Clinical trial NCT00220805: Use of Immune Globulin Intravenous (Human) To Treat Age-Related Macular Degeneration
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Macular Degeneration
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2005-09-22
Enrollment: 96
Sex: ALL
Minimum age (years): 51
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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)
timeFrame: 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 outcomes:
measure: Proportion of Subjects Who Improve Visual Acuity From Baseline to Endpoint by ≥ 0.1 LogMAR
timeFrame: Last measurement at or later than Week 8
measure: Proportion of Subjects Who Improve Visual Acuity From Baseline to Endpoint by ≥ 0.2 LogMAR
timeFrame: Last measurement at or later than Week 8
measure: Mean Change in LogRAD Score From Baseline to Endpoint (RADNER Test)
timeFrame: Last measurement at or later than Week 8
measure: 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
timeFrame: Last measurement at or later than Week 8
measure: Presence of Fibrosis and Location Assessed by Slit-lamp
timeFrame: Last measurement at or later than Week 8
measure: Mean Change From Baseline to Endpoint in Size of Lesion (Largest Dimension Relative to Disk Diameter) Assessed by Central Fluorescein Angiogram Reading Center
timeFrame: At end of treatment (12 weeks)
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Universitatsklinikum Aachen, Augenklinik
city: Duisburg
country: Germany
facility: Augenklinik Tausendfensterhaus
city: Düsseldorf
country: Germany
facility: St. Martinus-Krankenhaus, Augenabteilung
city: Essen
country: Germany
facility: Medizinische Eirnrichtungen der Universitat Essen, Klinik fur Erkrankungen des hinteren Augenabschnittes
city: Freiburg
country: Germany
facility: Kliniken und Polikliniken der Albert Ludwigs Universität
city: Koln
country: Germany
facility: Medizinische Einrichtungen der Universitat zu Koln, Centrum fur Augenheilkunde
city: Tubingen
country: Germany
facility: Klininkum der Eberhard-Karls-Universitat Tubingen, Universitats-Augenklinik
Study officials:
affiliation: Center of Ophthalmology, University of Cologne, Germany
name: Richard Brunner, MD
role: PRINCIPAL_INVESTIGATOR
References: