Macular Degeneration
Conditions
Keywords
Alprostadil, prostaglandin E1, Prostavasin®, macular degeneration
Brief summary
Evaluation of efficacy of alprostadil (prostaglandin E1) for treatment of patients suffering from dry age-related macula degeneration
Detailed description
Results of the planned interim analysis indicated that the number of originally planned patients were not sufficient to reach statistical significance in the primary end point. Instead of increasing the sample size accordingly, it was decided to terminate the study and plan future proceedings based on a careful analysis of the unblinded results.
Interventions
Alprostadil 20 µg ampoules; 60 µg alprostadil/d i.v. for 15 days.
OTHERPlacebo
Placebo/d i.v. for 15 days
Sponsors
UCB Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female subjects older than 50 years of age. * Dry age-related macula degeneration (AMD) with hard drusen and possibly beginning geographic atrophy in one eye * Visual acuity between 0.2 and 0.7 (logMAR) assessed with ETDRS charts
Exclusion criteria
* Dry AMD AREDS category 3 or 4 in both eyes * Wet AMD in at least one eye * Detachment of the pigmentary epithelium * Glaucoma * Diabetic retinopathy * Medical history of retinal vein occlusion * Uveitis * Cataract surgery during the study * High myopia (\< -6 dpt) with pathological findings of the retina * Medical history of any opthalmic surgery with complications * Medical history of cataract surgery without complications within the last 12 weeks * Medical history of vitrectomy * AREDS medication within the last 2 days * Opthalmologic dietary supplements within the last 2 days * Medical history of retinal hemorrhage * Cardiac failure (NYHA grade II or higher) * Inadequately controlled coronary heart disease or cardiac arrhythmia * Subject has a medical history and/or suspicion of pulmonary edema or pulmonary infiltration * Subject has a peripheral edema * Myocardial infarction within 6 months prior to enrollment * Subject has renal insufficiency, compensated retention (creatinine \> 1,5 mg/dL) * Subject has known existing malignant disease * Severe chronic obstructive pulmonary disease * Subject has a venoocclusive lung disease * Known hepatic disease * Inadequately controlled or untreated hypertension (systolic blood pressure ≥ 180 mmHg, diastolic blood pressure ≥ 110 mmHg) * Subject has upper grade cardiac valvular disorders * Pregnancy or lactation period * Known hypersensitivity to PGE1 or to any component of the trial medication * Subject has a history of chronic alcohol or drug abuse within the past 2 years * Subject has known lactose intolerance * Poor general state of health or other criteria * Subject has other serious illness * Laboratory values outside the normal range unless considered not clinically relevant by the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Visual Acuity Between Measurements at 3 Months After Drug Intervention and Measurements at Baseline (Assessed Within Early Treatment Diabetic Retinopathy Study (ETDRS) Chart) | From baseline to 3 months | Difference in visual acuity was measured with the standard ETDRS chart with letters arranged in lines of five. The first line is assumed to have letters of a specific size and each subsequent line to consist of letters of a smaller size. The subject starts reading the first line and continues reading the following lines until failing a line. Passing a line means to name at least three of the five letters correctly. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Difference in Visual Acuity Between Measurements at 6 Months After Intervention and Measurements at Baseline | From baseline to 6 months | Difference in visual acuity was measured with the standard ETDRS chart with letters arranged in lines of five. The first line is assumed to have letters of a specific size and each subsequent line to consist of letters of a smaller size. The subject starts reading the first line and continues reading the following lines until failing a line. Passing a line means to name at least three of the five letters correctly. |
| Progression of the Dry Age-related Macular Degeneration | From baseline to 6 months | Severity of the diagnosed dry age-related macular degeneration (AMD) was assessed in comparison to Baseline and classified as 1. Progression 2. Stabilization 3. Amelioration |
| Development of a Wet Age-related Macular Degeneration | From baseline to 6 months | A wet age-related macular degeneration (AMD) is defined as the development of choroidal neovascularization of the study-eye (worse eye). Development is categorized in Yes and No, where Yes means that a subject who had no wet AMD at Screening has developed a wet AMD at Week 29. |
| The Difference in Contrast Sensitivity Between Measurements Immediately After Intervention and Measurements at Baseline | From baseline to time immediately after intervention | Difference in contrast sensitivity was measured with the Pelli-Robson test, using a chart with letters arranged in groups of three. The first group has unit contrast and each subsequent group has a lower contrast. Passing a group means to read correctly at least two of the three letters. A Pelli-Robson score of 2.0 indicates normal contrast sensitivity of 100 percent. Scores less than 2.0 signify poorer contrast sensitivity. Pelli-Robson contrast sensitivity score of less than 1.5 is consistent with visual impairment and a score of less than 1.0 represents visual disability. |
| The Difference in Visual Acuity Between Measurements Immediately After Intervention and Measurements at Baseline | From baseline to time immediately after intervention | Difference in visual acuity was measured with the standard ETDRS chart with letters arranged in lines of five. The first line is assumed to have letters of a specific size and each subsequent line to consist of letters of a smaller size. The subject starts reading the first line and continues reading the following lines until failing a line. Passing a line means to name at least three of the five letters correctly. |
| The Difference in Contrast Sensitivity Between Measurements at 6 Months After Intervention and Measurements at Baseline | From baseline to 6 months | Difference in contrast sensitivity was measured with the Pelli-Robson test, using a chart with letters arranged in groups of three. The first group has unit contrast and each subsequent group has a lower contrast. Passing a group means to read correctly at least two of the three letters. A Pelli-Robson score of 2.0 indicates normal contrast sensitivity of 100 percent. Scores less than 2.0 signify poorer contrast sensitivity. Pelli-Robson contrast sensitivity score of less than 1.5 is consistent with visual impairment and a score of less than 1.0 represents visual disability. |
| The Difference in Color Vision Between Measurements Immediately After Intervention and Measurements at Baseline | From baseline to time immediately after intervention | The difference in color vision after intervention in comparison to Baseline was assessed by the investigator as 'Changed from Normal to Pathologic', 'Finding unchanged', and 'Changed from Pathologic to Normal'. |
| The Difference in Color Vision Between Measurements at 3 Months After Intervention and Measurements at Baseline | From baseline to 3 months | The difference in color vision after intervention in comparison to Baseline was assessed by the investigator as 'Changed from Normal to Pathologic', 'Finding unchanged', and 'Changed from Pathologic to Normal'. |
| The Difference in Color Vision Between Measurements at 6 Months After Intervention and Measurements at Baseline | From baseline to 6 months | The difference in color vision after intervention in comparison to Baseline was assessed by the investigator as 'Changed from Normal to Pathologic', 'Finding unchanged', and 'Changed from Pathologic to Normal'. |
| The Difference in Contrast Sensitivity Between Measurements at 3 Months After Intervention and Measurements at Baseline | From baseline to 3 months | Difference in contrast sensitivity was measured with the Pelli-Robson test, using a chart with letters arranged in groups of three. The first group has unit contrast and each subsequent group has a lower contrast. Passing a group means to read correctly at least two of the three letters. A Pelli-Robson score of 2.0 indicates normal contrast sensitivity of 100 percent. Scores less than 2.0 signify poorer contrast sensitivity. Pelli-Robson contrast sensitivity score of less than 1.5 is consistent with visual impairment and a score of less than 1.0 represents visual disability. |
Countries
Germany
Participant flow
Recruitment details
The Full Analysis Set (FAS) includes all randomized subjects treated with at least one infusion and having valid Baseline and Post-Baseline measurements. The Randomized Set (RS) consists of all randomized subjects who have completed Visit 16 or terminated prematurely.
Pre-assignment details
Participant Flow shows the RS. Baseline Characteristics refer to the FAS.
Participants by arm
| Arm | Count |
|---|---|
| Alprostadil Alprostadil 60 mcg/day i.v. for 15 days | 16 |
| Placebo Placebo i.v. for 15 days | 17 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Investigator planned Cataract Operation | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Termination of the Study by the Sponsor | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Alprostadil | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 15 Participants | 13 Participants | 28 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 4 Participants | 5 Participants |
| Age, Continuous | 76.1 years STANDARD_DEVIATION 8.5 | 71.7 years STANDARD_DEVIATION 8.1 | 73.8 years STANDARD_DEVIATION 8.5 |
| Body Mass Index (BMI) | 26.20 kg/ (m^2) STANDARD_DEVIATION 3.38 | 26.70 kg/ (m^2) STANDARD_DEVIATION 3.32 | 26.45 kg/ (m^2) STANDARD_DEVIATION 3.31 |
| Height (cm) | 171.06 centimeter (cm) STANDARD_DEVIATION 9.29 | 168.59 centimeter (cm) STANDARD_DEVIATION 8.69 | 169.79 centimeter (cm) STANDARD_DEVIATION 8.93 |
| Sex: Female, Male Female | 6 Participants | 9 Participants | 15 Participants |
| Sex: Female, Male Male | 10 Participants | 8 Participants | 18 Participants |
| Weight | 77.14 kilogramm (kg) STANDARD_DEVIATION 14.71 | 76.46 kilogramm (kg) STANDARD_DEVIATION 14.49 | 76.79 kilogramm (kg) STANDARD_DEVIATION 14.37 |
| White | 16 participants | 17 participants | 33 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 18 | 6 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 |
Outcome results
Primary
Difference in Visual Acuity Between Measurements at 3 Months After Drug Intervention and Measurements at Baseline (Assessed Within Early Treatment Diabetic Retinopathy Study (ETDRS) Chart)
Difference in visual acuity was measured with the standard ETDRS chart with letters arranged in lines of five. The first line is assumed to have letters of a specific size and each subsequent line to consist of letters of a smaller size. The subject starts reading the first line and continues reading the following lines until failing a line. Passing a line means to name at least three of the five letters correctly.
Time frame: From baseline to 3 months
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alprostadil | Difference in Visual Acuity Between Measurements at 3 Months After Drug Intervention and Measurements at Baseline (Assessed Within Early Treatment Diabetic Retinopathy Study (ETDRS) Chart) | 0.94 Lines read in ETDRS chart | Standard Deviation 1.84 |
| Placebo | Difference in Visual Acuity Between Measurements at 3 Months After Drug Intervention and Measurements at Baseline (Assessed Within Early Treatment Diabetic Retinopathy Study (ETDRS) Chart) | 0.53 Lines read in ETDRS chart | Standard Deviation 1.66 |
Comparison: The primary goal of the study was to test the following null hypothesis:~H0: μAlprostadil ≤ μPlacebo, against the alternative hypothesis H1: μAlprostadil \> μPlacebo, where μ denotes the mean differences in visual acuity between measurements at 3 months after the end of study drug infusion minus measurements at baseline as assessed as line difference on the standard ETDRS charts.p-value: 0.12295% CI: [-0.674, 2.55]ANCOVA
Secondary
Development of a Wet Age-related Macular Degeneration
A wet age-related macular degeneration (AMD) is defined as the development of choroidal neovascularization of the study-eye (worse eye). Development is categorized in Yes and No, where Yes means that a subject who had no wet AMD at Screening has developed a wet AMD at Week 29.
Time frame: From baseline to 6 months
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alprostadil | Development of a Wet Age-related Macular Degeneration | Yes | 0 Participants |
| Alprostadil | Development of a Wet Age-related Macular Degeneration | No | 16 Participants |
| Placebo | Development of a Wet Age-related Macular Degeneration | Yes | 0 Participants |
| Placebo | Development of a Wet Age-related Macular Degeneration | No | 17 Participants |
Secondary
Progression of the Dry Age-related Macular Degeneration
Severity of the diagnosed dry age-related macular degeneration (AMD) was assessed in comparison to Baseline and classified as 1. Progression 2. Stabilization 3. Amelioration
Time frame: From baseline to 6 months
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alprostadil | Progression of the Dry Age-related Macular Degeneration | Stabilization of disease | 1 Participants |
| Alprostadil | Progression of the Dry Age-related Macular Degeneration | Progression in disease | 11 Participants |
| Alprostadil | Progression of the Dry Age-related Macular Degeneration | Amelioration of disease | 4 Participants |
| Placebo | Progression of the Dry Age-related Macular Degeneration | Progression in disease | 10 Participants |
| Placebo | Progression of the Dry Age-related Macular Degeneration | Stabilization of disease | 3 Participants |
| Placebo | Progression of the Dry Age-related Macular Degeneration | Amelioration of disease | 4 Participants |
Secondary
The Difference in Color Vision Between Measurements at 3 Months After Intervention and Measurements at Baseline
The difference in color vision after intervention in comparison to Baseline was assessed by the investigator as 'Changed from Normal to Pathologic', 'Finding unchanged', and 'Changed from Pathologic to Normal'.
Time frame: From baseline to 3 months
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alprostadil | The Difference in Color Vision Between Measurements at 3 Months After Intervention and Measurements at Baseline | Changed from Normal to Pathologic | 1 Participants |
| Alprostadil | The Difference in Color Vision Between Measurements at 3 Months After Intervention and Measurements at Baseline | Finding unchanged | 13 Participants |
| Alprostadil | The Difference in Color Vision Between Measurements at 3 Months After Intervention and Measurements at Baseline | Changed from Pathologic to Normal | 2 Participants |
| Placebo | The Difference in Color Vision Between Measurements at 3 Months After Intervention and Measurements at Baseline | Changed from Normal to Pathologic | 0 Participants |
| Placebo | The Difference in Color Vision Between Measurements at 3 Months After Intervention and Measurements at Baseline | Finding unchanged | 14 Participants |
| Placebo | The Difference in Color Vision Between Measurements at 3 Months After Intervention and Measurements at Baseline | Changed from Pathologic to Normal | 3 Participants |
Secondary
The Difference in Color Vision Between Measurements at 6 Months After Intervention and Measurements at Baseline
The difference in color vision after intervention in comparison to Baseline was assessed by the investigator as 'Changed from Normal to Pathologic', 'Finding unchanged', and 'Changed from Pathologic to Normal'.
Time frame: From baseline to 6 months
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alprostadil | The Difference in Color Vision Between Measurements at 6 Months After Intervention and Measurements at Baseline | Changed from Normal to Pathologic | 1 Participants |
| Alprostadil | The Difference in Color Vision Between Measurements at 6 Months After Intervention and Measurements at Baseline | Finding unchanged | 12 Participants |
| Alprostadil | The Difference in Color Vision Between Measurements at 6 Months After Intervention and Measurements at Baseline | Changed from Pathologic to Normal | 3 Participants |
| Placebo | The Difference in Color Vision Between Measurements at 6 Months After Intervention and Measurements at Baseline | Changed from Normal to Pathologic | 0 Participants |
| Placebo | The Difference in Color Vision Between Measurements at 6 Months After Intervention and Measurements at Baseline | Finding unchanged | 15 Participants |
| Placebo | The Difference in Color Vision Between Measurements at 6 Months After Intervention and Measurements at Baseline | Changed from Pathologic to Normal | 2 Participants |
Secondary
The Difference in Color Vision Between Measurements Immediately After Intervention and Measurements at Baseline
The difference in color vision after intervention in comparison to Baseline was assessed by the investigator as 'Changed from Normal to Pathologic', 'Finding unchanged', and 'Changed from Pathologic to Normal'.
Time frame: From baseline to time immediately after intervention
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alprostadil | The Difference in Color Vision Between Measurements Immediately After Intervention and Measurements at Baseline | Changed from Normal to Pathologic | 1 Participants |
| Alprostadil | The Difference in Color Vision Between Measurements Immediately After Intervention and Measurements at Baseline | Finding unchanged | 15 Participants |
| Alprostadil | The Difference in Color Vision Between Measurements Immediately After Intervention and Measurements at Baseline | Changed from Pathologic to Normal | 0 Participants |
| Placebo | The Difference in Color Vision Between Measurements Immediately After Intervention and Measurements at Baseline | Changed from Normal to Pathologic | 0 Participants |
| Placebo | The Difference in Color Vision Between Measurements Immediately After Intervention and Measurements at Baseline | Finding unchanged | 13 Participants |
| Placebo | The Difference in Color Vision Between Measurements Immediately After Intervention and Measurements at Baseline | Changed from Pathologic to Normal | 4 Participants |
Secondary
The Difference in Contrast Sensitivity Between Measurements at 3 Months After Intervention and Measurements at Baseline
Difference in contrast sensitivity was measured with the Pelli-Robson test, using a chart with letters arranged in groups of three. The first group has unit contrast and each subsequent group has a lower contrast. Passing a group means to read correctly at least two of the three letters. A Pelli-Robson score of 2.0 indicates normal contrast sensitivity of 100 percent. Scores less than 2.0 signify poorer contrast sensitivity. Pelli-Robson contrast sensitivity score of less than 1.5 is consistent with visual impairment and a score of less than 1.0 represents visual disability.
Time frame: From baseline to 3 months
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alprostadil | The Difference in Contrast Sensitivity Between Measurements at 3 Months After Intervention and Measurements at Baseline | 0.084 Unit on a scale | Standard Deviation 0.205 |
| Placebo | The Difference in Contrast Sensitivity Between Measurements at 3 Months After Intervention and Measurements at Baseline | -0.026 Unit on a scale | Standard Deviation 0.324 |
Secondary
The Difference in Contrast Sensitivity Between Measurements at 6 Months After Intervention and Measurements at Baseline
Difference in contrast sensitivity was measured with the Pelli-Robson test, using a chart with letters arranged in groups of three. The first group has unit contrast and each subsequent group has a lower contrast. Passing a group means to read correctly at least two of the three letters. A Pelli-Robson score of 2.0 indicates normal contrast sensitivity of 100 percent. Scores less than 2.0 signify poorer contrast sensitivity. Pelli-Robson contrast sensitivity score of less than 1.5 is consistent with visual impairment and a score of less than 1.0 represents visual disability.
Time frame: From baseline to 6 months
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alprostadil | The Difference in Contrast Sensitivity Between Measurements at 6 Months After Intervention and Measurements at Baseline | 0.028 Unit on a scale | Standard Deviation 0.221 |
| Placebo | The Difference in Contrast Sensitivity Between Measurements at 6 Months After Intervention and Measurements at Baseline | 0.009 Unit on a scale | Standard Deviation 0.373 |
Secondary
The Difference in Contrast Sensitivity Between Measurements Immediately After Intervention and Measurements at Baseline
Difference in contrast sensitivity was measured with the Pelli-Robson test, using a chart with letters arranged in groups of three. The first group has unit contrast and each subsequent group has a lower contrast. Passing a group means to read correctly at least two of the three letters. A Pelli-Robson score of 2.0 indicates normal contrast sensitivity of 100 percent. Scores less than 2.0 signify poorer contrast sensitivity. Pelli-Robson contrast sensitivity score of less than 1.5 is consistent with visual impairment and a score of less than 1.0 represents visual disability.
Time frame: From baseline to time immediately after intervention
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alprostadil | The Difference in Contrast Sensitivity Between Measurements Immediately After Intervention and Measurements at Baseline | 0.009 Unit on a scale | Standard Deviation 0.282 |
| Placebo | The Difference in Contrast Sensitivity Between Measurements Immediately After Intervention and Measurements at Baseline | 0.018 Unit on a scale | Standard Deviation 0.224 |
Secondary
The Difference in Visual Acuity Between Measurements at 6 Months After Intervention and Measurements at Baseline
Difference in visual acuity was measured with the standard ETDRS chart with letters arranged in lines of five. The first line is assumed to have letters of a specific size and each subsequent line to consist of letters of a smaller size. The subject starts reading the first line and continues reading the following lines until failing a line. Passing a line means to name at least three of the five letters correctly.
Time frame: From baseline to 6 months
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alprostadil | The Difference in Visual Acuity Between Measurements at 6 Months After Intervention and Measurements at Baseline | 1.31 Lines read in ETDRS chart | Standard Deviation 1.45 |
| Placebo | The Difference in Visual Acuity Between Measurements at 6 Months After Intervention and Measurements at Baseline | 0.29 Lines read in ETDRS chart | Standard Deviation 2.11 |
Secondary
The Difference in Visual Acuity Between Measurements Immediately After Intervention and Measurements at Baseline
Difference in visual acuity was measured with the standard ETDRS chart with letters arranged in lines of five. The first line is assumed to have letters of a specific size and each subsequent line to consist of letters of a smaller size. The subject starts reading the first line and continues reading the following lines until failing a line. Passing a line means to name at least three of the five letters correctly.
Time frame: From baseline to time immediately after intervention
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alprostadil | The Difference in Visual Acuity Between Measurements Immediately After Intervention and Measurements at Baseline | 1.29 Lines read in ETDRS chart | Standard Deviation 1.44 |
| Placebo | The Difference in Visual Acuity Between Measurements Immediately After Intervention and Measurements at Baseline | 0.38 Lines read in ETDRS chart | Standard Deviation 1.54 |