A Phase 2 Study to Evaluate the Efficacy and Safety of Live SK08 Powder in Adult Patients with Active Mild to Moderate Ulcerative Colitis

A Phase 2, Multi-center, Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Live SK08 Powder (Bacteroides Fragilis) in Adult Patients with Active Mild to Moderate Ulcerative Colitis

This is a Phase 2, multi-center, randomized, double-blind, placebo-controlled study to preliminarily evaluate the efficacy and safety of SK08 in adult patients with active mild to moderate UC. Each subject will undergo three study periods: screening, induction treatment period and a safety follow-up period.

Study Overview

• Status: Not yet recruiting
• Conditions: Ulcerative Colitis (UC)
• Intervention / Treatment: Drug: Placebo; Drug: Live SK08 powder

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yangyang Liu, MD; Phone Number: China: 020-82515346; Email: liuyangyang@zypharm.com.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects who voluntarily sign the informed consent form and are able to comply with the study protocol and have the ability to follow relevant procedures.
2. Male and female subjects aged 18-75 years (inclusive) at the time of signing the informed consent.
3. Ulcerative colitis diagnosed by routine clinical, endoscopy, and pathologic criteria for at least 3 months.
4. Subjects with active mild to moderate UC as defined by modified Mayo Score (mMS) of 4-10 (both inclusive), including an endoscopy sub-score of at least 2 and a rectal bleeding sub-score of at least 1.
5. The lesion extends beyond the rectum (colonoscopy shows that the lesion is > 15 cm from the anal verge).
6. Have had no response to, an inadequate response to, or an intolerance to standard 5-ASA treatment (including 5-ASA local treatment), no response or inadequate response means patients have persistent symptoms during treatment with 5-ASA at the recommended dose and treatment duration, intolerance means patients discontinue the 5-ASA treatment due to adverse events. Subjects receiving concurrent stable dose 5-ASA (i.e. no change in medication within 4 weeks of study enrollment and is not expected to change during the study) are permitted to be enrolled.
7. If female, the subject is non-lactating, and is either: Not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or hysterectomy; Of childbearing potential and is practicing at least 1 highly effective method of birth control including the barrier method; oral or parenteral contraceptives; a vasectomized partner; or abstinence from sexual intercourse from the time of signing informed consent and until at least 3 months after the last dose of the study drug. The Investigator will discuss with the subject the option of practicing more than 1 of the above methods for the duration of the study. Subjects must have a negative serum pregnancy test within 7 days prior to the first dose of the study drug.
8. If male and partner is of childbearing potential, the subject agrees to practice at least one highly effective method of birth control from the time of signing the informed consent until at least 3 months after the last dose of the study drug.

Exclusion Criteria:

1. Subjects with Crohn's disease, radiation colitis, diverticulitis, ischemic colitis, microscopic colitis, drug-related (e.g., NSAIDs, tretinoin, immune checkpoint inhibitors, mycophenolate, etc.) colitis, patients with indeterminate colitis, and patients with endoscopy/biopsy showing ileitis/granulomas with clinical suspicion of Crohn's disease.
2. Malignancy or history of malignancy within the previous 5 years except for resected cutaneous basal cell or squamous cell carcinoma that has been treated with no evidence of recurrence.
3. Subjects who received surgery within 30 days before the first dose of study drug or who plan to undergo surgery during the study.
4. Subjects with other pathological conditions in the intestine, including colon dysplasia, intestinal stricture, tumor, intestinal fistula, intestinal obstruction, celiac disease, etc.
5. Presence of any active or chronic recurrent infections.
6. Subjects with previous colectomy, ostomy, J-pouch, or previous intestinal surgery (excluding cholecystectomy, appendectomy).
7. Subjects with severe, progressive or uncontrolled renal, hepatic, hematological, endocrine, immune, cardiovascular, respiratory, neurological, or psychiatric disease.
8. Subjects with poor concurrent medical risks with a clinically significant co-morbid disease such that, in the opinion of the Investigator, the subject should not be enrolled including: Subjects with decompensated liver cirrhosis (Child-Pugh Class B or C) or uncontrolled liver disease; History of pancreatitis; QTc > 450 msec or QTc > 480 msec for participants with bundle branch block at screening and Day 1. The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF); Prior history of bone marrow transplant; Known Hypogammaglobulinemia; Known severe immunodeficiency; AST ≥ 2 × the upper limit of normal (ULN) and/or ALT ≥ 2 × ULN and/or total bilirubin ≥ 2 × ULN; eGFR < 60 mL/min/1.73 m² by Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) calculation; Absolute neutrophil count (ANC) < 500 cells/μL.
9. Subjects with anti-hepatitis C virus (HCV) antibody positive, human immunodeficiency virus (HIV) antibody positive, or hepatitis B surface antigen (HBsAg) positive and need antiviral therapy during the screening period.
10. Subjects have known or suspected hypersensitivity to the study drug and its excipients (maltodextrin, silicon dioxide, magnesium stearate).
11. Subjects who cannot discontinue steroid hormones (such as budesonide multi-matrix (MMX)) oral/topical (suppositories, enemas, etc.), or systemic corticosteroids within 2 weeks before the first dose of study drug.
12. Patients who cannot discontinue other drugs that affect gastrointestinal function, including systemic antibiotics, anti-diarrheal agents, etc., within 2 weeks before the first dose of study drug.
13. Received any probiotic medicines or fecal bacteria transplant within 30 days prior to the first dose.
14. Received treatment with biological agents (infliximab, adalimumab, golimumab, certolizumab, vedolizumab, ustekinumab, natalizumab, etc.) within 8 weeks before the first dose (or 5 half lives of the drug); or received any non-biological agents (cyclosporine, tacrolimus, thalidomide, methotrexate, tofacitinib, etc.) treatment within 30 days before the first dose (or 5 half-lives of the drug).
15. Received (attenuated) live vaccination within 4 weeks of Day 1 or plan to receive during the study until follow-up.
16. Subjects who have participated in any clinical trial within 3 months before screening.
17. Subjects with a history of alcohol and drug abuse.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SK08 low dose group; 1 × 10^7 CFU ~ 2.5 × 10^8 CFU/dose, twice daily (BID), taken orally for 8 weeks	Drug: Live SK08 powder; SK08 is an investigational live biotherapeutic product containing a nontoxigenic B. fragilis(NTBF) strain as an active ingredient.
Experimental: SK08 high dose group; 1 × 10^9 CFU ~ 2.5 × 10^10 CFU/dose, BID, taken orally for 8 weeks	Drug: Live SK08 powder; SK08 is an investigational live biotherapeutic product containing a nontoxigenic B. fragilis(NTBF) strain as an active ingredient.
Placebo Comparator: Placebo group; BID, taken orally for 8 weeks.	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects achieving clinical remission at Week 8	Clinical remission is defined as a total mMS score of 0 to 2, including the following three components: Stool frequency sub-score = 0 or 1.; Rectal bleeding sub-score = 0; Centrally read endoscopy sub-score = 0 or 1 (score of 1 modified to exclude friability)	0-8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportion of subjects with clinical response at Week 8	Clinical response is defined as a decrease from baseline in the total mMS of ≥ 2 points and at least a 30 percent reduction from baseline, and a decrease in rectal bleeding subs-core of greater than or equal to 1 or an absolute rectal bleeding sub-score of 0 or 1.	0-8 weeks
proportion of subjects with endoscopic improvement at Week 8	Endoscopic improvement is defined as a centrally read endoscopy sub-score of 0 or 1.	0-8 weeks
proportion of subjects with endoscopic remission at Week 8	Endoscopic remission is defined as a centrally read endoscopy sub-score of 0.	0-8 weeks
change from baseline in the total modified Mayo Score at Week 8		0-8 weeks
mean change in rectal bleeding and stool frequency sub-scores from baseline to Weeks 2, 4, 6 and 8		0-2, 0-4, 0-6, 0-8 weeks

Other Outcome Measures

Outcome Measure	Time Frame
change from baseline in the IBDQ at Week 8.	0-8 weeks
Changes from baseline in fecal calprotectin over time	0-8 weeks
Changes from baseline in serum high-sensitivity C-reactive protein (hsCRP) over time	0-8 weeks

Collaborators and Investigators

• Sponsor: Guangzhou Zhiyi Biotechnology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: December 5, 2024
• First Submitted That Met QC Criteria: December 5, 2024
• First Posted (Actual): December 9, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 11, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Ulcerative Colitis
• Additional Relevant MeSH Terms: Pathologic Processes; Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Colitis; Colitis, Ulcerative; Ulcer
• Other Study ID Numbers: SK08UC-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No