PCV, Polypoidal Choroidal Vasculopathy
Conditions
Keywords
PEARL2, PCV, Polypoidal Choroidal Vasculopathy
Brief summary
This is a 24-month study of ranibizumab (2.0 mg and 1.0 mg) in subjects with polypoidal choroidal vasculopathy as diagnosed by fluorescein/indocyanine green (FA/ICG) angiography.
Interventions
DRUGhigh-dose ranibizumab
20mg ranibizumab vials, 0.05ml injected intravitreally, monthly
DRUGranibizumab
3 mg ranibizumab, liquid, vials, 0.1ml injected intravitreally monthly
Sponsors
Genentech, Inc.
Hawaii Pacific Health
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
25 Years to 95 Years
Healthy volunteers
No
Inclusion criteria
* Ability to provide written informed consent and comply with study assessments for the full duration of the study * Age \> 25 years * Polypoidal choroidal vasculopathy as noted on fluorescein and ICG angiography: active leakage, active bleeding or recent decrease in vision * BCVA using ETDRS of 20/32 to 20/400
Exclusion criteria
* Any history of previous vitrectomy * Any prior treatment with verteporfin photodynamic therapy in the study eye. * Previous cataract surgery within the preceding 2 months of Day 0 * Active intraocular inflammation in the study eye * Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye * A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure, cardiovascular disease) * Participation in an investigational trial within 30 days of randomization that involved treatment with any drug that has not received regulatory approval at the time of study entry. * Prior anti-vascular endothelial growth factor (VEGF) (Macugen, Avastin, Lucentis) in the study eye prior within 30 days prior to enrollment in this study * Known allergy to any component of the study drug * Blood pressure \>180/110 (systolic above 180 or diastolic above 110) If blood pressure if brought below 180/110 by anti-hypertensive treatment, the patient can become eligible. * Major surgery within 28 days prior to randomization or major surgery planned within the next 12 months. Major surgery is defined as a surgical procedure that is more extensive than needle biopsy/aspiration placement of a central venous access device, removal/biopsy of a skin lesion, or placement of a peripheral venous catheter. * Myocardial infraction, other cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 6 months prior to randomization. * Systemic anti-VEGF or pro-VEGF treatment within 3 months prior to randomization. * History of recurrent significant infections or bacterial infections * Pregnancy (positive pregnancy test) or lactation * Premenopausal women not using adequate contraception. The following are considered effective means of contraception, surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicide gel, an intra uterine device (IUD), or contraceptive hormone implant or patch * Prior enrollment in the study * Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated * Participation in another simultaneous medical investigation or trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| BCVA | From Baseline to Month 12 | Mean change in best corrected visual acuity (BCVA), as assessed by the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) eye chart at a starting test distance of 4 meters from Baseline to Month 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Systemic AEs | Monthly | Incidence and severity of other adverse events, as identified by physical examination, subject reporting, and changes in vital signs |
| BCVA | at Baseline, Day 14, Month 1, Month 3, Month 6, Month 9 , Month 12, Month 15, Month 18, Month 21 and Month 24 | Best corrected visual acuity (BCVA), as assessed by the number of letters read correctly on the ETDRS eye chart at a starting test distance of 4 meters, at Baseline, Day 14, Month 1, Month 3, Month 6, Month 9 , Month 12, Month 15, Month 18, Month 21 and Month 24 |
| Ocular Adverse Events (AE) | Monthly | Incidence and severity of ocular adverse events, as identified by eye examination (including visual acuity testing) |
| PCV Anatomic Changes | Baseline, Months 6, 12, 24 | Decrease and/or resolution in the branching vascular network of the PCV complex as measured by mean size of the branched vascular network (BVN) on ICG and fluorescein angiography Decrease and/or resolution of the polyps of the PCV complex as measured on ICG and fluorescein angiography |
| Fundus Clinical Findings | Baseline, Months 6, 12, 24 | Decrease in subretinal hemorrhage or exudates as measured by mean size as noted on fundus photography and clinic exam |
| Macular Edema | Baseline, Day 14, Month 1-24 | Optical Coherence Tomography (OCT) central macular and peripapillary thickness |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 24 months of monthly, intravitreal injections of ranibizumab 1.0mg
ranibizumab: 1 mg/0.1 ml ranibizumab, liquid, vials, 0.1ml injected intravitreally monthly | 4 |
| Cohort 2 6-months of monthly, intravitreal injections of ranibizumab 2.0mg followed by 18 months of monthly, intravitreal injections of ranibizumab 1.0mg
high-dose ranibizumab: 2.0mg/0.05ml ranibizumab, 0.05ml injected intravitreally, monthly
ranibizumab: 1 mg/0.1 ml ranibizumab, liquid, vials, 0.1ml injected intravitreally monthly | 2 |
| Cohort 3 12 monthly, intravitreal injections of 2.0mg ranibizumab followed by 12 monthly, intravitreal injections of 1.0mg ranibizumab
high-dose ranibizumab: 2.0mg/0.05ml ranibizumab, 0.05ml injected intravitreally, monthly
ranibizumab: 1 mg/0.1 ml ranibizumab, liquid, vials, 0.1ml injected intravitreally monthly | 15 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Cohort 3 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 1 Participants | 13 Participants | 17 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Age, Continuous | 75.75 years STANDARD_DEVIATION 13.72 | 71.00 years STANDARD_DEVIATION 19.8 | 77.47 years STANDARD_DEVIATION 8.37 | 77.17 years STANDARD_DEVIATION 2.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 2 Participants | 15 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 4 participants | 2 participants | 15 participants | 21 participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 5 Participants | 7 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 10 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 4 | 1 / 3 | 7 / 15 |
| serious Total, serious adverse events | 1 / 4 | 0 / 2 | 0 / 15 |
Outcome results
Primary
BCVA
Mean change in best corrected visual acuity (BCVA), as assessed by the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) eye chart at a starting test distance of 4 meters from Baseline to Month 12.
Time frame: From Baseline to Month 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | BCVA | -3.50 number of letters read correctly | Standard Deviation 21.52 |
| Cohort 2 | BCVA | 29.50 number of letters read correctly | Standard Deviation 24.75 |
| Cohort 3 | BCVA | 8.60 number of letters read correctly | Standard Deviation 12.57 |
Primary
BCVA
Mean change in best corrected visual acuity (BCVA), as assessed by the number of letters read correctly on the ETDRS eye chart at a starting test distance of 4 meters from Baseline to Month 24
Time frame: Baseline to M24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | BCVA | -5.75 number of letters read correctly | Standard Deviation 24.58 |
| Cohort 2 | BCVA | 23.5 number of letters read correctly | Standard Deviation 44.54 |
| Cohort 3 | BCVA | 5.13 number of letters read correctly | Standard Deviation 15.98 |
Secondary
BCVA
Best corrected visual acuity (BCVA), as assessed by the number of letters read correctly on the ETDRS eye chart at a starting test distance of 4 meters, at Baseline, Day 14, Month 1, Month 3, Month 6, Month 9 , Month 12, Month 15, Month 18, Month 21 and Month 24
Time frame: at Baseline, Day 14, Month 1, Month 3, Month 6, Month 9 , Month 12, Month 15, Month 18, Month 21 and Month 24
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | BCVA | Month 15 | 48.00 number of letters read correctly | Standard Deviation 34.97 |
| Cohort 1 | BCVA | Month 3 | 48.50 number of letters read correctly | Standard Deviation 32.6 |
| Cohort 1 | BCVA | Month 21 | 50.00 number of letters read correctly | Standard Deviation 33.34 |
| Cohort 1 | BCVA | Month 9 | 51.75 number of letters read correctly | Standard Deviation 32.9 |
| Cohort 1 | BCVA | Month 6 | 47.50 number of letters read correctly | Standard Deviation 31.65 |
| Cohort 1 | BCVA | Month 12 | 51.50 number of letters read correctly | Standard Deviation 33.16 |
| Cohort 1 | BCVA | Day 14 | 52.00 number of letters read correctly | Standard Deviation 18.92 |
| Cohort 1 | BCVA | Baseline | 55.00 number of letters read correctly | Standard Deviation 19.06 |
| Cohort 1 | BCVA | Month 18 | 48.00 number of letters read correctly | Standard Deviation 32.38 |
| Cohort 1 | BCVA | Month 1 | 47.00 number of letters read correctly | Standard Deviation 27.83 |
| Cohort 1 | BCVA | Month 24 | 49.25 number of letters read correctly | Standard Deviation 31.92 |
| Cohort 2 | BCVA | Month 6 | 82.50 number of letters read correctly | Standard Deviation 4.95 |
| Cohort 2 | BCVA | Month 12 | 79.50 number of letters read correctly | Standard Deviation 3.54 |
| Cohort 2 | BCVA | Baseline | 50.00 number of letters read correctly | Standard Deviation 28.28 |
| Cohort 2 | BCVA | Day 14 | 52.50 number of letters read correctly | Standard Deviation 24.75 |
| Cohort 2 | BCVA | Month 1 | 70.00 number of letters read correctly | Standard Deviation 8.49 |
| Cohort 2 | BCVA | Month 3 | 78.50 number of letters read correctly | Standard Deviation 6.36 |
| Cohort 2 | BCVA | Month 9 | 72.50 number of letters read correctly | Standard Deviation 2.12 |
| Cohort 2 | BCVA | Month 15 | 80.50 number of letters read correctly | Standard Deviation 0.71 |
| Cohort 2 | BCVA | Month 18 | 83.00 number of letters read correctly | Standard Deviation 4.24 |
| Cohort 2 | BCVA | Month 21 | 67.50 number of letters read correctly | Standard Deviation 9.19 |
| Cohort 2 | BCVA | Month 24 | 73.50 number of letters read correctly | Standard Deviation 16.26 |
| Cohort 3 | BCVA | Month 21 | 68.533 number of letters read correctly | Standard Deviation 12.14 |
| Cohort 3 | BCVA | Month 15 | 70.80 number of letters read correctly | Standard Deviation 10.35 |
| Cohort 3 | BCVA | Day 14 | 64.07 number of letters read correctly | Standard Deviation 18.47 |
| Cohort 3 | BCVA | Month 12 | 71.40 number of letters read correctly | Standard Deviation 10.66 |
| Cohort 3 | BCVA | Month 18 | 69.93 number of letters read correctly | Standard Deviation 10.91 |
| Cohort 3 | BCVA | Baseline | 62.80 number of letters read correctly | Standard Deviation 17.11 |
| Cohort 3 | BCVA | Month 6 | 69.33 number of letters read correctly | Standard Deviation 15.43 |
| Cohort 3 | BCVA | Month 3 | 69.13 number of letters read correctly | Standard Deviation 18.19 |
| Cohort 3 | BCVA | Month 24 | 67.93 number of letters read correctly | Standard Deviation 13.08 |
| Cohort 3 | BCVA | Month 9 | 71.67 number of letters read correctly | Standard Deviation 9.64 |
| Cohort 3 | BCVA | Month 1 | 65.67 number of letters read correctly | Standard Deviation 16.6 |
Secondary
Fundus Clinical Findings
Decrease in subretinal hemorrhage or exudates as measured by mean size as noted on fundus photography and clinic exam
Time frame: Baseline, Months 6, 12, 24
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Fundus Clinical Findings | Month 24 | 1 Participants with Fundus Findings |
| Cohort 1 | Fundus Clinical Findings | Month 6 | 1 Participants with Fundus Findings |
| Cohort 1 | Fundus Clinical Findings | Month 12 | 1 Participants with Fundus Findings |
| Cohort 1 | Fundus Clinical Findings | Baseline | 0 Participants with Fundus Findings |
| Cohort 2 | Fundus Clinical Findings | Month 12 | 2 Participants with Fundus Findings |
| Cohort 2 | Fundus Clinical Findings | Month 24 | 2 Participants with Fundus Findings |
| Cohort 2 | Fundus Clinical Findings | Baseline | 0 Participants with Fundus Findings |
| Cohort 2 | Fundus Clinical Findings | Month 6 | 2 Participants with Fundus Findings |
| Cohort 3 | Fundus Clinical Findings | Month 24 | 8 Participants with Fundus Findings |
| Cohort 3 | Fundus Clinical Findings | Month 6 | 8 Participants with Fundus Findings |
| Cohort 3 | Fundus Clinical Findings | Month 12 | 8 Participants with Fundus Findings |
| Cohort 3 | Fundus Clinical Findings | Baseline | 0 Participants with Fundus Findings |
Secondary
Macular Edema
Optical Coherence Tomography (OCT) central macular and peripapillary thickness
Time frame: Baseline, Day 14, Month 1-24
Population: Patient in Cohort 2 missed several visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Macular Edema | Month 17 | 219.75 microns | Standard Deviation 22.51 |
| Cohort 1 | Macular Edema | Month 3 | 244.25 microns | Standard Deviation 12.18 |
| Cohort 1 | Macular Edema | Day 14 | 265.00 microns | Standard Deviation 69.58 |
| Cohort 1 | Macular Edema | Month 21 | 214 microns | Standard Deviation 23.83 |
| Cohort 1 | Macular Edema | Month 6 | 232.75 microns | Standard Deviation 24.7 |
| Cohort 1 | Macular Edema | Month 1 | 276.25 microns | Standard Deviation 22.56 |
| Cohort 1 | Macular Edema | Month 19 | 218.33 microns | Standard Deviation 24.54 |
| Cohort 1 | Macular Edema | Month 5 | 245.75 microns | Standard Deviation 20.95 |
| Cohort 1 | Macular Edema | Month 2 | 252.50 microns | Standard Deviation 15.46 |
| Cohort 1 | Macular Edema | Month 22 | 211.5 microns | Standard Deviation 27.01 |
| Cohort 1 | Macular Edema | Month 7 | 234.00 microns | Standard Deviation 19.29 |
| Cohort 1 | Macular Edema | Month 11 | 223.25 microns | Standard Deviation 19.87 |
| Cohort 1 | Macular Edema | Month 18 | 237075 microns | Standard Deviation 57.72 |
| Cohort 1 | Macular Edema | Month 23 | 209.25 microns | Standard Deviation 28.92 |
| Cohort 1 | Macular Edema | Month 12 | 225.00 microns | Standard Deviation 18.22 |
| Cohort 1 | Macular Edema | Month 10 | 217.00 microns | Standard Deviation 7 |
| Cohort 1 | Macular Edema | Month 4 | 238.25 microns | Standard Deviation 16.6 |
| Cohort 1 | Macular Edema | Month 13 | 221.67 microns | Standard Deviation 17.16 |
| Cohort 1 | Macular Edema | Month 20 | 216.00 microns | Standard Deviation 25.97 |
| Cohort 1 | Macular Edema | Month 8 | 233.00 microns | Standard Deviation 16.79 |
| Cohort 1 | Macular Edema | Month 14 | 244.50 microns | Standard Deviation 34.32 |
| Cohort 1 | Macular Edema | Month 24 | 214.25 microns | Standard Deviation 22.65 |
| Cohort 1 | Macular Edema | Month 9 | 229.75 microns | Standard Deviation 17.93 |
| Cohort 1 | Macular Edema | Month 15 | 220.25 microns | Standard Deviation 17.56 |
| Cohort 1 | Macular Edema | Baseline | 370.25 microns | Standard Deviation 148.14 |
| Cohort 1 | Macular Edema | Month 16 | 220.25 microns | Standard Deviation 20.71 |
| Cohort 2 | Macular Edema | Month 4 | 224.00 microns | Standard Deviation 15.56 |
| Cohort 2 | Macular Edema | Month 16 | 227.5 microns | Standard Deviation 10.61 |
| Cohort 2 | Macular Edema | Month 17 | 238 microns | — |
| Cohort 2 | Macular Edema | Month 9 | 222.50 microns | Standard Deviation 9.19 |
| Cohort 2 | Macular Edema | Month 18 | 230.50 microns | Standard Deviation 14.85 |
| Cohort 2 | Macular Edema | Month 3 | 220.00 microns | Standard Deviation 12.73 |
| Cohort 2 | Macular Edema | Month 19 | 231.5 microns | Standard Deviation 9.19 |
| Cohort 2 | Macular Edema | Month 20 | 237 microns | — |
| Cohort 2 | Macular Edema | Month 10 | 233.00 microns | — |
| Cohort 2 | Macular Edema | Month 21 | 218.5 microns | Standard Deviation 17.68 |
| Cohort 2 | Macular Edema | Month 22 | 239.50 microns | Standard Deviation 12.02 |
| Cohort 2 | Macular Edema | Month 23 | 244.50 microns | Standard Deviation 21.92 |
| Cohort 2 | Macular Edema | Month 5 | 224.50 microns | Standard Deviation 12.02 |
| Cohort 2 | Macular Edema | Month 24 | 231.00 microns | Standard Deviation 1.41 |
| Cohort 2 | Macular Edema | Baseline | 347.50 microns | Standard Deviation 194.45 |
| Cohort 2 | Macular Edema | Day 14 | 251.00 microns | Standard Deviation 65.05 |
| Cohort 2 | Macular Edema | Month 1 | 228.00 microns | Standard Deviation 24.04 |
| Cohort 2 | Macular Edema | Month 6 | 224.00 microns | Standard Deviation 9.9 |
| Cohort 2 | Macular Edema | Month 2 | 218.50 microns | Standard Deviation 14.85 |
| Cohort 2 | Macular Edema | Month 11 | 228.50 microns | Standard Deviation 12.02 |
| Cohort 2 | Macular Edema | Month 7 | 223.00 microns | Standard Deviation 12.73 |
| Cohort 2 | Macular Edema | Month 12 | 226.50 microns | Standard Deviation 9.19 |
| Cohort 2 | Macular Edema | Month 13 | 222.00 microns | Standard Deviation 15.56 |
| Cohort 2 | Macular Edema | Month 14 | 223.00 microns | Standard Deviation 15.56 |
| Cohort 2 | Macular Edema | Month 8 | 232.00 microns | — |
| Cohort 2 | Macular Edema | Month 15 | 228.50 microns | Standard Deviation 12.02 |
| Cohort 3 | Macular Edema | Month 14 | 211.27 microns | Standard Deviation 32.19 |
| Cohort 3 | Macular Edema | Month 3 | 216.29 microns | Standard Deviation 33.5 |
| Cohort 3 | Macular Edema | Month 4 | 214.36 microns | Standard Deviation 26.33 |
| Cohort 3 | Macular Edema | Month 5 | 215.53 microns | Standard Deviation 40.77 |
| Cohort 3 | Macular Edema | Month 7 | 215.67 microns | Standard Deviation 30.9 |
| Cohort 3 | Macular Edema | Month 8 | 209.67 microns | Standard Deviation 34.01 |
| Cohort 3 | Macular Edema | Month 9 | 203.29 microns | Standard Deviation 31.04 |
| Cohort 3 | Macular Edema | Month 10 | 215.80 microns | Standard Deviation 30.05 |
| Cohort 3 | Macular Edema | Month 22 | 212.13 microns | Standard Deviation 36.5 |
| Cohort 3 | Macular Edema | Baseline | 282.47 microns | Standard Deviation 44.55 |
| Cohort 3 | Macular Edema | Day 14 | 235.07 microns | Standard Deviation 35.45 |
| Cohort 3 | Macular Edema | Month 1 | 216.67 microns | Standard Deviation 33.47 |
| Cohort 3 | Macular Edema | Month 6 | 211.47 microns | Standard Deviation 36.32 |
| Cohort 3 | Macular Edema | Month 11 | 206.93 microns | Standard Deviation 32.04 |
| Cohort 3 | Macular Edema | Month 12 | 207.80 microns | Standard Deviation 29.33 |
| Cohort 3 | Macular Edema | Month 13 | 209.71 microns | Standard Deviation 39.34 |
| Cohort 3 | Macular Edema | Month 2 | 212.20 microns | Standard Deviation 33.06 |
| Cohort 3 | Macular Edema | Month 15 | 210.20 microns | Standard Deviation 29.27 |
| Cohort 3 | Macular Edema | Month 16 | 212.00 microns | Standard Deviation 31.18 |
| Cohort 3 | Macular Edema | Month 17 | 209.29 microns | Standard Deviation 31.94 |
| Cohort 3 | Macular Edema | Month 18 | 213.67 microns | Standard Deviation 32.73 |
| Cohort 3 | Macular Edema | Month 19 | 217.08 microns | Standard Deviation 41.69 |
| Cohort 3 | Macular Edema | Month 20 | 217.93 microns | Standard Deviation 36.11 |
| Cohort 3 | Macular Edema | Month 21 | 209.07 microns | Standard Deviation 32.46 |
| Cohort 3 | Macular Edema | Month 23 | 216.08 microns | Standard Deviation 33.64 |
| Cohort 3 | Macular Edema | Month 24 | 215.27 microns | Standard Deviation 38.83 |
Secondary
Ocular Adverse Events (AE)
Incidence and severity of ocular adverse events, as identified by eye examination (including visual acuity testing)
Time frame: Monthly
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Ocular Adverse Events (AE) | 0 Ocular adverse events |
| Cohort 2 | Ocular Adverse Events (AE) | 0 Ocular adverse events |
| Cohort 3 | Ocular Adverse Events (AE) | 0 Ocular adverse events |
Secondary
PCV Anatomic Changes
Decrease and/or resolution in the branching vascular network of the PCV complex as measured by mean size of the branched vascular network (BVN) on ICG and fluorescein angiography Decrease and/or resolution of the polyps of the PCV complex as measured on ICG and fluorescein angiography
Time frame: Baseline, Months 6, 12, 24
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | PCV Anatomic Changes | Month 24 (PCV) | 4 Participants with PCV Anatomic Changes |
| Cohort 1 | PCV Anatomic Changes | Month 12 (PCV) | 2 Participants with PCV Anatomic Changes |
| Cohort 1 | PCV Anatomic Changes | Month 24 (BVN) | 1 Participants with PCV Anatomic Changes |
| Cohort 1 | PCV Anatomic Changes | Month 12 (BVN) | 2 Participants with PCV Anatomic Changes |
| Cohort 1 | PCV Anatomic Changes | Baseline (BVN) | 0 Participants with PCV Anatomic Changes |
| Cohort 1 | PCV Anatomic Changes | Baseline (PCV) | 0 Participants with PCV Anatomic Changes |
| Cohort 1 | PCV Anatomic Changes | Month 6 (BVN) | 0 Participants with PCV Anatomic Changes |
| Cohort 1 | PCV Anatomic Changes | Month 6 (PCV) | 3 Participants with PCV Anatomic Changes |
| Cohort 2 | PCV Anatomic Changes | Baseline (BVN) | 0 Participants with PCV Anatomic Changes |
| Cohort 2 | PCV Anatomic Changes | Month 6 (PCV) | 2 Participants with PCV Anatomic Changes |
| Cohort 2 | PCV Anatomic Changes | Month 12 (PCV) | 1 Participants with PCV Anatomic Changes |
| Cohort 2 | PCV Anatomic Changes | Month 24 (PCV) | 2 Participants with PCV Anatomic Changes |
| Cohort 2 | PCV Anatomic Changes | Month 6 (BVN) | 0 Participants with PCV Anatomic Changes |
| Cohort 2 | PCV Anatomic Changes | Month 12 (BVN) | 0 Participants with PCV Anatomic Changes |
| Cohort 2 | PCV Anatomic Changes | Month 24 (BVN) | 0 Participants with PCV Anatomic Changes |
| Cohort 2 | PCV Anatomic Changes | Baseline (PCV) | 0 Participants with PCV Anatomic Changes |
| Cohort 3 | PCV Anatomic Changes | Month 24 (PCV) | 9 Participants with PCV Anatomic Changes |
| Cohort 3 | PCV Anatomic Changes | Baseline (BVN) | 0 Participants with PCV Anatomic Changes |
| Cohort 3 | PCV Anatomic Changes | Month 12 (BVN) | 1 Participants with PCV Anatomic Changes |
| Cohort 3 | PCV Anatomic Changes | Month 24 (BVN) | 2 Participants with PCV Anatomic Changes |
| Cohort 3 | PCV Anatomic Changes | Baseline (PCV) | 0 Participants with PCV Anatomic Changes |
| Cohort 3 | PCV Anatomic Changes | Month 6 (PCV) | 8 Participants with PCV Anatomic Changes |
| Cohort 3 | PCV Anatomic Changes | Month 12 (PCV) | 8 Participants with PCV Anatomic Changes |
| Cohort 3 | PCV Anatomic Changes | Month 6 (BVN) | 1 Participants with PCV Anatomic Changes |
Secondary
Systemic AEs
Incidence and severity of other adverse events, as identified by physical examination, subject reporting, and changes in vital signs
Time frame: Monthly
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Systemic AEs | 0 Number of Participants with Systemic AEs |
| Cohort 2 | Systemic AEs | 0 Number of Participants with Systemic AEs |
| Cohort 3 | Systemic AEs | 1 Number of Participants with Systemic AEs |