Complement Inhibition With Eculizumab for the Treatment of Non-Exudative Macular Degeneration (AMD)

NCT ID: NCT00935883

Last Updated: 2017-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2013-08-31

Brief Summary

To evaluate the safety and efficacy of eculizumab for the treatment of dry AMD as evaluated by the change in drusen volume and area of geographic atrophy.

Detailed Description

This is a randomized, double-arm, double-masked study designed to evaluate the safety and efficacy of eculizumab for the treatment of patients with dry AMD. There are three stages in the study: the screening period, the treatment period, and the follow-up period.During the screening period patients will be evaluated for eligibility. Eligible patients will receive either eculizumab or placebo for 24 weeks.

A total of 60 patients will be enrolled and divided equally between the drusen cohort and the GA cohort. A 2:1 randomization will result in 20 patients in each cohort receiving eculizumab while 10 patients receive placebo.

The treatment period will begin two weeks after administration of the meningococcal vaccine. During the treatment period, patients will receive eculizumab or placebo over a period of approximately 26 weeks. Patient will treatment according to the following regimen:

Induction Period: patient will receive eculizumab 600 mg or 900 mg via IV infusion over approximately 30 minutes once a week (7 ± 2 days) for 4 weeks followed by 900 mg eculizumab for the fifth dose 7 days later (7 ± 2 days).

Maintenance Period: patient will receive eculizumab 900 mg or 1200 mg via IV infusion over approximately 30 minutes every 2 weeks (14 ± 2 days).

After the final scheduled dose of eculizumab or Placebo at week 24, patients will return for follow-up exam 2 weeks, 3 months, and 6 months after the final dose.

Conditions

Age-Related Macular Degeneration

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Saline

Randomized patients in the drusen or the GA cohort will receive placebo saline infusions as a comparator

Group Type: PLACEBO_COMPARATOR

Saline

Intervention Type: DRUG

Induction Period: patient will receive saline via IV infusion over approximately 30 minutes once a week (7 ± 2 days) for 4 weeks followed by saline for the fifth dose 7 days later (7 ± 2 days).

Maintenance Period: patient will receive saline via IV infusion over approximately 30 minutes every 2 weeks (14 ± 2 days) until week 24.

Observation period: patient will then be observed for 6 months off treatment with follow-up visits scheduled for 9 months and 12 months.

Eculizumab

Randomized patients in the drusen or the GA cohort will receive active treatment with eculizumab

Group Type: ACTIVE_COMPARATOR

Eculizumab

Intervention Type: DRUG

Induction Period: patient will receive eculizumab 600 mg or 900 mg via IV infusion over approximately 30 minutes once a week (7 ± 2 days) for 4 weeks followed by 900 mg or 1200 mg eculizumab for the fifth dose 7 days later (7 ± 2 days).

Maintenance Period: patient will receive eculizumab 900 mg or 1200 mg via IV infusion over approximately 30 minutes every 2 weeks (14 ± 2 days) until week 24.

Observation period: patient will then be observed for 6 months off treatment with follow-up visits scheduled for 9 months and 12 months.

Interventions

Eculizumab

Induction Period: patient will receive eculizumab 600 mg or 900 mg via IV infusion over approximately 30 minutes once a week (7 ± 2 days) for 4 weeks followed by 900 mg or 1200 mg eculizumab for the fifth dose 7 days later (7 ± 2 days).

Maintenance Period: patient will receive eculizumab 900 mg or 1200 mg via IV infusion over approximately 30 minutes every 2 weeks (14 ± 2 days) until week 24.

Observation period: patient will then be observed for 6 months off treatment with follow-up visits scheduled for 9 months and 12 months.

Intervention Type: DRUG

Saline

Induction Period: patient will receive saline via IV infusion over approximately 30 minutes once a week (7 ± 2 days) for 4 weeks followed by saline for the fifth dose 7 days later (7 ± 2 days).

Maintenance Period: patient will receive saline via IV infusion over approximately 30 minutes every 2 weeks (14 ± 2 days) until week 24.

Observation period: patient will then be observed for 6 months off treatment with follow-up visits scheduled for 9 months and 12 months.

Intervention Type: DRUG

Other Intervention Names

Soliris; PBS

Eligibility Criteria

Inclusion Criteria

• Ability to provide written informed consent and comply with study assessments for the full duration of the study
• Age > 50 years
• In the study eye(s), the presence of non-exudative AMD documented by fundus photography, autofluorescence, fluorescein angiography, and spectral domain OCT.
• Visual acuity of 20/63 or better (BCVA score of at least 59 letters) as measured on an ETDRS chart.
• Able and willing to comply with study procedures.

Exclusion Criteria

• Visual acuity worse than 20/63
• Any history of choroidal neovascularization in the study eye
• Unresolved meningococcal disease.
• Confounding ocular conditions such as amblyopia; aphakia; myopia requiring >6 diopters of correction; pigment epithelial detachment; uncontrolled glaucoma (intraocular pressure ≥ 25 mmHg despite treatment with anti-glaucoma medication); steroid-induced ocular hypertension; retinal inflammatory disease; central serous choroidopathy; prior or current retinal detachment; macular edema; cystic lesion (individual cysts or cystoid macular edema); ocular herpes simplex virus; severe non-proliferative or worse diabetic retinopathy; anterior ischemic optic neuropathy; RPE tear involving the macula; pseudovitelliform macular degeneration; vitreo-retinal traction maculopathy; vitreous hemorrhage, history of or current rhegmatogenous retinal detachment or macular hole; uveitis; diffuse choroidal atrophy; optic atrophy (as evidenced by pallor); intraocular inflammation; ocular or periocular infection; moderate or worse dry eye syndrome; clinically significant cataract or opacification of the posterior capsule which, in the Investigator's opinion, would progress during the course of the study and could affect central vision; other ocular conditions that the Investigator believes may be a confounding factor in this study
• Refusal to be vaccinated against Neisseria meningitides or an active Neisseria meningitides infection

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

Philip J. Rosenfeld, MD, PhD

OTHER

Sponsor Role: lead

Responsible Party

Philip J. Rosenfeld, MD, PhD

Professor of Ophthalmology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Philip J Rosenfeld, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

Bascom Palmer Eye Institute

Miami, Florida, United States

Countries

United States

References

Yehoshua Z, de Amorim Garcia Filho CA, Nunes RP, Gregori G, Penha FM, Moshfeghi AA, Zhang K, Sadda S, Feuer W, Rosenfeld PJ. Systemic complement inhibition with eculizumab for geographic atrophy in age-related macular degeneration: the COMPLETE study. Ophthalmology. 2014 Mar;121(3):693-701. doi: 10.1016/j.ophtha.2013.09.044. Epub 2013 Nov 26.

Reference Type: RESULT

PMID: 24289920 (View on PubMed)

Garcia Filho CA, Yehoshua Z, Gregori G, Nunes RP, Penha FM, Moshfeghi AA, Zhang K, Feuer W, Rosenfeld PJ. Change in drusen volume as a novel clinical trial endpoint for the study of complement inhibition in age-related macular degeneration. Ophthalmic Surg Lasers Imaging Retina. 2014 Jan-Feb;45(1):18-31. doi: 10.3928/23258160-20131217-01.

Reference Type: RESULT

PMID: 24354307 (View on PubMed)

Tzoumas N, Riding G, Williams MA, Steel DH. Complement inhibitors for age-related macular degeneration. Cochrane Database Syst Rev. 2023 Jun 14;6(6):CD009300. doi: 10.1002/14651858.CD009300.pub3.

Reference Type: DERIVED

PMID: 37314061 (View on PubMed)

Stetson PF, Yehoshua Z, Garcia Filho CA, Portella Nunes R, Gregori G, Rosenfeld PJ. OCT minimum intensity as a predictor of geographic atrophy enlargement. Invest Ophthalmol Vis Sci. 2014 Feb 10;55(2):792-800. doi: 10.1167/iovs.13-13199.

Reference Type: DERIVED

PMID: 24408973 (View on PubMed)

Other Identifiers

20090055

Identifier Type: -

Identifier Source: org_study_id