A Phase 3 interventional study of Infliximab and Cyclophosphamide in Idiopathic Refractory Scleritis, sponsored by Hospices Civils de Lyon. Withdrawn. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-07-20.
Sponsored by Hospices Civils de Lyon · Phase 3, Interventional, and Treatment
This study will evaluate the Efficacy and Safety of Infliximab versus Cyclophosphamide in Subjects with Idiopathic Refractory Scleritis.
The term scleritis describes a chronic inflammation that involves the outermost cost and skeleton of the eye. Scleritis is classified anatomically as either anterior or posterior based on the principal location of the inflammation. Thirty to forty percent of scleritis cases are associated with systemic autoimmune conditions including rheumatoid arthritis and granulomatosis with polyangiitis. Infectious causes including herpes virus and varicella zoster account for 5 to 10% of patients. The remaining 50% of cases are classified as idiopathic.
CIRIS, is the first prospective randomized, head to head study, comparing infliximab to cyclophosphamide in refractory idiopathic scleritis. There is no firm evidence or randomized controlled trials directly addressing the best biologic agent in severe and refractory idiopathic scleritis. If left untreated or insufficiently treated, scleritis can progress to peripheral ulcerative keratitis, uveitis and glaucoma. Visual loss occurs in approximately 10% of patients with anterior scleritis and in up to 75% of patients with posterior scleritis. The incidence of burden in ocular inflammation (uveitis and scleritis) has been dramatically reduced in the recent years with the use of biologics, raising the question of whether these compounds should be used earlier in the treatment of severe non infectious scleritis. Contrasting with other immunosuppressors, cyclophosphamide and infliximab act rapidly and are highly effective in steroid's sparing.
Despite a strong rationale, these compounds are not yet approved in idiopathic refractory scleritis, which guarantees the innovative nature of this study that aims selecting or dropping any arm when evidence of efficacy already exists.
Hospices Civils de Lyon is the lead sponsor of 1,866 studies on the registry; 448 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Topical corticosteroids and/or NSAIDs are permitted provided the dose regimen has been stable for 2 weeks prior to Screening and remains stable throughout the study. Topical treatment for cycloplegia is permitted.
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Exclusion Criteria:
Infectious disease:
Laboratory values assessed during Screening:
Use of the following systemic treatments during the specified periods:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Reproductive potential
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients will receive prednisone and infliximab (5 mg/kg at week 0, 2, 6, 11 and 16 as an intravenous (IV) infusion) in association with low-dose methotrexate (10 mg/week) for 16 weeks.
Drug: Infliximab
Patients will receive prednisone and cyclophosphamide intravenously (700 mg/m2 every 4 weeks intravenously) (n=25) for 16 weeks.
Drug: Cyclophosphamide
Patients will receive prednisone and infliximab (5 mg/kg at week 0, 2, 6, 11 and 16 as an intravenous (IV) infusion) in association with low-dose methotrexate (10 mg/week) for 16 weeks.
Patients will receive prednisone and cyclophosphamide intravenously (700 mg/m2 every 4 weeks intravenously) (n=25) for 16 weeks.
percentage of patients with resolution (score=0) of the scleral inflammation and with a prednisone dose lower than 0.1 mg/kg/day
Scleritis will be graded and scored according to the grading system defined by Sen for sclera inflammation (gradings from 0 to 4): these findings will be documented by drawings, photography or both for central review.
Time frame: Week 20
percentage of patients with a decrease of at least 2 in sclera inflammation with a prednisone dose lower or equal to 0.1 mg/kg/day.
according to Sen and al gradation at week 20 and with a prednisone dose lower or equal to 0.1 mg/kg/day.
Time frame: Week 20
Mean change in sclera inflammation from baseline to Week 20.
from baseline to Week 20 (according to Sen and al gradation)
Time frame: Week 20
Time to response onset (total resolution in sclera inflammation).
Time frame: Week 26
Mean change in Best corrected visual acuity
from baseline to week 20 (ETDRS letter score)
Time frame: Week 20
percentage of patients meeting targets: ≤ 0.1 mg/day prednisone
Time frame: Week 20
mean change dose of corticosteroid
* mean dose at week 20, * cumulative dose.
Time frame: Week 26
Mean dose of corticosteroid
Time frame: Week 20
Cumulative dose of corticosteroid
Time frame: Week 26
Frequency to relapse of scleritis
Relapse will be diagnosed when inflammation will restart within 6 months of tapering or discontinuation of medication.Early relapse will be distinguished to later relapse. Early relapse corresponds to any scleritis relapse within the 3 months after discontinuation of medication and later relapse corresponds to any scleritis relapse after 3 months after discontinuation of medication.
Time frame: Week 26
Characteristics of scleritis at worsening.
Time frame: Week 26
Frequency to relapse of scleritis and the characteristics of scleritis at worsening.
Relapse will be diagnosed when inflammation will restart within 6 months of tapering or discontinuation of medication.Early relapse will be distinguished to later relapse. Early relapse corresponds to any scleritis relapse within the 3 months after discontinuation of medication and later relapse corresponds to any scleritis relapse after 3 months after discontinuation of medication.
Time frame: Week 52
Characteristics of scleritis at worsening.
Time frame: Week 52
Time to relapse of scleritis
Relapse will be diagnosed when inflammation will restart within 6 months of tapering or discontinuation of medication. Early relapse will be distinguished to later relapse. Early relapse corresponds to any scleritis relapse within the 3 months after discontinuation of medication and later relapse corresponds to any scleritis relapse after 3 months after discontinuation of medication.
Time frame: Week 26
Time to relapse of scleritis
Relapse will be diagnosed when inflammation will restart within 6 months of tapering or discontinuation of medication. Early relapse will be distinguished to later relapse. Early relapse corresponds to any scleritis relapse within the 3 months after discontinuation of medication and later relapse corresponds to any scleritis relapse after 3 months after discontinuation of medication.
Time frame: Week 52
Mean change in quality of life
assessed using the 36-Item Short Form Health Survey (SF-36) - from baseline to W16 and W26
Time frame: Week 16 ; Week 26
Mean change in of vision-related quality of life
assessed by the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) - from baseline to W16 and W26
Time frame: Week 16 ; Week 26
No study locations are listed for this record.
This study is withdrawn, as verified in Jul 2022. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Infliximab · Cyclophosphamide