Clinical trial NCT03721107: A Trial for New Treatment of Adult Participants With Irritable Bowel Syndrome
Official title: A Phase II Randomized, Double Blind, Placebo-controlled, Parallel Group, Multicenter Study to Evaluate the Safety and Efficacy of Repeated Oral Doses of Blautix in Adult Subjects With Irritable Bowel Syndrome (IBS) Subtypes IBS-C and IBS-D
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Irritable Bowel Syndrome
Keywords: constipation
diarrhea
Lead sponsor: 4D pharma plc
Sponsor class: INDUSTRY
First posted: 2018-10-26
Enrollment: 366
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A study to evaluate the effectiveness of oral doses of Blautix in adult participants with irritable bowel syndrome (IBS).

Detailed description: Participants with a diagnosis of IBS will be enrolled as defined by Rome IV criteria and will be classified into cohorts according to the Rome IV classification of IBS subtypes.

Each cohort (Cohort C and Cohort D) will recruit participants who will randomly receive either Blautix or matching placebo in a 1:1 ratio overall of treated to control participants.

Participants will undergo five visits in total across approximately 13 weeks. During the study treatment phase, participants will be asked to complete a variety of Quality of Life questionnaires at certain time points. These will consist of abdominal pain intensity score, IBS symptom severity (IBS-SSS), IBS quality of life (IBS-QoL), hospital anxiety and depression score (HADS), stool frequency, stool consistency \& food frequency questionnaire.

Participants will be required to produce relevant blood, urine and faecal samples at pre-determined timepoints from screening through to End of Treatment and follow up visits.

Eligibility criteria: Inclusion Criteria:

1. Written consent on an Institutional Review Board (IRB)/ Independent Ethics Committee (IEC) approved informed consent form before any study specific evaluation
2. Males and Females between 18 and 70 years of age
3. Body Mass Index (BMI): 18-39 kg/m\^2
4. Having IBS-C or IBS-D as defined by Rome IV\* including Subtype Classification as defined in Table 2

   \* Recurrent abdominal pain on average, at least 1 day/week in the last 3 months associated with two or more of the following criteria:
   * Related to defecation
   * Associated with a change in frequency of stool
   * Associated with a change in form (appearance) of stool
5. Have a moderate or severe IBS symptom severity score (\> 175) as defined by IBS-SSS

Table 2:

IBS -C Abdominal Pain Intensity: weekly average of worst daily (in past 24 hours) abdominal pain score of \> 3.0 on a 0 to 10-point scale And Stool Frequency: more than 25% of bowel movements with a consistency of Type 1 or Type 2 Bristol stool chart and less than 25% of bowel movements with Bristol stool form Type 6 or Type 7. Participants must have fewer than 3 complete spontaneous bowel movements (CSBMs) within a one week period (7 days)

IBS-D Abdominal Pain Intensity: weekly average of worst daily (in past 24 hours) abdominal pain score of \> 3.0 on a 0 to 10-point scale And Stool Consistency: more than 25% of bowel movements with a consistency of Type 6 or Type 7 Bristol stool chart and less than 25% of bowel movements with Bristol stool form Type 1 or Type 2.Participants must have at least one Type 6 or Type 7 bowel movements on at least four days within a one week period (7 days).

Exclusion Criteria:

1. Males or females \<18 and \>70 years of age
2. Have a IBS symptom severity score \< 175 as defined by IBS-SSS
3. BMI: \<18 or \>39 kg/m\^2
4. Have a significant acute or chronic coexisting illness (cardiovascular, gastrointestinal, endocrine, immunological, metabolic or any condition which contraindicates, in the investigators' judgment, entry to the study)
5. Confirmed clinical diagnosis of bile acid malabsorption and / or on medication for bile acid malabsorption
6. Individuals who, in the opinion of the investigator, are poor attendees or unlikely for any reason to be able to comply with the study requirements
7. Participant is currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s), or participant is receiving other investigational agent(s)
8. Have a malignant disease or any concomitant end-stage organ disease.
9. Females who are pregnant or breast feeding
10. Refusal to use acceptable methods of birth control (true abstinence, sterilisation, birth control pills, injections or contraceptive implants) for fertile participants (females) while on treatment and following completion of 2 menstrual cycles/ months after the last dose of study treatment. For Males, a barrier method of birth control from randomisation until the Follow-Up visit
11. Use of antibiotics within 1 month of screening
12. Use of systemic steroids within the last month
13. Change in dose or introduction of an antipsychotic within the last month
14. Have suffered from a major psychiatric disorder
15. Clinically diagnosed Lactose intolerance
16. Clinically diagnosed Coeliac disease
17. Change of diet e.g. FODMAP, gluten-free within last 3 months
18. Those \> 50 will be excluded if their diagnosis of IBS is recent (\<12 months) and if they have not had a sigmoidoscopy or colonoscopy within previous 5 years.
19. Any gastrointestinal-related abdominal surgery other than hernia repair or appendectomy
20. Participants taking prucalopride
21. Other investigational procedures while participating in this study are excluded
22. Known HIV infection, or hepatitis A, B, or C active infection
23. Participants with abnormal laboratory values at screening deemed by the investigator to be clinically significant
24. Participants who have taken commercially available probiotics within the last month (30 days prior to randomization)
25. Participants with known or suspected hereditary fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltose insufficiency
26. Participants taking guanylate cyclase agonists, such as linaclotide and lubiprostone

Primary outcomes:
measure: Percentage of Participants With Overall Response
timeFrame: Baseline up to Week 8
Secondary outcomes:
measure: Number of Participants With Treatment-Related Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to follow-up visit (up to Week 14)
measure: Number of Participants With Response to Subject Global Assessment of Relief
timeFrame: Week 1, 4, 8, follow-up visit (Week 12, 13 and 14)
measure: Change in Percentage of Days Per Week With Undesired Stool Consistency From Baseline at Week 1, 4, 8, Follow-up Visit (Week 12, 13 and 14)
timeFrame: Baseline, Week 1, 4, 8, follow-up visit (Week 12, 13 and 14)
measure: Percent Change From Baseline in Stool Consistency Assessed by Bristol Stool Form Scale (BSFS) at Week 1, 4, 8, Follow-up Visit (Week 12, 13 and 14)
timeFrame: Baseline, Week 1, 4, 8, follow-up visit (Week 12, 13 and 14)
measure: Change From Baseline in Weekly Average Stool Frequency Assessed by Bristol Stool Form Scale (BSFS) at Week 1, 4, 8, Follow-up Visit (Week 12, 13 and 14)
timeFrame: Baseline, Week 1, 4, 8, follow-up visit (Week 12, 13 and 14)
measure: Change From Baseline in IBS Quality of Life (IBS-QOL) Questionnaire Subscale and Total Scores at Week 4, 8 and Follow-up Visit (Weeks 12-14)
timeFrame: Baseline, Week 4, 8, follow-up visit (Weeks 12-14)
measure: Change From Baseline in IBS Symptom Severity Score (IBS-SSS) at Week 4, 8 and Follow-up Visit (Weeks 12-14)
timeFrame: Baseline, Week 4, 8, follow-up visit (Weeks 12-14)
measure: Change From Baseline in Hospital Anxiety and Depression (HADS) Total Score at Week 4, 8 and Follow-up Visit (Weeks 12-14)
timeFrame: Baseline, Week 4, 8, follow-up visit (Weeks 12-14)
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Clinical Research Associates
state: Alabama
city: Phoenix
country: United States
facility: Elite Clinical Studies
state: Arizona
city: North Hollywood
country: United States
facility: Translational Research Group, Inc
state: California
city: Riverside
country: United States
facility: Probe Clinical Research
state: California
city: Bristol
country: United States
facility: Connecticut Gastroenterology Clinical Research
state: Connecticut
city: Coral Springs
country: United States
facility: Digestive CARE of North Broward, LLC
state: Florida
city: Jacksonville
country: United States
facility: Borland-Groover Clinic
state: Florida
city: Orlando
country: United States
facility: Orlando Florida BioClinica Research Network
state: Florida
city: Pompano Beach
country: United States
facility: Clinical Research Center of Florida
state: Florida
city: Saint Augustine
country: United States
facility: East Coast Institute for Research, LLC.
state: Florida
city: Tampa
country: United States
facility: Guardian Angel Research Center
state: Florida
city: Snellville
country: United States
facility: Georgia Medical Associates
state: Georgia
city: Evanston
country: United States
facility: Evanston Premier Healthcare & Research, LLC.
state: Illinois
city: Lake Charles
country: United States
facility: Centex Research, Inc.
state: Louisiana
city: Rockville
country: United States
facility: Capitol Research
state: Maryland
city: Saint Louis
country: United States
facility: Specialists in Gastroenterology
state: Missouri
city: Greensboro
country: United States
facility: PharmQuest
state: North Carolina
city: Columbus
country: United States
facility: Aventiv Research Inc.
state: Ohio
city: Mount Pleasant
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Chattanooga
country: United States
facility: WR-ClinSearch
state: Tennessee
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions, Inc
state: Tennessee
city: Houston
country: United States
facility: Houston Methodist Gastroenterology Associates
state: Texas
city: Missouri City
country: United States
facility: Gulf Coast Medical Research, LLC.
state: Texas
city: Lynchburg
country: United States
facility: Blue Ridge Medical Research
state: Virginia
city: Cork
country: Ireland
facility: Cork University Hospital
city: Barnsley
country: United Kingdom
facility: MAC Clinical Research (Barnsley)
city: Blackpool
country: United Kingdom
facility: MAC Clinical Research (Blackpool)
city: Cannock
country: United Kingdom
facility: MAC Clinical Research (Cannock)
city: Glasgow
country: United Kingdom
facility: CPS Research
city: Leeds
country: United Kingdom
facility: MAC Clinical Research (Leeds)
city: Liverpool
country: United Kingdom
facility: MAC Clinical Research (Liverpool)
city: Manchester
country: United Kingdom
facility: MAC Clinical Research (Manchester)
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital
city: Stockton-on-Tees
country: United Kingdom
facility: MAC Clinical Research (Stockton-on-Tees)
Study officials:
affiliation: Houston Methodist Gastroenterology Clinical Research Foundation, Houston, Texas
name: Eamonn Quigley
role: PRINCIPAL_INVESTIGATOR
References:
citation: Quigley EMM, Markinson L, Stevenson A, Treasure FP, Lacy BE. Randomised clinical trial: efficacy and safety of the live biotherapeutic product MRx1234 in patients with irritable bowel syndrome. Aliment Pharmacol Ther. 2023 Jan;57(1):81-93. doi: 10.1111/apt.17310. Epub 2022 Nov 11.