Phase 2b IBS-C Microbiome Therapeutic Trial, UK/US

Restoring intestinal symbiosis for efficacy in IBS

ISRCTN	ISRCTN15681288
DOI	https://doi.org/10.1186/ISRCTN15681288
Integrated Research Application System (IRAS)	1012072
Protocol serial number	EBX-004
Sponsor	EnteroBiotix Limited
Funder	EnteroBiotix Limited

Submission date 11/06/2025 Registration date 23/04/2026 Last edited 23/04/2026 Recruitment status Not yet recruiting Overall study status Ongoing Condition category Digestive System Prospectively registered Protocol Statistical analysis plan Results Individual participant data Record updated in last year

Plain English summary of protocol

Background and study aims
Irritable bowel syndrome (IBS) affects up to 21% of the population and can have a significant impact on quality of life. While the exact cause of IBS is not fully understood, research indicates that disruptions in the gut microbiome contribute. Therefore, restoring structure and function in the gut microbiome may relieve symptoms and improve quality of life.

This study is testing two formulations of the same drug: EBX-102-02 (pooled from multiple donors) and EBX-102-02 SD (derived from a single donor), which is being developed for people with IBS with constipation (IBS-C). In a Phase 2a clinical trial evaluating EBX-102-02 in moderate-to-severe IBS-C subjects, EBX-102-02 was associated with improvements in IBS symptom severity, stool form and bowel movements.

EBX-102-02, the study's biological drug is a microbiome therapeutic, containing dried gut bacteria derived from rigorously screened stool samples from healthy donors. EBX-102-02 / EBX-102-02 SD is delivered as an oral capsule. Each dose consists of eight capsules that contain an off-white, odourless powder.

Who can participate?
Patients aged ≥18 years or older up to 70 years old with a clinical diagnosis of IBS-C.

What does the study involve?
Approximately 300 adults with IBS-C will take part in this study in the UK and the US. Participants will be randomly assigned to receive either EBX-102-02 or EBX-102-02 SD or a placebo (approximately 100 participants per group). The study will last for up to 18 weeks, during which participants will attend six visits and undergo screening for up to 4 weeks. At four visits, participants will take a single dose of eight capsules. Neither the participants nor the study team will know who is receiving the study drug or the placebo.

During the study, participants will be asked to complete event-based and daily diaries to track bowel habits and report any side effects, weekly questionnaires to record severity and changes in abdominal pain, constipation and monthly questionnaires to track changes in IBS symptoms and quality of life. At each visit, the study team will review symptoms, assess overall health, and carry out a physical examination. Participants will be asked to provide stool samples at several points during the study, so researchers can track changes in the microbiome and monitor safety.

What are the possible benefits and risks of participating?
Participation in the study may help restore a more diverse gut microbiome, with the potential for participants who receive the study drug to see improvement in some of their IBS symptoms. However, there is no guarantee that they will receive a medical benefit from participating in this study.

There are risks, discomforts, and inconveniences associated with any research study. Some of the general risks may not have been previously reported. A summary of potential risks of participating in the study is below:
• Blood collection: taking blood samples may cause bruising and discomfort and a risk of infection or blood clots at the site of the blood collection.
• Study treatment: will be taken in a clinic under direct medical supervision.
• Potential exposure to pathogens: due to the nature of the study treatment, there is a risk of exposure to pathogens. However, the sponsor operates a robust biosafety programme focused on ensuring that the study drug is appropriately and extensively screened, rendering it safe for its intended use. Safety data is also regularly monitored for indications that pathogens have been transmitted.
• Known side effects of EBX-102-02 do not occur in everybody and include feeling sick, bloating, diarrhoea, vomiting and stomach cramps. The study doctor may provide additional medications to ease the experience of side effects; however, typically, symptoms resolve within a few days.
• Unknown Risks: side effects, which are unknown at this time, may occur during the study. Any new information that may affect participants' health or which may make the participants want to stop taking part in the study will be shared with them as soon as it becomes available.
• Pregnancy Prevention: There may be a risk in exposing an unborn child to study drugs, and all risks are not known at this time. Precautions to avoid exposure are described in the Patient Information Sheet.
Participants will be informed of the risks in the Patient Information Sheet and will be asked to notify their study doctor or study staff should they experience any side effects during the study. Participants will be monitored throughout the study to minimise risks.

EBX-102-02 SD has not yet been evaluated in clinical studies; however, its anticipated risk-benefit profile is expected to be consistent with that of EBX-102-02.

Where is the study run from?
EnteroBiotix Ltd

When is the study starting and how long is it expected to run for?
May 2026 to April 2027

Who is funding the study?
EnteroBiotix Ltd

Who is the main contact?
Shinofa Rizan, clinops@enterobiotix.com

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Contact information

Dr Akil Jackson
Scientific EnteroBiotix Limited
Phoenix House, Phoenix Crescent, Strathclyde Business Park
Bellshill
ML4 3NJ
United Kingdom

	medical@enterobiotix.com

Dr Paul Goldsmith
Principal investigator Manchester University NHS Foundation Trust
262 Deansgate
Manchester
M3 4BG
United Kingdom

	paul.goldsmith@mft.nhs.uk

Shinofa Rizan
Public EnteroBiotix Limited
Phoenix House, Phoenix Crescent, Strathclyde Business Park
Bellshill
ML4 3NJ
United Kingdom

	clinops@enterobiotix.com

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Study information

Primary study design	Interventional
Allocation	Randomized controlled trial
Masking	Blinded (masking used)
Control	Placebo
Assignment	Parallel
Purpose	Treatment
Scientific title	A phase 2b, randomised, double-blind, placebo-controlled multicentre study to evaluate the efficacy, safety and tolerability of orally administered full-spectrum microbiome therapeutic (EBX-102-02) in participants with moderate to severe irritable bowel syndrome with constipation
Study acronym	RISE IBS-C
Study objectives	The study is designed to evaluate the efficacy, safety, and tolerability of EBX-102-02 compared to placebo when administered orally to participants with IBS-C.

The two primary objectives of the study are to evaluate:
• IBS symptomatology measured on the IBS Symptom Severity Scale (IBS-SSS) at 14 weeks.
• the safety and tolerability of orally administered full-spectrum microbiome therapeutic (EBX-102-02) (through 14 weeks).

The study will also evaluate, as a key secondary objective:
• The efficacy of EBX-102-02 compared to placebo in improving abdominal pain and stool frequency in adult participants with IBS-C |
| Ethics approval(s) | Approved 16/03/2026, - (-, -, -, United Kingdom; -; -), ref: 25/LO/0468 |
| Health condition(s) or problem(s) studied | Irritable Bowel Syndrome - constipation predominant (IBS-C) |
| Intervention | Trial arms:
Participants will be randomly assigned in a 1:1:1 ratio to three treatment arms:
1) active treatment arm 1 – participants will receive study drug EBX-102-02
2) active treatment arm 2 – participants will receive study drug EBX-102-02 SD
3) control group – participants will receive a ‘placebo’ treatment.

Neither the participants nor the study team will know who is receiving the study drug or the placebo.

Study drugs:
EBX-102-02 and EBX-102-02 SD are gastro-resistant hard hydroxypropyl methylcellulose (HPMC) capsules containing dried gut bacteria derived from rigorously screened human stool samples. EBX-102-02 (containing material pooled from multiple donors) and EBX-102-02 SD (derived from a single donor) are two versions of the same investigational medicinal product with similar types and numbers of gut bugs.

Visual and weight-matched placebo capsules are utilised to maintain the blind.

Randomisation:
Participants will be randomly assigned by an interactive web-based Randomization and Trial Supply Management (RTSM) tool. Randomisation will be performed using a stratified approach according to baseline disease severity (moderate and severe), with allocation balanced across treatment arms.

Dose, schedule and Frequency:
The study will last for up to 18 weeks, including a screening period of up to 4 weeks ahead of dosing, with participants attending a total of six visits.

Each dose consists of eight capsules taken in the clinic at four of these visits (at Week 0, 1, 5 and 9 after screening). Participants will be followed up for 5 weeks after the last dose.

Route of administration: Oral Administration. |
| Intervention type | Biological/Vaccine |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | EBX-102-02 [EBX-102], EBX-102-02 SD [EBX-102] |
| Primary outcome measure(s) | 1. Irritable bowel symptom severity measured using the Irritable Bowel Syndrome Symptom Severity Scale (IBS-SSS) questionnaire at baseline and week 14
2. Incidence and type of treatment emergent adverse events (TEAEs) measured using data collected during safety monitoring assessments at screening, baseline, weeks 1, 5, 9 and 14, clinically significant abnormal vital signs at baseline, weeks 1, 5, 9 and 14 and clinically significant abnormal ECG and clinical laboratory assessments at screening and week 14 |
| Key secondary outcome measure(s) | 1. Overall response rate measured using a composite weekly responder criterion (requiring both ≥30% reduction from baseline in the weekly average of daily worst abdominal pain scores AND an increase of ≥1 complete spontaneous bowel movement (CSBM) per week from baseline, met in ≥50% of planned treatment weeks) at weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14 |
| Completion date | 30/04/2027 |

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Eligibility

Participant type(s)	Patient
Age group	Mixed
Lower age limit	18 Years
Upper age limit	70 Years
Sex	All
Target sample size at registration	300
Key inclusion criteria	1. Participant must be 18 to 70 years of age, inclusive, at the time of signing the informed consent

1. Participants who: 2.1. Have a clinical diagnosis of IBS-C, as confirmed by Rome IV grading criteria (including only participants with at least moderate disease intensity by using an IBS-SSS inclusion of ≥ 175 (recorded at both screening assessment and confirmed at the baseline entry), AND 2.2. Reported IBS-C symptom onset at least 6 months before Screening Date
2. Willing to discontinue all medications for bowel habit abnormalities (IBS-C, IBS-D, and IBS-M) after providing consent.
3. Report an average weekly worst abdominal pain intensity score ≥ 3.0 on a 0-10 numeric scale
4. Have fewer than three (3) complete spontaneous bowel movements (CSBMs) per week recorded in DIBSS-C during the Screening assessment
5. Willing to abstain from consuming regular ‘over-the-counter’ pre- or probiotics from pharmacies or other retailers from screening through to end of follow-up
6. No clinically significant abnormalities in vital signs (blood pressure, heart/pulse rate, respiratory rate, oral temperature) determined within 28 days before first dose of study drug
7. No clinically significant abnormalities in 12-lead electrocardiogram (ECG) determined within 28 days before first dose of study drug.
8. Participants with lactose intolerance who are on a dairy free diet or use lactase-containing products when consuming dairy may be included in the study
9. Body Mass Index within the range 17.5 to 35 kg/m2 (inclusive)
10. Contraceptive use by participants or their partners should be consistent with the requirements stipulated in the study protocol
11. Signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in the study protocol
12. Willing and able to comply with all study requirements. | | Key exclusion criteria | 1. Diarrhoeal illness within 7 days prior to Screening based on clinical judgement
13. Infectious diarrhoea including C. difficile or diarrhoea associated with foreign travel within 12 months of screening
14. Other clinically significant chronic gastrointestinal (GI) disease, as per the opinion of the Investigator including: inflammatory bowel disease, diverticulitis (uncomplicated diverticulosis will not exclude a participant from the study), gastro-oesophageal reflux disease uncontrolled by medication, eosinophilic oesophagitis or other eosinophilic GI diseases, microscopic colitis, malabsorption syndromes e.g. coeliac disease. Further guidance and examples are provided in the study protocol.
15. Any history of malignant tumours (primary or secondary) affecting any part of the GI tract including participants with known familial colorectal cancer syndromes (e.g. Lynch) or any conditions associated with increased risk of GI cancer (e.g., familial adenomatous polyposis coli - FAP)
16. History of colectomy/ileostomy at any time
17. History of colonic perforation or fistula at any time
18. History of any malignancy within the 5 years prior to screening, excluding non-melanoma skin cancers
19. Participants with clinically significant dysphagia, or inability to ingest capsules (e.g. severe nausea, vomiting, delayed gastric emptying) as per the opinion of the Investigator, or history of ‘choking’ on capsules
20. Any significant abdominal surgical intervention with the following exceptions: appendectomy, hernia repair, laparoscopic cholecystectomy, and gynaecological and urological procedures including hysteroscopy and cystoscopy. None of these noted surgical exceptions are allowed within 12 months prior to Screening. No upper endoscopy or colonoscopy within 2 months prior to Screening.
21. History of human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, regardless of current viral status and test results
22. Any autoimmune or oncologic disease requiring, or that may require, systemic treatment with steroids and/or other immunosuppressants/immunomodulators
23. Significant bleeding disorder
24. Anaphylactic food allergy
25. Clinically significant (in the investigator’s opinion) valvular heart disease or known structural defects of the heart
26. Participants with active SARS-CoV-2 infection or complications related to COVID-19 that could interfere with the conduct of the study
27. History of prior or current use of the investigational medicinal product (EBX-102-02)
28. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 3 × upper limit of normal (ULN)
29. Ongoing requirement for medications known to cause constipation e.g. Iron supplementation, opiates, anti-diarrhoeal agents
30. Use of any colonic enemas at any time during the study
31. Use of any prohibited medications for which a participant cannot complete the appropriate washout period
32. Use of oral or intravenous antibiotic therapy (amoxicillin, doxycycline, cephalexin, ciprofloxacin) for non-IBS indications within 7 days prior to starting the daily bowel habit or weekly global impressions questionnaire, or intended use during the study (or antibiotic therapy use [rifaximin, neomycin] for IBS within 90 days prior to starting the daily bowel habit or weekly global impressions questionnaire
33. Requirement for vasopressors
34. Have taken an investigational medicinal product (IMP) within the last 3 months or 5x the half-life of the IMP, whichever is longer or planned or active participation in any other study with an IMP
35. Confirmed current (within 12 months prior to screening) diagnosis of IBS-D, mixed type IBS (IBS-M), or unclassified IBS (IBS-U)
36. Women who are pregnant, breastfeeding, or planning to become pregnant during the course of the study
37. Planned surgery requiring general anaesthetic, or lower-gastrointestinal endoscope procedure during the course of the study
38. Participants who are planning to significantly change their diet (e.g. weight loss programme, changing from an omnivorous diet to a vegan diet) during the study period. Participants established on a low fermentation diet can continue without changes to it
39. Intestinal microbiota transplantation within the past 12 months
40. History of sensitivity to any of the study drug components, or a history of drug allergy that in the opinion of the Investigator contraindicates study participation, for example to another IMT product
41. Clinically significant medical or surgical history or any condition that could interfere with study participation or confound the assessments in the opinion of the study Investigator
42. Participants who are study site staff members or relatives of those study site staff members or participants who are employees of EBX or directly involved in the conduct of study

Exclusion during the Study:
32. Acute illness or fever within 48 hours of the day of planned study drug dosing
33. Probiotics use within the last 48 hours of the day of planned study drug dosing. Food substances and nutritional feeds containing pre- or probiotics are permitted
34. Antibiotic use within 48 hours of the day of planned study drug dosing. |
| Date of first enrolment | 04/05/2026 |
| Date of final enrolment | 31/12/2026 |

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Locations

Countries of recruitment

• United Kingdom
• England

Study participating centres

The Functional Gut Clinic (Manchester) 262 Deansgate
Manchester
M3 4BG
England The Functional Gut Clinic 8 Dorset Square
London
NW1 6PU
England The Functional Gut Clinic 63 Bateman Street
Cambridge
CB2 1LR
England University Hospital of North Durham North Road
Durham
DH1 5TW
England NIHR Commercial Research Delivery Centre: Newcastle Queen Victoria Rd
Newcastle upon Tyne
NE1 4LP
England

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Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not expected to be made available
IPD sharing plan

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Editorial Notes

07/08/2025: ISRCTN received notification of combined HRA/MHRA approval for this trial on 07/08/2025.
11/06/2025: Study's existence confirmed by Health Research Authority (HRA) (UK)