Idiopathic Refractory ScleritisPhase 3CIRISNCT03088293
Cyclophosphamide vs. Infliximab for Refractory Idiopathic Scleritis (CIRIS)
A Phase 3 study testing Infliximab and Cyclophosphamide in people with Idiopathic Refractory Scleritis, run by Hospices Civils de Lyon.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Idiopathic Refractory Scleritis
- What is being tested?
- Infliximab and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 11 Jun 2020to Jul 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provide written informed consent prior to the performance of any study-specific procedures
- Male or female, subject aged > or = 18 at Screening
- Weight 40 - 120 kg at Screening
- Diagnosis of anterior idiopathic scleritis or anterior and posterior idiopathic scleritis at least one eye. Scleritis is classified anatomically as anterior based on the principal location of the inflammation. Clinically, anterior scleritis can be divided into diffuse, nodular or necrotizing types.
- Active disease: Currently uncontrolled scleritis disease. Uncontrolled scleritis disease is defined as (at least) a 2 in sclera inflammation, according to the grading system defined by Sene for sclera inflammation (gradings from 0 to 4).
- Refractory disease: At screening, subjects must be receiving oral corticosteroids (>10 mg/day prednisone equivalent and <80 mg/day) and at least one other immunosuppressive for more than 4 months (azathioprine, methotrexate, mycophenolate mofetyl, cyclosporine, leflunomide) or be intolerant to such immunosuppressive therapies.
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- 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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- Chest X-ray results (postero-anterior and lateral) within 12 weeks prior to the randomization visit with no evidence of active Tuberculosis, active infection, or malignancy.
- For female subjects of child-bearing age, a negative serum pregnancy test. A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient (definition of the Clinical Trial Facilitation Group).
- For subjects with reproductive potential, a willingness to use adequate contraceptive measures to prevent the subject or the subject's partner from becoming pregnant during the study. For women in period of childbearing adequate contraceptive measures include hormonal methods used for two or more cycles prior to Screening and 6 months after the last dose treatment should be used (e.g., oral contraceptive pills, contraceptive patch, or contraceptive vaginal ring), barrier methods (e.g., contraceptive sponge, diaphragm used in conjunction with contraceptive foam or jelly, or condom used in conjunction with contraceptive foam or jelly), intrauterine devices (IUD), sterilization (e.g., tubal ligation or a monogamous relationship with a vasectomized partner), and abstinence. For men who are sexually active with a women in period of childbearing adequate contraceptive measures from screening to 6 months after the last dose treatment should be used (For men: barrier methods (condom used in conjunction with contraceptive foam or jelly), sterilization (vasectomy) and abstinence. For his partner: hormonal methods (e.g., oral contraceptive pills, contraceptive patch, or contraceptive vaginal ring), barrier methods (e.g., contraceptive sponge, diaphragm used in conjunction with contraceptive foam or jelly), intrauterine devices (IUD), sterilization (e.g., tubal ligation)).
- A negative QuantiFERON®-Tuberculosis (TB) test result or, in the event that their QuantiFERON®-TB test result at Screening is positive, all subjects must agree to complete an INH treatment course of at least 6 months.
- Affiliated to the French social security system.
Who cannot join
- medical contraindication to administer experimental drugs: Cyclophosphamide (urinary obstruction, bladder inflammation…) or Infliximab (moderate or severe heart failure, classe III /IV classification NYHA…)/low dose Methotrexate (chronic respiratory insufficiency…); and non-experimental drugs (10 % phenylephrine instillation, prednisone, paracetamol, polaramine, folic acid and uromitexan)
- Infectious scleritis, posterior idiopathic scleritis or scleritis related to systemic diseases (i.e. granulomatosis with polyangiitis, rheumatoid arthritis, lupus, relapsing chondritis, etc)
- Blindness or very low visual acuity (<1/20) of the no study eye
- Active tuberculosis or history of untreated tuberculosis
- Known positive syphilis serology, HIV antibody, . Positive serology for hepatitis B or C virus is not considered as non-inclusion criteria. These tests should be performed during the screening, and in case of positive result the opinion of a hepatologist will be requested
- History of malignancy within 5 years prior to Screening other than carcinoma in situ of the cervix or adequately treated, non-metastatic squamous or basal cell carcinoma of the skin.
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- History of severe allergic or anaphylactic reactions to monoclonal antibodies. Hypersensitivity known to cyclophosphamide, to infliximab, to other murine proteins, to methotrexate or to any of the excipients.
- Infectious disease:
- Fever or infection requiring treatment with antibiotics within 3 weeks prior to Screening or between Screening and Day 0.
- History of recurrent infection or predisposition to infection.
- Known immunodeficiency
- History of multiple sclerosis and/or demyelinating disorder
- Laboratory values assessed during Screening:
- Hemoglobin <8.5 g/dL
- WBC <3.0 x 103/mm3
- Platelet count <100 x 103/mm3
- Glomerular filtration rates (GFR) <30 ml/min.
- AST/ALT >1.5 x upper limit of normal (ULN)
- Absolute Neutrophil Count <2.0 x 103/mm3
- Absolute Lymphocyte Count <0.5 x 103/mm3
- Use of the following systemic treatments during the specified periods:
- Any other previous systemic biological therapy, including anti-TNF
- Treatment with any systemic alkylating agents within 12 months prior to Screening or between Screening and Day 0 (e.g., cyclophosphamide, chlorambucil)
- Any live (attenuated) vaccine within 3 months prior to Screening or between Screening and Day 0; recombinant or killed virus vaccines are permitted. Live seasonal flu and H1N1 vaccines are permitted ≥2 weeks prior to Screening.
- Participation to another interventional research.
- Inability to understand information concerning the protocol.
- Pregnant or lactating women.
- Patient under guardianship
About this study
Official title: A Multicenter Randomized Open-label Trial Comparing the Efficacy and Safety of Infliximab Versus Cyclophosphamide in Subjects With Idiopathic Refractory Scleritis
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.
Read more
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.
- Conditions
- Idiopathic Refractory Scleritis
- Being tested
- Infliximab, Cyclophosphamide
- Keywords
- idiopathic refractory scleritis, infliximab, cyclophosphamide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InfliximabDrug
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.
CyclophosphamideDrug
Patients will receive prednisone and cyclophosphamide intravenously (700 mg/m2 every 4 weeks intravenously) (n=25) for 16 weeks.
| Study group | Role | What they receive |
|---|---|---|
| infliximab | Experimental | 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. Receives: Drug: Infliximab |
| cyclophosphamide | Experimental | Patients will receive prednisone and cyclophosphamide intravenously (700 mg/m2 every 4 weeks intravenously) (n=25) for 16 weeks. Receives: Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 20
Secondary outcomes (16)
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.
Measured: Week 20
Mean change in sclera inflammation from baseline to Week 20.
from baseline to Week 20 (according to Sen and al gradation)
Measured: Week 20
Time to response onset (total resolution in sclera inflammation).
Measured: Week 26
Mean change in Best corrected visual acuity
from baseline to week 20 (ETDRS letter score)
Measured: Week 20
percentage of patients meeting targets: ≤ 0.1 mg/day prednisone
Measured: Week 20
mean change dose of corticosteroid
- mean dose at week 20,
- cumulative dose.
Measured: Week 26
Mean dose of corticosteroid
Measured: Week 20
Cumulative dose of corticosteroid
Measured: 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.
Measured: Week 26
Characteristics of scleritis at worsening.
Measured: 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.
Measured: Week 52
Characteristics of scleritis at worsening.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: Week 16 ; Week 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2017
- Study start11 Jun 2020
- Primary completionOct 2023 (estimated)
- Study completionJul 2024 (estimated)
Why it stopped: recruiting difficulties
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Idiopathic Refractory ScleritisStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pascal SEVE, Principal investigator, Hospices Civils de Lyon - Hopital de la Croix Rousse - Médecine Interne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03088293
- Sponsor's protocol ID
- 69HCL17_0028
- Other IDs
- 2017-004969-27, 2017
- Acronym
- CIRIS
- Status last verified
- Jul 2022
- First submitted
- 17 Mar 2017
- Last updated
- 20 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Randomized Open-label Trial Comparing the Efficacy and Safety of Infliximab Versus Cyclophosphamide in Subjects With Idiopathic Refractory Scleritis
- ClinicalTrials.gov ID
- NCT03088293
- Acronym / sponsor ID
- CIRIS / 69HCL17_0028
- Conditions
- Idiopathic Refractory Scleritis
- Keywords
- idiopathic refractory scleritis, infliximab, cyclophosphamide
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: recruiting difficulties
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 11 Jun 2020 (actual)
- Primary completion
- Oct 2023 (estimated)
- Study completion
- Jul 2024 (estimated)
- First posted
- 23 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| infliximab | Experimental | Drug: InfliximabPatients 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. |
| cyclophosphamide | Experimental | Drug: CyclophosphamidePatients will receive prednisone and cyclophosphamide intravenously (700 mg/m2 every 4 weeks intravenously) (n=25) for 16 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Provide written informed consent prior to the performance of any study-specific procedures
- Male or female, subject aged > or = 18 at Screening
- Weight 40 - 120 kg at Screening
- Diagnosis of anterior idiopathic scleritis or anterior and posterior idiopathic scleritis at least one eye. Scleritis is classified anatomically as anterior based on the principal location of the inflammation. Clinically, anterior scleritis can be divided into diffuse, nodular or necrotizing types.
- Active disease: Currently uncontrolled scleritis disease. Uncontrolled scleritis disease is defined as (at least) a 2 in sclera inflammation, according to the grading system defined by Sene for sclera inflammation (gradings from 0 to 4).
Key exclusion criteria (28 listed)
- medical contraindication to administer experimental drugs: Cyclophosphamide (urinary obstruction, bladder inflammation…) or Infliximab (moderate or severe heart failure, classe III /IV classification NYHA…)/low dose Methotrexate (chronic respiratory insufficiency…); and non-experimental drugs (10 % phenylephrine instillation, prednisone, paracetamol, polaramine, folic acid and uromitexan)
- Infectious scleritis, posterior idiopathic scleritis or scleritis related to systemic diseases (i.e. granulomatosis with polyangiitis, rheumatoid arthritis, lupus, relapsing chondritis, etc)
- Blindness or very low visual acuity (<1/20) of the no study eye
- Active tuberculosis or history of untreated tuberculosis
- Known positive syphilis serology, HIV antibody, . Positive serology for hepatitis B or C virus is not considered as non-inclusion criteria. These tests should be performed during the screening, and in case of positive result the opinion of a hepatologist will be requested
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| InfliximabPatients 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 |
| CyclophosphamidePatients will receive prednisone and cyclophosphamide intravenously (700 mg/m2 every 4 weeks intravenously) (n=25) for 16 weeks. | Drug | cyclophosphamide |
Primary outcome
percentage of patients with resolution (score=0) of the scleral inflammation and with a prednisone dose lower than 0.1 mg/kg/day
Time frame: Week 20
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.
16 secondary outcomes
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.
Time frame: Week 20
Mean change in sclera inflammation from baseline to Week 20.
Time frame: Week 20
Time to response onset (total resolution in sclera inflammation).
Time frame: Week 26
Mean change in Best corrected visual acuity
Time frame: Week 20
percentage of patients meeting targets: ≤ 0.1 mg/day prednisone
Time frame: Week 20
mean change dose of corticosteroid
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
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.
Time frame: Week 52
Characteristics of scleritis at worsening.
Time frame: Week 52
Time to relapse of scleritis
Time frame: Week 26
Time to relapse of scleritis
Time frame: Week 52
Mean change in quality of life
Time frame: Week 16 ; Week 26
Mean change in of vision-related quality of life
Time frame: Week 16 ; Week 26
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2022.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pascal SEVE principal investigator
Hospices Civils de Lyon - Hopital de la Croix Rousse - Médecine Interne
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Infliximab and Cyclophosphamide in people with Idiopathic Refractory Scleritis, run by Hospices Civils de Lyon.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 20 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
percentage of patients with resolution (score=0) of the scleral inflammation and with a prednisone dose lower than 0.1 mg/kg/day (time frame: Week 20). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2022; AzTrials last refreshed its copy on 2 Nov 2026.