Phase II Randomized, Placebo-Controlled Study of Rifamycin SV Sodium In Situ Gelling Solution for Mild to Moderate Left-Sided Ulcerative Colitis
- Trial ID
- 2023-506917-23-00
- Protocol
- CB-01-35/01
- Sponsor
- Cosmo Technologies Limited
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of a novel investigational medicinal product, Rifamycin 1% in situ gelling solution, compared to a matching placebo, in inducing clinical remission in patients with mild to moderate left-sided **ulcerative colitis**. This is clinically relevant as achieving remission is a critical goal in the management of ulcerative colitis, aiming to improve patient outcomes and quality of life.
Secondary objectives include:
- Investigating the efficacy of the investigational product in inducing clinical improvement of the underlying disease compared to placebo.
- Assessing the efficacy in inducing endoscopic remission and/or improvement of the disease.
- Evaluating the efficacy in improving bowel urgency.
- Examining the safety and tolerability of the investigational product compared to placebo.
Participants
The clinical trial involves **adult subjects** aged 18 years or older, diagnosed with mildly to moderately active left-sided **ulcerative colitis** or ulcerative proctitis. The study population includes both male and female participants, with no vulnerable populations selected. Participants must have a confirmed diagnosis of the disease for at least three months, as defined by the Montreal classification system, and must meet specific histological and endoscopic criteria. The trial does not provide information on the total number of participants, as this data was not disclosed by the sponsor. Participants are required to have stable treatment regimens, with no concomitant medications for ulcerative colitis, except for mesalamine or sulfasalazine, which must be stable for at least two weeks prior to screening. Women of childbearing potential must adhere to effective contraception methods, and all participants must demonstrate the ability to comprehend the study's nature and comply with its requirements. Lifestyle factors such as diet and physical activity are not specified in the trial data.
Plans and Procedures
The clinical trial is a **randomized**, placebo-controlled Phase II study designed to evaluate the efficacy and safety of a novel **rifamycin SV** in situ gelling rectal solution administered by enema to patients with mild to moderate left-sided **ulcerative colitis**. The primary objective is to assess the investigational product's ability to induce clinical remission compared to a matching placebo. The trial is expected to commence recruitment on January 31, 2024, and conclude by May 31, 2025. Participants will be involved for a maximum treatment period of 44 days, with the study's total duration extending over several months to accommodate recruitment, treatment, and follow-up phases.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, and disease extent as defined by the Montreal classification. The screening will include endoscopic and histological confirmation of the disease, along with a signed informed consent. Following successful screening, participants will be randomized to receive either the test product or placebo. The study will include regular follow-up visits to monitor safety, efficacy, and compliance, with assessments such as the modified Mayo score and Geboes histology score. The primary endpoint is the proportion of patients achieving clinical remission after six weeks of treatment, defined by specific subscores of the modified Mayo score.
Secondary endpoints include comparisons of partial remission rates, clinical response, endoscopic remission, and improvement, as well as urgency improvement and adverse drug reactions. The end-of-study visit will occur after the six-week treatment period, where final assessments will be conducted. Participants may be withdrawn from the study early due to adverse events, non-compliance, or withdrawal of consent. The trial is structured to ensure rigorous data collection and analysis, maintaining the integrity and scientific validity of the results.
Treatment
The clinical trial involves the administration of **Rifamycin 1% in situ gelling solution** for rectal use. This investigational medicinal product is formulated as a gelling solution and is provided in an 80 mL volume for administration via enema. The active substance in this formulation is **rifamycin sodium**, a chemical compound. The maximum daily dose is 800 mg, with a total maximum dose of 35,200 mg over a treatment period of 44 days. The product is manufactured by Cosmo Technologies Ltd and is identified by the sponsor product code SUB04246MIG. The primary objective of the study is to evaluate the efficacy of this investigational product in inducing clinical remission in patients with mild to moderate left-sided ulcerative colitis.
The study also includes a **placebo** control, which is a matching in situ gelling solution without the active ingredient, rifamycin sodium. This placebo is also administered rectally in an 80 mL volume. The placebo is designed to match the investigational product in appearance and administration method to ensure blinding in the study. The use of a placebo control allows for a comparison of the investigational product's efficacy against a non-active treatment, providing a robust assessment of its therapeutic potential.
Efficacy
The efficacy of the investigational medicinal product in this clinical trial will be assessed primarily by evaluating the proportion of patients achieving **clinical remission** after 6 weeks of treatment. Clinical remission of ulcerative colitis is defined as a total modified Mayo score of 2 or less, which includes the following subscores: stool frequency subscore of 1 or less, rectal bleeding subscore of 0, and endoscopy subscore of 1 (excluding the component "friability").
Secondary efficacy endpoints include several parameters: the proportion of patients in partial remission, defined as improvement in at least one clinical assessment (stool frequency subscore, rectal bleeding subscore); the proportion of patients achieving a clinical response, characterized by a decrease from baseline in the modified Mayo score by 2 points and at least 30%, along with a decrease in rectal bleeding subscore by 1 or an absolute rectal bleeding subscore of 0 or 1. Additionally, endoscopic remission and improvement will be evaluated, defined as a centrally read endoscopy subscore of 0 and 0 or 1, respectively, after 6 weeks of treatment. Urgency improvement will be assessed using the urgency NRS at weeks 1 through 6. The proportion of subjects with remission in the primary endpoint and a Physician’s Global Assessment (PGA) score of 1 or less at week 6 will also be compared between treatments. Furthermore, the trial will compare the proportion of patients with and the number of adverse drug reactions after 6 weeks of treatment.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Main selection criteria: Adult subjects, 18 years or older, with a diagnosis of mildly to moderately active left-sided ulcerative colitis or ulcerative proctitis will be enrolled in the study. Disease extent will be defined according to the Montreal classification of ulcerative colitis, as follows: 1. Ulcerative proctitis: involvement limited to the rectum (that is, proximal extent of inflammation is distal to the rectosigmoid junction), with at least 8 cm of inflammation extent from the anal canal. 2.Left-sided ulcerative colitis (distal ulcerative colitis): involvement limited to a proportion of the colorectum distal to the splenic flexure. The final classification of a participant’s underlying disease as ulcerative proctitis or left-sided colitis will be made by the central endoscopist based on his assessment of the video of the endoscopy performed at Visit 2.
- Informed consent: signed written informed consent before inclusion in the study
- Sex and age: men/women, ≥18 years old inclusive
- Ulcerative colitis: a ≥1 month old diagnosis of mildly to moderately active left-sided ulcerative colitis or ulcerative proctitis with at least 8 cm of inflammation extent from the anal canal (defined by Montreal classification system of ulcerative colitis) even in cases involving only one of the distal regions, i.e. rectum, sigmoid or descending colon, confirmed by endoscopy and histology as follows: a. modified Mayo score ≥4 and ≤7; b. modified Mayo endoscopic subscore ≥2; c. Geboes histology score ≥2 in at least one segment of the left colon segments (descending colon, sigmoid colon or rectum)
- Contraception (women only): women of childbearing potential must use at least one of the following highly effective methods of contraception. a. Hormonal combined oral, intravaginal, or transdermal, contraceptives for at least 2 months before the screening visit b. Progestogen-only hormonal oral, implantable, or injectable contraceptives for at least 2 months before the screening visit c. A non-hormonal intrauterine device or an intrauterine hormone-releasing system for at least 2 months before the screening visit d. Bilateral tubal occlusion e. A sterile sexual partner f. True abstinence, i.e., refraining from heterosexual intercourse when this is in line with the preferred and usual lifestyle of the subject. Women of non-childbearing potential or in post-menopausal status must have been in that status for at least one year. For all women of childbearing potential, serum pregnancy test result must be negative at screening
- Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the study
- Compliance with baseline diary entry: a minimum of 3 consecutive days of completed diary entries or 4 non-consecutive days within a 7-day period are necessary (not including the day of bowel preparation day and day of endoscopy)
Exclusion Criteria
- Prior and concomitant gastrointestinal diseases: a. severe left-sided ulcerative colitis or ulcerative proctitis defined as presenting with a modified Mayo score >7 at baseline; b. ulcerative proctitis with inflammation involving less than 8 cm from the anal canal; c. extensive ulcerative colitis (defined by Montreal classification system of ulcerative colitis) extending beyond the splenic flexure (partial or total involvement of either the caecum or the transverse colon or the ascending colon), as assessed through screening endoscopic examination (Mayo endoscopic score >1 in any of these segments) or available endoscopic documentation not older than 12 months; d. acute severe or fulminant colitis, as defined by Truelove & Witts ; e. Crohn’s disease; f. active peptic ulcer disease; g. infectious colitis; h. positive for Clostridium difficile as detected by stool test; i. current or recurrent disease that could affect the colon or the action, absorption or disposition of the study medication including diverticulitis, collagenous colitis, recurrent pancreatic or known gallbladder disease (except for asymptomatic gallstones or chronic, non-inflammatory gallbladder disease under the Investigator’s judgment), toxic megacolon, fistula (except for non-inflammatory bowel disease fistulas), perforation or abscess or any other significant condition which the Investigator considers may affect the safety of the patient or the outcome of the study; j. clinically significant caecal patch, i.e., indicative of Crohn’s disease or extensive ulcerative colitis or which the Investigator considers may affect the safety of the patient or the outcome of the study; k. colonic dysplasia or polypoid lesions; l. participants with a recently diagnosed (within the previous 6 months) coeliac disease who are not following a strict gluten-free diet and continue to experience coeliac disease-related gastrointestinal symptoms. Participants with prior diagnosis who are on a strict gluten-free diet and have no on-going symptoms may be included.
- Prior and concomitant diseases other than gastroenteric: a. bleeding disorders; b. history of chronic liver disease (e.g. liver cirrhosis) with platelets under 50,000 and international normalised ratio >1.5; c. current or relevant previous history of serious, severe or unstable (acute or progressive) physical or psychiatric illness; d. any medical disorder that may require treatment or make the patient unlikely to fully complete the study or any condition that presents undue risk from the study medication or procedures; e. clinically significant metabolic /electrolyte imbalance; f. malignancy in the last 5 years prior to screening; g. active cytomegalovirus infection, i.e., with positive or negative IgG and positive IgM, that is symptomatic or clinically significant
- Prior surgeries or medical procedures: cytapheresis therapy < 4 weeks prior to screening; previous colonic surgery (excluding appendectomy)
- Prior and concomitant treatments: a. injectable systemic steroids within 2 weeks prior to screening; b. rectal steroids within 2 weeks prior to baseline; c. oral systemic steroids unless on a stable dose for at least 2 weeks before screening and allowing to be tapered during the screening period; d. enteric or colonic oral steroids (e.g., budesonide 9 mg extended-release tablets) can be stopped before screening without tapering; e. mesalamine (also known as 5-ASA or mesalazine) or sulfasalazine therapy unless on a stable dose for at least 2 weeks before screening; f. rectal treatments other than those with steroids within 2 weeks before screening; g. immunosuppressant or immunomodulator agents (for instance, azathioprine, 6-mercaptopurine, cyclosporine, tofacitinib, filgotinib, ozanimod, etc.), within 6 weeks prior to baseline excluding systemic immunosuppressant or immunomodulator therapies used for indications other than ulcerative colitis, provided that: • they have no established therapeutic effect on ulcerative colitis • they are taken at a stable dose for at least 12 weeks before screening; h. monoclonal antibodies (for instance, infliximab, adalimumab, vedolizumab, etc.) within 4 weeks prior to baseline or any intake in the screening period; i. ustekinumab within 16 weeks prior to baseline; j. antibiotics within 14 days before screening; k. repeatedly used non-steroidal anti-inflammatory drugs (e.g. aspirin or ibuprofen) other than mesalamine or sulfasalazine within 7 days prior to baseline. Prophylactic use of a stable dose of aspirin up to 100 mg/day for cardiac disease is permitted.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Bulgaria | Not Recruiting | 31 Jan 2024 | 48 |
 Estonia | Not Recruiting | 31 Jan 2024 | 6 |
 Hungary | Not Recruiting | 31 Jan 2024 | 12 |
 Latvia | Not Recruiting | 31 Jan 2024 | 6 |
 Lithuania | Not Recruiting | 31 Jan 2024 | 12 |
 Poland | Not Recruiting | 31 Jan 2024 | 48 |
 Romania | Not Recruiting | 31 Jan 2024 | 18 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Rifamycin 1% in situ gelling solution (80 mL) for rectal administration | Test | GELLING SOLUTION | RECTAL USE | 800 | 44 | PRD10743739 |
Rifamycin SV sodium in situ gelling solution matching placebo
(80 mL) for rectal administration | Placebo | N/A | — | — | — | N/A |