Protocol summary

Study aim
Investigation of efficacy of Rhofanib® as induction and maintenance therapy in biologic refractory ulcerative colitis
Design
In this clinical trial study, the national registration system for patients with inflammatory bowel disease is used. According to the inclusion criteria, 40 patients with severe ulcerative colitis resistant to biologic treatment will be initially included in the phase 1-2 study
Settings and conduct
Patients will be examined according to the following protocol in Tehran University of Medical Sciences and will be treated with Rhofanib® 10 mg twice daily for 8 weeks and 5 mg twice a day until the end of 24 weeks. Finally, the effectiveness of this drug in improving clinical symptoms, colonoscopy and pathology will be evaluated.
Participants/Inclusion and exclusion criteria
Inclusion: Known case of moderate to severe Ulcerative Colitis No clinical response or clinical remission (failed treatment) after ant TNF defined or History of intolerance to at least one type of Anti-TNF drug, Be able to use less than 30 mg per day prednisolone or 9mg per day budesonide, immunosuppressants (Azaram, 6MP, MTX) or Mesalazine and antibiotics. Exculsion: Symptoms of infection Surgery and removal of a large part of the intestine Ileostomy, colostomy, well-known symptoms of small bowel stenosis. Use of biologic drugs 60 days before registration. Previously been treated with drugs such as Rituximab, Natalizumab Vedolizumab Contraindications of Rhofanib Absence from all visits or non adherence to study protocol
Intervention groups
Intervention group: Treated with Rhofanib® 10 mg twice daily for 8 weeks and 5 mg twice daily for 24 weeks
Main outcome variables
Severity of disease: relative Mayo score consists of the Mayo Clinic Score minus Sigmoidoscopy sub score in the range 0-9 with higher numbers indicates more severe disease.

General information

Reason for update
Acronym
IRCT registration information
IRCT registration number: IRCT20181217042020N3
Registration date: 2022-06-20, 1401/03/30
Registration timing: prospective

Last update: 2022-06-20, 1401/03/30
Update count: 0
Registration date
2022-06-20, 1401/03/30
Registrant information
Name
Ali Reza Sima
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 21 8241 5238
Email address
a-sima@tums.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2022-09-23, 1401/07/01
Expected recruitment end date
2022-10-23, 1401/08/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Evaluation of efficacy of Rhofanib® as induction and maintenance therapy in biologic refractory ulcerative colitis
Public title
Efficacy of Rhofanib® in biologic refractory ulcerative colitis
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Be able to give informed consent. Known case of moderate to severe Ulcerative Colitis as Mayo score ≥6 or Sigmoidoscopy Sub Score ≥2 and expansion ≥2 15cm from Anal Verge with at least one of the followings: CRP≥ 2.87 mg/L or ≥ 3 large ulcers in colonoscopy or ≥ 10 aphthous ulcer or stool calprotectin ≥ 250 mg/gr No clinical response or clinical remission (failed treatment) after ant TNF defined as: 1- Signs and symptoms of stable active disease despite taking more than or equal to 14 weeks of the following medication regimens 1-1)infliximab 5mg/kg IV at least 2 doses with 2 weeks interval 1-2) adalimumab 80 mg SC first dose then 40 mg SC with 2 weeks intervals 1-3) Recurrence of symptoms after initial recovery when the patient is on anti-TNF maintenance therapy 2- History of intolerance to at least one type of Anti-TNF drug, including injection-induced allergies, demyelination, infection, and congestive heart failure. Be able to use less than 30 mg per day prednisolone or 9mg per day budesonide, immunosuppressants (Azaram, 6MP, MTX) or Mesalazine and antibiotics.
Exclusion criteria:
Symptoms of infection such as abdominal abscess or Toxic Mega Colon during patient visits Surgery and removal of a large part of the intestine (complete or subtotal colectomy, history of more than 3 times surgery and resection of the small intestine or diagnosis of short bowel syndrome), symptomatic colonic stenosis, ostomy. Ileostomy, colostomy, well-known symptoms of small bowel stenosis. Use of Anti-TNF drugs 60 days before registration. Use of cyclosporine, Thalidomide or research drugs within 30 days prior to registration. Previously been treated with drugs such as Rituximab, Natalizumab Vedolizumab Chronic hepatitis B or C infection Clostridium difficile infection during the last 60 days Active or latent tuberculosis Do not have the results of TB diagnostic test. Amoebiasis trophozoite infection in fecal examination Immune deficiency (HIV infection or congenital immunodeficiency) Has received live vaccines in the last 30 days. Pregnancy or breastfeeding An unstable or uncontrolled medical disorder that requires hospitalization or major surgery at the initial visit A surgical procedure that required general anesthesia during the last 30 days Existence of colon dysplasia Any malignant cancer WBC less than 3000 lymphocyte less than 500 platelet less than 100000 or more than 1200000 ALT or AST greater than 3 times the maximum normal value ALP greater than 3 times the maximum normal value Serum Cr more than 2 times the maximum normal value Absence from all visits or non adherence to study protocol
Age
From 18 years old to 80 years old
Gender
Both
Phase
2
Groups that have been masked
No information
Sample size
Target sample size: 40
Randomization (investigator's opinion)
N/A
Randomization description
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Single
Other design features
In this study, the infrastructure of the national registration system for patients with inflammatory bowel disease is used. According to the inclusion criteria, 40 patients with severe ulcerative colitis resistant to anti-TNF treatment will be initially included in the study and will be examined according to the following protocol and will be treated with Rhofanib® 10 mg twice daily for 8 weeks and 5 mg twice a day until the end of 24 weeks.. Finally, the effectiveness of this drug in improving clinical symptoms, colonoscopy and pathology will be evaluated.

Secondary Ids

empty

Ethics committees

1

Ethics committee
Name of ethics committee
Ethic committee of Digestive Disease Research Institute of Tehran University of Medical Sciences
Street address
Digestive Disease Research Institute, Shariati hospital, North Kargar street
City
Tehran
Province
Tehran
Postal code
1411713135
Approval date
2020-10-14, 1399/07/23
Ethics committee reference number
IR.TUMS.DDRI.REC.1399.025

Health conditions studied

1

Description of health condition studied
Ulcerative Colitis
ICD-10 code
K51
ICD-10 code description
Ulcerative colitis

Primary outcomes

1

Description
Mayo score
Timepoint
During induction treatment at weeks 2, 4, 6 and 10 and then every 4 weeks until week 52
Method of measurement
The Mayo Score is a standard method for assessing the severity of ulcerative colitis in clinical trials and consists of 4 components, 2 of which are reported by the patient (including lower gastrointestinal bleeding and the number of defecation) and an evaluation by a physician and an endoscopic examination. Each component consists of a score of 3-0, the total score being calculated from 1-12 (a higher score indicates that the patient is more severe). Relative Mayo Clinic Score consists of the Mayo Clinic Score minus Sigmoidoscopy sub score in the range 0-9 with higher numbers indicates more severe disease.

Secondary outcomes

1

Description
Clinical Remission
Timepoint
Week 10 and 24
Method of measurement
Defined as 2 ≥ Mayo Score in week 10

2

Description
Mucosal healing
Timepoint
Week 10 and 24
Method of measurement
Colonoscopy

Intervention groups

1

Description
Intervention group: Treated with Rhofanib® 10 mg twice daily for 8 weeks and 5 mg twice daily for one year (52 weeks)
Category
Treatment - Drugs

Recruitment centers

1

Recruitment center
Name of recruitment center
Digestive Disease Research Institute
Full name of responsible person
Ali Reza Sima
Street address
Digestive Disease Research Institute, Shariati hospital, North Kargar street,
City
Tehran
Province
Tehran
Postal code
1411713135
Phone
+98 21 8241 5000
Email
simaalireza@gmail.com

Sponsors / Funding sources

1

Sponsor
Name of organization / entity
Digestive Disease Research Institute of Tehran University of Medical Sciences
Full name of responsible person
Dr. Reza Malekzadeh
Street address
Digestive Disease Research Institute, Shariati hospital, North Kargar street
City
Tehran
Province
Tehran
Postal code
1411713135
Phone
+98 21 8241 5000
Fax
+98 21 8241 5400
Email
dr.reza.malekzadeh@gmail.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Digestive Disease Research Institute of Tehran University of Medical Sciences
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic

Person responsible for general inquiries

Contact
Name of organization / entity
Digestive Disease Research Institute
Full name of responsible person
Ali Reza Sima
Position
Assistant professor
Latest degree
Subspecialist
Other areas of specialty/work
Gastroenterology
Street address
Digestive Disease Research Institute, Shariati hospital, North Kargar street,
City
Tehran
Province
Tehran
Postal code
1411713135
Phone
+98 21 8241 5000
Fax
+98 21 8241 5400
Email
simaalireza@gmail.com

Person responsible for scientific inquiries

Contact
Name of organization / entity
Digestive Disease Research Institute of Tehran University of Medical Sciences
Full name of responsible person
Ali Reza Sima
Position
Assistant professor
Latest degree
Subspecialist
Other areas of specialty/work
Gastroenterology
Street address
Digestive Disease Research Institute, Shariati hospital, North Kargar street
City
Tehran
Province
Tehran
Postal code
1411713135
Phone
+98 21 8241 5000
Email
simaalireza@gmail.com

Person responsible for updating data

Contact
Name of organization / entity
Digestive Disease Research Institute of Tehran University of Medical Sciences
Full name of responsible person
Alireza Sima
Position
Assistant professor
Latest degree
Subspecialist
Other areas of specialty/work
Gastroenterology
Street address
Digestive Disease Research Institute, Shariati hospital, North Kargar street
City
Tehran
Province
Tehran
Postal code
1411713135
Phone
+98 21 8241 5000
Email
simaalireza@gmail.com

Sharing plan

Deidentified Individual Participant Data Set (IPD)
Yes - There is a plan to make this available
Study Protocol
No - There is not a plan to make this available
Statistical Analysis Plan
No - There is not a plan to make this available
Informed Consent Form
Yes - There is a plan to make this available
Clinical Study Report
Yes - There is a plan to make this available
Analytic Code
No - There is not a plan to make this available
Data Dictionary
No - There is not a plan to make this available
Title and more details about the data/document
Data of participants: at the end of study and after publication of results, the file of the primary and secondary outcomes as well as demographic and past medical history of participants could be shared. the consent form: the approved consent form could be shared
When the data will become available and for how long
Start date of sharing:Three months after publication of results End date of sharing: Nine months after publication of results
To whom data/document is available
Academic researchers
Under which criteria data/document could be used
In case academic researchers are interested in obtaining these data, they should contact (by official academic email) the scientific responsible of this study and ask for data. the data can not be used for publishing the paper
From where data/document is obtainable
For requesting the data, thee academic researcher should contact by academic email the scientific responsible of the study Dr Ali Reza Sima simaalireza@gmail.com
What processes are involved for a request to access data/document
The reason for requesting the data and type of use should be mentioned in request. if the conditions are satisfactory for the scientific responsible of study and other collaborators of the study, then the requested data will be shared. This process might take up to one month.
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