Macular DegenerationNCT00605943
Detection of Neutralizing Antibodies in Patients Treated With Bevacizumab or Ranibizumab
An observational study of Macular Degeneration, run by National Eye Institute (NEI) at 1 site in United States.
Trial summary
This study will measure antibody levels in the blood of people with bleeding or swelling in the retina who have or have not been treated with bevacizumab (Avastin[Trademark]or ranibizumab (Lucentis[Trademark]). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Macular Degeneration
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Jan 2008to 4 Aug 2009
- Phase
- Observational
- 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
- Subjects will include adults being treated for exudative AMD, or macular edema secondary to DR or venous occlusion. The 3 clinical categories, which will each be composed of 10 subjects, are:
- Category 1: Patients treated with long term (greater than 1 year) with bevacizumab or ranibizumab in which decreased drug efficacy has been documented. They must have received at least one treatment in the prior 3 months.
- Decreased drug efficacy will be defined as follows: Presence of a therapeutic response (reduction in macula fluid as determined by optical coherence tomography (OCT) or reduction in extent of leakage on fluorescein angiography (FA)) in the first 3 injections, followed by a subsequent decrease in response as evidenced by persistence of intraretinal cysts and/or subretinal fluid on OCT and/or leakage on fluorescein angiography (FA).
- Category 2: Patients treated with long term (greater than 1 year) bevacizumab or ranibizumab in which decreased drug efficacy has not been documented. They must have received at least one treatment in the prior 3 months.
- The presence of continued drug efficacy will be defined as follows: Patients who are being treated with bevacizumab or ranibizumab and are demonstrating a good clinical response as demonstrated by the presence of a fluid-free macula on OCT and/or the absence of leakage on FA after treatment.
- Category 3: Patients who are na ve to treatment with bevacizumab and ranibizumab
- When possible, patients in the 3 categories will be matched by underlying retinal disease type, race, gender, and age.
Who cannot join
- Patients in the following categories will be excluded from participating in this study:
- Patients who are currently receiving any form of systemic immunosuppressive or immunomodulatory therapy, including corticosteroids. Immunosuppressive medication could lower the titers of neutralizing that are present in a given patient, and this could give the false impression that such a patient has little to no immune response against bevacizumab or ranibizumab.
- Patients who have autoimmune or rheumatologic disease. Patients with autoimmune diseases tend to have various autoantibodies in their serum. These naturally present autoantibodies in this patient group could cross-react with bevacizumab or ranibizumab. This would give the false impression that these patients have developed neutralizing antibodies against bevacizumab or ranibizumab, when in fact these naturally occurring cross-reactive autoantibodies were present in the patient all along and are not related to bevacizumab or ranibizumab exposure.
- Patients with evidence of active systemic infection. Patients with active systemic infection could have various antibodies in the serum, and some of these could cross-react with bevacizumab or ranibizumab. This would give the false impression that these patients have developed neutralizing antibodies against bevacizumab or ranibizumab, when in fact these cross-reactive antibodies were present in the patient secondary to the presence of active systemic infection and are not related to bevacizumab or ranibizumab.
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
Official title: Pilot Study for the Detection of Neutralizing Antibodies in Patients Treated With Bevacizumab Avastin or Ranibizumab Lucentis
This study will measure antibody levels in the blood of people with bleeding or swelling in the retina who have or have not been treated with bevacizumab (Avastin[Trademark]or ranibizumab (Lucentis[Trademark]). These drugs have been useful in reducing retinal bleeding and swelling in people with eye diseases that cause these symptoms, but the drugs' effects usually wear off and they have to be given repeatedly. In some patients, the benefits become less and less. It is possible that over time, patients taking these drugs may produce antibodies that act against the drugs, thus neutralizing their effects and preventing them from working properly.
People 18 year of age and older who are participating in a current NEI protocol and meet the following criteria may be eligible for this study:
Read more
- Are receiving injections of bevacizumab or ranibizumab for bleeding or swelling in the retina, but the treatment is becoming less effective
- Are receiving injections of bevacizumab or ranibizumab for bleeding or swelling in the retina and the treatment is still effective
- Have bleeding or swelling in the retina, but have never received either bevacizumab or ranibizumab
Participants have blood samples drawn once when they start the study, once in the middle of the study, and once at the end of the study. They are asked permission for study researchers to review the results of their eye examinations at NIH.
Read the detailed description
Objective
Over the past two years, the field of ophthalmology has witnessed a dramatic paradigm shift in the treatment of exudative and hemorrhagic diseases affecting the retina. This has been due largely to the introduction of two agents, bevacizumab and ranibizumab, into the clinical setting. These agents are humanized monoclonal antibodies which target vascular endothelial growth factor (VEGF). We have observed that, in some patients, a diminished response to these agents occurs with time. One possible explanation for this is the emergence of neutralizing antibodies in patients who have become refractory to bevacizumab or ranibizumab.
Study Population
We will recruit patients from the National Eye Institute (NEI) who are currently receiving treatment with bevacizumab or ranibizumab for various exudative or hemorrhagic disease of the retina. We will also recruit patients with recently diagnosed exudative or hemorrhagic disease of the retina who are na ve to these medications and are going to be treated with them.
Design
This will be a prospective, observational study.
Outcome Measures
The main outcome measure will be the titer of neutralizing antibodies which is measured in patient sera using enzyme-linked immunosorbent assay (ELISA). This will be compared between three groups of patients: 1) 10 patients treated with long term (greater than 1 year) bevacizumab and/or ranibizumab in which decreased drug efficacy has been documented; 2) 10 patients treated with long term (greater than one year) bevacizumab and/or ranibizumab in which decreased drug efficacy has not been documented; and 3) 10 patients who are na ve to treatment with bevacizumab and ranibizumab.
- Conditions
- Macular Degeneration
- Keywords
- Retinal Disease, Bevacizumab, Ranibizumab, Retinal Eye Disease, Macular Degeneration
- Medical subject headings
- Macular Degeneration, Retinal Diseases
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2008 (estimated)
- Study start16 Jan 2008
- Primary completion4 Aug 2009
- Study completion4 Aug 2009
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 Macular DegenerationStudies 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
- Observational
- Time perspective
- Prospective
- Enrolment
- 30 participants
Sponsor and investigators
- Lead sponsor
- National Eye Institute (NEI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00605943
- Sponsor's protocol ID
- 080061
- Other IDs
- 08-EI-0061
- Status last verified
- 4 Aug 2009
- First submitted
- 23 Jan 2008
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Bhisitkul RB. Vascular endothelial growth factor biology: clinical implications for ocular treatments. Br J Ophthalmol. 2006 Dec;90(12):1542-7. doi: 10.1136/bjo.2006.098426.
PubMed 17114590Noma H, Funatsu H, Yamasaki M, Tsukamoto H, Mimura T, Sone T, Hirayama T, Tamura H, Yamashita H, Minamoto A, Mishima HK. Aqueous humour levels of cytokines are correlated to vitreous levels and severity of macular oedema in branch retinal vein occlusion. Eye (Lond). 2008 Jan;22(1):42-8. doi: 10.1038/sj.eye.6702498. Epub 2006 Jul 7.
PubMed 16826241Boyd SR, Zachary I, Chakravarthy U, Allen GJ, Wisdom GB, Cree IA, Martin JF, Hykin PG. Correlation of increased vascular endothelial growth factor with neovascularization and permeability in ischemic central vein occlusion. Arch Ophthalmol. 2002 Dec;120(12):1644-50. doi: 10.1001/archopht.120.12.1644.
PubMed 12470137
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study for the Detection of Neutralizing Antibodies in Patients Treated With Bevacizumab Avastin or Ranibizumab Lucentis
- ClinicalTrials.gov ID
- NCT00605943
- Acronym / sponsor ID
- 080061
- Conditions
- Macular Degeneration
- Keywords
- Retinal Disease, Bevacizumab, Ranibizumab, Retinal Eye Disease, Macular Degeneration
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants
- Lead sponsor
- National Eye Institute (NEI)US National Institutes of Health
- Study start
- 16 Jan 2008
- Primary completion
- 4 Aug 2009 (actual)
- Study completion
- 4 Aug 2009 (actual)
- First posted
- 31 Jan 2008 (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.
This study will measure antibody levels in the blood of people with bleeding or swelling in the retina who have or have not been treated with bevacizumab (Avastin[Trademark]or ranibizumab (Lucentis[Trademark]). These drugs have been useful in reducing retinal bleeding and swelling in people with eye diseases that cause these symptoms, but the drugs' effects usually wear off and they have to be given repeatedly. In some patients, the benefits become less and less. It is possible that over time, patients taking these drugs may produce antibodies that act against the drugs, thus neutralizing their effects and preventing them from working properly.
People 18 year of age and older who are participating in a current NEI protocol and meet the following criteria may be eligible for this study:
- Are receiving injections of bevacizumab or ranibizumab for bleeding or swelling in the retina, but the treatment is becoming less effective
- Are receiving injections of bevacizumab or ranibizumab for bleeding or swelling in the retina and the treatment is still effective
- Have bleeding or swelling in the retina, but have never received either bevacizumab or ranibizumab
Participants have blood samples drawn once when they start the study, once in the middle of the study, and once at the end of the study. They are asked permission for study researchers to review the results of their eye examinations at NIH.
Detailed description
Objective
Over the past two years, the field of ophthalmology has witnessed a dramatic paradigm shift in the treatment of exudative and hemorrhagic diseases affecting the retina. This has been due largely to the introduction of two agents, bevacizumab and ranibizumab, into the clinical setting. These agents are humanized monoclonal antibodies which target vascular endothelial growth factor (VEGF). We have observed that, in some patients, a diminished response to these agents occurs with time. One possible explanation for this is the emergence of neutralizing antibodies in patients who have become refractory to bevacizumab or ranibizumab.
Study Population
We will recruit patients from the National Eye Institute (NEI) who are currently receiving treatment with bevacizumab or ranibizumab for various exudative or hemorrhagic disease of the retina. We will also recruit patients with recently diagnosed exudative or hemorrhagic disease of the retina who are na ve to these medications and are going to be treated with them.
Design
This will be a prospective, observational study.
Outcome Measures
The main outcome measure will be the titer of neutralizing antibodies which is measured in patient sera using enzyme-linked immunosorbent assay (ELISA). This will be compared between three groups of patients: 1) 10 patients treated with long term (greater than 1 year) bevacizumab and/or ranibizumab in which decreased drug efficacy has been documented; 2) 10 patients treated with long term (greater than one year) bevacizumab and/or ranibizumab in which decreased drug efficacy has not been documented; and 3) 10 patients who are na ve to treatment with bevacizumab and ranibizumab.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Subjects will include adults being treated for exudative AMD, or macular edema secondary to DR or venous occlusion. The 3 clinical categories, which will each be composed of 10 subjects, are:
- Decreased drug efficacy will be defined as follows: Presence of a therapeutic response (reduction in macula fluid as determined by optical coherence tomography (OCT) or reduction in extent of leakage on fluorescein angiography (FA)) in the first 3 injections, followed by a subsequent decrease in response as evidenced by persistence of intraretinal cysts and/or subretinal fluid on OCT and/or leakage on fluorescein angiography (FA).
- The presence of continued drug efficacy will be defined as follows: Patients who are being treated with bevacizumab or ranibizumab and are demonstrating a good clinical response as demonstrated by the presence of a fluid-free macula on OCT and/or the absence of leakage on FA after treatment.
- When possible, patients in the 3 categories will be matched by underlying retinal disease type, race, gender, and age.
Key exclusion criteria (4 listed)
- Patients who are currently receiving any form of systemic immunosuppressive or immunomodulatory therapy, including corticosteroids. Immunosuppressive medication could lower the titers of neutralizing that are present in a given patient, and this could give the false impression that such a patient has little to no immune response against bevacizumab or ranibizumab.
- Patients who have autoimmune or rheumatologic disease. Patients with autoimmune diseases tend to have various autoantibodies in their serum. These naturally present autoantibodies in this patient group could cross-react with bevacizumab or ranibizumab. This would give the false impression that these patients have developed neutralizing antibodies against bevacizumab or ranibizumab, when in fact these naturally occurring cross-reactive autoantibodies were present in the patient all along and are not related to bevacizumab or ranibizumab exposure.
- Patients with evidence of active systemic infection. Patients with active systemic infection could have various antibodies in the serum, and some of these could cross-react with bevacizumab or ranibizumab. This would give the false impression that these patients have developed neutralizing antibodies against bevacizumab or ranibizumab, when in fact these cross-reactive antibodies were present in the patient secondary to the presence of active systemic infection and are not related to bevacizumab or ranibizumab.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
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 2 Jul 2017.
- Background: PubMed 17114590Bhisitkul RB. Vascular endothelial growth factor biology: clinical implications for ocular treatments. Br J Ophthalmol. 2006 Dec;90(12):1542-7. doi: 10.1136/bjo.2006.098426.
- Background: PubMed 16826241Noma H, Funatsu H, Yamasaki M, Tsukamoto H, Mimura T, Sone T, Hirayama T, Tamura H, Yamashita H, Minamoto A, Mishima HK. Aqueous humour levels of cytokines are correlated to vitreous levels and severity of macular oedema in branch retinal vein occlusion. Eye (Lond). 2008 Jan;22(1):42-8. doi: 10.1038/sj.eye.6702498. Epub 2006 Jul 7.
- Background: PubMed 12470137Boyd SR, Zachary I, Chakravarthy U, Allen GJ, Wisdom GB, Cree IA, Martin JF, Hykin PG. Correlation of increased vascular endothelial growth factor with neovascularization and permeability in ischemic central vein occlusion. Arch Ophthalmol. 2002 Dec;120(12):1644-50. doi: 10.1001/archopht.120.12.1644.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Macular Degeneration, 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 7 inclusion and 4 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 2 Jul 2017. 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.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00605943, 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 2 Jul 2017.