Retinopathy of Prematurity
Conditions
Keywords
intravitreal ranibizumab, laser ablation therapy, retinopathy of prematurity, preterm infants, RAINBOW
Brief summary
The purpose of this study was to determine if intravitreal ranibizumab is superior to laser ablation therapy in the treatment of retinopathy of prematurity (ROP).
Detailed description
The study consisted of a screening period (screening and randomization could occur up to 3 days before the administration of the first investigational treatment), followed by a treatment and follow-up period (Day 1 to Day 169).
Interventions
DRUGRanibizumab
Administered as an intravitreal injection
PROCEDURELaser therapy
Transpupillary diode or frequency-doubled yttrium aluminum garnet (YAG) laser ablative therapy, following anesthesia or sedation
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* preterm infants with a birth weight of less than 1500 g * bilateral ROP with one of the following retinal findings in each eye: Zone I, stage 1+, 2+, 3 or 3+ disease, or Zone II, stage 3+ disease, or Aggressive posterior retinopathy of prematurity (AP-ROP)
Exclusion criteria
* ROP disease characteristic in either eye other than that listed above at the time of the first investigational treatment * A history of hypersensitivity (either the patient or the mother) to any of the investigational treatments or to drugs of similar chemical classes * Had received any previous surgical or nonsurgical treatment for ROP (e.g., ablative laser therapy or cryotherapy, vitrectomy) * Had been previously exposed to any intravitreal or systemic anti-VEGF agent (either the patient or the mother during this child's pregnancy) * Had used (either the patient or the mother) other investigational drugs as part of another clinical study (other than vitamins and minerals) within 30 days or within 5 half-lives of the other investigational drug, whichever was longer * Had ocular structural abnormalities that were assessed by the Investigator to have had a clinically significant impact on study assessments * Had active ocular infection within 5 days before or on the day of first investigational treatment * Had a history of hydrocephalus requiring treatment * Had a history of any other neurological conditions that are assessed by the Investigator to have a significant risk of severe impact on visual function * Had any other medical conditions or clinically significant comorbidities or personal circumstances that were assessed by the Investigator to have a clinically relevant impact on study participation, any of the study procedures, or on efficacy assessments (e.g., poor life expectancy, pupil not able to be adequately dilated, unable to comply with the visit schedule)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Absence of Active ROP and Absence of Unfavorable Structural Outcomes in Both Eyes at Week 24 | Week 24 | To achieve this outcome, patients must fulfill all the following criteria, 1) survival, 2) no intervention with a second modality for ROP, 3) absence of active ROP and 4) absence of unfavorable structural outcome. Retinopathy of prematurity (ROP) is a pathologic process that occurs in the incompletely vascularized, developing retina of low birth-weight preterm neonates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing an Event, From the First Study Treatment to the Last Study Visit | Day 1 (after initiation of study treatment) up to study exit (Day 169) | An event was defined as death, treatment switch, or the first occurrence of unfavorable structural outcomes in either eye. Only descriptive analysis done. |
| Percentage of Participants Having Recurrent ROP and Receiving Any Post-baseline Intervention at or Before Week 24 | Week 24 | Recurrence of ROP is defined as subjects receiving any post-baseline intervention in either eye at or before 24 weeks (ranibizumab re-treatment or switch to laser in the ranibizumab groups, switch to ranibizumab treatment in the laser group). Zone I consists of a circle, the radius of which extends from the center of the optic disc to twice the distance from the center of the optic disc to the center of the macula. Zone II extends centrifugally from the edge of zone I to the nasal ora serrata. Only descriptive analysis done. |
| Percent of Participants With Ocular Adverse Events by Primary System Organ (SOCs) at Week 24 | Week 24 | Percent of Participants with Ocular Adverse Events regardless of Study Treatment and Procedure Relationship by Primary System Organ (SOCs) reported categorically (Mild, Moderate, Severe) 24 weeks after the first study treatment. Only descriptive analysis done. |
| Mean Change in Ranibizumab Concentration in Pharmacokinetic Serum Samples Over Time at Day 1, Day 15 and Day 29 | Day 1 (Baseline), Day 15 and Day 29 | Blood samples for the determination of ranibizumab concentrations were collected in the Ranibizumab treatment arms only at the following time points: within 24 hours after the first administration of ranibizumab, at Day 15 and at Day 29. Only descriptive analysis done. |
| Mean Change in Vascular Endothelial Growth Factor (VEGF) Levels Over Time at Day 1, Day 15 and Day 29 | Day 1 (Baseline), Day 15 and Day 29 | Blood samples for the determination of systemic VEGF levels were collected at the following time points: before the first investigational treatment, at Day 15 and at Day 29. Only descriptive analysis done. |
| Percentage of Participants Requiring Interventions With a Second Modality for ROP at Week 24 | Week 24 | Intervention for ROP in either eye at or before the 24-week assessment visit with a treatment modality other than the modality of the first study treatment. Only descriptive analysis done. |
| Percent of Participants With Non-Ocular Adverse Events by Primary System Organ (SOCs) at Week 24 | Week 24 | Percent of Participants with Non-Ocular Adverse Events regardless of Study Treatment and Procedure Relationship by Primary System Organ (SOCs) reported categorically (Mild, Moderate, Severe) 24 weeks after the first study treatment. Only descriptive analysis done. |
| Mean Change From Baseline in Vital Signs (Body Length, Head Circumference and Knee to Heel Length) at Day 85 and Day 169 | Baseline, Day 85, Day 169 | Body Length, Head Circumference and Knee to Heel Length were assessed. Only descriptive analysis done. |
| Mean Change From Baseline in Vital Signs (Weight) at Day 85 and Day 169 | Baseline, Day 85, Day 169 | Body weight was measured. Only descriptive analysis done. |
| Mean Change From Baseline in Vital Signs (Sitting Blood Pressure) at Day 85 and Day 169 | Baseline, Day 85, Day 169 | Blood Pressure measurements were not required by the protocol. Instead, the most recent Systolic and Diastolic Blood Pressure expressed in millimeters of mercury (mmHg) measured as part of the routine clinical care were used. Only descriptive analysis done. |
| Total Number of Ranibizumab Injections Received at Week 24 | Week 24 | Patients randomized to receive Ranibizumab 0.1 mg or 0.2 mg received a single dose of intravitreal Ranibizumab to each eye on Day 1 (Baseline). Only descriptive analysis done. |
Countries
Austria, Belgium, Croatia, Czechia, Denmark, Egypt, Estonia, France, Germany, Greece, Hungary, India, Italy, Japan, Lithuania, Malaysia, Mexico, Poland, Romania, Russia, Saudi Arabia, Slovakia, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
This study was conducted in 87 sites: Austria(2), Belgium(2), Croatia(2), Czech Republic(3), Denmark(1), Egypt(1), Estonia(1), France(2), Germany(2), Greece(3), Hungary(2), India(6), Italy(4), Japan(17), Lithuania(1), Malaysia(2), Mexico(1), Poland(2), Romania(3), Russia(5), Saudi Arabia(1), Slovakia(1), Taiwan(2), Turkey(6), UK(3) and USA(12).
Pre-assignment details
One patient was discontinued prior to receiving any study treatment and was later re-randomized; this patient is counted twice in the Randomized Set (FAS) (225). The number of unique participants randomized in the study is 224.
Participants by arm
| Arm | Count |
|---|---|
| Ranibizumab 0.2 mg 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required | 74 |
| Ranibizumab 0.1 mg 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required | 77 |
| Laser Therapy Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed | 74 |
| Total | 225 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Follow-Up Phase (up to Day 169) | Adverse Event | 1 | 0 | 0 |
| Follow-Up Phase (up to Day 169) | Death | 4 | 4 | 4 |
| Follow-Up Phase (up to Day 169) | Subject/Guardian Decision | 1 | 0 | 1 |
| Follow-Up Phase (up to Day 169) | Withdrawal of Consent | 1 | 1 | 0 |
| Treatment (Day 1 - Baseline) | Adverse Event | 0 | 0 | 1 |
| Treatment (Day 1 - Baseline) | Lost to Follow-up | 0 | 0 | 1 |
| Treatment (Day 1 - Baseline) | Physician Decision | 1 | 1 | 1 |
| Treatment (Day 1 - Baseline) | Subj/Guardian Decision | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Ranibizumab 0.2 mg | Ranibizumab 0.1 mg | Laser Therapy | Total |
|---|---|---|---|---|
| Age, Continuous | 25.8 Weeks STANDARD_DEVIATION 2.25 | 26.5 Weeks STANDARD_DEVIATION 2.57 | 26.2 Weeks STANDARD_DEVIATION 2.59 | 26.1 Weeks STANDARD_DEVIATION 2.48 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 27 Participants | 22 Participants | 23 Participants | 72 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 6 Participants | 3 Participants | 13 Participants |
| Race (NIH/OMB) White | 43 Participants | 45 Participants | 45 Participants | 133 Participants |
| Sex: Female, Male Female | 41 Participants | 40 Participants | 37 Participants | 118 Participants |
| Sex: Female, Male Male | 33 Participants | 37 Participants | 37 Participants | 107 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 73 | 4 / 76 | 4 / 69 |
| other Total, other adverse events | 43 / 73 | 47 / 76 | 37 / 69 |
| serious Total, serious adverse events | 26 / 73 | 24 / 76 | 24 / 69 |
Outcome results
Primary
Percentage of Participants With Absence of Active ROP and Absence of Unfavorable Structural Outcomes in Both Eyes at Week 24
To achieve this outcome, patients must fulfill all the following criteria, 1) survival, 2) no intervention with a second modality for ROP, 3) absence of active ROP and 4) absence of unfavorable structural outcome. Retinopathy of prematurity (ROP) is a pathologic process that occurs in the incompletely vascularized, developing retina of low birth-weight preterm neonates.
Time frame: Week 24
Population: The Full Analysis Set (FAS), which consisted of all participants with an observed value, was considered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ranibizumab 0.2 mg | Percentage of Participants With Absence of Active ROP and Absence of Unfavorable Structural Outcomes in Both Eyes at Week 24 | 80.0 Percentage of Participants |
| Ranibizumab 0.1 mg | Percentage of Participants With Absence of Active ROP and Absence of Unfavorable Structural Outcomes in Both Eyes at Week 24 | 75.0 Percentage of Participants |
| Laser Therapy | Percentage of Participants With Absence of Active ROP and Absence of Unfavorable Structural Outcomes in Both Eyes at Week 24 | 66.2 Percentage of Participants |
p-value: 0.025495% CI: [0.9932, 4.8235]Cochran-Mantel-Haenszel
Secondary
Mean Change From Baseline in Vital Signs (Body Length, Head Circumference and Knee to Heel Length) at Day 85 and Day 169
Body Length, Head Circumference and Knee to Heel Length were assessed. Only descriptive analysis done.
Time frame: Baseline, Day 85, Day 169
Population: The Safety Set was considered. Only patients with evaluable data at each time point were analyzed for that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranibizumab 0.2 mg | Mean Change From Baseline in Vital Signs (Body Length, Head Circumference and Knee to Heel Length) at Day 85 and Day 169 | Day 169 / Body Length | 18.7 centimeter (cm) | Standard Deviation 3.28 |
| Ranibizumab 0.2 mg | Mean Change From Baseline in Vital Signs (Body Length, Head Circumference and Knee to Heel Length) at Day 85 and Day 169 | Day 85 / Knee to Heel Length | 2.9 centimeter (cm) | Standard Deviation 1.9 |
| Ranibizumab 0.2 mg | Mean Change From Baseline in Vital Signs (Body Length, Head Circumference and Knee to Heel Length) at Day 85 and Day 169 | Day 85 / Body Length | 10.1 centimeter (cm) | Standard Deviation 2.59 |
| Ranibizumab 0.2 mg | Mean Change From Baseline in Vital Signs (Body Length, Head Circumference and Knee to Heel Length) at Day 85 and Day 169 | Day 85 / Head Circumference | 6.9 centimeter (cm) | Standard Deviation 1.96 |
| Ranibizumab 0.2 mg | Mean Change From Baseline in Vital Signs (Body Length, Head Circumference and Knee to Heel Length) at Day 85 and Day 169 | Day 169 / Knee to Heel Length | 5.4 centimeter (cm) | Standard Deviation 2.86 |
| Ranibizumab 0.2 mg | Mean Change From Baseline in Vital Signs (Body Length, Head Circumference and Knee to Heel Length) at Day 85 and Day 169 | Day 169 / Head Circumference | 10.4 centimeter (cm) | Standard Deviation 2.12 |
| Ranibizumab 0.1 mg | Mean Change From Baseline in Vital Signs (Body Length, Head Circumference and Knee to Heel Length) at Day 85 and Day 169 | Day 169 / Knee to Heel Length | 5.1 centimeter (cm) | Standard Deviation 2.19 |
| Ranibizumab 0.1 mg | Mean Change From Baseline in Vital Signs (Body Length, Head Circumference and Knee to Heel Length) at Day 85 and Day 169 | Day 85 / Body Length | 11.0 centimeter (cm) | Standard Deviation 3.33 |
| Ranibizumab 0.1 mg | Mean Change From Baseline in Vital Signs (Body Length, Head Circumference and Knee to Heel Length) at Day 85 and Day 169 | Day 169 / Head Circumference | 10.3 centimeter (cm) | Standard Deviation 2.56 |
| Ranibizumab 0.1 mg | Mean Change From Baseline in Vital Signs (Body Length, Head Circumference and Knee to Heel Length) at Day 85 and Day 169 | Day 169 / Body Length | 18.6 centimeter (cm) | Standard Deviation 3.66 |
| Ranibizumab 0.1 mg | Mean Change From Baseline in Vital Signs (Body Length, Head Circumference and Knee to Heel Length) at Day 85 and Day 169 | Day 85 / Head Circumference | 6.5 centimeter (cm) | Standard Deviation 2.31 |
| Ranibizumab 0.1 mg | Mean Change From Baseline in Vital Signs (Body Length, Head Circumference and Knee to Heel Length) at Day 85 and Day 169 | Day 85 / Knee to Heel Length | 3.1 centimeter (cm) | Standard Deviation 1.65 |
| Laser Therapy | Mean Change From Baseline in Vital Signs (Body Length, Head Circumference and Knee to Heel Length) at Day 85 and Day 169 | Day 85 / Knee to Heel Length | 3.1 centimeter (cm) | Standard Deviation 2.02 |
| Laser Therapy | Mean Change From Baseline in Vital Signs (Body Length, Head Circumference and Knee to Heel Length) at Day 85 and Day 169 | Day 85 / Head Circumference | 7.2 centimeter (cm) | Standard Deviation 2.13 |
| Laser Therapy | Mean Change From Baseline in Vital Signs (Body Length, Head Circumference and Knee to Heel Length) at Day 85 and Day 169 | Day 169 / Head Circumference | 10.6 centimeter (cm) | Standard Deviation 2.61 |
| Laser Therapy | Mean Change From Baseline in Vital Signs (Body Length, Head Circumference and Knee to Heel Length) at Day 85 and Day 169 | Day 169 / Body Length | 19.0 centimeter (cm) | Standard Deviation 4.5 |
| Laser Therapy | Mean Change From Baseline in Vital Signs (Body Length, Head Circumference and Knee to Heel Length) at Day 85 and Day 169 | Day 169 / Knee to Heel Length | 5.3 centimeter (cm) | Standard Deviation 2.15 |
| Laser Therapy | Mean Change From Baseline in Vital Signs (Body Length, Head Circumference and Knee to Heel Length) at Day 85 and Day 169 | Day 85 / Body Length | 11.1 centimeter (cm) | Standard Deviation 3.65 |
Secondary
Mean Change From Baseline in Vital Signs (Sitting Blood Pressure) at Day 85 and Day 169
Blood Pressure measurements were not required by the protocol. Instead, the most recent Systolic and Diastolic Blood Pressure expressed in millimeters of mercury (mmHg) measured as part of the routine clinical care were used. Only descriptive analysis done.
Time frame: Baseline, Day 85, Day 169
Population: The Safety Set was considered. Only patients with evaluable data at each time point were analyzed for that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranibizumab 0.2 mg | Mean Change From Baseline in Vital Signs (Sitting Blood Pressure) at Day 85 and Day 169 | Day 169 / Sitting Diastolic Blood Pressure | 11.5 millimeters of mercury (mmHg) | Standard Deviation 15.6 |
| Ranibizumab 0.2 mg | Mean Change From Baseline in Vital Signs (Sitting Blood Pressure) at Day 85 and Day 169 | Day 85 / Sitting Diastolic Blood Pressure | 8.1 millimeters of mercury (mmHg) | Standard Deviation 14.66 |
| Ranibizumab 0.2 mg | Mean Change From Baseline in Vital Signs (Sitting Blood Pressure) at Day 85 and Day 169 | Day 169 / Sitting Systolic Blood Pressure | 10.2 millimeters of mercury (mmHg) | Standard Deviation 16.15 |
| Ranibizumab 0.2 mg | Mean Change From Baseline in Vital Signs (Sitting Blood Pressure) at Day 85 and Day 169 | Day 85 / Sitting Systolic Blood Pressure | 6.3 millimeters of mercury (mmHg) | Standard Deviation 15.85 |
| Ranibizumab 0.1 mg | Mean Change From Baseline in Vital Signs (Sitting Blood Pressure) at Day 85 and Day 169 | Day 169 / Sitting Diastolic Blood Pressure | 11.8 millimeters of mercury (mmHg) | Standard Deviation 14.42 |
| Ranibizumab 0.1 mg | Mean Change From Baseline in Vital Signs (Sitting Blood Pressure) at Day 85 and Day 169 | Day 85 / Sitting Systolic Blood Pressure | 9.4 millimeters of mercury (mmHg) | Standard Deviation 15.73 |
| Ranibizumab 0.1 mg | Mean Change From Baseline in Vital Signs (Sitting Blood Pressure) at Day 85 and Day 169 | Day 85 / Sitting Diastolic Blood Pressure | 7.0 millimeters of mercury (mmHg) | Standard Deviation 14.25 |
| Ranibizumab 0.1 mg | Mean Change From Baseline in Vital Signs (Sitting Blood Pressure) at Day 85 and Day 169 | Day 169 / Sitting Systolic Blood Pressure | 11.2 millimeters of mercury (mmHg) | Standard Deviation 13.45 |
| Laser Therapy | Mean Change From Baseline in Vital Signs (Sitting Blood Pressure) at Day 85 and Day 169 | Day 85 / Sitting Systolic Blood Pressure | 15.5 millimeters of mercury (mmHg) | Standard Deviation 16.85 |
| Laser Therapy | Mean Change From Baseline in Vital Signs (Sitting Blood Pressure) at Day 85 and Day 169 | Day 85 / Sitting Diastolic Blood Pressure | 9.8 millimeters of mercury (mmHg) | Standard Deviation 16.95 |
| Laser Therapy | Mean Change From Baseline in Vital Signs (Sitting Blood Pressure) at Day 85 and Day 169 | Day 169 / Sitting Systolic Blood Pressure | 17.7 millimeters of mercury (mmHg) | Standard Deviation 19.35 |
| Laser Therapy | Mean Change From Baseline in Vital Signs (Sitting Blood Pressure) at Day 85 and Day 169 | Day 169 / Sitting Diastolic Blood Pressure | 14.7 millimeters of mercury (mmHg) | Standard Deviation 17.05 |
Secondary
Mean Change From Baseline in Vital Signs (Weight) at Day 85 and Day 169
Body weight was measured. Only descriptive analysis done.
Time frame: Baseline, Day 85, Day 169
Population: The Safety Set was considered. Only patients with evaluable data at each time point were analyzed for that time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranibizumab 0.2 mg | Mean Change From Baseline in Vital Signs (Weight) at Day 85 and Day 169 | Day 85 / Weight | 2198.9 gram (g) | Standard Deviation 615.68 |
| Ranibizumab 0.2 mg | Mean Change From Baseline in Vital Signs (Weight) at Day 85 and Day 169 | Day 169 / Weight | 3794.3 gram (g) | Standard Deviation 782.48 |
| Ranibizumab 0.1 mg | Mean Change From Baseline in Vital Signs (Weight) at Day 85 and Day 169 | Day 85 / Weight | 2149.9 gram (g) | Standard Deviation 754.27 |
| Ranibizumab 0.1 mg | Mean Change From Baseline in Vital Signs (Weight) at Day 85 and Day 169 | Day 169 / Weight | 3716.7 gram (g) | Standard Deviation 897.15 |
| Laser Therapy | Mean Change From Baseline in Vital Signs (Weight) at Day 85 and Day 169 | Day 85 / Weight | 2182.7 gram (g) | Standard Deviation 612.7 |
| Laser Therapy | Mean Change From Baseline in Vital Signs (Weight) at Day 85 and Day 169 | Day 169 / Weight | 3826.0 gram (g) | Standard Deviation 882.17 |
Secondary
Mean Change in Ranibizumab Concentration in Pharmacokinetic Serum Samples Over Time at Day 1, Day 15 and Day 29
Blood samples for the determination of ranibizumab concentrations were collected in the Ranibizumab treatment arms only at the following time points: within 24 hours after the first administration of ranibizumab, at Day 15 and at Day 29. Only descriptive analysis done.
Time frame: Day 1 (Baseline), Day 15 and Day 29
Population: The PK Set, which consisted of all participants with at least one valid PK concentration value, was considered.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranibizumab 0.2 mg | Mean Change in Ranibizumab Concentration in Pharmacokinetic Serum Samples Over Time at Day 1, Day 15 and Day 29 | Day 1 (Baseline) | 24700.0 picogram/milliliter (pg/mL) | Standard Deviation 52400 |
| Ranibizumab 0.2 mg | Mean Change in Ranibizumab Concentration in Pharmacokinetic Serum Samples Over Time at Day 1, Day 15 and Day 29 | Day 15 | 5830.0 picogram/milliliter (pg/mL) | Standard Deviation 4750 |
| Ranibizumab 0.2 mg | Mean Change in Ranibizumab Concentration in Pharmacokinetic Serum Samples Over Time at Day 1, Day 15 and Day 29 | Day 29 | 1810.0 picogram/milliliter (pg/mL) | Standard Deviation 2990 |
| Ranibizumab 0.1 mg | Mean Change in Ranibizumab Concentration in Pharmacokinetic Serum Samples Over Time at Day 1, Day 15 and Day 29 | Day 1 (Baseline) | 12100.0 picogram/milliliter (pg/mL) | Standard Deviation 25500 |
| Ranibizumab 0.1 mg | Mean Change in Ranibizumab Concentration in Pharmacokinetic Serum Samples Over Time at Day 1, Day 15 and Day 29 | Day 15 | 27700.0 picogram/milliliter (pg/mL) | Standard Deviation 144000 |
| Ranibizumab 0.1 mg | Mean Change in Ranibizumab Concentration in Pharmacokinetic Serum Samples Over Time at Day 1, Day 15 and Day 29 | Day 29 | 732.0 picogram/milliliter (pg/mL) | Standard Deviation 535 |
Secondary
Mean Change in Vascular Endothelial Growth Factor (VEGF) Levels Over Time at Day 1, Day 15 and Day 29
Blood samples for the determination of systemic VEGF levels were collected at the following time points: before the first investigational treatment, at Day 15 and at Day 29. Only descriptive analysis done.
Time frame: Day 1 (Baseline), Day 15 and Day 29
Population: The VEGF Set, which consisted of all participants with at least one valid VEGF concentration value, was considered.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranibizumab 0.2 mg | Mean Change in Vascular Endothelial Growth Factor (VEGF) Levels Over Time at Day 1, Day 15 and Day 29 | Day 1 | 239.0 picogram/milliliter (pg/mL) | Standard Deviation 226 |
| Ranibizumab 0.2 mg | Mean Change in Vascular Endothelial Growth Factor (VEGF) Levels Over Time at Day 1, Day 15 and Day 29 | Day 1 / no treatment modality switch | 239.0 picogram/milliliter (pg/mL) | Standard Deviation 226 |
| Ranibizumab 0.2 mg | Mean Change in Vascular Endothelial Growth Factor (VEGF) Levels Over Time at Day 1, Day 15 and Day 29 | Day 15 | 466.0 picogram/milliliter (pg/mL) | Standard Deviation 1500 |
| Ranibizumab 0.2 mg | Mean Change in Vascular Endothelial Growth Factor (VEGF) Levels Over Time at Day 1, Day 15 and Day 29 | Day 15 / no treatment modality switch | 498.0 picogram/milliliter (pg/mL) | Standard Deviation 1560 |
| Ranibizumab 0.2 mg | Mean Change in Vascular Endothelial Growth Factor (VEGF) Levels Over Time at Day 1, Day 15 and Day 29 | Day 29 | 117.0 picogram/milliliter (pg/mL) | Standard Deviation 84 |
| Ranibizumab 0.2 mg | Mean Change in Vascular Endothelial Growth Factor (VEGF) Levels Over Time at Day 1, Day 15 and Day 29 | Day 29 / no treatment modality switch | 117.0 picogram/milliliter (pg/mL) | Standard Deviation 84 |
| Ranibizumab 0.1 mg | Mean Change in Vascular Endothelial Growth Factor (VEGF) Levels Over Time at Day 1, Day 15 and Day 29 | Day 29 / no treatment modality switch | 139.0 picogram/milliliter (pg/mL) | Standard Deviation 75.3 |
| Ranibizumab 0.1 mg | Mean Change in Vascular Endothelial Growth Factor (VEGF) Levels Over Time at Day 1, Day 15 and Day 29 | Day 1 | 230.0 picogram/milliliter (pg/mL) | Standard Deviation 224 |
| Ranibizumab 0.1 mg | Mean Change in Vascular Endothelial Growth Factor (VEGF) Levels Over Time at Day 1, Day 15 and Day 29 | Day 15 / no treatment modality switch | 124.0 picogram/milliliter (pg/mL) | Standard Deviation 134 |
| Ranibizumab 0.1 mg | Mean Change in Vascular Endothelial Growth Factor (VEGF) Levels Over Time at Day 1, Day 15 and Day 29 | Day 29 | 176.0 picogram/milliliter (pg/mL) | Standard Deviation 142 |
| Ranibizumab 0.1 mg | Mean Change in Vascular Endothelial Growth Factor (VEGF) Levels Over Time at Day 1, Day 15 and Day 29 | Day 1 / no treatment modality switch | 239.0 picogram/milliliter (pg/mL) | Standard Deviation 233 |
| Ranibizumab 0.1 mg | Mean Change in Vascular Endothelial Growth Factor (VEGF) Levels Over Time at Day 1, Day 15 and Day 29 | Day 15 | 118.0 picogram/milliliter (pg/mL) | Standard Deviation 129 |
| Laser Therapy | Mean Change in Vascular Endothelial Growth Factor (VEGF) Levels Over Time at Day 1, Day 15 and Day 29 | Day 1 / no treatment modality switch | 233.0 picogram/milliliter (pg/mL) | Standard Deviation 245 |
| Laser Therapy | Mean Change in Vascular Endothelial Growth Factor (VEGF) Levels Over Time at Day 1, Day 15 and Day 29 | Day 15 | 180.0 picogram/milliliter (pg/mL) | Standard Deviation 214 |
| Laser Therapy | Mean Change in Vascular Endothelial Growth Factor (VEGF) Levels Over Time at Day 1, Day 15 and Day 29 | Day 29 / no treatment modality switch | 163.0 picogram/milliliter (pg/mL) | Standard Deviation 138 |
| Laser Therapy | Mean Change in Vascular Endothelial Growth Factor (VEGF) Levels Over Time at Day 1, Day 15 and Day 29 | Day 15 / no treatment modality switch | 177.0 picogram/milliliter (pg/mL) | Standard Deviation 224 |
| Laser Therapy | Mean Change in Vascular Endothelial Growth Factor (VEGF) Levels Over Time at Day 1, Day 15 and Day 29 | Day 1 | 232.0 picogram/milliliter (pg/mL) | Standard Deviation 240 |
| Laser Therapy | Mean Change in Vascular Endothelial Growth Factor (VEGF) Levels Over Time at Day 1, Day 15 and Day 29 | Day 29 | 161.0 picogram/milliliter (pg/mL) | Standard Deviation 132 |
Secondary
Number of Participants Experiencing an Event, From the First Study Treatment to the Last Study Visit
An event was defined as death, treatment switch, or the first occurrence of unfavorable structural outcomes in either eye. Only descriptive analysis done.
Time frame: Day 1 (after initiation of study treatment) up to study exit (Day 169)
Population: The Full Analysis Set (FAS), which consisted of all participants with an observed value, was considered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ranibizumab 0.2 mg | Number of Participants Experiencing an Event, From the First Study Treatment to the Last Study Visit | 14 Participants |
| Ranibizumab 0.1 mg | Number of Participants Experiencing an Event, From the First Study Treatment to the Last Study Visit | 18 Participants |
| Laser Therapy | Number of Participants Experiencing an Event, From the First Study Treatment to the Last Study Visit | 23 Participants |
Secondary
Percentage of Participants Having Recurrent ROP and Receiving Any Post-baseline Intervention at or Before Week 24
Recurrence of ROP is defined as subjects receiving any post-baseline intervention in either eye at or before 24 weeks (ranibizumab re-treatment or switch to laser in the ranibizumab groups, switch to ranibizumab treatment in the laser group). Zone I consists of a circle, the radius of which extends from the center of the optic disc to twice the distance from the center of the optic disc to the center of the macula. Zone II extends centrifugally from the edge of zone I to the nasal ora serrata. Only descriptive analysis done.
Time frame: Week 24
Population: The Full Analysis Set (FAS), which consisted of all participants with an observed value, was considered.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ranibizumab 0.2 mg | Percentage of Participants Having Recurrent ROP and Receiving Any Post-baseline Intervention at or Before Week 24 | ZONE I | 35.7 Percentage of participants |
| Ranibizumab 0.2 mg | Percentage of Participants Having Recurrent ROP and Receiving Any Post-baseline Intervention at or Before Week 24 | All participants | 31.1 Percentage of participants |
| Ranibizumab 0.2 mg | Percentage of Participants Having Recurrent ROP and Receiving Any Post-baseline Intervention at or Before Week 24 | ZONE II | 28.3 Percentage of participants |
| Ranibizumab 0.1 mg | Percentage of Participants Having Recurrent ROP and Receiving Any Post-baseline Intervention at or Before Week 24 | ZONE I | 53.3 Percentage of participants |
| Ranibizumab 0.1 mg | Percentage of Participants Having Recurrent ROP and Receiving Any Post-baseline Intervention at or Before Week 24 | All participants | 31.2 Percentage of participants |
| Ranibizumab 0.1 mg | Percentage of Participants Having Recurrent ROP and Receiving Any Post-baseline Intervention at or Before Week 24 | ZONE II | 17.4 Percentage of participants |
| Laser Therapy | Percentage of Participants Having Recurrent ROP and Receiving Any Post-baseline Intervention at or Before Week 24 | All participants | 18.9 Percentage of participants |
| Laser Therapy | Percentage of Participants Having Recurrent ROP and Receiving Any Post-baseline Intervention at or Before Week 24 | ZONE II | 13.0 Percentage of participants |
| Laser Therapy | Percentage of Participants Having Recurrent ROP and Receiving Any Post-baseline Intervention at or Before Week 24 | ZONE I | 28.6 Percentage of participants |
Secondary
Percentage of Participants Requiring Interventions With a Second Modality for ROP at Week 24
Intervention for ROP in either eye at or before the 24-week assessment visit with a treatment modality other than the modality of the first study treatment. Only descriptive analysis done.
Time frame: Week 24
Population: The Full Analysis Set (FAS), which consisted of all participants with an observed value, was considered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ranibizumab 0.2 mg | Percentage of Participants Requiring Interventions With a Second Modality for ROP at Week 24 | 14.9 Percentage of participants |
| Ranibizumab 0.1 mg | Percentage of Participants Requiring Interventions With a Second Modality for ROP at Week 24 | 16.9 Percentage of participants |
| Laser Therapy | Percentage of Participants Requiring Interventions With a Second Modality for ROP at Week 24 | 24.3 Percentage of participants |
Secondary
Percent of Participants With Non-Ocular Adverse Events by Primary System Organ (SOCs) at Week 24
Percent of Participants with Non-Ocular Adverse Events regardless of Study Treatment and Procedure Relationship by Primary System Organ (SOCs) reported categorically (Mild, Moderate, Severe) 24 weeks after the first study treatment. Only descriptive analysis done.
Time frame: Week 24
Population: The Safety Set was considered.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ranibizumab 0.2 mg | Percent of Participants With Non-Ocular Adverse Events by Primary System Organ (SOCs) at Week 24 | Severe | 23.3 Percent of participants |
| Ranibizumab 0.2 mg | Percent of Participants With Non-Ocular Adverse Events by Primary System Organ (SOCs) at Week 24 | Mild | 37.0 Percent of participants |
| Ranibizumab 0.2 mg | Percent of Participants With Non-Ocular Adverse Events by Primary System Organ (SOCs) at Week 24 | Moderate | 24.7 Percent of participants |
| Ranibizumab 0.1 mg | Percent of Participants With Non-Ocular Adverse Events by Primary System Organ (SOCs) at Week 24 | Severe | 19.7 Percent of participants |
| Ranibizumab 0.1 mg | Percent of Participants With Non-Ocular Adverse Events by Primary System Organ (SOCs) at Week 24 | Moderate | 34.2 Percent of participants |
| Ranibizumab 0.1 mg | Percent of Participants With Non-Ocular Adverse Events by Primary System Organ (SOCs) at Week 24 | Mild | 27.6 Percent of participants |
| Laser Therapy | Percent of Participants With Non-Ocular Adverse Events by Primary System Organ (SOCs) at Week 24 | Severe | 17.4 Percent of participants |
| Laser Therapy | Percent of Participants With Non-Ocular Adverse Events by Primary System Organ (SOCs) at Week 24 | Moderate | 27.5 Percent of participants |
| Laser Therapy | Percent of Participants With Non-Ocular Adverse Events by Primary System Organ (SOCs) at Week 24 | Mild | 31.9 Percent of participants |
Secondary
Percent of Participants With Ocular Adverse Events by Primary System Organ (SOCs) at Week 24
Percent of Participants with Ocular Adverse Events regardless of Study Treatment and Procedure Relationship by Primary System Organ (SOCs) reported categorically (Mild, Moderate, Severe) 24 weeks after the first study treatment. Only descriptive analysis done.
Time frame: Week 24
Population: The Safety Set was considered.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ranibizumab 0.2 mg | Percent of Participants With Ocular Adverse Events by Primary System Organ (SOCs) at Week 24 | Moderate | 4.1 Percent of participants |
| Ranibizumab 0.2 mg | Percent of Participants With Ocular Adverse Events by Primary System Organ (SOCs) at Week 24 | Mild | 23.3 Percent of participants |
| Ranibizumab 0.2 mg | Percent of Participants With Ocular Adverse Events by Primary System Organ (SOCs) at Week 24 | Severe | 2.7 Percent of participants |
| Ranibizumab 0.1 mg | Percent of Participants With Ocular Adverse Events by Primary System Organ (SOCs) at Week 24 | Moderate | 6.6 Percent of participants |
| Ranibizumab 0.1 mg | Percent of Participants With Ocular Adverse Events by Primary System Organ (SOCs) at Week 24 | Mild | 32.9 Percent of participants |
| Ranibizumab 0.1 mg | Percent of Participants With Ocular Adverse Events by Primary System Organ (SOCs) at Week 24 | Severe | 1.3 Percent of participants |
| Laser Therapy | Percent of Participants With Ocular Adverse Events by Primary System Organ (SOCs) at Week 24 | Mild | 17.4 Percent of participants |
| Laser Therapy | Percent of Participants With Ocular Adverse Events by Primary System Organ (SOCs) at Week 24 | Severe | 2.9 Percent of participants |
| Laser Therapy | Percent of Participants With Ocular Adverse Events by Primary System Organ (SOCs) at Week 24 | Moderate | 13.0 Percent of participants |
Secondary
Total Number of Ranibizumab Injections Received at Week 24
Patients randomized to receive Ranibizumab 0.1 mg or 0.2 mg received a single dose of intravitreal Ranibizumab to each eye on Day 1 (Baseline). Only descriptive analysis done.
Time frame: Week 24
Population: The Safety Set was considered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ranibizumab 0.2 mg | Total Number of Ranibizumab Injections Received at Week 24 | 73 Injections |
| Ranibizumab 0.1 mg | Total Number of Ranibizumab Injections Received at Week 24 | 76 Injections |
| Laser Therapy | Total Number of Ranibizumab Injections Received at Week 24 | 13 Injections |