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

Retinopathy of Prematurity (ROP) Clinical Trial

— CARE-ROP  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02134457
• Other study ID #: CARE-ROP
• Secondary ID: 2013-002539-13
• Status: Completed
• Phase: Phase 2
• First received: April 26, 2014
• Last updated: March 8, 2017
• Start date: August 2014
• Est. completion date: January 2017

Study information

• Verified date: March 2017
• Source: University Hospital Freiburg
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Premature Birth
• Retinal Diseases
• Retinopathy of Prematurity
• Retinopathy of Prematurity (ROP)

Intervention

Biological:
• ranibizumab

Locations

Country	Name	City	State
Germany	University Eye Hospital	Bonn
Germany	University Eye Hospital	Duesseldorf
Germany	University Eye Hospital	Freiburg	Baden-Wuerttemberg
Germany	University Eye Hospital	Kiel
Germany	University Eye Hospital	Magdeburg
Germany	University Eye Hospital	Muenster
Germany	University Eye Hospital	Munich
Germany	University Eye Hospital	Regensburg
Germany	University Eye Hospital	Tuebingen

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Freiburg

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of late recurrences of ROP during the follow-up period		Up to 5 years post first injection
Other	Number of patients progressing to stage 4 or 5 ROP after the core study		Up to 5 years post first injection
Other	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		Up to 5 years post first injection
Other	Long-term ophthalmological development: visual acuity (if possible), orthoptic status, cycloplegic retinoscopy, refraction, IOP, fundoscopy including fundus photographs	At one year and at 5 years an ophthalmological visit will take place.	Up to 5 years post first injection
Other	Long-term pediatric development: Bayley-test, weight, height, cognitive, motor and sensory development		Up to 5 years post first injection
Other	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		Up to 5 years post first injection
Primary	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	Regression of plus disease		Up to 24 weeks post first injection
Secondary	Regression of preretinal vascularized ridge		Up to 24 weeks post first injection
Secondary	Progression of peripheral intraretinal vascularization beyond ridge		Up to 24 weeks post first injection
Secondary	Number and kind of AEs and SAEs		Up to 24 weeks post first injection
Secondary	Changes in vascular endothelial growth factor (VEGF) levels in the systemic circulation		Up to 24 weeks post first injection
Secondary	Number of re-injections of study dose		Up to 24 weeks post first injection
Secondary	Number of patients progressing to stage 4 or 5 ROP		Up to 24 weeks post first injection
Secondary	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