Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity

Study Overview
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Brief Summary
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This study is designed as an exploratory study to assess safety and efficacy of two different doses of the anti-VEGF agent ranibizumab (0.12 mg vs. 0.20 mg) in the treatment of infants with retinopathy of prematurity. Furthermore it shall help to improve safety in the treatment of ROP and provide explorative data on long-term effects of ranibizumab after intravitreal injection in neonates. The primary objective is to assess clinical efficacy of ranibizumab in children with ROP

Official Title
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Multicenter Randomized Double Masked Parallel Design Exploratory Study to Assess Safety and Efficacy of Two Different Doses of Intravitreal Anti-VEGF Treatment With Ranibizumab (0.12 mg vs. 0.20 mg) in Infants With Retinopathy of Prematurity (ROP)

Conditions
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Retinopathy of Prematurity (ROP)

Intervention / Treatment
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* Biological: ranibizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Bilateral ROP in zone I (stage 1+, 2+, 3+/-, AP-ROP) or ROP in central (=posterior) zone II (stage 3+, AP-ROP). Zone I is defined as twice the distance from the optic disc to the fovea measured temporally, posterior zone II is defined as three times the distance from the optic disc to the fovea measured temporally. Legal representatives or their designates willing and able to attend regular study visits with the study infant. Written informed consent to participate in the study (signed by all patient's legal representatives). Exclusion Criteria: Pediatric conditions rendering the infant ineligible to anti-VEGF treatment or to repeated blood draws as evaluated by a neonatal ICU specialist and a study ophthalmologist. Congenital brain lesions significantly impairing optic nerve function. Severe hydrocephalus with significantly increased intracranial pressure. Advanced stages of ROP with partial or complete retinal detachment (ROP stage 4 and 5). ROP involving only the peripheral retina (i.e. peripheral zone II or zone III). Known hypersensitivity to the study drug or to drugs with similar chemical structures. Contraindications for an intravitreal injection as listed in ranibizumab SmPC. Systemic use of anti-VEGF therapeutics. Use of other investigational drugs - excluding vitamins and minerals - at the time of enrollment, or within 30 days or 5 half-lives prior to enrollment, whichever is longer.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ranibizumab 0.12 mg<br>20 µl of the 6 mg/ml ranibizumab concentration will be applied intravitreally. After an initial response the same dose as in the first injection can be re-applied after at least four weeks post injection. A maximum number of 3 regular re-injections can be applied. | Biological: ranibizumab<br> <br> * Other names: Lucentis;|
| Experimental: Ranibizumab 0.20 mg<br>20 µl of the 10 mg/ml ranibizumab concentration will be applied intravitreally. After an initial response the same dose as in the first injection can be re-applied after at least four weeks post injection. A maximum number of 3 re-injections can be applied. | Biological: ranibizumab<br> <br> * Other names: Lucentis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of treatment | Efficacy is determined by the number of infants without need for rescue treatment up to week 24 post first injection. Re-injection of study dose is not considered rescue treatment if applied after an initial response to treatment and after at least 4 weeks post injection. | Up to 24 weeks post first injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Regression of plus disease |  | Up to 24 weeks post first injection | 
| Regression of preretinal vascularized ridge |  | Up to 24 weeks post first injection | 
| Progression of peripheral intraretinal vascularization beyond ridge |  | Up to 24 weeks post first injection | 
| Number and kind of AEs and SAEs |  | Up to 24 weeks post first injection | 
| Changes in vascular endothelial growth factor (VEGF) levels in the systemic circulation |  | Up to 24 weeks post first injection | 
| Number of re-injections of study dose |  | Up to 24 weeks post first injection | 
| Number of patients progressing to stage 4 or 5 ROP |  | Up to 24 weeks post first injection | 
| Number of patients with complete vascularization of the peripheral retina to within one disc diameter of the ora serrata |  | Up to 24 weeks post first injection |