The Efficacy and Safety of Combining Probiotic VSL#3 With Vedolizumab for the Treatment of Moderate Ulcerative Colitis

NCT06609447 | Recruiting Phase 4

• 1 other identifier: 2024-0602
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 12

Brief Summary

An imbalance in the gut microbiota and mucosal immune dysfunction leading to intestinal inflammation are central to the pathogenesis of ulcerative colitis (UC). Both international and domestic inflammatory bowel disease (IBD) guidelines consistently recommend the use of the probiotic VSL#3 for inducing or maintaining remission in cases of mild-to-moderate UC. While the development of biologic therapies in recent years has provided new directions for IBD treatment, classic biologics such as infliximab may increase the risk of opportunistic infections and malignancies. Vedolizumab, when used for the induction therapy of UC, has a response rate of less than 80%, a slightly slower onset of action, and a slight increase in Clostridioides difficile infection (CDI) incidence. Currently, there is a lack of clinical data on the adjunctive use of VSL#3 with biologic agents in the treatment of UC globally. Therefore, this project aims to design a multi-center, randomized, placebo-controlled, double-blind study. The primary objective is to compare the changes in clinical response in patients with moderately active UC treated with either VSL#3 or placebo in combination with vedolizumab (VDZ) for six weeks.

Conditions

Ulcerative Colitis

Outcome Measures

Primary Outcomes (1)

• Clinical Response rate at week 6

  The proportion of participants with a SCCAI score reduction of ≥3 points from baseline in the experimental group compared to the control group at week 6

  At week 6

Secondary Outcomes (7)

• Clinical Response rate at week 14

  At Week 14

• Clinical Remission rate at week 14

  At Week 14

• Steroid-free Clinical Remission rate at week 14

  At Week 14

• At week 2 on PRO2 and Urgency NRS through dairy daily

  At Week 2

• Inflammatory Bowel Disease Questionnaire (IBDQ) variation

  At the end of treatment weeks 6 and 14

Study Arms (2)

VSL#3 combine with Vedolizumab Arm

EXPERIMENTAL

Treatment with probiotic VSL#3 combined with vedolizumab; Subjects will receive two sachets daily of VSL#3, each containing 450 billion bacteria (totaling 900 billion bacteria per day), for 14 weeks. Vedolizumab will be administere as per clinical practice with the following schedule: 300 mg ev at 0, 2 and 6, 14 weeks.

Dietary Supplement: VSL#3; Drug: Vedolizumab

Placebo combine with Vedolizumab Arm

PLACEBO COMPARATOR

Treatment with placebo combined with vedolizumab; Subjects will receive two sachets daily of Placebo for 14 weeks. Vedolizumab will be administere as per clinical practice with the following schedule: 300 mg ev at 0, 2 and 6, 14 weeks.

Dietary Supplement: Placebo; Drug: Vedolizumab

Interventions

VSL#3 DIETARY_SUPPLEMENT

VSL#3 450 billion CFU/sachet

VSL#3 combine with Vedolizumab Arm

Placebo DIETARY_SUPPLEMENT

Placebo sachets with maltose, cornstarch and dioxide

Also known as: Placebo (for VSL#3)

Placebo combine with Vedolizumab Arm

Vedolizumab DRUG

Patients will start combined therapy with vedolizumab and VSL#3 or placebo at the same time. Vedolizumab will be administered according to clinical practice with the following schedule: 300 mg intravenously on Baseline (Day 1 / Week 0) and Weeks 2, 6, and 14, with a flexibility of ±3 days relative to the start of VSL#3 administration.

Also known as: Vedolizumab 300 mg Injection

Placebo combine with Vedolizumab Arm; VSL#3 combine with Vedolizumab Arm

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must be a man or woman aged 18-85 years, inclusive.
• Diagnosed with ulcerative colitis (UC) at least 90 days prior to baseline, supported by comprehensive colonoscopy findings and histopathological evidence obtained within the past year. Participants must provide full colonoscopy or sigmoidoscopy reports along with pathology results conducted within the last 3 months, as well as blood indicators (within 1 week) at baseline screening. Individuals currently experiencing infection, dysplasia, or malignancy will be excluded from participation.
• Subject has moderate active UC and had a Mayo score of 6-10 at screening.
• Planned treatment with Vedolizumab as initial therapy or reinduction, with reinduction defined as no vedolizumab treatment within 1 year.
• Confirmed by the investigator that despite receiving at least one of the following treatments, the subject has shown an inadequate response, loss of response, or intolerance:
• Oral aminosalicylates (e.g., mesalamine, sulfasalazine, olsalazine, balsalazide), where the subject exhibits ongoing signs and symptoms of active disease during at least 4 weeks of treatment with mesalamine 2.4 g/day, sulfasalazine 4 g/day, olsalazine 1 g/day, or balsalazide 6.75 g/day.
• Immunosuppressants: failure to respond after receiving at least 42 consecutive days of treatment with azathioprine, 6-mercaptopurine, or methotrexate (MTX) injections prior to baseline (Week 0), with minimum doses of azathioprine ≥ 0.75 mg/kg/day or 6-MP ≥ 0.5 mg/kg/day (rounded to the nearest tablet dose) or MTX ≥ 15 mg/week (SC/IM), or the highest tolerated dose due to adverse effects such as leukopenia, elevated liver enzymes, or nausea.
• No increase in dose of oral 5-ASA and Immunosuppressants could be allowed if it is maintained stable at least 2 weeks before screening.
• Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
• Willing and able to complete the required Subject Diary.
• Willing and able to meet all study requirements, including attending all assessment visits and phone calls.

You may not qualify if:

• Diagnosis of Crohn's disease, undetermined IBD or other colitis.
• UC disease limited to the rectum (\<15 cm from the anal verge)
• Steroid therapy initiation within 2 weeks before screening visit.
• Used antibiotics for intestinal or other infections within 2 weeks of the screening
• Use of other probiotics preparations within the last 2 weeks before study entry (screening)
• Used rectal 5-ASA within the past week before study entry (screening)
• Adjustment of oral 5-ASA and immunosuppressant dosages due to disease progression after colonoscopy screening until enrollment.
• Within 1 week prior to screening, the participant has taken nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-diarrheal medications for 5 consecutive days.
• Positive Clostridioides difficile detection toxin results within the past month prior to screening.
• Pregnancy and breastfeeding women
• Other biologics/advanced therapies are used as concomitant therapy and Previous use of other biologics
• History of allergy to maltose and/or cornstarch and/or silica
• Subjects with severe primary heart, liver, lung, kidney, hematologic, or serious diseases that affect their survival, such as cancer, AIDS, asthma, kidney stones, renal dysfunction; urine protein \>+, microscopic hematuria, ALT \>2N (N is the upper limit of normal), Cr \> normal upper limit, platelet count \<50x10\^9/L, white blood cell count \<3.0x10\^9/L.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (12)

The Seventh Medical Center, PLA General Hospital

Beijing, Beijing Municipality, 100000, China

NOT YET RECRUITING

Chongqing General Hospital

Chongqing, Chongqing Municipality, 401147, China

RECRUITING

The Sixth Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510655, China

NOT YET RECRUITING

Renmin Hospital of Wuhan University

Wuhan, Hubei, 430060, China

RECRUITING

The Second Affiliated Hospital of Xi&#39;an Jiaotong University

Xi’an, Shanxi, 710004, China

NOT YET RECRUITING

West China Hospital of Sichuan University

Chengdu, Sichuan, 610041, China

NOT YET RECRUITING

Zhejiang Provincial Hospital of Traditional Chinese Medicine

Hangzhou, Zhejiang, 310006, China

RECRUITING

2nd Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310009, China

NOT YET RECRUITING

Huzhou City Central Hospital

Huzhou, Zhejiang, 313000, China

NOT YET RECRUITING

Jinhua City Central Hospital

Jinhua, Zhejiang, 321000, China

NOT YET RECRUITING

Quzhou City People's Hospital

Quzhou, Zhejiang, 324000, China

NOT YET RECRUITING

The Second Affiliated Hospital, Wenzhou Medical University

Wenzhou, Zhejiang, 325000, China

NOT YET RECRUITING

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

vedolizumab; Injections

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Central Study Contacts

Yan Chen, PhD

CONTACT

chenyan72_72@zju.edu.cn

Qiao Yu, PhD

CONTACT

+86 13456820567; yuqiao@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A Multicenter, Randomized, Double-blind, Placebo-controlled trial in adult subjects with moderate active ulcerative colitis

Study Record Dates

• First Submitted: September 22, 2024
• First Posted: September 24, 2024
• Study Start: September 21, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: September 24, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (12)