Efficacy and Safety Study of MAX-002 Suppository Versus Placebo and Active Medicine in Mild to Moderate Ulcerative Proctitis

Study Overview
=================
Brief Summary
-----------------
This is a prospective, multicenter, double-blind (DB), controlled, randomized, parallel group comparison Phase 3a study to evaluate the efficacy and safety of new mesalamine suppositories (MAX-002) as compared to placebo and active medicine after 6 weeks of treatment in adults with mild to moderate ulcerative proctitis (UP).

Detailed Description
-----------------
The present study consists of screening period (2 weeks before randomization), DB phase (6 weeks), OL phase (8 weeks) and follow-up visits at Week 3, Week 6 and Week 14. Participants who are eligible will be randomized to receive 1g MAX-002, 1g Canasa® and placebo suppository once daily in the DB phase. Participants who complete or discontinue the study at Week 6 will either receive 1g MAX-002 suppositories on a voluntary basis, standard care treatment as per investigator's discretion or no treatment during the next 8 weeks of the OL phase. Total duration of treatment will be of 14 weeks. Efficacy will primarily be evaluated by percentage of participants who show response as per Mayo DAI Score at Week 6. Participants' safety will be monitored throughout the study.

Official Title
-----------------
A Multicenter, Double-blind, Controlled, Randomized, Parallel Group Comparison Phase IIIa Treatment Investigation on the Efficacy and Safety of MAX-002 Suppository Versus Placebo and Active Medicine in Mild to Moderate Ulcerative Proctitis

Conditions
-----------------
Proctitis, Ulcerative

Intervention / Treatment
-----------------
* Drug: MAX-002
* Drug: Placebo
* Drug: Canasa®


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants who are 18 years old or older Participants with total Mayo DAI score between 5 to 10 at Screening and participants with score of 2 or more for the rectal bleeding and for the findings of flexible proctosigmoidoscopy or colonoscopy sub-scores of the Mayo DAI Participants with confirmed mild to moderate active UP not extending above rectum as evidenced by flexible proctosigmoidoscopy and histopathology assessments Female participants of child-bearing age who have negative serum beta-human chorionic gonadotropin (β-HCG) at the time of entry into the study Female participants of child-bearing age who use medically acceptable form of birth control Participants who are smokers and non-smokers must not change their smoking habits or nicotine use during the DB treatment period Participants who are literate and have legal ability to sign informed consent form Exclusion Criteria: Participants with other digestive diseases interfering with the measurement of any sub-score of the Mayo DAI Participants with known presence or suspicion of malignant disease of the digestive system or presence or history of neoplasms other than carcinoma in situ of the cervix or basal carcinoma of the skin Participants with clinically significant electrocardiographic abnormalities that would compromise its participation in the study Participants who are chronically using oral 5-aminosalicylic acid (5-ASA) at a dose greater than 4g daily, change in the oral 5-ASA dosing, or use of any form of rectal 5-ASA formulations during the 30 days prior to randomization Participants with significant use of corticosteroids ,immunosuppressant's or biologic response modifiers that may have a therapeutic effect on ulcerative proctitis during the 45 days before the date of consent Participants who use any rectally administered medicine during the 30 days prior to randomization Participants who have contraindication to the use of mesalamine or suppository vehicle, analgesia, flexible proctosigmoidoscopy or colonoscopy Participants who have blood parameters of grade 3 or higher on the common terminology criteria for adverse events (CTCAE) 5-point scale Participants with severe renal or hepatic impairment with parameters of grade 3 or higher on the CTCAE Participants with clinically significant urinary tract obstruction and history of idiopathic pancreatitis Participants with presence of other known clinically significant medical and/or psychological illnesses precluding participation Participants who participate in clinical studies other than observational studies during the 90 days before the date of the informed consent form signature Participants who are unable or unwilling to complete the follow-up evaluations required for the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MAX-002<br> | Drug: MAX-002<br>* MAX-002 suppository 1 gram (g) rectally once daily at bedtime for 6 weeks during the DB phase. Participants will then receive either MAX-002 suppository, standard care treatment or no treatment (as per Investigator's judgment) for 8 weeks during the open-label (OL) phase.<br>* Other names: Mesalamine;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Matching placebo suppository rectally once daily at bedtime for 6 weeks during the DB phase. Participants will then receive either MAX-002 suppository, standard care treatment or no treatment (as per Investigator's judgment) for 8 weeks during the OL phase.<br>|
| Active Comparator: Canasa®<br> | Drug: Canasa®<br>* Canasa® suppository 1 g rectally once daily at bedtime for 6 weeks during the DB phase. Participants will then receive either MAX-002 suppository, standard care treatment or no treatment (as per Investigator's judgment) for 8 weeks during the OL phase.<br>* Other names: Mesalamine;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Were Responders at Week 6 | Participants were considered as responders if they had total Mayo Disease Activity Index (DAI) score less than 3 points and no individual sub-scores greater than or equal to 2. Mayo DAI is a semi-quantitative scale which consists of 4 sub-scales: stool frequency, rectal bleeding, findings of flexible proctosigmoidoscopy or colonoscopy and physician global assessment, each sub-scale ranged from 0 to 3 (0=normal, 3=severe). The total Mayo DAI score ranges from 0 (normal or inactive disease) to 12 (severe disease). | Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Were Responders at Week 3 | Participants considered as responders if they had total Mayo DAI score less than 3 points and no individual sub-scores greater than or equal to 2. Mayo DAI is a semi-quantitative scale which consists of 4 sub-scales: stool frequency, rectal bleeding, findings of flexible proctosigmoidoscopy or colonoscopy and physician global assessment, each sub-scale ranged from 0 to 3 (0=normal, 3=severe). The total Mayo DAI score ranges from 0 (normal or inactive disease) to 12 (severe disease). | Week 3 | 
| Time to Relief of Rectal Bleeding | Time to relief of rectal bleeding was defined as number of days from randomization (Day 1) up to the first date of 3 consecutive days without observation of rectal bleeding during the double-blind phase. | Day 1 up to Week 6 | 
| Change From Baseline in Total Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 6 | The IBDQ is used to measure disease specific quality of life. The IBDQ consists of a self-administered 32-item questionnaire that evaluates quality of life across 4 domains of wellness: bowel symptoms (10 questions), systemic symptoms (5 questions), social symptoms (5 questions) and emotional function (12 questions). The response to each question is graded on 7-point likert scale, ranging from 1 (worst aspect) to 7 (best aspect). The total IBDQ is computed as the sum of the responses to the individual IBDQ questions. The total score ranges from 32 to 224 with higher scores indicating a better quality of life. | Baseline, Week 6 | 
| Time to Relief of Tenesmus | Time to relief of tenesmus (feeling of constantly needing to pass stools, even if the bowels are already empty) was defined as the number of days from randomization (Day 1) up to the first date of 3 consecutive days without observation of tenesmus during the double-blind phase. | Day 1 up to Week 6 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ulcerative proctitis, Proctocolitis, Inflammatory Bowel Disease, Gastrointestinal Diseases, Colonic Diseases, Mesalamine, 5-ASA