Age-Related Maculopathy
Conditions
Keywords
Phase 2, Advanced Dry Age-Related Macular Degeneration, Geographic Atrophy, RN6G
Brief summary
The purpose of this study is to determine the efficacy, safety and tolerability of multiple doses of RN6G in subjects with Geographic Atrophy Secondary to Age-related Macular Degeneration.
Detailed description
The trial was terminated early on April 12, 2013 due to an organizational decision, which was not based on safety or efficacy concerns. Subjects who were already enrolled into the study were followed.
Interventions
BIOLOGICALRN6G
Intravenous, 11 doses, 30 minute infusion, dose ranging from 2.5 mg/kg up to a maximum of 15 mg/kg
BIOLOGICALPlacebo
Intravenous, 11 doses, 30 minute infusion
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Men and women between the ages of 60 and 90 years. * Diagnosis of a geographic atrophy (GA) secondary to dry Age-Related Macular Degeneration. * Best Corrected Visual Acuity (BCVA) of 20/80 or better in the study eye
Exclusion criteria
* Evidence of ocular disease other than geographic atrophy (GA) secondary to dry Age-Related Macular Degeneration in the study eye. * History or diagnosis of exudative (wet) Age-Related Macular Degeneration, with subretinal or choroidal neovascular lesions in the study eye. * Presence of disease or condition that might compromise the cardiovascular, hematological, renal, hepatic, pulmonary, endocrine, central nervous, immune, or gastrointestinal system
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Reduction (in Study Eye) in Rate of Growth of Geographic Atrophy (GA) at Day 309 | Baseline and Day 309 | GA is the advanced form of dry age-related macular degeneration (AMD). The reduction in GA area of the study eye was based on Fundus Autofluorescence (FAF) at 30 days post last dose administration (Day 309). |
| Mean Reduction (in Study Eye) in Rate of Growth of GA at Day 449 (End of Study) | Baseline and Day 449 | GA is the advanced form of dry AMD. The reduction in GA area in the study eye was based on FAF at end of study (Day 449). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Best Corrected Visual Acuity (BCVA) at 9, 12, 15 Months and End of Study | Baseline, Month 9, Month 12, Month 15, and End of Study | BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). |
| Percentage Change From Baseline in BCVA Correct Number of Letters at 9, 12, 15 Months and End of Study | Baseline, Month 9, Month 12, Month 15, and End of Study | BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). |
| Percentage Change From Baseline in BCVA Correct Number of Lines at Months 9, 12, 15 Months and End of Study | Baseline, Month 9, Month 12, Month 15, and End of Study | BCVA is measured using an eye chart and is reported as the number of lines read correctly in the study eye. The lower the number of lines read correctly on the eye chart, the worse the vision (or visual acuity). |
| Mean Low Luminance Best Corrected Visual Acuity (LL-BCVA) at 9, 12, 15 Months and End of Study | Baseline, Month 9, Month 12, Month 15, and End of Study | LL-BCVA is the measure of visual acuity under low light conditions. |
| Percentage Change From Baseline in LL-BCVA Correct Number of Letters at 9, 12, 15 Months and End of Study | Baseline, Month 9, Month 12, Month 15, and End of Study | LL-BCVA is the measure of visual acuity under low light conditions. |
| Percentage Change From Baseline in LL-BCVA Correct Number of Lines at 9, 12, 15 Months and End of Study | Baseline, Month 9, Month 12, Month 15, and End of Study | LL-BCVA is the measure of visual acuity under low light conditions. |
| Change From Baseline in Contrast Sensitivity at 9, 12, 15 Months and End of Study | Baseline, Month 9, Month 12, Month 15, and End of Study | Contrast sensitivity was measured using the Pelli-Robson chart at 1 meter. Participants 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. |
| Percentage Change From Baseline in Contrast Sensitivity at 9, 12, 15 Months and End of Study | Baseline, Month 9, Month 12, Month 15, and End of Study | 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. |
| Change From Baseline in Reading Speed at 9, 12, 15 Months and End of Study | Baseline, Month 9, Month 12, Month 15, and End of Study | Reading speed in the study eye was assessed using modified Bailey-Lovie word charts. Participants read the chart for 2 minutes and the number of words read correctly per minute was totaled. An increase in the number of words read correctly indicated an improvement and a decrease in the number of words read correctly indicated a worsening. |
| Change From Placebo in Reading Speed at 9, 12, 15 Months and End of Study | Baseline, Month 9, Month 12, Month 15, and End of Study | Reading speed in the study eye was assessed using modified Bailey-Lovie word charts. Participants read the chart for 2 minutes and the number of words read correctly per minute was totaled. An increase in the number of words read correctly indicated an improvement and a decrease in the number of words read correctly indicated a worsening. |
| Percentage Change From Baseline in Reading Speed at 9, 12, 15 Months and End of Study | Baseline, Month 9, Month 12, Month 15, and End of Study | Reading speed in the study eye was assessed using modified Bailey-Lovie word charts. Participants read the chart for 2 minutes and the number of words read correctly per minute was totaled. An increase in the number of words read correctly indicated an improvement and a decrease in the number of words read correctly indicated a worsening. |
| Change From Baseline in Reading Acuity at 9, 12, 15 Months and End of Study | Baseline, Month 9, Month 12, Month 15, and End of Study | Reading Acuity was measured using the Radner reading charts and expressed in terms of logRAD (logrithmic Reading Acuity Determination). |
| Change From Placebo in Reading Acuity at 9, 12, 15 Months and End of Study | Baseline, Month 9, Month 12, Month 15, and End of Study | Reading Acuity was measured using the Radner reading charts and expressed in terms of logRAD. |
| Percentage Change From Baseline in Reading Acuity at 9, 12, 15 Months and End of Study | Baseline, Month 9, Month 12, Month 15, and End of Study | Reading Acuity was measured using the Radner reading charts and expressed in terms of logRAD. |
| Change From Baseline in Critical Print Size Reading at 9, 12, 15 Months and End of Study | Baseline, Month 9, Month 12, Month 15, and End of Study | The critical print size is the smallest print size at which participants can read with their maximum reading speed. |
| Change From Placebo in Critical Print Size Reading at 9, 12, 15 Months and End of Study | Baseline, Month 9, Month 12, Month 15, and End of Study | The critical print size is the smallest print size at which participants can read with their maximum reading speed. |
| Number of Participants With Treatment-Emergent Laboratory Abnormalities | Day 85 and Day 169 | Laboratory assessments include: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid albumin, total protein); coagulation assessments. |
| Number of Participants With Abnormal Change From Baseline in Vital Signs | Screening, Days 28, 57, 85, 113, 141, and 169 | Vital sign assessments include: supine systolic and diastolic blood pressure, pulse rate and body temperature. |
| Number of Participants With Clinically Significant Treatment-Emergent Electrocardiogram (ECG) Findings | Days 28, 57, 85, 113 and 169 | Clinically significant ECG findings include: corrected QT (QTc) \> 450 msec, QTc \>500 msec, change in QTc between 30 and 60 msec, change in QTc greater than or equal to 60 msec. |
| Number of Participants With Positive Anti-Drug Antibody (ADA) | Day 57 and Day 169 | The number of participants with positive ADA was to be summarized for each treatment arm. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) According to Seriousness | Days 28, 57, 85, 113, 141 and 169 | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Seriousness of an AE was assessed under the criteria of serious adverse event (SAE). An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. |
| Number of Participants With Treatment-Related TEAEs | Days 28, 57, 85, 113, 141 and 169 | An AE was an untoward medical occurrence in a participant who received study drug without regard to causal relationship. An investigator's relationship assessment is the determination of whether there exists a reasonable possibility that the investigational product caused or contributed to an AE. |
| Maximum Observed Plasma Concentration (Cmax) | Days 1, 28,57, 85, 169, 253, 281, 309, 337, and 449 | — |
| Minimum Observed Plasma Trough Concentration (Cmin) | Days 1, 28,57, 85, 169, 253, 281, 309, 337, and 449 | — |
| Area Under the Concentration-Time Curve From Time Zero Until Last Sampling Time (AUCt) | Days 1, 28,57, 85, 169, 253, 281, 309, 337, and 449 | — |
| Clearance at Steady State (CLss) | Days 1, 28,57, 85, 169, 253, 281, 309, 337, and 449 | Steady state total body clearance equals infusion rate (zero order) divided by steady state plasma concentration of study drug (R0/Css) |
| Accumulation Ratio (Rac) for AUCt | Days 1, 28,57, 85, 169, 253, 281, 309, 337, and 449 | — |
| Plasma Population PK Parameters | Days 1, 28, 57, 85, 169, 253, 281, 309, 337 and 449 | Population PK parameters were to be evaluated for Cmax, AUCt, Cmin, CLss, and Rac for AUCt between the first and last (11th) doses. |
| Change From Baseline in Total Amyloid Beta (A-Beta) 1-x Plasma Concentration at End of Study (Day 449) | Baseline, Day 449 | Concentration of total amino acid peptide, known as A-Beta 1-x, in plasma. |
| Change From Baseline in Amyloid Beta (A-Beta) 1-40 Plasma Concentration at End of Study (Day 449) | Baseline, Day 449 | Concentration of amino acid peptide, known as A-Beta 1-40, in plasma. |
| Change From Baseline in Amyloid Beta (A-Beta) 1-42 Plasma Concentration at End of Study (Day 449) | Baseline, Day 449 | Concentration of amino acid peptide, known as A-Beta 1-42, in plasma. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PF-04382923 2.5 mg/kg PF-04382923 (RN6G) at 2.5 milligrams per kilogram (mg/kg) was administered as an intravenous (IV) infusion over 30 minutes every 28 days for 11 doses. | 2 |
| PF-04382923 7.5 mg/kg PF-04382923 at 7.5 mg/kg was administered as an IV infusion over 30 minutes every 28 days for 11 doses. | 3 |
| PF-04382923 15.0 mg/kg PF-04382923 at 15.0 mg/kg was administered as an IV infusion over 30 minutes every 28 days for 11 doses. | 3 |
| Placebo Placebo was administered as an IV infusion over at least 30 minutes every 28 days for 11 doses. | 2 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Discontinued | 2 | 1 | 2 | 2 |
| Overall Study | Ongoing at Date of Cut-Off | 0 | 2 | 1 | 0 |
Baseline characteristics
| Characteristic | PF-04382923 2.5 mg/kg | PF-04382923 7.5 mg/kg | PF-04382923 15.0 mg/kg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 82.5 years STANDARD_DEVIATION 0.7 | 71.0 years STANDARD_DEVIATION 6.2 | 74.0 years STANDARD_DEVIATION 12.2 | 73.0 years STANDARD_DEVIATION 11.3 | 74.6 years STANDARD_DEVIATION 8.6 |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 3 Participants | 0 Participants | 7 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 2 | 0 / 3 | 1 / 3 | 1 / 2 |
| serious Total, serious adverse events | 1 / 2 | 0 / 3 | 0 / 3 | 0 / 2 |
Outcome results
Primary
Mean Reduction (in Study Eye) in Rate of Growth of GA at Day 449 (End of Study)
GA is the advanced form of dry AMD. The reduction in GA area in the study eye was based on FAF at end of study (Day 449).
Time frame: Baseline and Day 449
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Primary
Mean Reduction (in Study Eye) in Rate of Growth of Geographic Atrophy (GA) at Day 309
GA is the advanced form of dry age-related macular degeneration (AMD). The reduction in GA area of the study eye was based on Fundus Autofluorescence (FAF) at 30 days post last dose administration (Day 309).
Time frame: Baseline and Day 309
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Accumulation Ratio (Rac) for AUCt
Time frame: Days 1, 28,57, 85, 169, 253, 281, 309, 337, and 449
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Area Under the Concentration-Time Curve From Time Zero Until Last Sampling Time (AUCt)
Time frame: Days 1, 28,57, 85, 169, 253, 281, 309, 337, and 449
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Change From Baseline in Amyloid Beta (A-Beta) 1-40 Plasma Concentration at End of Study (Day 449)
Concentration of amino acid peptide, known as A-Beta 1-40, in plasma.
Time frame: Baseline, Day 449
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Change From Baseline in Amyloid Beta (A-Beta) 1-42 Plasma Concentration at End of Study (Day 449)
Concentration of amino acid peptide, known as A-Beta 1-42, in plasma.
Time frame: Baseline, Day 449
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Change From Baseline in Contrast Sensitivity at 9, 12, 15 Months and End of Study
Contrast sensitivity was measured using the Pelli-Robson chart at 1 meter. Participants 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, Month 9, Month 12, Month 15, and End of Study
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Change From Baseline in Critical Print Size Reading at 9, 12, 15 Months and End of Study
The critical print size is the smallest print size at which participants can read with their maximum reading speed.
Time frame: Baseline, Month 9, Month 12, Month 15, and End of Study
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Change From Baseline in Reading Acuity at 9, 12, 15 Months and End of Study
Reading Acuity was measured using the Radner reading charts and expressed in terms of logRAD (logrithmic Reading Acuity Determination).
Time frame: Baseline, Month 9, Month 12, Month 15, and End of Study
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Change From Baseline in Reading Speed at 9, 12, 15 Months and End of Study
Reading speed in the study eye was assessed using modified Bailey-Lovie word charts. Participants read the chart for 2 minutes and the number of words read correctly per minute was totaled. An increase in the number of words read correctly indicated an improvement and a decrease in the number of words read correctly indicated a worsening.
Time frame: Baseline, Month 9, Month 12, Month 15, and End of Study
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Change From Baseline in Total Amyloid Beta (A-Beta) 1-x Plasma Concentration at End of Study (Day 449)
Concentration of total amino acid peptide, known as A-Beta 1-x, in plasma.
Time frame: Baseline, Day 449
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Change From Placebo in Critical Print Size Reading at 9, 12, 15 Months and End of Study
The critical print size is the smallest print size at which participants can read with their maximum reading speed.
Time frame: Baseline, Month 9, Month 12, Month 15, and End of Study
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Change From Placebo in Reading Acuity at 9, 12, 15 Months and End of Study
Reading Acuity was measured using the Radner reading charts and expressed in terms of logRAD.
Time frame: Baseline, Month 9, Month 12, Month 15, and End of Study
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Change From Placebo in Reading Speed at 9, 12, 15 Months and End of Study
Reading speed in the study eye was assessed using modified Bailey-Lovie word charts. Participants read the chart for 2 minutes and the number of words read correctly per minute was totaled. An increase in the number of words read correctly indicated an improvement and a decrease in the number of words read correctly indicated a worsening.
Time frame: Baseline, Month 9, Month 12, Month 15, and End of Study
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Clearance at Steady State (CLss)
Steady state total body clearance equals infusion rate (zero order) divided by steady state plasma concentration of study drug (R0/Css)
Time frame: Days 1, 28,57, 85, 169, 253, 281, 309, 337, and 449
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Maximum Observed Plasma Concentration (Cmax)
Time frame: Days 1, 28,57, 85, 169, 253, 281, 309, 337, and 449
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Mean Best Corrected Visual Acuity (BCVA) at 9, 12, 15 Months and End of Study
BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity).
Time frame: Baseline, Month 9, Month 12, Month 15, and End of Study
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Mean Low Luminance Best Corrected Visual Acuity (LL-BCVA) at 9, 12, 15 Months and End of Study
LL-BCVA is the measure of visual acuity under low light conditions.
Time frame: Baseline, Month 9, Month 12, Month 15, and End of Study
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Minimum Observed Plasma Trough Concentration (Cmin)
Time frame: Days 1, 28,57, 85, 169, 253, 281, 309, 337, and 449
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Number of Participants With Abnormal Change From Baseline in Vital Signs
Vital sign assessments include: supine systolic and diastolic blood pressure, pulse rate and body temperature.
Time frame: Screening, Days 28, 57, 85, 113, 141, and 169
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Number of Participants With Clinically Significant Treatment-Emergent Electrocardiogram (ECG) Findings
Clinically significant ECG findings include: corrected QT (QTc) \> 450 msec, QTc \>500 msec, change in QTc between 30 and 60 msec, change in QTc greater than or equal to 60 msec.
Time frame: Days 28, 57, 85, 113 and 169
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Number of Participants With Positive Anti-Drug Antibody (ADA)
The number of participants with positive ADA was to be summarized for each treatment arm.
Time frame: Day 57 and Day 169
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) According to Seriousness
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Seriousness of an AE was assessed under the criteria of serious adverse event (SAE). An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time frame: Days 28, 57, 85, 113, 141 and 169
Population: The safety analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04382923 2.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) According to Seriousness | AE | 2 Participants |
| PF-04382923 2.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) According to Seriousness | SAE | 1 Participants |
| PF-04382923 7.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) According to Seriousness | SAE | 0 Participants |
| PF-04382923 7.5 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) According to Seriousness | AE | 0 Participants |
| PF-04382923 15.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) According to Seriousness | AE | 1 Participants |
| PF-04382923 15.0 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) According to Seriousness | SAE | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) According to Seriousness | AE | 1 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) According to Seriousness | SAE | 0 Participants |
Secondary
Number of Participants With Treatment-Emergent Laboratory Abnormalities
Laboratory assessments include: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid albumin, total protein); coagulation assessments.
Time frame: Day 85 and Day 169
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Number of Participants With Treatment-Related TEAEs
An AE was an untoward medical occurrence in a participant who received study drug without regard to causal relationship. An investigator's relationship assessment is the determination of whether there exists a reasonable possibility that the investigational product caused or contributed to an AE.
Time frame: Days 28, 57, 85, 113, 141 and 169
Population: The safety analysis set included all participants who received at least one dose of study product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-04382923 2.5 mg/kg | Number of Participants With Treatment-Related TEAEs | 0 Participants |
| PF-04382923 7.5 mg/kg | Number of Participants With Treatment-Related TEAEs | 0 Participants |
| PF-04382923 15.0 mg/kg | Number of Participants With Treatment-Related TEAEs | 0 Participants |
| Placebo | Number of Participants With Treatment-Related TEAEs | 0 Participants |
Secondary
Percentage Change From Baseline in BCVA Correct Number of Letters at 9, 12, 15 Months and End of Study
BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity).
Time frame: Baseline, Month 9, Month 12, Month 15, and End of Study
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Percentage Change From Baseline in BCVA Correct Number of Lines at Months 9, 12, 15 Months and End of Study
BCVA is measured using an eye chart and is reported as the number of lines read correctly in the study eye. The lower the number of lines read correctly on the eye chart, the worse the vision (or visual acuity).
Time frame: Baseline, Month 9, Month 12, Month 15, and End of Study
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Percentage Change From Baseline in Contrast Sensitivity at 9, 12, 15 Months and End of Study
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, Month 9, Month 12, Month 15, and End of Study
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Percentage Change From Baseline in LL-BCVA Correct Number of Letters at 9, 12, 15 Months and End of Study
LL-BCVA is the measure of visual acuity under low light conditions.
Time frame: Baseline, Month 9, Month 12, Month 15, and End of Study
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Percentage Change From Baseline in LL-BCVA Correct Number of Lines at 9, 12, 15 Months and End of Study
LL-BCVA is the measure of visual acuity under low light conditions.
Time frame: Baseline, Month 9, Month 12, Month 15, and End of Study
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Percentage Change From Baseline in Reading Acuity at 9, 12, 15 Months and End of Study
Reading Acuity was measured using the Radner reading charts and expressed in terms of logRAD.
Time frame: Baseline, Month 9, Month 12, Month 15, and End of Study
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Percentage Change From Baseline in Reading Speed at 9, 12, 15 Months and End of Study
Reading speed in the study eye was assessed using modified Bailey-Lovie word charts. Participants read the chart for 2 minutes and the number of words read correctly per minute was totaled. An increase in the number of words read correctly indicated an improvement and a decrease in the number of words read correctly indicated a worsening.
Time frame: Baseline, Month 9, Month 12, Month 15, and End of Study
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).
Secondary
Plasma Population PK Parameters
Population PK parameters were to be evaluated for Cmax, AUCt, Cmin, CLss, and Rac for AUCt between the first and last (11th) doses.
Time frame: Days 1, 28, 57, 85, 169, 253, 281, 309, 337 and 449
Population: Analysis was not performed due to early study termination. As only 10 participants enrolled at the time of termination, there were not enough subjects or data to perform meaningful analyses (8 were assigned to active drug \[1 was not dosed and there was notable variability on how many doses were received by the other 7\]; 2 were assigned to placebo).