Phase III Multicentre Trial of Oral Mesalazine in Patients With Mild to Moderate Ulcerative Colitis.

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.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Colitis, Ulcerative
• Intervention / Treatment: Drug: Mesalazine

• Study Type: Interventional
• Enrollment (Estimated): 376
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Be ≥ 18 years of age.
2. Provide written informed consent.
3. Be willing and able to follow all instructions, undergo all assessments, complete the electronic diary and attend all trial visits.
4. Have UC symptoms with UC diagnosis established by clinical, histological and endoscopic evidence.
5. Have active, mild to moderate UC at the time of screening.
6. Have a recent colonoscopy documenting the degree and extent of mucosal inflammation; otherwise, a colonoscopy must be performed during the screening period.
7. Be able and willing to avoid all disallowed medications for the appropriate washout period before randomisation and during the rest trial.
8. 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. 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.
9. 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.

Exclusion Criteria:

1. Have known contraindications or sensitivities to the use of the IMPs or any of its components.
2. History of difficulty in swallowing.
3. Be pregnant, planning a pregnancy or breastfeeding.
4. Have severe UC.
5. Have a history of colonic resection (excluding appendectomy).
6. Present moderate to severe renal disorder.
7. Present moderate to severe hepatic disorder.
8. 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.
9. Have ulcerative proctitis (restricted to rectum).
10. Suspected or documented infectious enterocolitis.
11. Have previous or current treatment with thiopurines, calcineurin inhibitors, methotrexate, JAK inhibitors and/or biologics.
12. Patients who previously were refractory to treatment with oral or rectal mesalazine.
13. Have a history of or current diagnosis of severe or uncontrolled pulmonary disease, myocarditis or pericarditis.
14. Severe or uncontrolled asthma, that in the opinion of the investigator, would compromise the patient safety.
15. Have a history of or current diagnosis of haemorrhagic diathesis.
16. 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.
17. 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.
18. Have any condition that, in the opinion of the investigator, may jeopardise the clinical trial conduct according to the protocol.
19. 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.
20. Patients unable to understand the informed consent or having a high probability of non-compliance with the trial procedures.
21. Be a person committed to an institution by virtue of an order issued either by judicial or other authorities.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mesalazine Experimental; Mesalazine oral formulation	Drug: Mesalazine; Oral Formulation
Active Comparator: Mesalazine Comparator; Mesalazine oral formulation	Drug: Mesalazine; Oral Formulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To assess the percentage of patients with clinical remission [Mayo Modified Score (MMS) ≤ 2] and Endoscopic remission [Mayo Endoscopic Score (MES) ≤ 1] after 8 weeks of treatment.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the percentage of patients achieving symptomatic remission using Modified Mayo Score.	Symptomatic remission defined by Modified Mayo Score (MMS)	8 weeks
To assess the percentage of patients achieving endoscopic remission using Mayo Endoscopic Score.	Endoscopic Remission defined by Mayo Endoscopic Score (MES)	8 weeks
To assess the percentage of patients achieving overall response using Mayo Modified Score	Reduction in Mayo Modified Score (MMS) from baseline with a decrease of rectal bleeding subscore.	8 weeks
To evaluate changes in the symptomatic assessments using Mayo Modified Score.	Mayo modified score: stool frequency and rectal bleeding.	8 weeks
To evaluate changes in the endoscopic score using Mayo Endoscopic Score.	Mayo Endoscopic Score	8 weeks
To assess the histological remission using Robarts Histopathology Index	Histologic Remission defined by Robarts Histopathology Index (RHI).	8 weeks
To assess the percentage of patients achieving overall remission	All modified Mayo subscores = 0	8 weeks
To assess patients' quality of life	Short Inflammatory Bowel Disease Questionnaire (SIBDQ)	8 weeks
To evaluate change in faecal calprotectin.	Stool sample for faecal calprotectin analysis	8 weeks
To evaluate the safety and tolerability by incidence of AEs.		8 weeks
To evaluate the safety and tolerability by clinically significant laboratory results.	Number of patients with clinically significant results at Week 8 in haematological, biochemistry and urinalysis parameters.	8 weeks
To evaluate the safety and tolerability by assessing clinically significant vital signs results.	Number of patients with clinically significant changes in vital signs parameters (blood pressure, heart rate and body temperature) from baseline to Week 8.	8 weeks
To evaluate the safety and tolerability by clinically significant physical examination findings.	Number of patients with clinically significant findings in physical examination (heart, lungs, abdomen) from baseline to Week 8.	8 weeks
To evaluate the safety and tolerability considering the percentage of patients withdrawn from the trial due to safety concerns.		8 weeks

Collaborators and Investigators

• Sponsor: Faes Farma, S.A.

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: December 4, 2023
• First Submitted That Met QC Criteria: December 16, 2023
• First Posted (Estimated): December 19, 2023

Study Record Updates

• Last Update Posted (Estimated): December 19, 2023
• Last Update Submitted That Met QC Criteria: December 16, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Mesalamine
• Other Study ID Numbers: CGRA-0121/ES

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No