Retinal and Retinal Pigment Epithelium (RPE) Autoimmunity in Age-related Macular Degeneration (AMD)

NCT00931489 | Completed Phase 2 Results

• 2 other identifiers: 217330FVF4479s
• Study Type: interventional
• Target: 131
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators hope to determine if "wet" AMD patients differ from patients with "dry" AMD or normal eyes in the production of anti-retinal pigment epithelium (anti-RPE) or anti-retinal antibody formation. To explain: the immune system can make antibodies that attack our own cells, specifically the RPE and the retina. Normally the RPE and retinal cells are ignored by the immune system, but when disease occurs, immune reactions can occur, making an autoantibody that can attack the patient's own cells and make things worse. This production of autoantibodies that react with our own RPE and retinal cells is what the investigators want to test in this proposal to see if they may contribute to, or are responsible for, a poor response to treatment. The investigators also want to know how those patients who initially respond to the standard-of-care treatment, ranibizumab injections, differ in the production of anti-RPE or anti-retinal antibody formation, from those patients who do not respond initially after 4 consecutive injections.

Conditions

Age Related Macular Degeneration

Keywords

Age Related Macular Degeneration; Lucentis; Ranibizumab; Antibodies; Retinal and RPE Autoimmunity

Outcome Measures

Primary Outcomes (1)

• Production of Anti-Retinal Pigment Epithelium (RPE) or Anti-retinal Antibody Formation in Neovascular ("Wet") Age-related Macular Degeneration Patients Compared to Population Normals.

  Blood samples were collected from all study participants at baseline and Western Blot analysis was performed to identify the presence of anti-retinal and anti-RPE antibodies. Presented are the number of subjects in which the presence of anti-retinal and anti-RPE antibodies (yes/no) were recorded by a masked observer.

  6 months

Secondary Outcomes (2)

• Change in Visual Acuity (VA) From Baseline to Month 6

  6 months

• Change in Ocular Coherence Tomography (OCT) From Baseline to Month 6

  6 months

Study Arms (5)

Wet AMD Patients Responders

ACTIVE COMPARATOR

Dilated eye exam once a month for 7 months; visual acuity and OCT once a month for 7 months; Lucentis(R)/ranibizumab injection once each month for the Baseline and Month 1-3 visits, then as needed at Month 4 and 5; 3 Tbls. blood draw at Baseline, Month 3 and Month 6 visits.

Drug: ranibizumab (Lucentis(R))

Normal Population

NO INTERVENTION

Dilated eye exam and 3 Tbls. blood draw at first and only study visit.

Wet AMD Patients Acute Non-responders

ACTIVE COMPARATOR

Participants in this Group will have not responded to 4 prior injections of Lucentis(R)/ranibizumab or other anti-VEGF treatment. Dilated eye exam at Month 4; visual acuity and OCT at Months 4-6; injection of anti-VEGF treatment as needed at Months 4 and 5; 3 Tbls. blood draw at Month 4

Drug: ranibizumab (Lucentis(R))

Dry AMD Population

NO INTERVENTION

Dilated eye exam and 3 Tbls. blood draw at first and only study visit.

Wet AMD Patients Chronic Non-responderes

ACTIVE COMPARATOR

Participants in this Group will have not responded to 4 or more prior injections of Lucentis(R)/ranibizumab or other anti-VEGF treatment. One visit at Month 4: Dilated eye exam with visual acuity and OCT; injection of anti-VEGF as needed; 3 Tbls. blood drawn

Drug: ranibizumab (Lucentis(R))

Interventions

ranibizumab (Lucentis(R)) DRUG

0.5 mg intravitreal injection once a month for 4 months, then as needed for 2 months

Also known as: Lucentis(R)

Wet AMD Patients Acute Non-responders; Wet AMD Patients Chronic Non-responderes; Wet AMD Patients Responders

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Group 1 (Ranibizumab Responders):
• Ability to provide written informed consent and comply with study assessments for the full duration of the study
• Age \> 50 years
• Patients with active neovascular "wet" AMD naïve to treatment
• Group 2 (Normal Controls):
• Age-sex-race matched to Group 1 patients
• Non-AMD
• Ability to provide written informed consent
• Group 3 (Anti-VEGF Initial Non-responders):
• "Wet" AMD patient treated with 4 or more monthly injections of anti-VEGF treatment without an adequate response (persistent fluid on OCT)
• Ability to provide written informed consent and comply with study assessments for the full duration of the study
• Age \> 50 years
• Group 4 ("Dry" AMD):
• Age-sex-race matched to Group 1 patients
• "Dry" AMD, category 2 or 3 by AREDS (Age-Related Eye Disease Study) criteria

You may not qualify if:

• Pregnancy (positive pregnancy test) or lactation
• Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an IUD, or contraceptive hormone implant or patch.
• Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated
• Participation in another simultaneous medical investigation or trial
• Concurrent eye disease in the study eye that could compromise visual acuity (e.g., diabetic retinopathy, advanced glaucoma)
• Previous AMD therapy
• Patients being treated for autoimmune or other disease with immunomodulatory drugs (i.e., prednisone, infliximab, methotrexate)
• Patients with recent (less than 6 months) ocular or systemic surgery

Sponsors & Collaborators

• Lawrence S. Morse, MD: lead
• Genentech, Inc.: collaborator

Study Sites (1)

University of California, Davis

Sacramento, California, 95817, United States

Location

MeSH Terms

Conditions

Macular Degeneration

Interventions

Ranibizumab

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Lawrence S. Morse, MD, PhD
• Organization: University of California Davis, Department of Ophthalmology & Vision Science

lsmorse@ucdavis.edu

916 734 6074

Study Officials

• Lawrence S Morse, MD, PhD

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 29, 2009
• First Posted: July 2, 2009
• Study Start: August 1, 2009
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: July 2, 2017
• Results First Posted: July 2, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)