Use of Immune Globulin Intravenous (Human) To Treat Age-Related Macular Degeneration

Condition(s) targeted: Macular Degeneration

Intervention: Immune Globulin Intravenous [Human], 10% Caprylate/Chromatography Purified (Drug); Albumin (Human) 25%, USP (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Talecris Biotherapeutics

Official(s) and/or principal investigator(s):
Richard Brunner, MD, Principal Investigator, Affiliation: Center of Ophthalmology, University of Cologne, Germany

This study will evaluate visual improvement in patients treated with Immune Globulin Intravenous (Human), 10% Caprylate/Chromatography Purified (IGIV-C) or placebo who have Age-Related Macular Degeneration (AMD) with occult Choroidal Neovascularization (CNV).

Official title: Multicenter, Randomized, Double-Blind, Placebo-Controlled, Study to Evaluate the Efficacy and Safety of IGIV-C, 10% Treatment in Subjects With Pure Occult Choroidal Neovascularization Due to Age Related Macular Degeneration

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: - Mean change in visual acuity [LogMAR] score from baseline to endpoint compared to placebo

Secondary outcome:

Proportion of subjects who improve visual acuity from baseline to endpoint by ≥ 0.1 LogMAR.

Proportion of subjects who improve visual acuity from baseline to endpoint by ≥ 0.2 LogMAR.

Mean change in LogRAD score from baseline to endpoint (RADNER-test).

Proportion of subjects with an increase ≥ 2 or more points in LOCS III for nuclear opalescence, nuclear color, cortical cataract or posterior subcapsular cataract categories.

Presence of fibrosis and location assessed by slit-lamp.

Mean change from baseline to endpoint in size, type and location of lesions and leakage assessed by central fluorescein angiogram reading center.

Detailed description: The purpose of this trial is to investigate the effect of IGIV-C in subjects suffering from AMD with occult CNV where fewer treatment options exist for patients with this disease form.

This study is designed as a randomized, double-blind, parallel group, placebo-controlled prospective trial. Sixty patients, 30 per treatment group, with newly diagnosed pure occult CNV defined by angiography diagnostic criteria will be enrolled. If a subject has more than one eye affected with occult CNV, the eye with the better vision as measured by visual acuity (LogMAR score) will be entered as the study eye.

Patients will be randomized to receive either IGIV-C at a dose of 2 g/kg body weight (bw) over 5 consecutive days or matching placebo. Additional 2 study drug treatment courses (IGIV-C or matching placebo) will be administered every 4 weeks at the same dose of 2 g/kg bw given over 5 days. Subjects' visual acuity will be measured and reported as LogMAR at screening, week 0 (baseline), day 5, week 4, week 8 and week 12. If at anytime during the study the subject's visual acuity worsens by ≥ 2 lines (0. 2 on the LogMAR score), then a slit lamp examination will be performed and an angiogram will be conducted; the patient would be discontinued if the worsening is due to some other reason outside of the occult CNV or if the disease has changed from pure occult to the classic or mixed form.

Subjects will be evaluated for efficacy (LogMAR score) at endpoint (at week 12 or at last LogMAR assessment at or after week 8, if the subject prematurely discontinues the trial).

At the end of the treatment period (week 12), patients will be entered into a 3 month observation period with monthly visual acuity LogMAR score assessments.

Minimum age: 51 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- The best corrected visual acuity must be in the range of 20/40 to 20/200 on the ETDRS

chart (0. 5 - 0. 1).

- Patient complaint of visual loss within the last three months prior to study entry.

- Documented visual loss on a visual acuity chart in the 3-month period prior to the

beginning of the run-in period.

- Signed written informed consent prior to initiation of any study-related procedures.

Exclusion Criteria:

- Treatment with IGIV within the last 3 months prior to the run-in.

- Previous PDT or vitrectomy or TTT or any specific pre-treatment of CNV

- Subfoveal blood in the study eye if ≥ 1/2 disc diameter as measured by slit lamp

during run-in period.

- History of anaphylaxis or severe systemic response to immunoglobulin or with a blood

product.

- Cardiac insufficiency (NYHA III/IV), cardiomyopathy, significant cardiac dysrhythmia

requiring treatment, unstable or advanced ischemic heart disease, or severe or uncontrolled hypertension (diastolic > 95 mmHg or systolic >170 mmHg)

- Females, who are pregnant, breast feeding, or if of childbearing potential, unwilling

to practice adequate contraception throughout the study.

- History of renal insufficiency or serum creatinine levels > 221 µmol/L (2. 5 mg/dL).

- Known selective IgA deficiency

- Other investigational drugs received within the past 3 months.

- Conditions whose symptoms and effects could alter protein catabolism and/or IgG

utilization (e. g. protein-losing enteropathies, nephrotic syndrome).

- Known hypercoagulable state.

- Patients on continuous systemic steroid treatment

- Mentally challenged adult subjects who cannot give independent informed consent.

- History of thromboembolic events.

- Diabetes mellitus requiring drug treatment.

- Known severe hypersensitivity to sodium fluorescein.

- Acute or known ocular diseases such as glaucoma, arterial or venous occlusions, acute

ischemic optic-neuropathy, impairment of visual acuity due to opacities in the lens (LOCSIII: NO 5-6 or C: 4-5 or P 4-5) or vitreous which may influence the evaluation of the therapeutic effect.

Medizinische Einrichtungen der Universitat zu Koln, Centrum fur Augenheilkunde, Koln 50931, Germany

Kliniken und Polikliniken der Albert Ludwigs Universität, Freiburg 79106, Germany

Augenklinik Tausendfensterhaus, Duisburg 47119, Germany

Klininkum der Eberhard-Karls-Universitat Tubingen, Universitats-Augenklinik, Tubingen 72076, Germany

Medizinische Eirnrichtungen der Universitat Essen, Klinik fur Erkrankungen des hinteren Augenabschnittes, Essen 45147, Germany

Universitatsklinikum Aachen, Augenklinik, Aachen 52074, Germany

St. Martinus-Krankenhaus, Augenabteilung, Düsseldorf 40219, Germany

Synopsis of Study Results

FDA Approved Product Labeling Information - Gamunex®

FDA Approved Product Labeling Information - Plasbumin®-20 (Low Aluminum)

FDA Product Approval

FDA Approved Product Labeling Information - Plasbumin®-25 (Low Aluminum)

Starting date: January 2004
Ending date: May 2005
Last updated: April 1, 2008