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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Faes Farma S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

24 Jul 2024 → ongoing

Decision date (initial)

2024-07-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

FAES FARMA S.A.

External identifiers

EU CT number

2023-509606-30-00

ClinicalTrials.gov

NCT06176560

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety, Others

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.

Secondary objectives 12

1. [Secondary efficacy:] To assess the percentage of patients achieving symptomatic remission at Week 8.
2. [Secondary efficacy:] To assess the percentage of patients achieving endoscopic remission at Week 8.
3. [Secondary efficacy:] To assess the percentage of patients achieving overall response at Week 8.
4. [Secondary efficacy:] To evaluate changes in the symptomatic assessments of the MMS (stool frequency and rectal bleeding), from baseline to Week 8.
5. [Secondary efficacy:] To evaluate changes in the MES, from baseline to Week 8.
6. [Secondary efficacy:] To assess the percentage of patients achieving histological remission at Week 8.
7. [Secondary efficacy:] To assess the percentage of patients achieving overall remission at Week 8.
8. [Secondary efficacy:] To assess the percentage of patients achieving clinical remission and histologic remission at Week 8.
9. [Secondary efficacy:] To assess patients’ quality of life from baseline to Week 8.
10. [Secondary efficacy:] To evaluate change in faecal calprotectin values from baseline to Week 8.
11. [Secondary safety and tolerability:] To assess the safety and tolerability of mesalazine treatments.
12. [Secondary safety and tolerability:] To evaluate the acceptability of the IMP.

Conditions and MedDRA coding

Ulcerative colitis

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Spanish Agency For Medicines And Health Products

Plan to share IPD

Yes

IPD plan description

In alignment with ethical standards and best practices, we commit to sharing deidentified IPD from this trial. Data access will be provided to qualified researchers affiliated with academic or research institutions. Interested researchers must submit a research proposal outlining objectives and methodology to [email protected] for sponsor assessment. Data requestors approved by the sponsor will need to sign a data access agreement. Details on the specific secure and controlled platform to access the data will be provided in the agreement. Once signed, the data, including data dictionaries, study protocols, and statistical analysis plans, will be available. Shared data includes individual participant data underlying the results reported, after deidentification (text, tables, figures, and appendices). Data access requests will be possible beginning 3 months and ending 5 years following article publication of primary results in a peer-reviewed journal.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Be ≥ 18 years of age at Visit 1.
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 for at least 3 months prior to Visit 1, and UC diagnosis established by clinical, histological and endoscopic evidence.
5. 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.
6. 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.
7. 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).
8. 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
9. 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.
10. 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 21

1. Have known contraindications or sensitivities to the use of the IMPs or any of its components.
2. XXXXXXXXXXXXXXXXXXX
3. Be pregnant, planning a pregnancy or breastfeeding.
4. 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.
5. Have a history of colonic resection (excluding appendectomy).
6. Present moderate to severe renal disorder, defined by eGFR < 45 mL/min/1.73m2.
7. 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).
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. [deleted]
10. Suspected or documented infectious enterocolitis within the 1 month prior to the Visit 1.
11. 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.
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 (e.g. asthma that has frequent exacerbations or is not controlled with high doses of inhaled glucocorticoids).
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 (for example, evidence of diseases, medications or laboratory abnormalities that could alter the conduct of the trial).
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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 14

1. [Secondary efficacy:] Percentage of patients achieving symptomatic remission (defined as stool frequency ≤ 1 and rectal bleeding = 0), after the 8-week treatment period
2. [Secondary efficacy:] Percentage of patients achieving endoscopic remission (defined as a MES ≤ 1), after the 8-week treatment period.
3. [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.
4. [Secondary efficacy:] Change in the symptomatic assessments of the MMS (stool frequency and rectal bleeding), from baseline to Week 8.
5. [Secondary efficacy:] Change in the MES, from baseline to Week 8.
6. [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.
7. [Secondary efficacy:] Percentage of patients achieving overall remission (all modified Mayo subscores = 0) at Week 8.
8. [Secondary efficacy:] Percentage of patients achieving clinical remission and histologic remission at Week 8.
9. [Secondary efficacy:] Change in Short Inflammatory Bowel Disease Questionnaire (SIBDQ), from baseline to Week 8.
10. [Secondary efficacy:] Change in faecal calprotectin values, from baseline (V2) to Week 8.
11. [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.
12. [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.
13. [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.
14. [Secondary safety and tolerability:] Preference of the pharmaceutical formulation of the IMP evaluated through the Treatment Satisfaction and Acceptability Questionnaire.

Investigational products

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

Test 1

Comparator 1

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Faes Farma S.A.

Sponsor organisation

Faes Farma S.A.

Address

Autonomia Etorbidea 10

City

Leioa

Postcode

48940

Country

Spain

Scientific contact point

Organisation

Faes Farma S.A.

Contact name

FAES FARMA Clinical department

Public contact point

Organisation

Faes Farma S.A.

Contact name

FAES FARMA Clinical department

Third parties 9

Locations

7 EU/EEA countries · 90 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 117 files

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

Application history

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