Clinical trial NCT06247046: A Study to Evaluate the Efficacy and Safety of Live SK08 Powder in Patients With IBS-D
Official title: A Multicenter, Randomized, Double-blind, Placebo Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Live SK08 Powder (Bacteroidetes Fragilis) in the Treatment of Patients With Irritable Bowel Syndrome With Diarrhea (IBS-D)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Irritable Bowel Syndrome With Diarrhea
Lead sponsor: Guangzhou Zhiyi Biotechnology Co., Ltd.
Sponsor class: OTHER
First posted: 2024-02-07
Enrollment: 1298
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter, Randomized, Double-blind, Placebo Controlled
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of Live SK08 Powder compared with placebo in the treatment of participants with irritable bowel syndrome with diarrhea.

Detailed description: Irritable Bowel Syndrome (IBS) is a chronic, functional bowel disease characterized by abdominal pain, bloating, or abdominal discomfort. Symptoms may improve after bowel movements, and are often accompanied by changes in bowel habits \[frequency and/or fecal trait \]. There is a lack of organic lesions that can be detected by routine clinical examination to explain these symptoms.

The pathogenesis of IBS is the result of a combination of factors, including visceral hypersensitivity, intestinal immunity and inflammation, gastrointestinal motility abnormalities, and intestinal flora. SK08 can relieve abdominal pain and diarrhea by protecting intestinal barrier function, regulating immunity (such as reducing inflammatory factors TNF-α etc., promoting macrophages to phagocytosis of pathogenic bacteria), and correcting bacterial imbalance, to achieve the therapeutic effect.

Eligibility criteria: Inclusion Criteria:

* 1.Voluntarily sign informed consent, be able to comply with the protocol and be able to carry out related procedures, including the completion of diary during the induction period and throughout the study period.
* 2. Age between 18 and 70 years old (including two-end values, based on the date of signing the Master Informed consent), regardless of gender.
* 3. IBS-D patients with clinical symptoms meeting the Rome IV definition, that is, the course of disease for at least 6 months, repeated abdominal pain in the past 3 months, an average of at least 1 day per week, combined with two or more of the following conditions: (1) Abdominal pain is related to defecation; ② Abdominal pain accompanied by changes in the frequency of defecation; ③ Abdominal pain accompanied by changes in fecal trait. When abnormal stool occurred in the last 3 months, the proportion of abnormal stool was \>25% for Bristol fecal trait type 6 or 7, and \<25% for Bristol fecal trait type 1 or 2 (see Appendix 13.3: IBS Rome IV diagnostic criteria and subtype classification criteria).
* 4. Colonoscopy has been completed within 12 months before the run-in period. The ileocecal part should be observed during endoscopy, and the ileocecal flap image recording should be included in the report. They may be included if one of the following conditions is met: (i) The colonoscopy report is normal; (ii) Abnormalities reported by colonoscopy, such as hemorrhoids and intestinal polyps (diameter ≤5mm and number ≤3), were determined by the investigator to be eligible for inclusion; (iii) Colonoscopy reported that the diameter of intestinal polyps was \>5mm or the number of intestinal polyps was \>3; after endoscopic treatment, the diameter of residual intestinal polyps was ≤5mm and the number of intestinal polyps was ≤3, and the investigators determined that they could be included in the group.
* 5. Colonoscopy or endoscopy should be performed at least 4 weeks before the run-in period, and IBS symptoms still occur before the run-in period.
* 6. During the run-in period, the average number of days with type 6 or type 7 fecal traits per week was ≥4 days, and the average NRS score (the highest score within 24 hours) of daily abdominal pain intensity on days with type 6 or type 7 fecal traits was ≥3.0.
* 7. Patients completed diary at least 5 days in the week before randomization (D-7 to D-1) and at least 10 days in the 2 weeks before randomization (D-14 to D-1).
* 8. The patient had not used any relief drugs or analgesics in the 14 days prior to randomization.
* 9. During the period from the signing of the master informed consent to the end of the final study visit, patients agreed to maintain their usual diet and lifestyle, such as no changes in dietary structure or exercise patterns.

Exclusion Criteria:

* 1. Patients with constipated, mixed and amorphous IBS.
* 2. Patients with organic gastrointestinal diseases were excluded from the following conditions: superficial gastritis, grade I erosive gastritis, chronic atrophic gastritis found by endoscopy but judged by the investigator to be eligible for admission (for example, no mucosal erosion or bleeding under endoscopy, and no abdominal distension, epigastric pain, acid reflux and other symptoms).
* 3. Parenteral diseases of the digestive system such as tuberculous peritonitis, pancreatitis, cirrhosis, and biliary tract diseases are present, except for fatty liver disease that has not progressed to hepatitis, and gallstones that lack related symptoms.
* 4. Known to have lactose intolerance and celiac disease.
* 5. There are other systemic diseases, including serious diseases of the heart, lungs and kidneys, malignant tumors, autoimmune diseases, metabolic diseases (such as diabetes, diseases affecting thyroid function), reproductive system diseases (such as nonphysiologic ovarian cysts, endometriosis, severe dysmenorrhea requiring medical treatment), etc.
* 6. Previous history of abdominal and pelvic surgery, except appendectomy, caesarean section or tubal ligation without intestinal complications, hernia repair.
* 7. Patients with a previously diagnosed psychiatric disorder or moderate to severe depression or generalized anxiety disorder requiring medication (PHQ-9≥10 or GAD-7≥10 during screening).
* 8. Fecal examination results showed occult blood (+) and above (except for cases caused by hemorrhoids or female menstrual periods) or white blood cells (+) and above, and were judged by the investigator to be clinically significant.
* 9. People who are positive for antibodies against hepatitis C virus (HCV), or human immunodeficiency virus (HIV), or syphilis, or hepatitis B surface antigen (HBsAg) and need antiviral therapy at the screening stage.
* 10. Laboratory tests showed significant abnormalities, and the investigator determined that the patient's participation in the study may compromise his or her safety, including but not limited to: (i) Creatinine ≥1.5 times the upper limit of normal (ULN); (ii) AST≥2 times upper limit of normal (ULN) and/or ALT≥2 times upper limit of normal (ULN) and/or total bilirubin ≥1.5 times upper limit of normal (ULN).
* 12. A history of drug or alcohol abuse.
* 13. Even with the help of liquids, patients are unable to take oral solid dosage forms.
* 14. Allergic to experimental drugs, rescue drugs and their ingredients.
* 15. During the trial, drugs that affect gastrointestinal movement and function cannot be discontinued, It includes antibiotics (such as erythromycin), drugs that regulate intestinal microecology (such as bifidobacterium), parasympathetic inhibitors (such as scopolamine, atropine, belladona, etc.), muscle relaxants (such as succinylcholine), antidiarrheal agents (such as loperamide, montmorillonite powder, etc.), opioids, drugs that inhibit gastric acid secretion, etc
* 16. A woman who is pregnant or breastfeeding.
* 17. At the time of the trial, both the patient and his partner were unable or unwilling to use reliable contraception to prevent pregnancy, or the female or male patient's partner had a recent pregnancy plan.
* 18. Have participated in any clinical trial and used the experimental drug or device within 3 months prior to signing the informed consent.
* 19. The patient had previously participated in a clinical study of SK08.
* 20.According to the judgment of the investigator, the participants are not suitable to participate in this clinical trial.

Primary outcomes:
measure: Percentage of Patients Who Were Composite Weekly Responders
timeFrame: 1-12 weeks
measure: Adverse events and serious adverse events
timeFrame: 1-52weeks
Secondary outcomes:
measure: Percentage of Patients Who Were Composite Weekly Responders
timeFrame: 1-8weeks、1-4weeks、5-8weeks、9-12weeks
measure: Percentage of Patients Who Were Abdominal Pain Weekly Responder
timeFrame: 1-12weeks、1-8weeks、1-4weeks、5-8weeks、9-12weeks
measure: Percentage of Patients Who Were Stool Consistency Weekly Responder
timeFrame: 1-12weeks、1-8weeks、1-4weeks、5-8weeks、9-12weeks
measure: Percentage of Patients Who Were Abdominal Bloating Weekly Responder
timeFrame: 1-12weeks、1-8weeks、1-4weeks、5-8weeks、9-12weeks
measure: Percentage of Participants Who Were Responders in IBS Symptoms Relief Scale
timeFrame: 1-12weeks、1-8weeks、1-4weeks、5-8weeks、9-12weeks
measure: Change from Baseline in the Weekly Average of Worst Abdominal Pain in the Past 24 hours
timeFrame: week1、week2、week3、week4、week5、week6、week7、week8、week9、week10、week11、week12.
measure: Change from Baseline in the Number of Days per Week with at Least One Stool with Consistency of Type 6 or 7
timeFrame: week1、week2、week3、week4、week5、week6、week7、week8、week9、week10、week11、week12.
measure: Change from Baseline in the Number of Stools of Type 6 or 7 per Week
timeFrame: week1、week2、week3、week4、week5、week6、week7、week8、week9、week10、week11、week12.
measure: Change from Baseline in the Weekly Average of Worst Abdominal Bloating in the Past 24 Hours Score
timeFrame: week1、week2、week3、week4、week5、week6、week7、week8、week9、week10、week11、week12.
measure: Change from baseline in Irritable Bowel Syndrome Severity Scale (IBS-SSS) Scores
timeFrame: week4、week8、week9、week12、week20、week28、week36、week44、week52
measure: Change from baseline in Irritable Bowel Syndrome Quality of Life Scale (IBS-QoL) Total Scores
timeFrame: week4、week8、week9、week12、week20、week28、week36、week44、week52
Other outcomes:
Locations:
city: Wuxi
country: China
facility: Wuxi People's Hospital
state: Jiangsu
city: Binzhou
country: China
facility: Binzhou Medical University Hospital
state: Shandong
Study officials:
affiliation: First Affiliated Hospital, Sun Yat-Sen University
name: Minhu Chen, Doctor
role: STUDY_CHAIR
affiliation: First Affiliated Hospital, Sun Yat-Sen University
name: Yinglian Xiao, Doctor
role: PRINCIPAL_INVESTIGATOR
References: