Clinical trial NCT02134457: Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Retinopathy of Prematurity (ROP)
Lead sponsor: University Hospital Freiburg
Sponsor class: OTHER
First posted: 2014-05-09
Enrollment: 19
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: Efficacy of treatment
timeFrame: Up to 24 weeks post first injection
Secondary outcomes:
measure: Regression of plus disease
timeFrame: Up to 24 weeks post first injection
measure: Regression of preretinal vascularized ridge
timeFrame: Up to 24 weeks post first injection
measure: Progression of peripheral intraretinal vascularization beyond ridge
timeFrame: Up to 24 weeks post first injection
measure: Number and kind of AEs and SAEs
timeFrame: Up to 24 weeks post first injection
measure: Changes in vascular endothelial growth factor (VEGF) levels in the systemic circulation
timeFrame: Up to 24 weeks post first injection
measure: Number of re-injections of study dose
timeFrame: Up to 24 weeks post first injection
measure: Number of patients progressing to stage 4 or 5 ROP
timeFrame: Up to 24 weeks post first injection
measure: Number of patients with complete vascularization of the peripheral retina to within one disc diameter of the ora serrata
timeFrame: Up to 24 weeks post first injection
Other outcomes:
measure: Number of late recurrences of ROP during the follow-up period
timeFrame: Up to 5 years post first injection
measure: Number of patients progressing to stage 4 or 5 ROP after the core study
timeFrame: Up to 5 years post first injection
measure: Number of patients with complete vascularization of the peripheral retina to within one disc diameter of the ora serrata after the end of the core study
timeFrame: Up to 5 years post first injection
measure: Long-term ophthalmological development: visual acuity (if possible), orthoptic status, cycloplegic retinoscopy, refraction, IOP, fundoscopy including fundus photographs
timeFrame: Up to 5 years post first injection
measure: Long-term pediatric development: Bayley-test, weight, height, cognitive, motor and sensory development
timeFrame: Up to 5 years post first injection
measure: Number and kind of AEs or SAEs per group between the end of the observational core study and the end of the follow-up period
timeFrame: Up to 5 years post first injection
Locations:
city: Freiburg
country: Germany
facility: University Eye Hospital
state: Baden-Wuerttemberg
city: Bonn
country: Germany
facility: University Eye Hospital
city: Duesseldorf
country: Germany
facility: University Eye Hospital
city: Kiel
country: Germany
facility: University Eye Hospital
city: Magdeburg
country: Germany
facility: University Eye Hospital
city: Muenster
country: Germany
facility: University Eye Hospital
city: Munich
country: Germany
facility: University Eye Hospital
city: Regensburg
country: Germany
facility: University Eye Hospital
city: Tuebingen
country: Germany
facility: University Eye Hospital
Study officials:
affiliation: University Eye Hospital Freiburg, Germany
name: Andreas Stahl, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stahl A, Krohne TU, Eter N, Oberacher-Velten I, Guthoff R, Meltendorf S, Ehrt O, Aisenbrey S, Roider J, Gerding H, Jandeck C, Smith LEH, Walz JM; Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity (CARE-ROP) Study Group. Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity: A Randomized Clinical Trial. JAMA Pediatr. 2018 Mar 1;172(3):278-286. doi: 10.1001/jamapediatrics.2017.4838.