Randomized, double-blind, placebo-controlled, multi-centre trial to evaluate the efficacy, safety and tolerability of oral treatment with living bacteria of E. coli DSM 17252 (Symbioflor®2) in patients with diarrhoea-predominant irritable bowel syndrome (IBS-D)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

SymbioPharm GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18], Diseases [C] - Immune System Diseases [C20], Diseases [C] - Digestive System Diseases [C06]

Trial duration

19 Nov 2019 → ongoing

Decision date (initial)

2024-08-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

SymbioPharm GmbH, Auf den Lüppen 10, D - 35745 Herborn

External identifiers

EU CT number

2024-512104-19-00

EudraCT number

2018-004626-28

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The objective of the trial is to investigate the effectiveness of oral treatment with Symbioflor®2 in patients with IBS-D compared to placebo in the improvement of the frequency and severity of IBS-D symptoms and to determine the safety and tolerability of Symbioflor®2

Secondary objectives 1

1. To determine the safety and tolerability of Symbioflor®2

Conditions and MedDRA coding

Irritable Bowel Syndrome

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. • Male or female outpatients aged ≥18 years • Diagnosis of irritable bowel syndrome according to Rome IV: 1. Recurrent abdominal pain, on average, at least 1 day per 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 2. Criteria fulfilled for the last 3 months and 3. IBS symptom onset ≥6 months 4. IBS-D subtype with abnormal stools being usually diarrhoea • Colonoscopy with no clinically relevant findings (performed for all patients younger than 50 years and for patients ≥50 years of age within the last 5 years) • Female patients of childbearing potential must be either surgically sterilized or use a highly effective method of contraception with a negative pregnancy test at screening and baseline/day 0 • Willingness to refrain from significant changes in diet, fibre intake, fluid intake, or physical activity during the study • Willingness to refrain from the use of other medications for IBS treatment, including probiotic medication • Ability to comply with treatment • Sufficient knowledge of German language to understand trial instructions and rating scales • Written informed consent prior to enrolment • Email account and internet access available

Exclusion criteria 1

1. • History of abdominal surgery within the 6 months prior to screening • Presence or suspected presence of unstable coronary artery disease, untreated organic gastrointestinal disease and uncontrolled metabolic diseases causing IBS-related symptoms, or collagen vascular disease within the 6 months prior to screening • Lactose or fructose intolerance explaining the symptoms (in doubtful cases, a diagnostic test has to be performed) • Coeliac disease (in doubtful cases, a diagnostic test has to be performed) • Confirmed bile acid malabsorption by SeHCAT-Test or successful treatment by bile acid sequestrant • Change of diet e.g. FODMAP, gluten-free within last 3 months • Abnormal endoscopy/ abdominal ultrasound requiring further investigation • Any alarm symptoms including uninvestigated anaemia, rectal bleeding, weight loss, or unresolved fever within the 6 months prior to screening • Participation in another clinical trial or use of any investigational drug within 30 days or 5 half-lives (whichever is longer) before dosing • Evidence of current or recent alcohol or drug abuse within 6 months prior to screening • History or evidence of current laxative abuse • Pregnancy or breast feeding • Any illness or condition that might impact the safety of study drug administration or evaluability of drug effect based on Investigator’s discretion • No consent to recording and processing of pseudonymised data according to legal requirements • Patients who are committed to a clinic or similar institution by official or judicial order • Hypersensitivity to active ingredient or any excipients of the medicinal product Patients will be excluded from randomization to a treatment group if they have/are: • Current intake of prohibited medications except for rescue purposes (refer to 9.3) • Serum potassium, magnesium, or calcium values outside the normal range at screening and clinically significant • Serum aspartate transaminase (AST), alanine transaminase (ALT), or gamma glutamyl-transferase (GGT) ≥3 times the upper limit of the normal range at screening or baseline, or a bilirubin value ≥2 times the upper limit of the normal range at screening • Abnormal thyroid stimulating hormone (TSH) value at screening, unless the free T4 value is normal; (Note: Levothyroxine will be allowed, if on stable dose for at least 30 days prior to screening and no changes expected during study) • Any further laboratory value(s) outside the laboratory reference range at screening considered clinically significant by the Investigator

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Response rate measured by Bristol Stool Scale. BSS response is defined as at least 50% reduction in the number of days with at least one stool that has a consistency of 6 or 7 per week compared to baseline for a minimum of 13 of the 26 measurements (i.e. at least 50% improvement of stool consistency during treatment) and 2. Response rate measured by the 11-point numeric rating scale (NRS). Abdominal Pain Intensity response is defined as a decrease in the weekly average of worst abdominal pain

Secondary endpoints 1

1. Response rate measured by the 7-point IBS Global Assessment of Improvement Scale (IBS-GAI) during the 26 weeks of treatment. IBS-GAI response is defined as at least 50% moderate or substantial improvement during the 26 weeks of treatment • Response rate measured by the 11-point numeric rating scale during the 26 weeks of treatment. Response is defined as ≥30% improvement in Abdominal Pain Intensity weekly response compared to baseline for a minimum of 20 of the 26 measurements (i.e. 75% improvem

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

SymbioPharm GmbH

Sponsor organisation

SymbioPharm GmbH

Address

Auf Den Lueppen 10, Hoerbach Hoerbach

City

Herborn

Postcode

35745

Country

Germany

Scientific contact point

Organisation

SymbioPharm GmbH

Contact name

Dr. Eleonore Laskowska-Kosegarten

Public contact point

Organisation

SymbioPharm GmbH

Contact name

Dr. Eleonore Laskowska-Kosegarten

Third parties 3

Locations

1 EU/EEA country · 33 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 31 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications