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

Age-Related Macular Degeneration Clinical Trial

— COMPLETE  

Official title:

Eculizumab for the Treatment of Non-Exudative Age-Related Macular Degeneration: An Exploratory Study to Evaluate the Effects of C5 Inhibition on Drusen and Geographic Atrophy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00935883
• Other study ID #: 20090055
• Status: Completed
• Phase: Phase 2
• First received: July 7, 2009
• Last updated: January 20, 2015
• Start date: July 2009
• Est. completion date: August 2013

Study information

• Verified date: January 2015
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: August 2013
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Age-Related Macular Degeneration
• Geographic Atrophy
• Macular Degeneration

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
United States	Bascom Palmer Eye Institute	Miami	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Philip J. Rosenfeld, MD, PhD	Alexion Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (2)

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 Sur — View Citation

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. Oph — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Growth of Geographic Atrophy		6 months	No
Primary	Decrease in Drusen Volume		6 Months	No
Secondary	Change in Visual Acuity for Drusen Group	ETDRS (Early Treatment Diabetic Retinopathy Studies) letters ETDRS is a widely accepted clinical vision research tool used to check a patient's vision which is preferred to the Snellen chart.	Baseline/ 6 Months	No
Secondary	Change in Visual Acuity for Geographic Atrophy Group		Baseline/ 6 Months	No