A randomised, double-blind, double-dummy, multicentre, phase III, non inferiority trial of an oral mesalazine formulation in patients with active mild to moderate ulcerative colitis for the induction of remission.

Phase 3

Recruiting

• Conditions: Ulcerative colitis

• Registration Number: 2023-509606-30-00
• Lead Sponsor: Faes Farma S.A.

Brief Summary

To assess the percentage of patients with clinical remission (MMS ≤ 2, including the following: symptomatic remission [stool frequency ≤ 1, rectal bleeding = 0] and endoscopic remission [centrally read MES ≤ 1]) after 8 weeks of treatment.

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-07-24
• Last Update Posted: 2025-06-01

Recruitment & Eligibility

• Status: Ongoing, recruiting
• Sex: Not specified
• Target Recruitment: 386

Inclusion Criteria

Be ≥ 18 years of age at Visit 1.

For males with female partners of childbearing potential: acceptance to use birth control methods (condom with or without spermicide, or effective methods of birth control of female partner) throughout the trial duration and until 2.5 months after last intake of IMP. Vasectomy or sexual abstinence (if defined as refraining from heterosexual intercourse during the entire period of risk associated with the trial treatment) are also acceptable methods. The investigator is responsible for determining whether the patient has adequate birth control for trial participation.

Provide written informed consent.

Be willing and able to follow all instructions, undergo all assessments, complete the electronic diary and attend all trial visits.

Have UC symptoms for at least 3 months prior to Visit 1, and UC diagnosis established by clinical, histological and endoscopic evidence, extending 15 cm or more from the anal verge.

Have active, mild to moderate UC at the time of screening, defined as: - Modified Mayo score 4 - 7, - Mayo endoscopic subscore ≥ 2, confirmed by central reader before randomisation.

Have a recent (≤ 31 days prior to Visit 1) endoscopy documenting the degree and extent of mucosal inflammation; otherwise, an endoscopy must be performed during the screening period to confirm a MES ≥ 2.

Be treatment naïve or currently treated with oral mesalazine ≤ 2.5 g per day or rectal mesalazine ≤ 1 g per day (combination of rectal and oral not allowed). Note: patients treated in past flares with higher doses of mesalazine or treated with glucocorticoids will be allowed.

Be able and willing to avoid all disallowed medications for the appropriate washout period before randomisation and during the rest trial (see Section 7.6 [of D1_Protocol 2023-509606-30-00] for concomitant medications): Medication group, Route, Washout period; Antibiotics, Systemic, 1 week; Anti-diarrhoeal, Systemic, 1 week; Glucocorticoid, Systemic, 4 weeks; Glucocorticoid, Rectal, 4 weeks

For females of childbearing potential only: willing to perform pregnancy tests, must agree to use effective methods of birth control throughout the trial until the trial ends (T3). Effective methods of birth control include: combined hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner (provided that partner is the sole sexual partner of the clinical trial patient and has documentation of azoospermia) or sexual abstinence (if defined as refraining from heterosexual intercourse during the entire period of risk associated with the trial treatment). The investigator is responsible for determining whether the patient has adequate birth control for trial participation.

Exclusion Criteria

Have known contraindications or sensitivities to the use of the IMPs or any of its components.

Suspected or documented infectious enterocolitis within the 1 month prior to the Visit 1.

Have previous or current treatment with thiopurines, calcineurin inhibitors, methotrexate, JAK inhibitors and/or biologics.

Patients who previously were refractory to treatment with oral or rectal mesalazine.

Have a history of or current diagnosis of severe or uncontrolled pulmonary disease, myocarditis or pericarditis.

Severe or uncontrolled asthma, that in the opinion of the investigator, would compromise the patient safety (e.g. asthma that has frequent exacerbations or is not controlled with high doses of inhaled glucocorticoids).

Have a history of or current diagnosis of haemorrhagic diathesis.

Have an active malignancy or treatment with antineoplastic agents during the last 5 years. Patients with a history of cancer other than colorectal cancer and at least 5 years of uneventful follow-up and no signs of recurrence may be eligible according to the investigator’s decision.

Have participated in another clinical trial in which an investigational drug (including investigational vaccines) or invasive investigational medical device has been taken within the past 90 days (or five half-lives of IMP whichever is longer) prior to Visit 1, or simultaneous participation in another clinical trial.

Have any condition that, in the opinion of the investigator, may jeopardise the clinical trial conduct according to the protocol (for example, evidence of diseases, medications or laboratory abnormalities that could alter the conduct of the trial).

Be an employee of the investigator or clinical trial unit, with direct involvement in the proposed trial or other studies under the direction of that investigator or clinical trial unit, as well as family members of the employees or the principal investigator.

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Patients unable to understand the informed consent or having a high probability of non-compliance with the trial procedures.

Be a person committed to an institution by virtue of an order issued either by judicial or other authorities.

Be pregnant, planning a pregnancy or breastfeeding.

Have severe UC, as defined by Truelove & Witts ([reference in D1_Protocol 2023-509606-30-00] 32) with the presence of ≥ 6 bloody stools per day, with one or more of the following: a. Temperature > 37.8 ºC. b. Heart rate > 90 beats/minute. c. Haemoglobin concentration < 10 g/dL.

Have a history of colonic resection (excluding appendectomy).

Present moderate to severe renal disorder, defined by eGFR < 45 mL/min/1.73m2.

Present moderate to severe hepatic disorder, characterised by serum transaminase (ALT or AST) or alkaline phosphatase values (ALP) ≥ 3 x ULN or total bilirubin (TBILI) ≥ 2 x ULN (except Gilbert syndrome).

Have a gastrointestinal disease that in the opinion of the investigator, would have interfered with the patient's participation in this study. Including but not limited to: Crohn’s disease, other forms of colitis, coeliac disease, malabsorption syndromes, present or past colorectal cancer, gastric or duodenal ulcer.

Have ulcerative proctitis (restricted to rectum).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Percentage of patients with clinical remission defined by MMS ≤ 2 with symptomatic remission (stool frequency ≤ 1, rectal bleeding = 0) and endoscopic remission (MES ≤ 1) after 8 weeks of treatment.		Percentage of patients with clinical remission defined by MMS ≤ 2 with symptomatic remission (stool frequency ≤ 1, rectal bleeding = 0) and endoscopic remission (MES ≤ 1) after 8 weeks of treatment.

Secondary Outcome Measures

Name	Time	Method
[Secondary efficacy:] Percentage of patients achieving symptomatic remission (defined as stool frequency ≤ 1 and rectal bleeding = 0), after the 8-week treatment period		[Secondary efficacy:] Percentage of patients achieving symptomatic remission (defined as stool frequency ≤ 1 and rectal bleeding = 0), after the 8-week treatment period
[Secondary efficacy:] Percentage of patients achieving endoscopic remission (defined as a MES ≤ 1), after the 8-week treatment period.		[Secondary efficacy:] Percentage of patients achieving endoscopic remission (defined as a MES ≤ 1), after the 8-week treatment period.
[Secondary efficacy:] Percentage of patients achieving overall response (defined as a reduction in MMS ≥ 3 and ≥ 30% from baseline, with a decrease of rectal bleeding subscore ≥ 1 or absolute rectal bleeding subscore ≤ 1), after the 8 week treatment period.		[Secondary efficacy:] Percentage of patients achieving overall response (defined as a reduction in MMS ≥ 3 and ≥ 30% from baseline, with a decrease of rectal bleeding subscore ≥ 1 or absolute rectal bleeding subscore ≤ 1), after the 8 week treatment period.
[Secondary efficacy:] Change in the symptomatic assessments of the MMS (stool frequency and rectal bleeding), from baseline to Week 8.		[Secondary efficacy:] Change in the symptomatic assessments of the MMS (stool frequency and rectal bleeding), from baseline to Week 8.
[Secondary efficacy:] Change in the MES, from baseline to Week 8.		[Secondary efficacy:] Change in the MES, from baseline to Week 8.
[Secondary efficacy:] Percentage of patients achieving histological remission (defined by RHI ≤ 3 with subscores = 0 for lamina propria neutrophils and neutrophils in epithelium) at Week 8.		[Secondary efficacy:] Percentage of patients achieving histological remission (defined by RHI ≤ 3 with subscores = 0 for lamina propria neutrophils and neutrophils in epithelium) at Week 8.
[Secondary efficacy:] Percentage of patients achieving overall remission (all modified Mayo subscores = 0) at Week 8.		[Secondary efficacy:] Percentage of patients achieving overall remission (all modified Mayo subscores = 0) at Week 8.
[Secondary efficacy:] Percentage of patients achieving clinical remission and histologic remission at Week 8.		[Secondary efficacy:] Percentage of patients achieving clinical remission and histologic remission at Week 8.
[Secondary efficacy:] Change in Short Inflammatory Bowel Disease Questionnaire (SIBDQ), from baseline to Week 8.		[Secondary efficacy:] Change in Short Inflammatory Bowel Disease Questionnaire (SIBDQ), from baseline to Week 8.
[Secondary efficacy:] Change in faecal calprotectin values, from baseline (V2) to Week 8.		[Secondary efficacy:] Change in faecal calprotectin values, from baseline (V2) to Week 8.
[Secondary safety and tolerability:] Monitoring adverse events: - Incidence of adverse events (related/unrelated). - Incidence of adverse events by maximum severity (related/unrelated). - Incidence of serious adverse events (related/unrelated). - Incidence of adverse events leading to discontinuation of trial drug. - Incidence of adverse events resulting in death.		[Secondary safety and tolerability:] Monitoring adverse events: - Incidence of adverse events (related/unrelated). - Incidence of adverse events by maximum severity (related/unrelated). - Incidence of serious adverse events (related/unrelated). - Incidence of adverse events leading to discontinuation of trial drug. - Incidence of adverse events resulting in death.
[Secondary safety and tolerability:] Biochemistry, haematology, and urinalysis: - Number of patients with clinically significant results at Week 8 in haematological parameters. - Number of patients with clinically significant results at Week 8 in biochemical parameters. - Number of patients with clinically significant results at Week 8 in urinalysis parameters.		[Secondary safety and tolerability:] Biochemistry, haematology, and urinalysis: - Number of patients with clinically significant results at Week 8 in haematological parameters. - Number of patients with clinically significant results at Week 8 in biochemical parameters. - Number of patients with clinically significant results at Week 8 in urinalysis parameters.
[Secondary safety and tolerability:] Physical examination and vital signs - Number of patients with clinically significant findings in physical examination from baseline (V2) to Week 8. - Changes in vital signs parameters from baseline (V2) to Week 8.		[Secondary safety and tolerability:] Physical examination and vital signs - Number of patients with clinically significant findings in physical examination from baseline (V2) to Week 8. - Changes in vital signs parameters from baseline (V2) to Week 8.
[Secondary safety and tolerability:] Preference of the pharmaceutical formulation of the IMP evaluated through the Treatment Satisfaction and Acceptability Questionnaire.		[Secondary safety and tolerability:] Preference of the pharmaceutical formulation of the IMP evaluated through the Treatment Satisfaction and Acceptability Questionnaire.

Trial Locations

Locations (88)

Eszak-Budai Szent Janos Centrumkorhaz; 🇭🇺 Budapest XII, Hungary

Csoeszi Endoszkopos Kft.; 🇭🇺 Kecskemet, Hungary

Heves Varmegyei Markhot Ferenc Oktatokorhaz Es Rendelointezet; 🇭🇺 Eger, Hungary

Semmelweis University; 🇭🇺 Budapest VIII, Hungary

Aranyklinika Kft.; 🇭🇺 Szeged, Hungary

BKS Research Kft.; 🇭🇺 Hatvan, Hungary

Clinfan Kft.; 🇭🇺 Szekszard, Hungary

Clinexpert Kft.; 🇭🇺 Budapest III, Hungary

University Of Szeged; 🇭🇺 Szeged, Hungary

Centre Hospitalier Universitaire De Nimes; 🇫🇷 Nimes Cedex 9, France

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Eszak-Budai Szent Janos Centrumkorhaz

🇭🇺Budapest XII, Hungary

György Székely

Site contact

+3614584500

szekelygy@gmail.com