A clinical trial to study the effects of Bacillus subtilis strain PB6, as add-on to standard maintenance therapy in the treatment of mild to moderate ulcerative colitis
Scientific Title of Study
Multi-center, randomized, double-blind, placebo-controlled study of two dosages of Bacillus subtilis strain PB6 for add-on treatment of mild to moderate active ulcerative colitis
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
KP229
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
S. Sivakumar
Designation
Affiliation
Address
Kemin Pharma, a division of Kemin Industries South Asia Pvt. Ltd. The Trapezium, No 39, Nelson Manickam Road Chennai TAMIL NADU 600029 India
Phone
04442202885
Fax
04442202810
Email
sivakumar.s@kemin.com
Details of Contact Person Scientific Query
Name
Dr. V.T.Sriraam
Designation
Affiliation
Senior Manager-Medical Affairs
Address
Kemin Pharma, a division of Kemin Industries South Asia Pvt. Ltd. The Trapezium, No 39, Nelson Manickam Road Chennai TAMIL NADU 600029 India
Phone
04432472446
Fax
04442202810
Email
sriraamvt@aurovillehealthcare.com
Details of Contact Person Public Query
Name
Ahmed Meeran
Designation
Affiliation
Address
Kemin Pharma, a division of Kemin Industries South Asia Pvt. Ltd. The Trapezium, No 39, Nelson Manickam Road Chennai TAMIL NADU 600029 India
Phone
04442202873
Fax
04442202810
Email
ahmed.meeran@kemin.com
Source of Monetary or Material Support
Kemin Pharma, a division of Kemin Industries South Asia Pvt. Ltd.
Chennai, India
Primary Sponsor
Name
Kemin Pharma
a division of Kemin Industries South Asia Pvt. Ltd.
The Trapezium, No 39, Nelson Manickam Road,
Chennai-600029, India
Address
Type of Sponsor
Details of Secondary Sponsor
Name
Address
NIL
Countries of Recruitment
India
Sites of Study
No of Sites = 15
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr. Shine Sadasivan
Amrita Institute of Medical Sciences and Research Centre
PB6 2E+9 spores arm: 2 PB6 1E+9 spores capsules, three times daily
Intervention
Bacillus Subtilis PB6
PB6 8E+9 spores arm: 2 PB6 4E+9 spores capsules, three times daily
Comparator Agent
Bacillus Subtilis PB6 Placebo
2 placebo capsules three times daily
Inclusion Criteria
Age From
Age To
Gender
Details
1. Must sign and date written informed consent prior to any study-related procedures and, in the opinion of the investigator, be willing and likely to comply with all requirements of the study
2. Male or non-pregnant female patients 18-65 years of age, inclusive
3. A history of UC for at least 6 months prior to time of screening
4. All subjects must have clinical and endoscopic confirmed diagnosis of active mild to moderate UC with disease extension beyond the rectum (>12 cm from the ano-rectal junction)
?confirmed by obligatory colonoscopy/endoscopy at screening: full report to be available and score equal to or greater than 2 (at least moderate friability)
?Ulcerative Colitis Disease Activity Index [UCDAI] of 5-10, inclusive, as assessed on screening (based on retrospective recall by the subject over the previous 3 days) and confirmed after 7 days of baseline observation, before inclusion in the randomization procedure, and not improving more than 2 score points during this run-in period
5. Duration of current relapse < 6 weeks from screening (according to patient)
6. Oral mesalazine/sulfasalazine maintenance therapy (eqaul to or less than 2 g/day) for no less than 30 days prior to screening.
7. Females of childbearing potential require a negative urine pregnancy test and must agree to abstinence or to use prescription contraceptives and to use a barrier contraceptive device along with a spermicidal product for the duration of the study. Subjects who are surgically sterile, menopausal or using contraceptive implants prior to the study enrolment are not required to utilize dual contraceptive techniques
8. Otherwise in general good health as judged by the investigator
ExclusionCriteria
Details
1. Proctitis (equal to or less than 12 cm from the ano-rectal junction)
2. Indeterminate colitis
3. Crohn's disease
4. Previous colonic surgery
5. Severe or fulminant UC [UCDAI >10] or requiring hospitalization
6. Evidence of other forms of inflammatory bowel disease
7. Subjects with a new diagnosis of UC
8. Subjects who altered their mesalazine/sulfasalazine dosage (dose regimen or dose) in the previous 2 weeks before screening
9. Subjects with a positive stool culture for any enteric pathogens that is clinically significant, pathogenic ova or parasites, or a positive enzyme immunoassay (EIA) that is subsequently confirmed by a positive cytotoxin assay for C. difficile toxin
10. Subjects who have used the following medications within the specified period
-Loperamide and other anti-diarrheal agents, probiotics, antibiotics: 1 week wash-out during baseline period
-Non steroidal anti-inflammatory drugs (NSAIDs) and Cyclo-oxygenase-2 (COX-2) inhibitors, within 14 days from screening
-Oral and injectable steroids, within 30 days from screening
-Rectally administered mesalazine/sulfasalazine or other 5-ASAs or steroids, within 7 days from screening. Topical dermatological corticosteroids are not excluded
-Antivirals or antifungals within 30 days
-Immunomodulating/suppressing drugs or biologicals (including anti TNF-α, cyclosporine, thalidomide, methotrexate) within 2 month
-Sulfasalazine or mesalazine at higher dose than for maintenance treatment (higher than 2g/day)
11. Failing to respond to steroids within the previous year prior to screening
12. Subjects who have any other clinically significant disease(s) which, in the opinion of the investigator, could compromise the subject?s involvement in the study or overall interpretation of the data, such as mental/emotional disorder, dysplasia or cancer, HIV, uncontrolled hematologic, renal, hepatic, metabolic pulmonary or cardiovascular disease, active alcohol or drug abuse
13. Needing enemas to treat their disease or to maintain remission
14. Subjects with abnormal laboratory values at admission which are clinically significant by the investigator (outlier values outside the normal values are allowed and to be marked as ?NCS? if considered Non-Clinically Significant (NCS) by the investigator based on the nature of the disease, quite some UC patients having an aberrant immune response and abnormal laboratory values due to the impaired absorption, and blood loss)
15. Subjects whose UCDAI score decreases ≥2 during the 7-day run-in period
16. Allergy to aspirin or salicylate derivatives
17. Subject with a history of drug allergy in general or hypersensitivity to probiotics
18. Participation in another clinical study within the 3 months prior to screening
19. Inability to comply with the protocol requirements or to fill in the diary cards
20. Pregnancy or breast-feeding women or women of child-bearing potential not agreeing to birth control
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Pre-numbered or coded identical Containers
Blinding/Masking
Participant, Investigator and Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
Proportion of patients in remission i.e. UCDAI score equal to or less than 2 with no individual subscore >1
At endpoint for ITT population and week 8 (visit 3) for PP population
Secondary Outcome
Outcome
TimePoints
Proportion of patients in Remission: UCDAI score ≤1 [stool frequency normal, rectal bleeding absent and a colonoscopy/endoscopy score reduction of 1 point or more from baseline]
Week 8 and end of treatment
UCDAI Score -Change from baseline (week 0, visit 0) in partial UCDAI score
Week 2, 4 and 8
UCDAI Score -Change from baseline (week 0, visit 0)
Week 8
Proportion of patients in: Complete remission: UCDAI score = 0 [=normal stool frequency, no rectal bleeding and a normal or quiescent appearance of mucosa on colonoscopy/endoscopy]
Week 8 and end of treatment
Proportion of patients in Colonoscopic/endoscopic remission: defined as UCDAI endoscopy score of ≤1
Week 8 and end of treatment
Proportion of patients in: Clinical remission (cessation of bleeding and normal stool frequency, scores of 0 for both symptoms)
Week 2, 4 and 8
Clinical Response - proportion of patients with: -Overall improvement, defined as a decrease in UCDAI ≥3 from baseline [stool frequency, rectal bleeding, Physicians rating of disease activity and colonoscopy/endoscopy]
Week 8
Clinical Response - proportion of patients with: Colonoscopy/endoscopic improvement, defined as change from baseline in UCDAI endoscopy score
Week 8
Clinical Response - proportion of patients with: Clinical improvement, defined as partial UCDAI score decreasing ≥ 2 from baseline [not including the endoscopy/colonoscopy, but including the 3 other scores (stools, bleeding, Physicians rating of disease activity)] (parameter found predictive for patient-reported improvement of disease activity)
Week 2, 4 and 8
Disease-Specific QoL
Global efficacy: feeling better than at baseline
Week 2, 4 and 8
Disease-Specific QoL
IBDQ (patient rating): change in the scores versus baseline
Week 4 and 8
Pilot HNPQ (patient rating) plus potentially objective parameters (maintenance of weight, hemoglobin)
Week 4 and 8
Safety: Tolerability score
2, 4 and 8 weeks
Vital signs: weight, pulse, blood pressure, respiratory rate and oral temperature at every visit
Every visit
Laboratory values (hematology, biochemistry)
At start, week 4 and week 8
Target Sample Size
Total Sample Size="0" Sample Size from India="" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 2
Date of First Enrollment (India)
Date Missing
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
10/09/2009
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="" Months="0" Days="0"
Recruitment Status of Trial (Global)
Completed
Recruitment Status of Trial (India)
Publication Details
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This is a multi-center, randomized, double-blind, placebo-controlled study of two dosages of Bacillus subtilis strain PB6 for add-on treatment of mild to moderate active ulcerative colitis. A total of 180 patients will be randomized in three treatment arms (60 patients in each arm) and the trial duration will be 9 weeks (1 week screening/run-in+8 weeks treatment period). The primary objective of the trial is to assess the efficacy of Bacillus subtilis strain PB6 in subjects with a flare-up of mild to moderate active UC while subjects are on their usual maintenance treatment with mesalazine/sulfasalazine. The primary outcome measure will be the proportion of patients in remission i.e. UCDAI score equal to or less than < 2 with no individual subscore >1. The secondary objectives are to determine the effective dose of Bacillus subtilis strain PB6 for induction of remission, to assess the tolerability of the two different doses of Bacillus subtilis strain PB6, to assess the quality of life by an appropriate questionnaire (IBDQ) and to ascertain the nutritional value of Bacillus subtilis strain PB6 in UC subjects.