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.

Prior treatment

• Suspected or documented infectious enterocolitis within the 1 month prior to the Visit 1.
• 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.
• Patients who previously were refractory to treatment with oral or rectal mesalazine.
• 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.

Other illness

• Have a history of or current diagnosis of severe or uncontrolled pulmonary disease, myocarditis or pericarditis.
• 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 a history of colonic resection (excluding appendectomy).
• 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.

Lab values

• 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).
• 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.
• 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).

Other

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