MESALAZINE for Ulcerative colitis

Inclusion criteria

• {"criterion_text":"- Be ≥ 18 years of age at Visit 1.\n- 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.\n- Provide written informed consent.\n- Be willing and able to follow all instructions, undergo all assessments, complete the electronic diary and attend all trial visits.\n- Have UC symptoms for at least 3 months prior to Visit 1, and UC diagnosis established by clinical, histological and endoscopic evidence.\n- 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.\n- 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.\n- Currently (at Visit 1) not receiving treatment for ulcerative colitis or receiving oral mesalazine ≤ 3.0g per day or rectal mesalazine ≤ 1.0 g per day (combination of rectal and oral mesalazine is not allowed).\n- 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\n- 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

• {"criterion_text":"- Have known contraindications or sensitivities to the use of the IMPs or any of its components.\n- Suspected or documented infectious enterocolitis within the 1 month prior to the Visit 1.\n- Have current treatment with thiopurines, calcineurin inhibitors, methotrexate, JAK inhibitors and/or biologics, or have received such treatment within the previous 20 weeks before Visit 1.\n- Patients who previously were refractory to treatment with oral or rectal mesalazine.\n- Have a history of or current diagnosis of severe or uncontrolled pulmonary disease, myocarditis or pericarditis.\n- 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).\n- Have a history of or current diagnosis of haemorrhagic diathesis.\n- 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.\n- 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.\n- 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).\n- 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.\n- XXXXXXXXXXXXXXXXXXX\n- Patients unable to understand the informed consent or having a high probability of non-compliance with the trial procedures.\n- Be a person committed to an institution by virtue of an order issued either by judicial or other authorities.\n- 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.\n- Be pregnant, planning a pregnancy or breastfeeding.\n- Have severe UC, as defined by Truelove & Witts ([reference in D1_Protocol 2023-509606-30-00] 33) 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.\n- Have a history of colonic resection (excluding appendectomy).\n- Present moderate to severe renal disorder, defined by eGFR < 45 mL/min/1.73m2.\n- 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).\n- 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.\n- [deleted]"}

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Clinical remission defined by Modified Mayo Score (MMS) ≤ 2 including symptomatic remission (stool frequency ≤ 1, rectal bleeding = 0) and endoscopic remission (MES ≤ 1). Endoscopic scores centrally read. Outcome assessed after 8 weeks of treatment."}

Secondary endpoints

• {"endpoint_text":"- [Secondary efficacy:] Percentage of patients achieving symptomatic remission (defined as stool frequency ≤ 1 and rectal bleeding = 0), after the 8-week treatment period","definition_or_measurement_approach":"Symptomatic remission defined as stool frequency ≤ 1 and rectal bleeding = 0; assessed at Week 8."}
• {"endpoint_text":"- [Secondary efficacy:] Percentage of patients achieving endoscopic remission (defined as a MES ≤ 1), after the 8-week treatment period.","definition_or_measurement_approach":"Endoscopic remission defined as Mayo endoscopic subscore (MES) ≤ 1; assessed at Week 8, centrally read."}
• {"endpoint_text":"- [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.","definition_or_measurement_approach":"Overall response defined as reduction in Modified Mayo Score (MMS) ≥ 3 and ≥ 30% from baseline plus rectal bleeding subscore improvement as specified; assessed at Week 8."}
• {"endpoint_text":"- [Secondary efficacy:] Change in the symptomatic assessments of the MMS (stool frequency and rectal bleeding), from baseline to Week 8.","definition_or_measurement_approach":"Change in MMS symptomatic components (stool frequency and rectal bleeding) from baseline to Week 8."}
• {"endpoint_text":"- [Secondary efficacy:] Change in the MES, from baseline to Week 8.","definition_or_measurement_approach":"Change in Mayo endoscopic subscore (MES) from baseline to Week 8; centrally read."}
• {"endpoint_text":"- [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.","definition_or_measurement_approach":"Histological remission defined by Robarts Histopathology Index (RHI) ≤ 3 with specified subscores = 0 for neutrophils; assessed at Week 8."}
• {"endpoint_text":"- [Secondary efficacy:] Percentage of patients achieving overall remission (all modified Mayo subscores = 0) at Week 8.","definition_or_measurement_approach":"Overall remission defined as all modified Mayo subscores = 0; assessed at Week 8."}
• {"endpoint_text":"- [Secondary efficacy:] Percentage of patients achieving clinical remission and histologic remission at Week 8.","definition_or_measurement_approach":"Combined outcome of clinical remission and histological remission at Week 8, per definitions above."}
• {"endpoint_text":"- [Secondary efficacy:] Change in Short Inflammatory Bowel Disease Questionnaire (SIBDQ), from baseline to Week 8.","definition_or_measurement_approach":"Change in SIBDQ quality-of-life score from baseline to Week 8."}
• {"endpoint_text":"- [Secondary efficacy:] Change in faecal calprotectin values, from baseline (V2) to Week 8.","definition_or_measurement_approach":"Change in fecal calprotectin measured at baseline visit (V2) and Week 8."}
• {"endpoint_text":"- [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.","definition_or_measurement_approach":"Standard AE and SAE monitoring and classification by relationship and severity; events leading to discontinuation and fatal events captured during study period."}
• {"endpoint_text":"- [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.","definition_or_measurement_approach":"Laboratory safety assessments comparing baseline to Week 8; counts of clinically significant abnormalities."}
• {"endpoint_text":"- [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.","definition_or_measurement_approach":"Physical exam findings and vital signs changes from baseline to Week 8; number with clinically significant changes reported."}
• {"endpoint_text":"- [Secondary safety and tolerability:] Preference of the pharmaceutical formulation of the IMP evaluated through the Treatment Satisfaction and Acceptability Questionnaire.","definition_or_measurement_approach":"Subject-reported treatment satisfaction and acceptability questionnaire assessing formulation preference."}

Methods

• Referral letters to/from GPs and endoscopy units (K2 recruitment material - referral letter).
• Site advertisements and public advertisements (K2 recruitment material - advertisement).
• Endoscopy posters / referral posters (K2 referral letter 2 - endoscopy poster).
• Site-based recruitment through participating hospital gastroenterology clinics and IBD units (local site recruitment arrangements).
• Country-specific recruitment materials and arrangements exist (documents available per Member State: ES, PL, BG, HU, CZ, SK, FR).

France

Earliest CTIS Part Ii Submission Date

20-06-2024

Latest Decision Or Authorization Date

14-03-2025

Processing Time Days

267

Number Of Participants

1

Slovakia

Earliest CTIS Part Ii Submission Date

02-07-2024

Latest Decision Or Authorization Date

30-09-2025

Processing Time Days

455

Number Of Participants

35

Czechia

Earliest CTIS Part Ii Submission Date

19-04-2024

Latest Decision Or Authorization Date

14-10-2025

Processing Time Days

543

Number Of Participants

70

Bulgaria

Earliest CTIS Part Ii Submission Date

01-07-2024

Latest Decision Or Authorization Date

07-11-2025

Processing Time Days

495

Number Of Participants

60

Hungary

Earliest CTIS Part Ii Submission Date

22-07-2024

Latest Decision Or Authorization Date

06-02-2026

Processing Time Days

564

Number Of Participants

50

Spain

Earliest CTIS Part Ii Submission Date

01-07-2024

Latest Decision Or Authorization Date

11-02-2026

Processing Time Days

590

Number Of Participants

60

Poland

Earliest CTIS Part Ii Submission Date

28-06-2024

Latest Decision Or Authorization Date

11-02-2026

Processing Time Days

594

Number Of Participants

130

Primary sponsor

Full Name

Faes Farma S.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Spain

Contract research organisations

Name

Pharmalex Spain S.L.U.

Responsibilities

Clinical trial services (sponsor duties code 8) as listed in CTIS third-parties

Name

Almac Clinical Services Limited

Responsibilities

Clinical services (sponsor duties code 14)

Name

GxP Brain GmbH

Responsibilities

GxP/operational support (sponsor duties code 3)

Name

Scope International AG

Responsibilities

Multiple roles including medical monitoring and regulatory support (codes and 'Medical monitoring' value listed)

Third parties

• {"country":"Belgium","full_name":"Stefanini","duties_or_roles":"Technical support level 1 for Banook Group (sponsorDuties code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Pharmalex Spain S.L.U.","duties_or_roles":"Sponsor duties code 8 (role not further described in public record)","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"LKF Laboratorium fuer Klinische Forschung GmbH","duties_or_roles":"Sponsor duties code 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"Sponsor duties code 14","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"GxP Brain GmbH","duties_or_roles":"Sponsor duties code 3","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Anju Software Inc.","duties_or_roles":"Sponsor duties code 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"France","full_name":"Banook Central Imaging","duties_or_roles":"Central imaging (sponsorDuties code 15; value: Central imaging)","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Klimopath Labor F Klinische U Molekulare Pathologie","duties_or_roles":"Laboratory analysis: histopathology","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"Scope International AG","duties_or_roles":"Multiple operational and regulatory responsibilities including medical monitoring (multiple sponsorDuties codes listed; value: Medical monitoring)","organisation_type":"Pharmaceutical company"}