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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1 | Experimental |
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| Group 2 | Placebo Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Immune Globulin Intravenous [Human], 10% Caprylate/Chromatography Purified | Drug | 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. |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Richard Brunner, MD | Center of Ophthalmology, University of Cologne, Germany | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Universitatsklinikum Aachen, Augenklinik | Aachen | 52074 | Germany | |||
| Medizinische Einrichtungen der Universitat zu Koln, Centrum fur Augenheilkunde |
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| Label | URL |
|---|---|
| FDA Approved Product Labeling Information - Gamunex® | View source |
| FDA Approved Product Labeling Information - Plasbumin®-20 (Low Aluminum) | View source |
| FDA Product Approval |
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Of the 96 enrolled subjects, 14 subjects withdrew their consent for participation before randomization and an additional 25 subjects were withdrawn before randomization because of violations of inclusion/exclusion criteria or because their angiograms were rejected by the central reading site as not meeting the pre-specified criteria.
A total of 96 subjects were enrolled (signed the informed consent and screened) in this study at 6 German study centers.
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| ID | Title | Description |
|---|---|---|
| FG000 | IGIV-C 10% | Immune Globulin Intravenous [Human], 10% Caprylate/Chromatography Purified |
| FG001 | Placebo | Albumin (Human) 25%, United States Pharmacopeia (USP) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Albumin (Human) 25%, United States Pharmacopeia (USP) | Drug | Albumin (Human) 20% or 25% will be diluted with 5% glucose to a final concentration of 0.1%. |
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| 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) |
| Cologne |
| 50931 |
| Germany |
| Augenklinik Tausendfensterhaus | Duisburg | 47119 | Germany |
| St. Martinus-Krankenhaus, Augenabteilung | Düsseldorf | 40219 | Germany |
| Medizinische Eirnrichtungen der Universitat Essen, Klinik fur Erkrankungen des hinteren Augenabschnittes | Essen | 45147 | Germany |
| Kliniken und Polikliniken der Albert Ludwigs Universität | Freiburg im Breisgau | 79106 | Germany |
| Klininkum der Eberhard-Karls-Universitat Tubingen, Universitats-Augenklinik | Tübingen | 72076 | Germany |
| View source |
| FDA Approved Product Labeling Information - Plasbumin®-25 (Low Aluminum) | View source |
| COMPLETED |
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| NOT COMPLETED |
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The intent to treat (ITT) population, which was defined as the primary analysis population, comprised 29 subjects treated with IGIV-C 10% and 24 subjects treated with placebo. A total of 4 subjects were excluded from the ITT population: 1 from IGIV-C 10% and 3 from Placebo.
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| ID | Title | Description |
|---|---|---|
| BG000 | IGIV-C 10% | Immune Globulin Intravenous [Human], 10% Caprylate/Chromatography Purified |
| BG001 | Placebo | Albumin (Human) 25%, United States Pharmacopeia (USP) |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Visual Acuity Score (VAS) of the Study Eyes | Mean | Standard Deviation | units on a scale |
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| Logarithm of the Minimum Angle of Resolution (LogMAR) of the Study Eyes | Mean | Standard Deviation | LogMAR |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The Intent-to-Treat (ITT) Population consisted of all randomized subjects who received any amount of study medication and had at least one evaluation of the primary efficacy variable (LogMAR score) at Week 8 or later and at Baseline. | Posted | Mean | Standard Deviation | LogMAR | 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 |
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| Secondary | Proportion of Subjects Who Improve Visual Acuity From Baseline to Endpoint by ≥ 0.1 LogMAR | Intent to Treat | Posted | Number | percentage of participants | Last measurement at or later than Week 8 |
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| Secondary | Proportion of Subjects Who Improve Visual Acuity From Baseline to Endpoint by ≥ 0.2 LogMAR | Intent to Treat | Posted | Number | percentage of participants | Last measurement at or later than Week 8 |
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| Secondary | 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. | Intent to Treat | Posted | Mean | Standard Deviation | LogRAD | Last measurement at or later than Week 8 |
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| Secondary | 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. | Intent to Treat subjects with cataract | Posted | Number | participants | Last measurement at or later than Week 8 |
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| Secondary | Presence of Fibrosis and Location Assessed by Slit-lamp | Intent to Treat | Posted | Number | participants | Last measurement at or later than Week 8 |
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| Secondary | Mean Change From Baseline to Endpoint in Size of Lesion (Largest Dimension Relative to Disk Diameter) Assessed by Central Fluorescein Angiogram Reading Center | Intent to Treat | Posted | Mean | Standard Deviation | Disk Diameter | At end of treatment (12 weeks) |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | IGIV-C 10% | Immune Globulin Intravenous [Human], 10% Caprylate/Chromatography Purified | 1 | 30 | 21 | 30 | ||
| EG001 | Placebo | Albumin (Human) 25%, United States Pharmacopeia (USP) | 5 | 27 | 15 | 27 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Stent placement | Surgical and medical procedures | MedDRA | Systematic Assessment |
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| Cerebrovascular accident | Nervous system disorders | MedDRA | Systematic Assessment |
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| Transient ischemic attack | Nervous system disorders | MedDRA | Systematic Assessment |
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| Cholelithiasis | Hepatobiliary disorders | MedDRA | Systematic Assessment |
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| Abdominal pain, upper | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Brain neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vertigo | Ear and labyrinth disorders | MedDRA | Systematic Assessment |
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| Abdominal pain, upper | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Fatigue | General disorders | MedDRA | Systematic Assessment |
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| Cystitis | Infections and infestations | MedDRA | Systematic Assessment |
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| Hand fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
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| Blood creatine phosphokinase increased | Investigations | MedDRA | Systematic Assessment |
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| Blood pressure increased | Investigations | MedDRA | Systematic Assessment |
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| Blood urea increased | Investigations | MedDRA | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
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| Pruritis | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
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The investigator must send a draft manuscript of the publication or abstract to the sponsor thirty days in advance of submission in order to obtain approval prior to submission of the final version for publication. This will be reviewed promptly and approval will not be withheld unreasonably. In case of a difference of opinion between the sponsor and the investigator(s), the contents of the publication will be discussed in order to find a solution which satisfies both parties.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Henry Li | Grifols Therapeutics | 1-800-520-2807 | henry.li@grifols.com |
| ID | Term |
|---|---|
| D008268 | Macular Degeneration |
| ID | Term |
|---|---|
| D012162 | Retinal Degeneration |
| D012164 | Retinal Diseases |
| D005128 | Eye Diseases |
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| ID | Term |
|---|---|
| D005719 | gamma-Globulins |
| D002210 | Caprylates |
| D016756 | Immunoglobulins, Intravenous |
| D000418 | Albumins |
| ID | Term |
|---|---|
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D007074 | Immunoglobulin G |
| D007132 | Immunoglobulin Isotypes |
| D000906 | Antibodies |
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| >=65 years |
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| Male |
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| Change End of treatment (EOT) minus Baseline |
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