Autoimmune DiseasePhase 1NCT01086631
Rituximab for Autoimmune Retinopathy
A Phase 1 study testing Rituximab in people with Autoimmune Disease, run by National Eye Institute (NEI) at 1 site in United States.
Trial summary
Background: Autoimmune retinopathy (AIR) is an inflammatory condition in which the patient s own immune system is attacking his or her eyes and causing vision loss. Patients with AIR are generally treated with immunosuppressive agents to treat the eye inflammation; however, the standard treatment for this disease is… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Autoimmune Disease
- What is being tested?
- Rituximab
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Jan 2010to 8 Jul 2014
- Phase
- Phase 1
- 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
- Participant must be 18 years of age or older.
- Participant must understand and sign the protocol s informed consent document.
- Participant must be willing to comply with the study procedures and expected to be able to return for all study visits.
- Participant must have a diagnosis of AIR according to the features listed below.
- Participants must have demonstrated evidence of anti-retinal antibodies as noted in criterion a and one or more of the clinical manifestations listed in either criterion b or c in order to be considered eligible.
- Serologic or immunohistochemical demonstration of serum anti-retinal antibodies (on normal, unfixed, frozen rhesus monkey or human retinas.
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- Visual field changes
- Defects in visual fields [on HFA (30-2) or GVF]
- Enlarged blind spot
- ERG changes
- Abnormal amplitudes
- Prolonged implicit times.
- Participant must have visual acuity of 20/200 or better in at least one eye.
- Participant must have normal renal function, liver function and blood cell counts, OR has mild abnormalities and is cleared for enrollment by internal medicine.
- Participant must agree not to receive any live or live-attenuated vaccinations (e.g., nasal flu vaccine [FluMist ] or Zostavax ) for the duration of the study.
- Participant must have clear ocular media and adequate pupillary dilation to permit quality imaging.
- Participant must have a negative PPD screening test as defined by the Centers for Disease Control (CDC) unless otherwise cleared by internal medicine (i.e., previously treated for a positive PPD or a history of Bacillus of Calmette and Guerin (BCG) vaccination).
- Female participants of childbearing potential must not be pregnant or breast-feeding, must have a negative serum pregnancy test at screening and must be willing to undergo pregnancy tests throughout the study.
- Both female participants of childbearing potential and male participants able to father a child must agree to practice two forms of adequate contraception throughout the course of the study and for 12 months following the last administration of the investigational product. Acceptable methods of contraception include hormonal contraception (i.e., birth control pills, injected hormones, dermal patch or vaginal ring), intrauterine device, barrier methods with spermicide (diaphragm with spermicide, condom with spermicide) or surgical sterilization (hysterectomy, tubal ligation or vasectomy).
- Childbearing potential must be determined
- Participants with a hysterectomy or vasectomy (or who have a partner with a hysterectomy or vasectomy) are exempt from using two methods of contraception. However, participants with a tubal ligation (or male participants who have a female partner with a tubal ligation) are not exempt, and are required to practice another acceptable method of contraception.
Who cannot join
- Participant received other biologic agents (e.g., infliximab, daclizumab or adalimumab) within three months prior to study enrollment.
- Participant is receiving more than two immunosuppressive agents or experienced a change in his/her AIR immunosuppressive medication regimen within the two months prior to enrollment.
- Participant received intraocular or periocular steroid injections within two months prior to study enrollment.
- Participant has a significant active infection (an infection requiring treatment as determined by the medical team) or a history of chronic or recurrent infections.
- Participant is HIV positive or has syphilis.
- Participant has a history of cancer (other than a non-melanoma skin cancer or non-Hodgkin s lymphoma [NHL]) diagnosed within the past five years.
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- Participant has or is a carrier of hepatitis B or C.
- Participant has a known hypersensitivity to sodium fluorescein dye.
- Participant has congestive heart failure, abnormal cardiac function or significant pulmonary disease.
- Participant is participating in another simultaneous investigational product treatment trial.
- Participant received a live or live-attenuated vaccine within the previous four weeks prior to study enrollment
- Participant had ocular surgery within 60 days prior to study enrollment or is anticipated to require elective intraocular surgery.
- Participant has inadequately controlled diabetes.
- Participant has a condition that, in the opinion of the investigator, would pose a significant hazard to the participant if the investigational product was initiated.
- Participant has any other condition that would be contraindicated to treatment with rituximab or their current immunosuppressive agent.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Background:
- Autoimmune retinopathy (AIR) is an inflammatory condition in which the patient s own immune system is attacking his or her eyes and causing vision loss. Patients with AIR are generally treated with immunosuppressive agents to treat the eye inflammation; however, the standard treatment for this disease is still being developed.
- Rituximab, an immunosuppressive agent, is a monoclonal antibody that is directed against a part of the immune system that may be an important cause of AIR. Rituximab is approved for the treatment of non-Hodgkin s lymphoma and rheumatoid arthritis, but is not approved for the treatment of AIR. Researchers are interested in determining whether rituximab may be used to treat AIR.
Read more
Objectives:
- To to investigate the safety, tolerability and possible efficacy of rituximab as a treatment for AIR.
Eligibility:
- Individuals at least 18 years of age who have been diagnosed with AIR and have visual acuity of 20/200 or better in at least one eye.
Design:
- Before the start of the study, participants will be screened with a medical history, immunization records, a series of eye examinations, a chest X-ray, an electrocardiogram, and blood tests.
- Participants will receive a maximum of two cycles of rituximab during the 18-month study. Each cycle will involve two separate intravenous infusions of rituximab given 2 weeks apart.
- Participants will return to the clinic 6 weeks after the first cycle of rituximab for a safety visit, which will include a routine eye and physical examinations. They will also provide blood and other samples for study.
- After the safety visit, participants will return every 3 months for follow-up visits.
- At the 6-month visit, participants who have successfully or partially responded to rituximab will receive another cycle of treatment. Those who do not respond will not receive another cycle, but will continue to be monitored until the end of the study.
Read the detailed description
Objective:
Autoimmune retinopathy (AIR) is an ophthalmic disorder in which autoantibodies damage the retina and its components, causing progressive vision loss. AIR has no established treatment, but systemic immunosuppression has shown favorable responses. Rituximab is an immunosuppressive agent which binds specifically to B lymphocytes. The objective of this study is to investigate the safety of rituximab as an effective treatment for AIR.
Study Population:
Five participants with AIR and visual acuity of 20/200 or better in at least one eye will receive rituximab. AIR must be confirmed by immunohistochemical demonstration of serum anti-retinal antibodies on normal, unfixed, frozen rhesus monkey or human retinas, as well as visual field and electroretinography (ERG) changes. Up to seven participants may be enrolled, in order to obtain the five participants to be included in the analysis if participants withdraw prior to receiving rituximab.
Design:
The study duration is 18 months. Rituximab is administered as a cycle consisting of two separate rituximab infusions of 1,000 mg each, two weeks apart. Participants will receive their first rituximab cycle at baseline and evaluated for a second cycle six months later. Treatment success is defined as experiencing a greater than a 25% improvement in ERG response amplitudes or greater than a 3 decibel (dB) improvement in mean deviation on Humphrey Field Analyzer [HFA (30-2)] or improvement in threshold values greater than 0.5 log in existing scotomas or greater than 25% improvement in the area of scotomas on Goldmann Visual Field (GVF) assessment as compared with baseline. As a result, participants could receive a maximum of two cycles in this study. Participants will return to the clinic 6 weeks and 3 months after their first infusion of each cycle for a safety visit. Study visits will continue every three months for the study duration.
Outcome Measures:
The primary outcome is the number of participants who meet the definition of treatment success within six months from baseline. Secondary efficacy outcomes include changes in visual acuity, the number of treatment successes at 9 and 12 months, the number of partial responders at 6, 9 and 12 months, changes in ERG or visual field as demonstrated by the HFA (30-2) or GVF, changes in optical coherence tomography (OCT), changes in fluorescein angiography (FA), changes in serum anti-retinal autoantibody or anti-retinal antibody staining, changes in color vision, positive visual symptoms or nyctalopia and changes in the participants quality-of-life as assessed by the NEI visual function questionnaire. For participants with greater than or equal to 2 ERG measurements available prior to enrollment, an attempt will be made to compare the rate of decline pre-study period to the rate of decline post-enrollment period. Safety outcomes include the number and severity of systemic and ocular toxicities, adverse events, and infections and the proportion of participants with a loss of greater than or equal to 15 ETDRS letter score.
- Conditions
- Autoimmune Disease
- Being tested
- Rituximab
- Keywords
- Autoimmune Retinopathy, RITUXAN, Rituximab, Immunosuppression
- Medical subject headings
- Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome is the number of participants who meet the definition of treatment success within six months from baseline.
Secondary outcomes (1)
Changes in visual acuity, number of treatment successes or partial responders, changes in ERG, HFA, OCT or FA, changes in serum antibody staining, changes in color vision, and changes in quality-of-life.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2010 (estimated)
- Study start22 Jan 2010
- Study completion8 Jul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Autoimmune DiseaseStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Eye Institute (NEI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Hatice N Sen, M.D., Principal investigator, National Eye Institute (NEI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01086631
- Sponsor's protocol ID
- 100040
- Other IDs
- 10-EI-0040
- Status last verified
- 8 Jul 2014
- First submitted
- 12 Mar 2010
- Last updated
- 5 Jul 2018
- Results posted
- No
Publications
Weinstein JM, Kelman SE, Bresnick GH, Kornguth SE. Paraneoplastic retinopathy associated with antiretinal bipolar cell antibodies in cutaneous malignant melanoma. Ophthalmology. 1994 Jul;101(7):1236-43. doi: 10.1016/s0161-6420(94)31183-3.
PubMed 8035987Jacobson DM, Thirkill CE, Tipping SJ. A clinical triad to diagnose paraneoplastic retinopathy. Ann Neurol. 1990 Aug;28(2):162-7. doi: 10.1002/ana.410280208.
PubMed 2171418Weleber RG, Watzke RC, Shults WT, Trzupek KM, Heckenlively JR, Egan RA, Adamus G. Clinical and electrophysiologic characterization of paraneoplastic and autoimmune retinopathies associated with antienolase antibodies. Am J Ophthalmol. 2005 May;139(5):780-94. doi: 10.1016/j.ajo.2004.12.104.
PubMed 15860281
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rituximab for Autoimmune Retinopathy
- ClinicalTrials.gov ID
- NCT01086631
- Acronym / sponsor ID
- 100040
- Conditions
- Autoimmune Disease
- Keywords
- Autoimmune Retinopathy, RITUXAN, Rituximab, Immunosuppression
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- National Eye Institute (NEI)US National Institutes of Health
- Study start
- 22 Jan 2010
- Study completion
- 8 Jul 2014 (actual)
- First posted
- 15 Mar 2010 (estimated)
- 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.
Background:
- Autoimmune retinopathy (AIR) is an inflammatory condition in which the patient s own immune system is attacking his or her eyes and causing vision loss. Patients with AIR are generally treated with immunosuppressive agents to treat the eye inflammation; however, the standard treatment for this disease is still being developed.
- Rituximab, an immunosuppressive agent, is a monoclonal antibody that is directed against a part of the immune system that may be an important cause of AIR. Rituximab is approved for the treatment of non-Hodgkin s lymphoma and rheumatoid arthritis, but is not approved for the treatment of AIR. Researchers are interested in determining whether rituximab may be used to treat AIR.
Objectives:
- To to investigate the safety, tolerability and possible efficacy of rituximab as a treatment for AIR.
Eligibility:
- Individuals at least 18 years of age who have been diagnosed with AIR and have visual acuity of 20/200 or better in at least one eye.
Design:
- Before the start of the study, participants will be screened with a medical history, immunization records, a series of eye examinations, a chest X-ray, an electrocardiogram, and blood tests.
- Participants will receive a maximum of two cycles of rituximab during the 18-month study. Each cycle will involve two separate intravenous infusions of rituximab given 2 weeks apart.
- Participants will return to the clinic 6 weeks after the first cycle of rituximab for a safety visit, which will include a routine eye and physical examinations. They will also provide blood and other samples for study.
- After the safety visit, participants will return every 3 months for follow-up visits.
- At the 6-month visit, participants who have successfully or partially responded to rituximab will receive another cycle of treatment. Those who do not respond will not receive another cycle, but will continue to be monitored until the end of the study.
Detailed description
Objective:
Autoimmune retinopathy (AIR) is an ophthalmic disorder in which autoantibodies damage the retina and its components, causing progressive vision loss. AIR has no established treatment, but systemic immunosuppression has shown favorable responses. Rituximab is an immunosuppressive agent which binds specifically to B lymphocytes. The objective of this study is to investigate the safety of rituximab as an effective treatment for AIR.
Study Population:
Five participants with AIR and visual acuity of 20/200 or better in at least one eye will receive rituximab. AIR must be confirmed by immunohistochemical demonstration of serum anti-retinal antibodies on normal, unfixed, frozen rhesus monkey or human retinas, as well as visual field and electroretinography (ERG) changes. Up to seven participants may be enrolled, in order to obtain the five participants to be included in the analysis if participants withdraw prior to receiving rituximab.
Design:
The study duration is 18 months. Rituximab is administered as a cycle consisting of two separate rituximab infusions of 1,000 mg each, two weeks apart. Participants will receive their first rituximab cycle at baseline and evaluated for a second cycle six months later. Treatment success is defined as experiencing a greater than a 25% improvement in ERG response amplitudes or greater than a 3 decibel (dB) improvement in mean deviation on Humphrey Field Analyzer [HFA (30-2)] or improvement in threshold values greater than 0.5 log in existing scotomas or greater than 25% improvement in the area of scotomas on Goldmann Visual Field (GVF) assessment as compared with baseline. As a result, participants could receive a maximum of two cycles in this study. Participants will return to the clinic 6 weeks and 3 months after their first infusion of each cycle for a safety visit. Study visits will continue every three months for the study duration.
Outcome Measures:
The primary outcome is the number of participants who meet the definition of treatment success within six months from baseline. Secondary efficacy outcomes include changes in visual acuity, the number of treatment successes at 9 and 12 months, the number of partial responders at 6, 9 and 12 months, changes in ERG or visual field as demonstrated by the HFA (30-2) or GVF, changes in optical coherence tomography (OCT), changes in fluorescein angiography (FA), changes in serum anti-retinal autoantibody or anti-retinal antibody staining, changes in color vision, positive visual symptoms or nyctalopia and changes in the participants quality-of-life as assessed by the NEI visual function questionnaire. For participants with greater than or equal to 2 ERG measurements available prior to enrollment, an attempt will be made to compare the rate of decline pre-study period to the rate of decline post-enrollment period. Safety outcomes include the number and severity of systemic and ocular toxicities, adverse events, and infections and the proportion of participants with a loss of greater than or equal to 15 ETDRS letter score.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Participant must be 18 years of age or older.
- Participant must understand and sign the protocol s informed consent document.
- Participant must be willing to comply with the study procedures and expected to be able to return for all study visits.
- Participant must have a diagnosis of AIR according to the features listed below.
- Participants must have demonstrated evidence of anti-retinal antibodies as noted in criterion a and one or more of the clinical manifestations listed in either criterion b or c in order to be considered eligible.
Key exclusion criteria (15 listed)
- Participant received other biologic agents (e.g., infliximab, daclizumab or adalimumab) within three months prior to study enrollment.
- Participant is receiving more than two immunosuppressive agents or experienced a change in his/her AIR immunosuppressive medication regimen within the two months prior to enrollment.
- Participant received intraocular or periocular steroid injections within two months prior to study enrollment.
- Participant has a significant active infection (an infection requiring treatment as determined by the medical team) or a history of chronic or recurrent infections.
- Participant is HIV positive or has syphilis.
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 |
|---|---|---|
| Rituximab | Drug | – |
Primary outcome
The primary outcome is the number of participants who meet the definition of treatment success within six months from baseline.
1 secondary outcome
Changes in visual acuity, number of treatment successes or partial responders, changes in ERG, HFA, OCT or FA, changes in serum antibody staining, changes in color vision, and changes in quality-of-life.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2018.
- Background: PubMed 8035987Weinstein JM, Kelman SE, Bresnick GH, Kornguth SE. Paraneoplastic retinopathy associated with antiretinal bipolar cell antibodies in cutaneous malignant melanoma. Ophthalmology. 1994 Jul;101(7):1236-43. doi: 10.1016/s0161-6420(94)31183-3.
- Background: PubMed 2171418Jacobson DM, Thirkill CE, Tipping SJ. A clinical triad to diagnose paraneoplastic retinopathy. Ann Neurol. 1990 Aug;28(2):162-7. doi: 10.1002/ana.410280208.
- Background: PubMed 15860281Weleber RG, Watzke RC, Shults WT, Trzupek KM, Heckenlively JR, Egan RA, Adamus G. Clinical and electrophysiologic characterization of paraneoplastic and autoimmune retinopathies associated with antienolase antibodies. Am J Ophthalmol. 2005 May;139(5):780-94. doi: 10.1016/j.ajo.2004.12.104.
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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.
Hatice N Sen, M.D. principal investigator
National Eye Institute (NEI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Rituximab in people with Autoimmune Disease, run by National Eye Institute (NEI) at 1 site in United States.
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 21 inclusion and 15 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: finished, as of the sponsor's last update on 5 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The primary outcome is the number of participants who meet the definition of treatment success within six months from baseline.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01086631, which also lists 3 linked publications.
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 5 Jul 2018; AzTrials last refreshed its copy on 31 Oct 2026.