Age Related Macular Degeneration (AMD), Choroidal Neovascularization (CNV), Macular Degeneration
Conditions
Keywords
neovascular age related macular degeneration, choroidal neovascularization
Brief summary
The purpose of this study is to determine the benefits of treating subjects with neovascular age-related macular degeneration (AMD) at an earlier stage of choroidal neovascularization (CNV) as compared to those with established CNV. Additionally, the study would like to determine the efficacy of Macugen in preserving visual function in those subjects having CNV secondary to neovascular AMD.
Detailed description
A decision was made by the sponsor (08 May 2009) to terminate this study early; the study had achieved the primary objective prior to termination. This study was not terminated due to safety reasons.
Interventions
DRUGPegaptanib Sodium 0.3 mg
Pegaptanib Sodium dosed every 6 weeks in affected eye.
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Evidence of neovascular AMD in at least one eye. In subjects with bilateral neovascular AMD, only one eye would be eligible for enrollment * Baseline visual acuity of greater than or equal to 20/320, or better than 25 ETDRS letters in the study eye
Exclusion criteria
* Previous treatment for CNV secondary to AMD, including any prior PDT with verteporfin, thermal laser photocoagulation, external beam radiation or transpupillary thermotherapy to the study eye * Subjects having subfoveal fibrosis/ scar or atrophy representing \> 25% of the total lesion size
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline Through Week 54 in Distance Visual Acuity (VA) in Subjects With Early and Established CNV Lesions | Baseline through Week 54 | The investigator assessed the best-corrected VA obtained by a protocol refraction using the retroilluminated modified Ferris-Bailey Early Treatment of Diabetic Retinopathy Study (ETDRS) charts recorded at a 2-meter distance from the chart. Distance VA was expressed as an ETDRS score (number of letters correctly read): the proportion of subjects losing \>=30 letters or \<15 letters from Baseline, gaining \>=0 or \>=15 letters from Baseline. The mean change in VA from Baseline at Week 54 was assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Distance VA in Subjects With Early and Established CNV Lesions | Baseline through Week 102, Week 54 through Week 102 | The investigator assessed the best-corrected VA obtained by a protocol refraction using the retroilluminated modified Ferris-Bailey ETDRS charts recorded at a 2-meter distance from the chart. Distance VA was expressed as an ETDRS score (number of letters correctly read): the proportion of subjects losing \>=30 letters or \<15 letters, gaining \>=0 or \>=15 letters. The mean changes in VA from Baseline/Week 102 and Week 52/102 were assessed. |
| Mean Change in Reading Speed | Baseline through Week 54, Baseline through Week 102, and Week 54 through Week 102 | For assessment of reading speed, subjects were asked to read a print steadily, without stopping or interruption, at a comfortable pace. On commencing reading, a timer was activated. The timer was stopped when the subject had finished reading all of the words on the chart or at 2 minutes, whichever was sooner. Only the total number of words read correctly was recorded. The time recorded for the reading speed test was the time required for the subject to finish reading all of the words on the chart in minutes and seconds (maximum 2 minutes). |
| Mean Change From Baseline in Near VA in Subjects With Early and Established CNV Lesions | Baseline through Week 54, Baseline through Week 102 | Near VA was measured with the modified Bailey-Lovie near-word reading charts at a distance of 25 centimeters using a +3.50 reading addition worn over the protocol refraction providing the best-corrected distance VA. The reading charts test the smallest word size identifiable from 0.0 logarithmic of the minimum angle of resolution (logMAR) to 1.6 logMAR. logMAR is the logarithm of the minimum angle of resolution. The ideal is 0.0 and represents 20/20 Snellen acuity. logMAR values \>0.00 indicate vision poorer than ideal and values \<0.0 indicate vision greater than ideal. |
| Mean Change in National Eye Institute - Visual Functioning Questionnaire (NEI-VFQ-25) Composite Score | Baseline through Week 54, Baseline through Week 102, and Week 54 through Week 102 | Subject reported vision-related functioning and Quality of Life (QoL) as measured using the 25 item NEI-VFQ-25. Items are grouped as the following - Composite: mean score items 1-25; General Health: item 1; General Vision: item 2; Ocular Pain: 4,19; Near Vision: 5,6,7; Distance Vision: 8,9,14; Social Functioning: 11,13; Mental Health Activities: 3,21,22,25; Role Difficulties: 17,18; Dependency: 20,23,24; Driving: 15c,16, 16a; Color Vision: 12; Peripheral Vision: 10. A positive change represents an increase in function/health, a negative change represents a decrease in function/health. |
| Mean Change in Euro QoL Questionnaire (EQ-5D) Score | Baseline through Week 54, Baseline through Week 102, and Week 54 through Week 102 | The EQ-5D is a validated, standardized QoL instrument assessing general health status based on the preference of a UK general population. It consists of two sections: a 100-point visual analog scale (VAS) and a descriptive system that contains five attributes (mobility, self-care, usual activities, pain or discomfort, and anxiety or depression) with three levels per attribute (no problem, some problems and extreme problems). A subject's responses to these domains were mapped to a corresponding score of the EQ-5D index. |
| Mean Change From Baseline in Contrast Sensitivity | Baseline through Week 54, Baseline through Week 102 | Contrast sensitivity was measured using the Pelli-Robson chart at 1 meter. Subjects were tested for contrast sensitivity using +0.50 addition over the protocol refraction providing the best-corrected distance VA. Contrast sensitivity was recorded as the log of the faintest triplet for which 2 of the 3 letters were read correctly. |
Countries
Austria, Belgium, Canada, Czechia, Denmark, Finland, France, Germany, Greece, Italy, Poland, Portugal, Spain, Turkey (Türkiye), United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Early AMD Subjects with early CNV lesions (assessed by the investigator at Baseline) were treated in the study eye with Macugen (0.3 mg) every 6 weeks for 48 weeks. All subjects completing the first year of therapy (54 weeks \[ie, 6 weeks after treatment at Week 48\]) continued treatment in the second year of the study (Weeks 54 to 102), with Macugen (0.3 mg) administered every 12 weeks (ie, Weeks 60, 72, 84, and 96). | 107 |
| Established AMD Subjects with established CNV lesions (as assessed by the investigator at Baseline) were treated in the study eye with Macugen (0.3 mg) every 6 weeks for 48 weeks. All subjects completing the first year of therapy (54 weeks \[ie, 6 weeks after treatment at Week 48\]) continued treatment in the second year of the study (Weeks 54 to 102), with Macugen (0.3 mg) administered every 12 weeks (ie, Weeks 60, 72, 84, and 96). | 179 |
| Total | 286 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 9 | 14 |
| Overall Study | Death | 1 | 4 |
| Overall Study | Lack of Efficacy | 7 | 19 |
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Other | 5 | 9 |
| Overall Study | Randomized, but not treated | 0 | 2 |
| Overall Study | Withdrawal by Subject | 6 | 12 |
Baseline characteristics
| Characteristic | Early AMD | Established AMD | Total |
|---|---|---|---|
| Age, Customized 45 through 64 years | 12 Participants | 24 Participants | 36 Participants |
| Age, Customized >= 65 years | 95 Participants | 155 Participants | 250 Participants |
| Sex: Female, Male Female | 59 Participants | 108 Participants | 167 Participants |
| Sex: Female, Male Male | 48 Participants | 71 Participants | 119 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 68 / 107 | 120 / 179 |
| serious Total, serious adverse events | 23 / 107 | 32 / 179 |
Outcome results
Primary
Mean Change From Baseline Through Week 54 in Distance Visual Acuity (VA) in Subjects With Early and Established CNV Lesions
The investigator assessed the best-corrected VA obtained by a protocol refraction using the retroilluminated modified Ferris-Bailey Early Treatment of Diabetic Retinopathy Study (ETDRS) charts recorded at a 2-meter distance from the chart. Distance VA was expressed as an ETDRS score (number of letters correctly read): the proportion of subjects losing \>=30 letters or \<15 letters from Baseline, gaining \>=0 or \>=15 letters from Baseline. The mean change in VA from Baseline at Week 54 was assessed.
Time frame: Baseline through Week 54
Population: The modified intent-to-treat (MITT) population included all subjects in the safety population who had a Baseline distance VA measurement and at least 1 post-Baseline VA measurement. Last observation carried forward (LOCF). Note: the number of participants analyzed refers to the number of subjects who had data that could be analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Early AMD | Mean Change From Baseline Through Week 54 in Distance Visual Acuity (VA) in Subjects With Early and Established CNV Lesions | -4.30 Scores on a scale | Standard Deviation 14.57 |
| Established AMD | Mean Change From Baseline Through Week 54 in Distance Visual Acuity (VA) in Subjects With Early and Established CNV Lesions | -5.51 Scores on a scale | Standard Deviation 15.08 |
Secondary
Mean Change From Baseline in Contrast Sensitivity
Contrast sensitivity was measured using the Pelli-Robson chart at 1 meter. Subjects were tested for contrast sensitivity using +0.50 addition over the protocol refraction providing the best-corrected distance VA. Contrast sensitivity was recorded as the log of the faintest triplet for which 2 of the 3 letters were read correctly.
Time frame: Baseline through Week 54, Baseline through Week 102
Population: MITT LOCF; Note: the number of participants analyzed refers to the number of subjects who had data that could be analyzed. n=number of subjects with evaluable data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early AMD | Mean Change From Baseline in Contrast Sensitivity | Baseline through Week 54 (n=93, n=152) | -0.06 Correctly read letters | Standard Deviation 0.26 |
| Early AMD | Mean Change From Baseline in Contrast Sensitivity | Baseline through Week 102 (n=94, n=152) | -0.16 Correctly read letters | Standard Deviation 0.37 |
| Established AMD | Mean Change From Baseline in Contrast Sensitivity | Baseline through Week 54 (n=93, n=152) | -0.03 Correctly read letters | Standard Deviation 0.33 |
| Established AMD | Mean Change From Baseline in Contrast Sensitivity | Baseline through Week 102 (n=94, n=152) | -0.09 Correctly read letters | Standard Deviation 0.39 |
Secondary
Mean Change From Baseline in Distance VA in Subjects With Early and Established CNV Lesions
The investigator assessed the best-corrected VA obtained by a protocol refraction using the retroilluminated modified Ferris-Bailey ETDRS charts recorded at a 2-meter distance from the chart. Distance VA was expressed as an ETDRS score (number of letters correctly read): the proportion of subjects losing \>=30 letters or \<15 letters, gaining \>=0 or \>=15 letters. The mean changes in VA from Baseline/Week 102 and Week 52/102 were assessed.
Time frame: Baseline through Week 102, Week 54 through Week 102
Population: MITT LOCF; Note: the number of participants analyzed refers to the number of subjects who had data that could be analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early AMD | Mean Change From Baseline in Distance VA in Subjects With Early and Established CNV Lesions | Baseline through Week 102 | -7.91 Scores on a scale | Standard Deviation 16.14 |
| Early AMD | Mean Change From Baseline in Distance VA in Subjects With Early and Established CNV Lesions | Week 54 through Week 102 | -3.61 Scores on a scale | Standard Deviation 9.83 |
| Established AMD | Mean Change From Baseline in Distance VA in Subjects With Early and Established CNV Lesions | Baseline through Week 102 | -8.95 Scores on a scale | Standard Deviation 17.34 |
| Established AMD | Mean Change From Baseline in Distance VA in Subjects With Early and Established CNV Lesions | Week 54 through Week 102 | -3.44 Scores on a scale | Standard Deviation 9.81 |
Secondary
Mean Change From Baseline in Near VA in Subjects With Early and Established CNV Lesions
Near VA was measured with the modified Bailey-Lovie near-word reading charts at a distance of 25 centimeters using a +3.50 reading addition worn over the protocol refraction providing the best-corrected distance VA. The reading charts test the smallest word size identifiable from 0.0 logarithmic of the minimum angle of resolution (logMAR) to 1.6 logMAR. logMAR is the logarithm of the minimum angle of resolution. The ideal is 0.0 and represents 20/20 Snellen acuity. logMAR values \>0.00 indicate vision poorer than ideal and values \<0.0 indicate vision greater than ideal.
Time frame: Baseline through Week 54, Baseline through Week 102
Population: MITT LOCF. Note: the number of participants analyzed refers to the number of subjects who had data that could be analyzed. n=number of subjects with evaluable data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early AMD | Mean Change From Baseline in Near VA in Subjects With Early and Established CNV Lesions | Baseline through Week 54 (n=104, n=172) | 0.10 Scores on a scale | Standard Deviation 0.27 |
| Early AMD | Mean Change From Baseline in Near VA in Subjects With Early and Established CNV Lesions | Baseline through Week 102 (n=105, n=172) | 0.19 Scores on a scale | Standard Deviation 0.34 |
| Established AMD | Mean Change From Baseline in Near VA in Subjects With Early and Established CNV Lesions | Baseline through Week 54 (n=104, n=172) | 0.15 Scores on a scale | Standard Deviation 0.32 |
| Established AMD | Mean Change From Baseline in Near VA in Subjects With Early and Established CNV Lesions | Baseline through Week 102 (n=105, n=172) | 0.22 Scores on a scale | Standard Deviation 0.36 |
Secondary
Mean Change in Euro QoL Questionnaire (EQ-5D) Score
The EQ-5D is a validated, standardized QoL instrument assessing general health status based on the preference of a UK general population. It consists of two sections: a 100-point visual analog scale (VAS) and a descriptive system that contains five attributes (mobility, self-care, usual activities, pain or discomfort, and anxiety or depression) with three levels per attribute (no problem, some problems and extreme problems). A subject's responses to these domains were mapped to a corresponding score of the EQ-5D index.
Time frame: Baseline through Week 54, Baseline through Week 102, and Week 54 through Week 102
Population: MITT. Note: the number of participants analyzed refers to the number of subjects who had data that could be analyzed. n=number of subjects with evaluable data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early AMD | Mean Change in Euro QoL Questionnaire (EQ-5D) Score | Baseline through Week 54 (n=90, n=146) | -0.00 Scores on a scale | Standard Deviation 0.26 |
| Early AMD | Mean Change in Euro QoL Questionnaire (EQ-5D) Score | Baseline through Week 102 (n=67, n=111) | -0.04 Scores on a scale | Standard Deviation 0.267 |
| Early AMD | Mean Change in Euro QoL Questionnaire (EQ-5D) Score | Week 54 through Week 102 (n=64, n=115) | -0.01 Scores on a scale | Standard Deviation 0.271 |
| Established AMD | Mean Change in Euro QoL Questionnaire (EQ-5D) Score | Baseline through Week 54 (n=90, n=146) | -0.01 Scores on a scale | Standard Deviation 0.227 |
| Established AMD | Mean Change in Euro QoL Questionnaire (EQ-5D) Score | Baseline through Week 102 (n=67, n=111) | -0.04 Scores on a scale | Standard Deviation 0.207 |
| Established AMD | Mean Change in Euro QoL Questionnaire (EQ-5D) Score | Week 54 through Week 102 (n=64, n=115) | -0.03 Scores on a scale | Standard Deviation 0.213 |
Secondary
Mean Change in National Eye Institute - Visual Functioning Questionnaire (NEI-VFQ-25) Composite Score
Subject reported vision-related functioning and Quality of Life (QoL) as measured using the 25 item NEI-VFQ-25. Items are grouped as the following - Composite: mean score items 1-25; General Health: item 1; General Vision: item 2; Ocular Pain: 4,19; Near Vision: 5,6,7; Distance Vision: 8,9,14; Social Functioning: 11,13; Mental Health Activities: 3,21,22,25; Role Difficulties: 17,18; Dependency: 20,23,24; Driving: 15c,16, 16a; Color Vision: 12; Peripheral Vision: 10. A positive change represents an increase in function/health, a negative change represents a decrease in function/health.
Time frame: Baseline through Week 54, Baseline through Week 102, and Week 54 through Week 102
Population: MITT. Note: the number of participants analyzed refers to the number of subjects who had data that could be analyzed. n=number of subjects with evaluable data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early AMD | Mean Change in National Eye Institute - Visual Functioning Questionnaire (NEI-VFQ-25) Composite Score | Baseline through Week 54 (n=90, n=146) | -1.54 Scores on a scale | Standard Deviation 12.946 |
| Early AMD | Mean Change in National Eye Institute - Visual Functioning Questionnaire (NEI-VFQ-25) Composite Score | Baseline through Week 102 (n=67, n=111) | -4.57 Scores on a scale | Standard Deviation 14.41 |
| Early AMD | Mean Change in National Eye Institute - Visual Functioning Questionnaire (NEI-VFQ-25) Composite Score | Week 54 through Week 102 (n=64, n=115) | -2.74 Scores on a scale | Standard Deviation 9.655 |
| Established AMD | Mean Change in National Eye Institute - Visual Functioning Questionnaire (NEI-VFQ-25) Composite Score | Baseline through Week 54 (n=90, n=146) | -1.03 Scores on a scale | Standard Deviation 13.264 |
| Established AMD | Mean Change in National Eye Institute - Visual Functioning Questionnaire (NEI-VFQ-25) Composite Score | Baseline through Week 102 (n=67, n=111) | -1.65 Scores on a scale | Standard Deviation 12.569 |
| Established AMD | Mean Change in National Eye Institute - Visual Functioning Questionnaire (NEI-VFQ-25) Composite Score | Week 54 through Week 102 (n=64, n=115) | -2.48 Scores on a scale | Standard Deviation 9.473 |
Secondary
Mean Change in Reading Speed
For assessment of reading speed, subjects were asked to read a print steadily, without stopping or interruption, at a comfortable pace. On commencing reading, a timer was activated. The timer was stopped when the subject had finished reading all of the words on the chart or at 2 minutes, whichever was sooner. Only the total number of words read correctly was recorded. The time recorded for the reading speed test was the time required for the subject to finish reading all of the words on the chart in minutes and seconds (maximum 2 minutes).
Time frame: Baseline through Week 54, Baseline through Week 102, and Week 54 through Week 102
Population: MITT LOCF; Note: the number of participants analyzed refers to the number of subjects who had data that could be analyzed. n=number of subjects with evaluable data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early AMD | Mean Change in Reading Speed | Baseline through Week 54 (n=92, n=151) | -9.15 Correctly read words per minute | Standard Deviation 28.78 |
| Early AMD | Mean Change in Reading Speed | Baseline through Week 102 (n=94, n=152) | -17.81 Correctly read words per minute | Standard Deviation 28.48 |
| Early AMD | Mean Change in Reading Speed | Week 54 through Week 102 (n=93, n=152) | -8.43 Correctly read words per minute | Standard Deviation 18.06 |
| Established AMD | Mean Change in Reading Speed | Baseline through Week 54 (n=92, n=151) | -10.98 Correctly read words per minute | Standard Deviation 22.31 |
| Established AMD | Mean Change in Reading Speed | Baseline through Week 102 (n=94, n=152) | -12.23 Correctly read words per minute | Standard Deviation 32.08 |
| Established AMD | Mean Change in Reading Speed | Week 54 through Week 102 (n=93, n=152) | -1.15 Correctly read words per minute | Standard Deviation 23.77 |