A Study to see effect and safety of PNB-001 capsules in Inflammatory bowel disease
Scientific Title of Study
A Phase II, Multicenter, Randomized, Double-blind, Placebo controlled Clinical study to
evaluate efficacy and safety of PNB-001 as an adjunct to Mesalamine compared to
Mesalamine alone in Subjects with Inflammatory bowel disease
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
BCR-PNB-003 Version 1.0 dated 25 Mar 2022
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Premashish Kar
Designation
Principal Investigator
Affiliation
Max Super Specialty Hospital, Vaishali
Address
A Unit of Crosslay Remedies Ltd. W-3, Sector-1, Vaishali, Ghaziabad-201012, Utttar Pradesh, India
Ghaziabad UTTAR PRADESH 201012 India
Phone
9811042164
Fax
Email
premashishkar@gmail.com
Details of Contact Person Scientific Query
Name
Dr Neeta Nargundkar
Designation
Managing Director
Affiliation
Biosphere Clinical Research Pvt.Ltd
Address
Office No. 02, 03 & 04, Second Floor,Highland Corporate Center,Kapurbawdi Junction, Thane (W) 400 607,
Maharashtra, India
Thane MAHARASHTRA 400607 India
Phone
02241006794
Fax
Email
drneeta@biospherecro.com
Details of Contact Person Public Query
Name
Dr Neeta Nargundkar
Designation
Managing Director
Affiliation
Biosphere Clinical Research Pvt.Ltd
Address
Office No. 02, 03 & 04, Second Floor,Highland Corporate Center,Kapurbawdi Junction, Thane (W) 400 607,
Maharashtra, India
MAHARASHTRA 400607 India
Phone
02241006794
Fax
Email
drneeta@biospherecro.com
Source of Monetary or Material Support
PNB Vesper Life Science Pvt. Ltd,Door No. 40/ 1045G, 5th floor,Amritha Towers, MG Road, KPCC Junction ,Kochi, Kerala 682011, India
Primary Sponsor
Name
PNB Vesper Life Science Pvt Ltd
Address
Door No. 40/ 1045G, 5th floor,Amritha Towers, MG Road, KPCC Junction ,Kochi, Kerala 682011, India
Type of Sponsor
Pharmaceutical industry-Indian
Details of Secondary Sponsor
Name
Address
Biosphere Clinical Research Pvt Ltd
Office No. 02, 03 & 04, Second Floor,
Highland Corporate Center,
Kapurbawdi Junction, Thane (W) 400 607,
Maharashtra, India
Department of Gastroenterology
Hospital Building S.No .15,Behind KPCT Mall,Fatima Nagar ,Pune-411040, Maharashtra, India Pune MAHARASHTRA
9823133390
sanjaysalunkhe@gmail.com
Dr Vaibhav S Ganjewar
GI One Hospital
Third Floor, Amrut Sai Solitaire, Besides Goldie Cinema, Railway Station Road,
Aurangabad-431005, Maharashtra, India Aurangabad MAHARASHTRA
7720035616
drvaibhavganjewar@gmail.com
DrTelli Venkata Pradeep Kumar
Great Eastern Medical School and Hospital, Srikakulam
Department of Gastroenterology,D.No 3-351,Ragolu, Srikakulam Andhra Pradesh - 532484 India Srikakulam ANDHRA PRADESH
7406355777
drtvpradeepresearch@gmail.com
Dr Ashok Dalal
Maulana Azad Medical College,(GIPMER)
Room A-210, Department of Gastroenterology, Academic Block,G.B.Pant Hospital,New Delhi-110002, India New Delhi DELHI
9718599219
drashokdalal83@gmail.com
Dr Premashish Kar
Max Super Specialty Hospital, Vaishali
Department of Gastroenterology and Hepatology,
A Unit of Crosslay Remedies Ltd. W-3, Sector-1, Vaishali, Ghaziabad-201012, Utttar Pradesh, India Ghaziabad UTTAR PRADESH
9811042164
premashishkar@gmail.com
Dr Dharmendra B L
Mysore Medical College & Research Institute and Associated Hospitals
Department of Surgical Gastroenterology,K.R. Hospital, Irwin Road, Mysuru-570001, Karnataka, India. Mysore KARNATAKA
9844400382
drdharmu21@gmail.com
Dr Kaivan Shah
Navneet Memorial Hospital
Sushrusha, Opposite Sardar Patel Seva Samaj Hall, In the Lane, Opp. Telephone Exchange, Navrangpura, Ahmedabad-380009, Gujarat, India. Ahmadabad GUJARAT
9833622433
drkaivanshah12@gmail.com
Dr Prashant Rahate
Rahate Surgical Hospital
517, Kolbaswami Square, CA Road, Juni Mangalwari, Near Telephone Exchange, Nagpur-440008, Maharashtra, India. Nagpur MAHARASHTRA
One capsule three times daily with water after meals with the stable dose of oral Mesalamine of at least 2.4 gm/day for 4 weeks
Intervention
PNB001 100mg
One capsule three times daily with water after meals with the stable dose of oral Mesalamine of at least 2.4 gm/day for 4 weeks
Intervention
PNB001 50 mg
One capsule three times daily with water after meals with the stable dose of oral Mesalamine of at least 2.4 gm/day for 4 weeks
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1.Male or female Subjects aged between 18 and 65 years (both Inclusive).
2.Subjects who are able to understand and willing to sign informed consent for participation in the study and willing to adhere to all protocol procedures.
3.Subjects on stable dose of oral Mesalamine of at least 2.4 gm/day for 2 weeks prior to screening.
Inclusion Criteria specific for Ulcerative Colitis Participants (Cohort 1)
1.Subjects have a documented history of idiopathic ulcerative colitis based on standard endoscopic (colonoscopic) and histological criteria involving the whole/part of left side of the colon [approximately 60 cm up from the anus (anal verge) to splenic flexure of colon], with mild to moderate active disease].
2.Subjects with Ulcerative Colitis Disease Activity Index (UCDAI) score of 4-10.
3.Rectal bleeding score of 1 or more at baseline
4.Mucosal appearance score (based on endoscopy) of 1 point or more at baseline
5.Stool Frequency subscore of 1 or more at baseline.
Inclusion Criteria specific for Crohn’s Disease Participants(Cohort 2)
1.Subjects have a documented history of Crohns Disease(CD) established at least 3 months prior to randomization by clinical and endoscopic evidence and corraborated by a histopathology report
2.Has mild to moderately active CD as determined by Crohns Disease Activity Index (CDAI) score of CDAI ≥200 and ≤400
3.Average of greater than two liquid or soft stools per day and an abdominal pain intensity score >1
ExclusionCriteria
Details
1. Documented history of proximal or universal ulcerative colitis (pan colitis).
2. Subjects who demonstrate signs and symptoms of fulminant colitis, bowel stricture, toxic megacolon, an anticipated need for blood transfusion for gastrointestinal bleeding, or demonstrate evidence of peritonitis.
3. Bowel resection within the previous 6 months.
4. Subjects with hemoglobin of ≤ 10 g/dl at screening.
5. Subjects with ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.
6. Prior documented history of evidence of high grade dysplasia on biopsy from endoscopic examinations.
7. Subjects with the following clinically significant laboratory abnormalities: SGOT, SGPT,
Serum Bilirubin > 2.5 times the Upper Limit Normal (ULN)) at screening visit.
8. Subjectswith abnormal Sr.Creatinine value of ≥ 2 mg/dl at screening visit.
9. Subjects with current or recurrent Clostridium difficile infection.
10. History of biological therapy with agents like infliximab, adalimumab, etanercept, etc. within the previous 8 weeks of screening and Subjects in need of such therapy during the study period.
11. Subjects who received systemic steroids or immunosuppressant’s within the previous 4 weeks
of screening.
12. Subjects not able to withdraw and in need of continuing other immunosuppressant’s like sirolimus or cyclosporine during the study period.
13. Subjects with alcohol or drug abuse
14. Subjects with history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-
HCV) positive, or other clinically active liver disease at screening.
15. Subjects with Type 1 Diabetes or Type 2 Diabetes Mellitus whose diabetes has not been stable
and uncontrolled for the previous three months and with HbA1c value greater than 8% at
screening.
16. Subjects with cerebrovascular disease in the previous 3 months
17. Subjects diagnosed or suffering from any Oncological Conditions since last 2 years will be
excluded from the study.
18. Subjects with pre-existent renal function disorders, liver function disorders, cardiac disease,
uncontrolled hypertension, clinically important hematological, metabolic, psychiatric, central
nervous system (CNS) or pulmonary disease.
19. Female subjects who are pregnant or lactating or planning to become pregnant during the study
period. Females who are not ready to use acceptable contraceptive methods during the course
of study
20. Subjects who participated in any other clinical or post-marketing study (not only for study
drugs but also for medical devices) 30 days before signing the informed consent
21. Any condition which the study physician judges to preclude safe participation in the study or to
confound the evaluation of the study outcome.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
An Open list of random numbers
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Cohort 1: Ulcerative Colitis Disease
1.Proportion of Subjects achieving clinical response at week 4 in test arm as compared to placebo arm.
Cohort 2: Crohn’s Disease
1.Percentage of Participants with a Clinical Response (CDAI
Decrease from Baseline of ≥100 Points) at Week 4.
Baseline, Day 14 and Day 28
Secondary Outcome
Outcome
TimePoints
Cohort 1: Ulcerative Colitis Disease
1. Change from baseline in the Ulcerative Colitis Disease Activity Index (UCDAI) score at 4
weeks.
2. Change from baseline in Rectal bleeding score at 4 weeks.
3.Time to resolution of rectal bleeding within 4 weeks.
4.Change from baseline in Stool Frequency score at 4 weeks.
5.Time to normalization of stool frequency within 4 weeks.
6.Change from baseline in mucosal appearance score (based on colonoscopy) at 4 weeks.
7.Change in ESR, CRP, CD4, CD8, TNFα, IL6 and FC levels at 4 weeks from baseline.
8.Short Inflammatory Bowel Disease Questionnaire (SIBDQ) assessment
28 Days
Cohort 2: Crohn’s Disease
1.Change from baseline in the Crohns Disease Activity Index (CDAI) score at 4 weeks.
2.Change from baseline in Stool Frequency score at 4 weeks.
3.Change in ESR, CRP, CD4, CD8, TNF α, IL6 and FC levels at 4 weeks from baseline.
4.Change from baseline in Simple Endoscopic Score for Crohn’s Disease (SES-CD) (based on colonoscopy) at 4 weeks.
5.Short Inflammatory Bowel Disease Questionnaire (SIBDQ).
28 Days
The assessment of safety will be based on the frequency of Adverse Events and changes in
laboratory values.
28 Days
Target Sample Size
Total Sample Size="45" Sample Size from India="45" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This study is a Phase II, Multicenter, Randomized, Double-blind, Placebo controlled Clinical study to evaluate the efficacy and safety of PNB-001 as an adjunct to Mesalamine compared to Mesalamine alone in Subjects with Inflammatory bowel disease.
Primary objective:
- To evaluate the efficacy of PNB-001 as an adjunct to Mesalamine compared to Mesalamine alone in Subjects with Inflammatory bowel disease.
Secondary objectives:
- To evaluate the safety of PNB-001 as an adjunct to Mesalamine compared to Mesalamine alone in Subjects with Inflammatory bowel disease
Cohort 1: Ulcerative Colitis Disease
Primary Endpoints
- Proportion of Subjects achieving clinical response at week 4 in test arm as compared to placebo arm.
Secondary Endpoints
- Change from baseline in the Ulcerative Colitis Disease Activity Index (UCDAI) score at 4 weeks.
- Change from baseline in Rectal bleeding score at 4 weeks.
- Time to resolution of rectal bleeding within 4 weeks.
- Change from baseline in Stool Frequency score at 4 weeks.
- Time to normalization of stool frequency within 4 weeks.
- Change from baseline in mucosal appearance score (based on colonoscopy) at 4 weeks.
- Change in ESR, CRP, CD4, CD8, TNFα, IL6 and FC levels at 4 weeks from baseline.
- Short Inflammatory Bowel Disease Questionnaire (SIBDQ) assessment.
Cohort 2: Crohn’s Disease
Primary Endpoints
- Percentage of Participants with a Clinical Response (CDAI Decrease from Baseline of ≥100 Points) at Week 4.
Secondary Endpoints
- Change from baseline in the Crohn’s Disease Activity Index CDAI) score at 4 weeks.
- Change from baseline in Stool Frequency score at 4 weeks.
- Change in ESR, CRP, CD4, CD8, TNFα, IL6 and FC levels at 4 weeks from baseline.
- Change from baseline in Simple Endoscopic Score for Crohn’s Disease (SES-CD) (based on colonoscopy) at 4 weeks.
- Short Inflammatory Bowel Disease Questionnaire (SIBDQ)