, V4) during the treatment period. Dosage of infliximab will be set based on the each patient. In order to prevent antibody production, the pre-treatment drug can be administered according to the judgement of the investigator before the treatment. Planned daily dose of each group is 4 capsules(2 capsules BID, 1,600 mg, oral). placebo group takes placebo every day for 14weeks. The daily dose is 4 capsules( 2 capsules BID, 1,600mg, oral)  
Number of Arms
Arm 1 Arm Label Treatment of active capsules 
Target Number of Participant 40 
Arm Type Experimental 
Arm Description Treatment of active capsules of Lactobacillus gasseri KBL697, for 14 weeks, every day(oral, 2 capsules BID(total 4 capsules/day, 1,600mg) 
Arm 2 Arm Label Treatment of placebo capsules 
Target Number of Participant 40 
Arm Type Placebo comparator 
Arm Description Treatment of placebo capsules of Lactobacillus gasseri KBL697, for 14 weeks, every day(oral, 2 capsules BID(total 4 capsules/day, 1,600mg) 

9. Subject Eligibility

Subject Eligibility Information
Condition(s) / Problem(s) * Diseases of the digestive system
 Ulcerative Colitis
Rare Disease Yes
Inclusion
Criteria
Gender Both 
Age 19 Year ~ 75 Year
Description 1) Patients who have the ability to understand and sign written consent to be obtained prior to the commencement of the test procedure, and who are able to comply with the requirements of the human application test. <br />2) Men or women under the age of 19-75 <br />3) A person diagnosed with moderate and severe ulcerative colitis (a total score of 6 to 12 points of Mayo Clinic Score (MCS), with at least 1 point of bowel movement, 1 point of rectal bleeding, 2 or more points of endoscopy, 2 or more points of doctor&#39;s opinion) <br />4) A person who is clinically deemed to need to be administered biological agents due to a lack of effectiveness in existing treatments; <br />5) Patients who have no previous experience in using biological agents (IFX, Adalimumab, etc.) as a treatment for ulcerative colitis and who are subject to infleximab administration indications. <br />6) Patients with oral administration of the following drugs for the purpose of maintaining the baseline criteria: <br />(1) Oral 5-Aminosalicylic acid (5-Aminosalicylic acid, 5-ASA) compound, Azatioprine (AZA), 6-mergaptopurine (6-Mercaptopurine, 6-MP), or metro-tracet (Metroxate) randomization (MetroxT) for more than four weeks before the baseline. <br />(2) A person who uses oral corticosteroid therapy (less than 30 mg/day of Prednisone and less than 9 mg/day of Budhesonide) for at least two weeks prior to the baseline and must be stable for 14 weeks after random assignment. <br />(However, steroids can be reduced by 5 mg per week until 10 mg/day, and 2.5 mg per week from 10 mg/day when clinical symptoms are improved or related based on Prednisolone under judge by principle investigator.) <br />7) A person who meets the following test values in a laboratory test: <br />(1) Liver Panel (AST, ALT, Total bilirubin) ≤ 2 × ULN <br />(2) Estimated CrCl ≥ 40 ml/min calculated by CC&G equation <br />(3) Blood pigment ≥ 8 g/dL, platelet ≥ 100 × 10^9/L <br />(4) Absolute Neutral Count (ANC) ≥ 1.5 × 10^9/L (1500/mm^3) <br />(5) White Blood Cell (WBC) L 3.0 x 10^9/L) Absolute Limphocyte Count (ALC) &gt; 750/mm^3  
Exclusion Criteria 1) Patients suspected of Crohn&#39;s colitis, indeterminate colitis, ischemic colitis, radiation colitis, colitis related to diverticular diseases, and microscopic colitis. <br />2) When acute severe ulcerative colitis is expressed; <br />(at least six blood stools a day and at least one of the following is body temperature 38 oC (100.4oF) or pulse 90 times/min or higher) <br />3) Patients who have had a intestinal surgery in the past or who are expected to need a intestinal surgery during the human application test period. <br />4) Patients with active tuberculosis lesions observed on chest X-rays (However, latent tuberculosis can participate in the study with the approval of the client.) <br />5) Patients with local medicine (workplace) within two weeks of screening <br />6) Patients whose fecal samples identify their fungi and pathogen toxins <br />- pathogenic Escherichia coli (E. coli), Salmonella spp, Shigella spp, Yesinia spp. <br />- Clostridium difficile (C. difficile) toxin A, B <br />(However, patients with strains and pathogens toxins can participate after treatment.) <br />7) Positive patients (but only at the discretion of the tester) in the ova and parasites test (O&P).) <br />8) Patients with a history of treating lymphocyte depletion therapy, such as Alemtozumab, cyclophosphamide, electrophoresis irradiation, and retoximab. <br />9) A person who has an overreaction history to IFX, its metabolites or its dosage form. <br />10) Patients with a history of major surgery or trauma within four weeks prior to screening <br />11) Patients with cancer history within five years prior to screening (except for non-black skin cancer or cervical epithelial cancer).) <br />12) Patients with a history of multiple myeloma or lymphoma <br />13) HIV-positive patients <br />14) Patients with hepatitis B or C and patients with liver failure <br />15) Patients who received the following medication before screening <br />(1) Patients who received oral anti-inflammatory drugs within two weeks prior to screening <br />(2) Patients who received intravenous anti-inflammatory drugs within four weeks prior to screening <br />(3) Patients who received a live vaccine within four weeks prior to screening <br />16) A person who has received other human-applied test foods within 30 days before taking human-applied test foods or has used human-applied test foods and clinical trial medicines; <br />17) Patients with a history of drug or alcohol abuse <br />18) Women who are pregnant or breast-feeding, men who plan to donate sperm within six weeks of the completion of the human application test, or women who are willing to donate eggs. <br />19) Men and women who are not willing to use proper contraception* during the human body application test period. <br />*Hormon contraceptives, intrauterine devices or intrauterine system implants, double-blocking (both male condoms and closed caps (both contraceptive septum or cervical caps)), infertility procedures (correctomy, bifurcation of both sides, etc.) <br />20) Patients who are deemed unfit by the investigator to participate in the human application study  
Healthy Volunteers No

10. Outcome Measure(s)

Outcome Measure(s) Information
Type of Primary Outcome Safety 
Primary Outcome(s) 1 
Outcome Evaluate the remission ratio based on the MCS in visit 5(14th week) compared to the baseline. 
Timepoint baseline, visit 5 (14th week) 
Secondary Outcome(s) 1 
Outcome Evaluate the steroid-free remission ratio in visit 5(14th week) compared to the baseline. 
Timepoint baseline, visit 5 (14th week) 
Secondary Outcome(s) 2 
Outcome Evaluate the clinical ratio of biopsy, bleeding, defecation in visit 5(14th week) compared to the baseline. 
Timepoint baseline, visit 5 (14th week) 
Secondary Outcome(s) 3 
Outcome Evaluate the patients ratio with subscore 0 on endoscopy test in visit 5(14th week) compared to the baseline. 
Timepoint baseline, visit 5 (14th week) 
Secondary Outcome(s) 4 
Outcome Evaluate the change of cytokines and immunological biomarker in blood serum in visit 5(14th week) compared to the baseline. 
Timepoint baseline, visit 5 (14th week) 
Secondary Outcome(s) 5 
Outcome Evaluate the change of bacterial flora of intestine in visit 5(14th week) compared to the baseline. 
Timepoint baseline, visit 5 (14th week) 
Secondary Outcome(s) 6 
Outcome Evaluate the change rate of CRP every visit. 
Timepoint screening, baseline, visit 3(2nd week), visit 4(6th week) 5 (14th week) 
Secondary Outcome(s) 7 
Outcome Evaluate the change rate of calprotectin in visit 5(14th week) compared to screening. 
Timepoint baseline, visit 5 (14th week) 
Secondary Outcome(s) 8 
Outcome Evaluate the change of average of short IBDQ score in visit 5(14th week) compared to baseline. 
Timepoint baseline, visit 5 (14th week) 

11. Study Results and Publication

Study Results and Publication Information
Result Registered No

12. Sharing of Study Data(Deidentified Individual-Patient Data, IPD)

Sharing of Study Data Information
Sharing Statement No 
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