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

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

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).

Study Overview

• Status: Completed
• Conditions: Macular Degeneration
• Intervention / Treatment: Drug: Immune Globulin Intravenous [Human], 10% Caprylate/Chromatography Purified; Drug: Albumin (Human) 25%, United States Pharmacopeia (USP)

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 ( Logarithm of the Minimum Angle of Resolution [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.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany, 52074
    • Universitatsklinikum Aachen, Augenklinik
  • Duisburg, Germany, 47119
    • Augenklinik Tausendfensterhaus
  • Düsseldorf, Germany, 40219
    • St. Martinus-Krankenhaus, Augenabteilung
  • Essen, Germany, 45147
    • Medizinische Eirnrichtungen der Universitat Essen, Klinik fur Erkrankungen des hinteren Augenabschnittes
  • Freiburg, Germany, 79106
    • Kliniken und Polikliniken der Albert Ludwigs Universität
  • Koln, Germany, 50931
    • Medizinische Einrichtungen der Universitat zu Koln, Centrum fur Augenheilkunde
  • Tubingen, Germany, 72076
    • Klininkum der Eberhard-Karls-Universitat Tubingen, Universitats-Augenklinik

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 51 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The best corrected visual acuity must be in the range of 20/40 to 20/200 on the Early Treatment Diabetic Retinopathy Study (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 photodynamic therapy (PDT) or vitrectomy or transpupillary thermotherapy (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 immunoglobulin A (IgA) deficiency
• Other investigational drugs received within the past 3 months.
• Conditions whose symptoms and effects could alter protein catabolism and/or immunoglobulin (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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1	Drug: Immune Globulin Intravenous [Human], 10% Caprylate/Chromatography Purified; The dose per infusion cycle was 2 g/kg body weight over 5 consecutive days (= 4 mL/kg body weight/infusion). The infusion duration was approximately 1.5 - 2 h.; Other Names: Gamunex®; IGIVnex®; Gaminex; IGIV-C; IGIV; BAY 41-1000; TAL-05-00004; IGIV-C, 10%; IVIG; NDC 13533-645-12; NDC 13533-645-15; NDC 13533-645-20; NDC 13533-645-24; NDC 13533-645-71; Immune Globulin IV (Human), 10% (IGIV); Immune Globulin IV (Human), 10% by Chromatography Process
Placebo Comparator: Group 2	Drug: Albumin (Human) 25%, United States Pharmacopeia (USP); Albumin (Human) 20% or 25% will be diluted with 5% glucose to a final concentration of 0.1%.; Other Names: Plasbumin®-25; Plasbumin®-25 (Low Aluminum); TAL-05-00025; BAY 34-9255; NDC 13533-684-16; NDC 13533-684-71; NDC 13533-692-16; NDC 13533-692-20; NDC 13533-692-71; Plasbumin®-20; Plasbumin®-20 (Low Aluminum); Albumin (Human) 20%, USP; TAL-05-00007; TAL-05-00008; TAL-05-00024; NDC 13533-683-20; NDC 13533-683-71; NDC 13533-684-20; NDC 13533-691-20; NDC 13533-691-71

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Visual Acuity (Logarithm of the Minimum Angle of Resolution [LogMAR]) Score From Baseline for IGIV-C, 10% Compared to Placebo at Week 12 or at Last LogMAR Assessment (Conducted at or After Week 8 of the Treatment Period)	Using the LogMAR score, lower values correspond to higher visual acuity. For example, a visual acuity of 20/20 corresponds to a LogMAR value of zero (0), and a visual acuity of 20/100 corresponds to a LogMAR value of 0.7.	At Week 12 or, if the Week 12 assessment is not available, at the last LogMAR assessment conducted at or after Week 8 of the Treatment Period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects Who Improve Visual Acuity From Baseline to Endpoint by ≥ 0.1 LogMAR		Last measurement at or later than Week 8
Proportion of Subjects Who Improve Visual Acuity From Baseline to Endpoint by ≥ 0.2 LogMAR		Last measurement at or later than Week 8
Mean Change in LogRAD Score From Baseline to Endpoint (RADNER Test)	The RADNER test gives not only information about the subject's reading performance, but also about the reading speed (life quality) and the faults while reading. The RADNER reading charts (1, 2, and 3) contain sentences in paragraphs having a range of print sizes starting with the largest print at the top.The subject was randomly assigned one of the RADNER charts, and the charts were different between consecutive visits. The reading distance was 25 cm. The subject's score was corrected for reading speed and errors. The range of possible logRAD scores was from 2.0 (could not read the first paragraph) to -0.2, with higher scores indicating lower reading acuity and lower scores indicating higher reading acuity.	Last measurement at or later than Week 8
Proportion of Subjects With an Increase ≥ 2 or More Points in Lens Opacity Classification System (LOCS III) for Nuclear Opalescence, Nuclear Color, Cortical Cataract or Posterior Subcapsular Cataract Categories	The LOCS III scale for cortical cataract and posterior subcapsular cataract opacity ranged from 1.0 to 5.0. The LOCS III scale for nuclear opalescence and for nuclear color was 1.0 to 6.0. For all scales, higher values indicate higher opacity, opalescence, or color.	Last measurement at or later than Week 8
Presence of Fibrosis and Location Assessed by Slit-lamp		Last measurement at or later than Week 8
Mean Change From Baseline to Endpoint in Size of Lesion (Largest Dimension Relative to Disk Diameter) Assessed by Central Fluorescein Angiogram Reading Center		At end of treatment (12 weeks)

Collaborators and Investigators

• Sponsor: Grifols Therapeutics LLC
• Investigators: Principal Investigator: Richard Brunner, MD, Center of Ophthalmology, University of Cologne, Germany

Publications and helpful links

Helpful Links

• FDA Product Approval

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Primary Completion (Actual): May 1, 2005
• Study Completion (Actual): May 1, 2005

Study Registration Dates

• First Submitted: September 14, 2005
• First Submitted That Met QC Criteria: September 14, 2005
• First Posted (Estimate): September 22, 2005

Study Record Updates

• Last Update Posted (Estimate): March 21, 2016
• Last Update Submitted That Met QC Criteria: February 22, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin; Immunoglobulin G
• Other Study ID Numbers: 100586