A Trial for New Treatment of Adult Participants With Irritable Bowel Syndrome
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| ClinicalTrials.gov Identifier: NCT03721107 |
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Recruitment Status :
Completed
First Posted : October 26, 2018
Results First Posted : January 11, 2022
Last Update Posted : January 11, 2022
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Sponsor:
4D pharma plc
Information provided by (Responsible Party):
4D pharma plc
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Brief Summary:
A study to evaluate the effectiveness of oral doses of Blautix in adult participants with irritable bowel syndrome (IBS).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Irritable Bowel Syndrome | Biological: Blautix Other: Placebo | Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 366 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Masking Description: | Double blind trial design |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | October 11, 2018 |
| Actual Primary Completion Date : | May 13, 2020 |
| Actual Study Completion Date : | May 13, 2020 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Cohort C: Blautix
Participants diagnosed with Irritable bowel syndrome subtype C (IBS-C) received two capsules of Blautix orally, twice daily for 8 weeks. Maximum daily dose of Blautix (strain of Blautia hydrogenotrophica) will be 10^10 to10^11 most probable number (MPN).
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Biological: Blautix
Blautix is a live biotherapeutic product consisting of a lyophilised formulation of a proprietary strain of bacterium. The study dosing regimen was two capsules two times per day for the duration of the treatment period.
Other Names:
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Placebo Comparator: Cohort C: Placebo
Participants diagnosed with IBS-C received two capsules of placebo matched to Blautix orally, twice daily for 8 weeks.
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Other: Placebo
Placebo control |
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Experimental: Cohort D: Blautix
Participants diagnosed with Irritable bowel syndrome subtype D (IBS-D) received two capsules of Blautix orally, twice daily for 8 weeks. Maximum daily dose of Blautix (strain of Blautia hydrogenotrophica) will be 10^10 to10^11 MPN.
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Biological: Blautix
Blautix is a live biotherapeutic product consisting of a lyophilised formulation of a proprietary strain of bacterium. The study dosing regimen was two capsules two times per day for the duration of the treatment period.
Other Names:
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Placebo Comparator: Cohort D Placebo
Participants diagnosed with IBS-D received two capsules of placebo matched to Blautix orally, twice daily for 8 weeks.
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Other: Placebo
Placebo control |
Primary Outcome Measures :
- Percentage of Participants With Overall Response [ Time Frame: Baseline up to Week 8 ]Overall responder was a participant who has at least 7 evaluable weeks of data and has reported an improvement in their weekly symptoms (abdominal pain intensity [API] and stool frequency [SF] or consistency [SC]) for greater than or equal to (>=) 50 percent (%) of the treatment period. Improvement for abdominal pain intensity was defined as decrease in weekly average of worst abdominal pain in the past 24 hours score of at least 30% compared with baseline for Cohort C and Cohort D, for stool frequency was defined as increase of 1 or more complete spontaneous bowel movements (CSBM) per week compared with baseline for Cohort C and for stool consistency was defined as decrease at least 50% in the proportion of days per week with at least one stool that has a consistency of Type 6 or 7 compared with baseline for Cohort D. Participants with <4 weeks available were considered non-responders.
Secondary Outcome Measures :
- Number of Participants With Treatment-Related Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Baseline up to follow-up visit (up to Week 14) ]An adverse event (AE) was any untoward medical occurrence in a participant administered study medication and which does not necessarily have a causal relationship with this treatment. A TEAE was defined as an AE that started or worsened in severity on or after the start date of the study treatment and includes all AEs recorded through the follow-up visit. A treatment-related TEAE was a TEAE possibly related to the study treatment.
- Number of Participants With Response to Subject Global Assessment of Relief [ Time Frame: Week 1, 4, 8, follow-up visit (Week 12, 13 and 14) ]The subject global assessment of relief was collected weekly through the electronic clinical outcome assessment (eCOA) system. It was a comparison of how the participant has felt over the past week with regards to their IBS to the way they felt before entering the study. It was measured on a 5-point Likert scale with the following responses: Completely relieved; considerably relieved; somewhat relieved; unchanged; worse. The total score ranged from 0-20, where higher scores indicated worsening of condition.
- 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) [ Time Frame: Baseline, Week 1, 4, 8, follow-up visit (Week 12, 13 and 14) ]Stool consistency of each bowel movement was rated on 7-level Bristol Stool Chart where Type 1 = separate hard lumps, like nuts (hard to pass), Type 2 = sausage-shaped but lumpy, Type 3 = like a sausage but with cracks on the surface, Type 4 = like a sausage or snake, smooth and soft, Type 5 = soft blobs with clear-cut edges (passed easily), Type 6 = fluffy pieces with ragged edges, a mushy stool, Type 7 = watery, no solid pieces; entirely liquid. A score range of 1 to 7 where, 1 or 2 indicates constipation and a score of 6 or 7 indicates diarrhea. Change in percentage of days per week with at least 1 stool with a undesired stool consistency of 1 or 2 for Cohort C and 6 or 7 for Cohort D on the Bristol Stool Chart from baseline at Week 1, 4, 8, Follow-up Visit (Week 12, 13 and 14) was reported.
- 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) [ Time Frame: Baseline, Week 1, 4, 8, follow-up visit (Week 12, 13 and 14) ]Stool consistency of each bowel movement was assessed by participants using the 7-point BSFS from 1 to 7 where Type 1 = separate hard lumps, like nuts (hard to pass), Type 2 = sausage-shaped but lumpy, Type 3 = like a sausage but with cracks on the surface, Type 4 = like a sausage or snake, smooth and soft, Type 5 = soft blobs with clear-cut edges (passed easily), Type 6 = fluffy pieces with ragged edges, a mushy stool, Type 7 = watery, no solid pieces; entirely liquid. A score of 1 or 2 indicates constipation and a score of 6 or 7 indicates diarrhea. Lower numbers represented more formed stools and higher numbers represented less formed stools. A negative change from Baseline indicates improvement.
- 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) [ Time Frame: Baseline, Week 1, 4, 8, follow-up visit (Week 12, 13 and 14) ]Stool frequency was defined as a sum of weekly CSBMs. Participants were reminded to rate all their bowel movements in the Bristol Stool Chart (BSC) before answering the question. Stool types were assessed using the 7-point BSFS where 1 = separate hard lumps, like nuts (hard to pass), 2 = sausage-shaped but lumpy, 3 = like a sausage but with cracks on the surface, 4 = like a sausage or snake, smooth and soft, 5 = soft blobs with clear-cut edges (passed easily), 6 = fluffy pieces with ragged edges, a mushy stool, 7 = watery, no solid pieces; entirely liquid. A score of 1 or 2 indicates constipation and a score of 6 or 7 indicates diarrhea. Weekly stool frequency was based on the daily stool frequency which was calculated as follows: if there was 1 or more entry for BSC, the number of BSC entries was summed up. If on that day laxative was used, the daily stool frequency was set to 0. If an answer to CSBMs, but no BSC entry was provided, the daily stool frequency was set to 0 on that day.
- 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) [ Time Frame: Baseline, Week 4, 8, follow-up visit (Weeks 12-14) ]Participants were asked to complete a QOL of 34 items which formed 8 scales: dysphoria (8 items), interference with activity (7 items), body image (4 items), health worry (3 items), food avoidance (3 items), social reaction (4 items), sexual (2 items), and relationships (3 items). All 8 scales were rated on a five-point response scale where, 1= not at all, 2= slightly, 3= moderately, 4= quite a bit, 5= extremely or a great deal. Scores for individual items were averaged to obtain a total score for each sub-scale of IBSQoL. Total and subscale scores were transformed to a 0 to 100 point scale (0=lowest score, 100=highest possible score) with higher scores indicating better IBS-specific quality of life. Transformed scale score = (Sum of the items-lowest possible score/Possible raw score range)∗100. A positive change from baseline indicates improved quality of life.
- Change From Baseline in IBS Symptom Severity Score (IBS-SSS) at Week 4, 8 and Follow-up Visit (Weeks 12-14) [ Time Frame: Baseline, Week 4, 8, follow-up visit (Weeks 12-14) ]Participants were asked to complete a questionnaire on the severity of abdominal distension and pain, frequency of abdominal pain, dissatisfaction with bowel habits, and interference of IBS symptoms with daily life. The IBS-SSS was measured on a Visual Analog Scale (VAS scale) in combination with reported numeric values which equated to an overall score. The scale range was from 0 (no symptoms) to 500 (maximum severity). Participants were categorized as having mild (74-174), moderate (175-299), or severe (>300) IBS symptoms based on symptomology. Higher scores were indicative of greater disease severity (worse outcome). A negative change from Baseline indicates improvement.
- Change From Baseline in Hospital Anxiety and Depression (HADS) Total Score at Week 4, 8 and Follow-up Visit (Weeks 12-14) [ Time Frame: Baseline, Week 4, 8, follow-up visit (Weeks 12-14) ]Participants were asked to complete the HADS which was a 14-item scale (7 items- anxiety and 7 items-depression) that generated ordinal data. Each question was rated on a scale from 0 - 3. The outcome of the HADS questionnaire was two total scores, the HADS-A (for anxiety) and the HADS-D (for depression). Both total scores are graded on a scale of 0 - 21 and can be categorized as Normal (0 - 7), Borderline Abnormal (8 - 10) and Abnormal (11 - 21). Higher scores indicate higher levels of anxiety and depression. A negative change from Baseline indicates improvement.
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| Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Written consent on an Institutional Review Board (IRB)/ Independent Ethics Committee (IEC) approved informed consent form before any study specific evaluation
- Males and Females between 18 and 70 years of age
- Body Mass Index (BMI): 18-39 kg/m^2
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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
- 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:
- Males or females <18 and >70 years of age
- Have a IBS symptom severity score < 175 as defined by IBS-SSS
- BMI: <18 or >39 kg/m^2
- 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)
- Confirmed clinical diagnosis of bile acid malabsorption and / or on medication for bile acid malabsorption
- 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
- 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)
- Have a malignant disease or any concomitant end-stage organ disease.
- Females who are pregnant or breast feeding
- 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
- Use of antibiotics within 1 month of screening
- Use of systemic steroids within the last month
- Change in dose or introduction of an antipsychotic within the last month
- Have suffered from a major psychiatric disorder
- Clinically diagnosed Lactose intolerance
- Clinically diagnosed Coeliac disease
- Change of diet e.g. FODMAP, gluten-free within last 3 months
- 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.
- Any gastrointestinal-related abdominal surgery other than hernia repair or appendectomy
- Participants taking prucalopride
- Other investigational procedures while participating in this study are excluded
- Known HIV infection, or hepatitis A, B, or C active infection
- Participants with abnormal laboratory values at screening deemed by the investigator to be clinically significant
- Participants who have taken commercially available probiotics within the last month (30 days prior to randomization)
- Participants with known or suspected hereditary fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltose insufficiency
- Participants taking guanylate cyclase agonists, such as linaclotide and lubiprostone
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03721107
Locations
Show 34 study locations
Sponsors and Collaborators
4D pharma plc
Investigators
| Principal Investigator: | Eamonn Quigley | Houston Methodist Gastroenterology Clinical Research Foundation, Houston, Texas |
Study Documents (Full-Text)
Documents provided by 4D pharma plc:
Documents provided by 4D pharma plc:
Study Protocol [PDF] March 31, 2020
Statistical Analysis Plan [PDF] September 16, 2020
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | 4D pharma plc |
| ClinicalTrials.gov Identifier: | NCT03721107 |
| Other Study ID Numbers: |
BHT-II-002 |
| First Posted: | October 26, 2018 Key Record Dates |
| Results First Posted: | January 11, 2022 |
| Last Update Posted: | January 11, 2022 |
| Last Verified: | December 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by 4D pharma plc:
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constipation diarrhea |
Additional relevant MeSH terms:
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Irritable Bowel Syndrome Syndrome Disease Pathologic Processes Colonic Diseases, Functional |
Colonic Diseases Intestinal Diseases Gastrointestinal Diseases Digestive System Diseases |