NCT02134457

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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
19

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Aug 2014

Geographic Reach
1 country

9 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 26, 2014

Completed
13 days until next milestone

First Posted

Study publicly available on registry

May 9, 2014

Completed
3 months until next milestone

Study Start

First participant enrolled

August 1, 2014

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2017

Completed
Last Updated

March 9, 2017

Status Verified

March 1, 2017

Enrollment Period

2.4 years

First QC Date

April 26, 2014

Last Update Submit

March 8, 2017

Conditions

Retinopathy of Prematurity (ROP)

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (8)

  • 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

  • +3 more secondary outcomes

Other Outcomes (6)

  • Number of late recurrences of ROP during the follow-up period

    Up to 5 years post first injection

  • Number of patients progressing to stage 4 or 5 ROP after the core study

    Up to 5 years post first injection

  • 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

  • +3 more other outcomes

Study Arms (2)

Ranibizumab 0.12 mg

EXPERIMENTAL

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

Ranibizumab 0.20 mg

EXPERIMENTAL

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

Interventions

ranibizumabBIOLOGICAL
Also known as: Lucentis
Ranibizumab 0.12 mgRanibizumab 0.20 mg

Eligibility Criteria

Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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).

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

University Eye Hospital

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

University Eye Hospital

Bonn, 53127, Germany

Location

University Eye Hospital

Düsseldorf, 40225, Germany

Location

University Eye Hospital

Kiel, 24105, Germany

Location

University Eye Hospital

Magdeburg, 39120, Germany

Location

University Eye Hospital

Munich, 80336, Germany

Location

University Eye Hospital

Münster, 48149, Germany

Location

University Eye Hospital

Regensburg, 93053, Germany

Location

University Eye Hospital

Tübingen, 72076, Germany

Location

Related Publications (1)

  • 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.

    PMID: 29309486DERIVED

MeSH Terms

Conditions

Retinopathy of Prematurity

Interventions

Ranibizumab

Condition Hierarchy (Ancestors)

Retinal DiseasesEye DiseasesInfant, Premature, DiseasesInfant, Newborn, DiseasesCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Andreas Stahl, MD

    University Eye Hospital Freiburg, Germany

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD

Study Record Dates

First Submitted

April 26, 2014

First Posted

May 9, 2014

Study Start

August 1, 2014

Primary Completion

January 1, 2017

Study Completion

January 1, 2017

Last Updated

March 9, 2017

Record last verified: 2017-03

Locations

DE(9)