Detection of Neutralizing Antibodies in Patients Treated With Bevacizumab or Ranibizumab
| Status: | Completed |
|---|---|
| Conditions: | Ocular |
| Therapuetic Areas: | Ophthalmology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | January 2008 |
| End Date: | August 2009 |
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:
- 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.
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.
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.
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.
- INCLUSION CRITERIA:
- 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:
1. 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).
2. 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.
3. 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.
EXCLUSION CRITERIA:
Patients in the following categories will be excluded from participating in this study:
1. 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.
2. 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.
3. 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.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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