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NCT03721107

A Trial for New Treatment of Adult Participants With Irritable Bowel Syndrome

Completed Phase 2 Results posted Last updated 11 January 2022
What this trial tests

Phase 2 trial testing Blautix in Irritable Bowel Syndrome in 366 participants. Completed in 13 May 2020.

Timeline
11 October 2018
Primary endpoint
13 May 2020
13 May 2020

Quick facts

Lead sponsor4D pharma plc
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment366
Start date11 October 2018
Primary completion13 May 2020
Estimated completion13 May 2020
Sites34 locations across United Kingdom, Ireland, United States

Drugs / interventions tested

Conditions studied

Sponsor

4D pharma plc — full company profile →

Who can join

Adults 18 to 70, any sex, with Irritable Bowel Syndrome. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Overall Response Primary · 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

GroupValue95% CI
Cohort C: Blautix25.0
Cohort C: Placebo17.1
Cohort D: Blautix23.4
Cohort D: Placebo17.8
Number of Participants With Treatment-Related Treatment-Emergent Adverse Events (TEAEs) Secondary · 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.

GroupValue95% CI
Cohort C: Blautix5
Cohort C: Placebo4
Cohort D: Blautix16
Cohort D: Placebo14
Number of Participants With Response to Subject Global Assessment of Relief Secondary · 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.

Week 1: Completely Relieved
GroupValue95% CI
Cohort C: Blautix0
Cohort C: Placebo2
Cohort D: Blautix2
Cohort D: Placebo0
Week 1: Considerably Relieved
GroupValue95% CI
Cohort C: Blautix1
Cohort C: Placebo3
Cohort D: Blautix1
Cohort D: Placebo0
Week 1: Somewhat Relieved
GroupValue95% CI
Cohort C: Blautix6
Cohort C: Placebo6
Cohort D: Blautix3
Cohort D: Placebo8
Week 1: Unchanged
GroupValue95% CI
Cohort C: Blautix58
Cohort C: Placebo56
Cohort D: Blautix72
Cohort D: Placebo76
Week 1: Worse
GroupValue95% CI
Cohort C: Blautix1
Cohort C: Placebo3
Cohort D: Blautix6
Cohort D: Placebo2
Week 4: Completely Relieved
GroupValue95% CI
Cohort C: Blautix1
Cohort C: Placebo1
Cohort D: Blautix2
Cohort D: Placebo1
Week 4: Considerably Relieved
GroupValue95% CI
Cohort C: Blautix13
Cohort C: Placebo7
Cohort D: Blautix13
Cohort D: Placebo14
Week 4: Somewhat Relieved
GroupValue95% CI
Cohort C: Blautix31
Cohort C: Placebo31
Cohort D: Blautix26
Cohort D: Placebo24
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) Secondary · 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

Change at Week 1
GroupValue95% CI
Cohort C: Blautix0.13± 22.859
Cohort C: Placebo3.38± 24.412
Cohort D: Blautix-25.67± 28.078
Cohort D: Placebo-23.70± 30.730
Change at Week 4
GroupValue95% CI
Cohort C: Blautix-4.23± 24.470
Cohort C: Placebo-1.99± 24.077
Cohort D: Blautix-32.43± 33.627
Cohort D: Placebo-33.73± 33.615
Change at Week 8
GroupValue95% CI
Cohort C: Blautix-5.93± 26.705
Cohort C: Placebo-0.10± 22.852
Cohort D: Blautix-40.36± 37.595
Cohort D: Placebo-36.91± 35.753
Change at Week 12
GroupValue95% CI
Cohort C: Blautix-5.66± 23.063
Cohort C: Placebo1.06± 27.027
Cohort D: Blautix-34.09± 41.128
Cohort D: Placebo-42.13± 31.500
Change at Week 13
GroupValue95% CI
Cohort C: Blautix10.88± 26.517
Cohort C: Placebo-5.16± 19.868
Cohort D: Blautix-29.38± 35.002
Cohort D: Placebo-32.21± 39.679
Change at Week 14
GroupValue95% CI
Cohort C: Blautix-15.48± 1.684
Cohort C: Placebo-2.98± 15.994
Cohort D: Blautix-40.00± 36.216
Cohort D: Placebo-38.10± 36.608
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) Secondary · 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 stoo

Percent Change at Week 1
GroupValue95% CI
Cohort C: Blautix15.05± 126.940
Cohort C: Placebo27.65± 129.217
Cohort D: Blautix32.30± 36.887
Cohort D: Placebo-27.27± 38.590
Percent Change at Week 4
GroupValue95% CI
Cohort C: Blautix-6.36± 122.165
Cohort C: Placebo-7.18± 112.425
Cohort D: Blautix-40.14± 42.757
Cohort D: Placebo-40.60± 40.128
Percent Change at Week 8
GroupValue95% CI
Cohort C: Blautix-12.00± 145.174
Cohort C: Placebo-4.64± 103.202
Cohort D: Blautix-49.32± 45.798
Cohort D: Placebo-42.64± 39.801
Percent Change at Week 12
GroupValue95% CI
Cohort C: Blautix-7.45± 125.537
Cohort C: Placebo14.75± 144.064
Cohort D: Blautix-36.96± 50.023
Cohort D: Placebo-49.94± 34.638
Percent Change at Week 13
GroupValue95% CI
Cohort C: Blautix41.07± 143.017
Cohort C: Placebo-40.31± 89.914
Cohort D: Blautix-33.29± 40.067
Cohort D: Placebo-35.91± 44.635
Percent Change at Week 14
GroupValue95% CI
Cohort C: Blautix-100.00± 0.000
Cohort C: Placebo-25.00± 106.066
Cohort D: Blautix-52.50± 49.319
Cohort D: Placebo-43.53± 44.353
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) Secondary · 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 constipat

Change at Week 1
GroupValue95% CI
Cohort C: Blautix1.33± 2.202
Cohort C: Placebo1.61± 2.416
Cohort D: Blautix-1.07± 2.441
Cohort D: Placebo-1.02± 3.119
Change at Week 4
GroupValue95% CI
Cohort C: Blautix2.14± 2.348
Cohort C: Placebo1.87± 2.809
Cohort D: Blautix-1.60± 2.543
Cohort D: Placebo-1.83± 3.389
Change at Week 8
GroupValue95% CI
Cohort C: Blautix2.00± 2.289
Cohort C: Placebo2.42± 2.751
Cohort D: Blautix-2.59± 3.012
Cohort D: Placebo-1.97± 3.048
Change at Week 12
GroupValue95% CI
Cohort C: Blautix1.76± 2.547
Cohort C: Placebo2.18± 2.762
Cohort D: Blautix-2.29± 2.599
Cohort D: Placebo-2.43± 3.299
Change at Week 13
GroupValue95% CI
Cohort C: Blautix2.09± 2.489
Cohort C: Placebo1.98± 2.539
Cohort D: Blautix-2.05± 3.242
Cohort D: Placebo-1.77± 2.804
Change at Week 14
GroupValue95% CI
Cohort C: Blautix2.56± 0.507
Cohort C: Placebo1.19± 0.860
Cohort D: Blautix-4.71± 2.626
Cohort D: Placebo-3.54± 4.063
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) Secondary · 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

Change at Week 4: Total score
GroupValue95% CI
Cohort C: Blautix5.67± 16.858
Cohort C: Placebo5.79± 21.908
Cohort D: Blautix5.62± 18.087
Cohort D: Placebo5.93± 13.113
Change at Week 4: Dysphoria score
GroupValue95% CI
Cohort C: Blautix5.95± 20.561
Cohort C: Placebo5.34± 22.881
Cohort D: Blautix9.17± 22.627
Cohort D: Placebo5.81± 17.429
Change at Week 4: Interference with activity Score
GroupValue95% CI
Cohort C: Blautix4.79± 16.952
Cohort C: Placebo6.71± 22.633
Cohort D: Blautix7.54± 18.230
Cohort D: Placebo8.26± 16.008
Change at Week 4: Body Image Score
GroupValue95% CI
Cohort C: Blautix4.88± 23.779
Cohort C: Placebo7.62± 23.239
Cohort D: Blautix5.83± 20.703
Cohort D: Placebo4.10± 17.860
Change at Week 4: Health Worry Score
GroupValue95% CI
Cohort C: Blautix10.98± 23.082
Cohort C: Placebo10.57± 26.940
Cohort D: Blautix6.85± 19.727
Cohort D: Placebo7.55± 19.056
Change at Week 4: Food Avoidance Score
GroupValue95% CI
Cohort C: Blautix6.50± 20.625
Cohort C: Placebo4.88± 29.461
Cohort D: Blautix5.56± 19.624
Cohort D: Placebo7.55± 19.960
Change at Week 4: Social Reaction Score
GroupValue95% CI
Cohort C: Blautix4.12± 16.922
Cohort C: Placebo2.44± 24.402
Cohort D: Blautix0.42± 23.963
Cohort D: Placebo6.64± 14.935
Change at Week 4: Sexual Score
GroupValue95% CI
Cohort C: Blautix7.32± 29.445
Cohort C: Placebo1.52± 24.716
Cohort D: Blautix-0.56± 20.288
Cohort D: Placebo0.39± 19.284
Change From Baseline in IBS Symptom Severity Score (IBS-SSS) at Week 4, 8 and Follow-up Visit (Weeks 12-14) Secondary · 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 disea

Change at Week 4
GroupValue95% CI
Cohort C: Blautix-128.87± 143.885
Cohort C: Placebo-141.30± 139.439
Cohort D: Blautix-125.75± 135.258
Cohort D: Placebo-100.97± 114.939
Change at Week 8
GroupValue95% CI
Cohort C: Blautix-168.46± 157.300
Cohort C: Placebo-173.53± 155.253
Cohort D: Blautix-143.55± 143.781
Cohort D: Placebo-133.63± 139.290
Change at Follow-up visit
GroupValue95% CI
Cohort C: Blautix-142.49± 149.678
Cohort C: Placebo-160.66± 150.174
Cohort D: Blautix-113.47± 135.064
Cohort D: Placebo-104.76± 146.447
Change From Baseline in Hospital Anxiety and Depression (HADS) Total Score at Week 4, 8 and Follow-up Visit (Weeks 12-14) Secondary · 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.

Change at Week 4: Anxiety total score
GroupValue95% CI
Cohort C: Blautix-0.02± 2.612
Cohort C: Placebo0.22± 2.954
Cohort D: Blautix0.09± 2.827
Cohort D: Placebo-0.27± 3.243
Change at Week 4: Depression total score
GroupValue95% CI
Cohort C: Blautix0.24± 3.527
Cohort C: Placebo-0.29± 3.303
Cohort D: Blautix0.22± 2.566
Cohort D: Placebo0.00± 2.410
Change at Week 8: Anxiety total score
GroupValue95% CI
Cohort C: Blautix0.08± 2.981
Cohort C: Placebo-0.09± 3.320
Cohort D: Blautix-0.32± 3.251
Cohort D: Placebo-0.40± 3.213
Change at Week 8: Depression total score
GroupValue95% CI
Cohort C: Blautix-0.18± 3.432
Cohort C: Placebo-0.06± 3.556
Cohort D: Blautix0.19± 2.787
Cohort D: Placebo-0.36± 3.169
Change at Follow-up visit: Anxiety total score
GroupValue95% CI
Cohort C: Blautix-0.53± 3.360
Cohort C: Placebo0.06± 2.714
Cohort D: Blautix-0.14± 3.029
Cohort D: Placebo-0.55± 3.375
Change at Follow-up visit: Depression total score
GroupValue95% CI
Cohort C: Blautix-0.85± 3.735
Cohort C: Placebo-0.14± 2.939
Cohort D: Blautix0.51± 3.024
Cohort D: Placebo-0.68± 2.886

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to follow-up visit (up to Week 14). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort C: Blautix
Serious: 0/80 (0%)
Deaths: 0/80
Cohort C: Placebo
Serious: 0/84 (0%)
Deaths: 0/84
Cohort D: Blautix
Serious: 1/97 (1%)
Deaths: 0/97
Cohort D: Placebo
Serious: 1/104 (1%)
Deaths: 0/104

Serious adverse events (2 terms)

ReactionSystemCohort C: BlautixCohort C: PlaceboCohort D: BlautixCohort D: Placebo
Atrial fibrillationCardiac disorders
CellulitisInfections and infestations
Other adverse events (100 terms — click to expand)

ReactionSystemCohort C: BlautixCohort C: PlaceboCohort D: BlautixCohort D: Placebo
NasopharyngitisInfections and infestations
DiarrhoeaGastrointestinal disorders
HeadacheNervous system disorders
Upper respiratory tract infectionInfections and infestations
GastroenteritisInfections and infestations
Abdominal painGastrointestinal disorders
DyspepsiaGastrointestinal disorders
Irritable bowel syndromeGastrointestinal disorders
FatigueGeneral disorders
CellulitisInfections and infestations
Vulvovaginal candidiasisInfections and infestations
ConstipationGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
HaemorrhoidsGastrointestinal disorders
NauseaGastrointestinal disorders
Abdominal distensionGastrointestinal disorders
Muscle strainInjury, poisoning and procedural complications
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
InsomniaPsychiatric disorders
Urinary tract infectionInfections and infestations
BronchitisInfections and infestations
InfluenzaInfections and infestations
PharyngitisInfections and infestations
Tooth infectionInfections and infestations
Viral upper respiratory tract infectionInfections and infestations
Acute sinusitisInfections and infestations
Ear infectionInfections and infestations
Herpes zosterInfections and infestations
Lice infestationInfections and infestations
Lower respiratory tract infectionInfections and infestations
Oral herpesInfections and infestations
Otitis mediaInfections and infestations
RhinitisInfections and infestations
SinusitisInfections and infestations
TonsillitisInfections and infestations
Vaginal infectionInfections and infestations
Viral infectionInfections and infestations
Viral rhinitisInfections and infestations
Vulvovaginal mycotic infectionInfections and infestations
VomitingGastrointestinal disorders

Most-reported serious reactions: Atrial fibrillation, Cellulitis.

Data from ClinicalTrials.gov NCT03721107 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Gut Microbiome-Brain Alliance: A Landscape View into Mental and Gastrointestinal Health and Disorders.
    Sasso JM, Ammar RM, Tenchov R, Lemmel S, et al · · 2023 · cited 100× · PMID 37156006 · DOI 10.1021/acschemneuro.3c00127
  2. <i>Lachnospiraceae</i> are emerging industrial biocatalysts and biotherapeutics.
    Zaplana T, Miele S, Tolonen AC. · · 2023 · cited 57× · PMID 38239921 · DOI 10.3389/fbioe.2023.1324396
  3. Microbial therapeutics: New opportunities for drug delivery.
    Jimenez M, Langer R, Traverso G. · · 2019 · cited 43× · PMID 31028093 · DOI 10.1084/jem.20190609
  4. Randomised clinical trial: efficacy and safety of the live biotherapeutic product MRx1234 in patients with irritable bowel syndrome.
    Quigley EMM, Markinson L, Stevenson A, Treasure FP, et al · · 2023 · cited 18× · PMID 36369645 · DOI 10.1111/apt.17310
  5. Recent advances in therapeutic probiotics: insights from human trials.
    Cho M-Y, Eom J-H, Choi E-M, Yang S-J, et al · · 2025 · cited 17× · PMID 40261032 · DOI 10.1128/cmr.00240-24
  6. The regulatory framework for microbiome-based therapies: insights into European regulatory developments.
    Rodriguez J, Cordaillat-Simmons M, Pot B, Druart C. · · 2025 · cited 13× · PMID 40155609 · DOI 10.1038/s41522-025-00683-0
  7. Designing bugs as drugs: exploiting the gut microbiome.
    Lamousé-Smith E, Kelly D, De Cremoux I. · · 2021 · cited 6× · PMID 33264062 · DOI 10.1152/ajpgi.00381.2019
  8. Signal Versus Noise: How to Analyze the Microbiome and Make Progress on Antimicrobial Resistance.
    Golob JL, Rao K. · · 2021 · cited 1× · PMID 33880565 · DOI 10.1093/infdis/jiab184

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