Evaluation the clinical trial of Rituximab (Zytux) efficacy in improving the skin stiffness and lung involvements of the patients with diffuse cutaneous Systemic sclerosis with diffuse skin involvement
Systemic sclerosis (SSc) is a chronic disease with increased skin and lung fibrosis. The treatments which are used have the limited effect on skin fibrosis. This disorder is a disabling disease which needs the new and effective treatments. Its pathogenesis is unknown, but it seems that B cells by antibody production, hypergammaglobulinemia and polycloncal hyperactivation has a significant role. In addition, CD19 expression is augmented in memory and naive B cells of SSc patient. The skin biopsy of the patients shows the CD20 positive cells infiltrate, consequently the B cells are targeted for treatment. Rituximab is a monocloncal antibody against CD20 which leads to decrease the peripheral B cells. Rituximab was used for other autoimmune disorders like systemic lupus erythematosus and vasculitis with limited side effects. Prescription of Rituximab for mouse model with skin stiffness leads to reducing the skin fibrosis. In addition the evidences are exist for graft versus host disease treatment. According to the results' of the investigations on SSc treatment, we have designed this study to evaluate the efficacy of Rituximab on skin fibrosis and lung involvement. The other results are listed below: In this study the Iranian biosimilar of Rituximab (Zytux) will be used; the efficacy of Rituximab was not evaluated previously on Iranian population; the results of the previous studies with the same subject were highly controversial; in addition to modified Rodnan skin score, the lung involvement and disease severity score will be also evaluated.
General information
Acronym
IRCT registration information
IRCT registration number:IRCT2016022126686N1
Registration date:2016-08-12, 1395/05/22
Registration timing:registered_while_recruiting
Last update:
Update count:0
Registration date
2016-08-12, 1395/05/22
Registrant information
Name
farhad gharibdoost
Name of organization / entity
tehran university
Country
Iran (Islamic Republic of)
Phone
+98 21 8822 0065
Email address
gharibdoost@sina.tums.ac.ir
Recruitment status
Recruitment complete
Funding source
Investigator
Expected recruitment start date
2016-07-22, 1395/05/01
Expected recruitment end date
2019-07-23, 1398/05/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Evaluation the clinical trial of Rituximab (Zytux) efficacy in improving the skin stiffness and lung involvements of the patients with diffuse cutaneous Systemic sclerosis with diffuse skin involvement
Public title
Evaluation the efficacy of Rituximab (Zytux) in diffuse cutaneous Systemic sclerosis treatment
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion Criteria: age more than 20 year old; patients with diffuse cutaneous Systemic sclerosis (SSc) with disease duration less than 7 years from the Raynaud's phenomen; modified Rodnan skin score (mRSS) more than 20; the presence of interstitial lung disease (ILD) in high resolution computed tomography (HRCT) or pulmonary function test (PFT) or both (if the ILD involvement is more than 20% it will be sufficient and in the other situation the ILD should be proved by HRCT and PFT); the mRSS should be remained unchanged after 6 months of the treatment with Endoxan or Cellcept as the previous therapy.
Exclusion Criteria: the previous history of Rituximab administration; the history of nervous system disorders like Multiple sclerosis; the history of viral hepatitis like Hepatitis B or C; the history of human immunodeficiency virus infection; the history of tuberculosis infection with PPD more than 5 millimeter; the history of malignancy; dyspnea at rest; the sign and symptoms of congestive heart failure at rest; the history of infectious diseases; the history of cardiac arhythmia on electrocardiogram; the history of prednisolone usage more than 10 mg per day; tricuspid regurgitation jet flow velocity more than 2.8; pulmonary arterial pressure more than 35 according to trans-thoracic ecocardiography; ejection fraction less than 40%; diffusion capacity of the lung for carbon monoxide less than 50%; forced vital capacity less than 50%; serum creatinine level more than 1.5; the history of scleroderma renal crisis; the history of co-morbid cardiac, pulmonary and renal diseases unrelated to SSc.
Age
No age limit
Gender
Both
Phase
3
Groups that have been masked
No information
Sample size
Target sample size:
20
Randomization (investigator's opinion)
N/A
Randomization description
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Single
Other design features
This project is designed in clinical trial without randomization and blindness. It is a before and after clinical trial.
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Technology and research management center of Tehran University of Medical Sciences
Street address
Number 6, Keshavarz boulevard, Ghods avenue, the central department of Tehran University of Medical Sciences
City
Tehran
Postal code
Approval date
2015-12-21, 1394/09/30
Ethics committee reference number
IR.TUMS.REC.1394.1454
Health conditions studied
1
Description of health condition studied
Systemic sclerosis (Scleroderma)
ICD-10 code
M34.8
ICD-10 code description
systemic sclerosis with lung involvementJ99.1*
Primary outcomes
1
Description
Skin stiffness (modified Rodnan skin score)
Timepoint
Before and after 6 months of treatment
Method of measurement
The examination by fixed Rheumatologist
2
Description
Lung involvement according to ground glass opacities and lung fibrosis
Timepoint
Before and after 6 months of treatment
Method of measurement
Spirometery, diffusion capacity of the lungs for carbon monoxide, high resolution computed tomography
Secondary outcomes
1
Description
The side effects of the biosimilar drug, Zytux
Timepoint
Three and six months after treatment if any side effect will present
Method of measurement
Clinical and laboratory examination and diagnosis
Intervention groups
1
Description
The Zytux which is Rituximab biosimilar with the Iran insurance approval will be administered intravenously with the dosage of 1 gram on the beginning of the treatment, followed by an other 1 gram in two weeks in the hospital. Before the administration, 10 milliliter diphenhydramin and 100 milligram hydrocortisone will be administered to the patients. All of the administrating processes will be under the monitoring.
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Rheumatology research center, Rheumatology department of Shariati hospital
Full name of responsible person
Street address
City
Tehran
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Aryogen pharmed
Full name of responsible person
Amir Farshchy
Street address
Number 140, corner of Tajbakhsh street, 24th kilometer KM Terhan-Karaj, Makhsous road, Alborz, Iran
City
Karaj
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Aryogen pharmed
Proportion provided by this source
100
Public or private sector
empty
Domestic or foreign origin
empty
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
empty
Person responsible for general inquiries
Contact
Name of organization / entity
Rheumatology research center
Full name of responsible person
Kourosh Sheikh Ahmadi
Position
Rheumatology fellowship
Other areas of specialty/work
Street address
Number 6, Kargar avenue, Shariati hospital, Rheumatology research center
City
Tehran
Postal code
Phone
+98 21 8822 0065
Fax
Email
maadarya@yahoo.com
Web page address
Person responsible for scientific inquiries
Contact
Name of organization / entity
Rheumatology research center
Full name of responsible person
Farhad Gharibdoost
Position
Full professor
Other areas of specialty/work
Street address
Number 6, Kargar avenue, Shariati hospital, Rheumatology research center