Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Grifols Therapeutics Inc.
ClinicalTrials.gov Identifier:
NCT00220805
First received: September 14, 2005
Last updated: February 22, 2016
Last verified: February 2016
  Purpose
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).

Condition Intervention Phase
Macular Degeneration
Drug: Immune Globulin Intravenous [Human], 10% Caprylate/Chromatography Purified
Drug: Albumin (Human) 25%, United States Pharmacopeia (USP)
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Grifols Therapeutics Inc.:

Primary Outcome Measures:
  • 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) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Proportion of Subjects Who Improve Visual Acuity From Baseline to Endpoint by ≥ 0.1 LogMAR [ Time Frame: Last measurement at or later than Week 8 ] [ Designated as safety issue: No ]
  • Proportion of Subjects Who Improve Visual Acuity From Baseline to Endpoint by ≥ 0.2 LogMAR [ Time Frame: Last measurement at or later than Week 8 ] [ Designated as safety issue: No ]
  • Mean Change in LogRAD Score From Baseline to Endpoint (RADNER Test) [ Time Frame: Last measurement at or later than Week 8 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Last measurement at or later than Week 8 ] [ Designated as safety issue: No ]
    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.

  • Presence of Fibrosis and Location Assessed by Slit-lamp [ Time Frame: Last measurement at or later than Week 8 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline to Endpoint in Size of Lesion (Largest Dimension Relative to Disk Diameter) Assessed by Central Fluorescein Angiogram Reading Center [ Time Frame: At end of treatment (12 weeks) ] [ Designated as safety issue: No ]

Enrollment: 96
Study Start Date: January 2004
Study Completion Date: May 2005
Primary Completion Date: May 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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-C, 10%
  • Immune Globulin IV (Human), 10% (IGIV)
  • Immune Globulin IV (Human), 10% by Chromatography Process
  • IGIV
  • IVIG
  • BAY 41-1000
  • TAL-05-00004
  • NDC 13533-645-12
  • NDC 13533-645-15
  • NDC 13533-645-20
  • NDC 13533-645-24
  • NDC 13533-645-71
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®-20
  • Plasbumin®-25
  • Plasbumin®-20 (Low Aluminum)
  • Plasbumin®-25 (Low Aluminum)
  • Albumin (Human) 20%, USP
  • TAL-05-00007
  • TAL-05-00008
  • TAL-05-00024
  • TAL-05-00025
  • BAY 34-9255
  • NDC 13533-683-20
  • NDC 13533-683-71
  • NDC 13533-684-16
  • NDC 13533-684-20
  • NDC 13533-684-71
  • NDC 13533-691-20
  • NDC 13533-691-71
  • NDC 13533-692-16
  • NDC 13533-692-20
  • NDC 13533-692-71

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

Ages Eligible for Study:   51 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00220805

Locations
Germany
Universitatsklinikum Aachen, Augenklinik
Aachen, Germany, 52074
Augenklinik Tausendfensterhaus
Duisburg, Germany, 47119
St. Martinus-Krankenhaus, Augenabteilung
Düsseldorf, Germany, 40219
Medizinische Eirnrichtungen der Universitat Essen, Klinik fur Erkrankungen des hinteren Augenabschnittes
Essen, Germany, 45147
Kliniken und Polikliniken der Albert Ludwigs Universität
Freiburg, Germany, 79106
Medizinische Einrichtungen der Universitat zu Koln, Centrum fur Augenheilkunde
Koln, Germany, 50931
Klininkum der Eberhard-Karls-Universitat Tubingen, Universitats-Augenklinik
Tubingen, Germany, 72076
Sponsors and Collaborators
Grifols Therapeutics Inc.
Investigators
Principal Investigator: Richard Brunner, MD Center of Ophthalmology, University of Cologne, Germany
  More Information

Additional Information:
Responsible Party: Grifols Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT00220805     History of Changes
Other Study ID Numbers: 100586 
Study First Received: September 14, 2005
Results First Received: September 24, 2009
Last Updated: February 22, 2016
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Macular Degeneration
Choroidal Neovascularization
Retinal Degeneration
Retinal Diseases
Eye Diseases
Choroid Diseases
Uveal Diseases
Neovascularization, Pathologic
Metaplasia
Pathologic Processes
Immunoglobulins, Intravenous
Gamma-Globulins
Rho(D) Immune Globulin
Immunoglobulins
Antibodies
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 30, 2016