RAINBOW Study: RAnibizumab Compared With Laser Therapy for the Treatment of INfants BOrn Prematurely With Retinopathy of Prematurity

Retinopathy of Prematurity Clinical Trial

— RAINBOW  

Official title:

RAINBOW Study: a Randomized, Controlled Study Evaluating the Efficacy and Safety of RAnibizumab Compared With Laser Therapy for the Treatment of INfants BOrn Prematurely With Retinopathy of Prematurity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02375971
• Other study ID #: CRFB002H2301
• Secondary ID: 2014-003041-10
• Status: Completed
• Phase: Phase 3
• Start date: December 30, 2015
• Est. completion date: December 14, 2017

Study information

• Verified date: October 2018
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 224
• Est. completion date: December 14, 2017
• Est. primary completion date: December 14, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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)

Related Conditions & MeSH terms

• Premature Birth
• Retinal Diseases
• Retinopathy of Prematurity

Intervention

Drug:
• Ranibizumab
Administered as an intravitreal injection

Procedure:
• Laser therapy
Transpupillary diode or frequency-doubled yttrium aluminum garnet (YAG) laser ablative therapy, following anesthesia or sedation

Locations

Country	Name	City	State
Austria	Novartis Investigative Site	Graz
Austria	Novartis Investigative Site	Vienna
Belgium	Novartis Investigative Site	Brugge
Belgium	Novartis Investigative Site	Gent
Croatia	Novartis Investigative Site	Osijek
Croatia	Novartis Investigative Site	Zagreb
Czechia	Novartis Investigative Site	Ostrava Poruba	Czech Republic
Czechia	Novartis Investigative Site	Praha
Czechia	Novartis Investigative Site	Praha 4 - Podoli	Czech Republic
Denmark	Novartis Investigative Site	Koebenhavn Ø
Egypt	Novartis Investigative Site	Alexandria
Estonia	Novartis Investigative Site	Tallinn
France	Novartis Investigative Site	Amiens Cedex 1
France	Novartis Investigative Site	Marseille
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Hannover
Greece	Novartis Investigative Site	Ampelokipi	GR
Greece	Novartis Investigative Site	Goudi- Athens
Greece	Novartis Investigative Site	Thessaloniki	GR
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen
India	Novartis Investigative Site	Ahmedabad	Gujarat
India	Novartis Investigative Site	Coimbatore	Tamil Nadu
India	Novartis Investigative Site	Madurai	Tamil Nadu
India	Novartis Investigative Site	Mumbai	Maharashtra
India	Novartis Investigative Site	New Delhi
India	Novartis Investigative Site	Vanchiyoor	Thiruvanantapuram
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Fiumicino	RM
Italy	Novartis Investigative Site	Perugia	PG
Italy	Novartis Investigative Site	Roma	Lazio
Japan	Novartis Investigative Site	Fuchu-city	Tokyo
Japan	Novartis Investigative Site	Fukuoka city	Fukuoka
Japan	Novartis Investigative Site	Fukuoka-city	Fukuoka
Japan	Novartis Investigative Site	Fukushima-city	Fukushima
Japan	Novartis Investigative Site	Izumi-city	Osaka
Japan	Novartis Investigative Site	Kurume city	Fukuoka
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Ohtsu-city	Shiga
Japan	Novartis Investigative Site	Ota-ku	Tokyo
Japan	Novartis Investigative Site	Sapporo-city	Hokkaido
Japan	Novartis Investigative Site	Setagaya-ku	Tokyo
Japan	Novartis Investigative Site	Shimajiri-Gun	Okinawa
Japan	Novartis Investigative Site	Sumida-ku	Tokyo
Japan	Novartis Investigative Site	Toshima-ku	Tokyo
Japan	Novartis Investigative Site	Yachiyo-city	Chiba
Japan	Novartis Investigative Site	Zentsuji-city	Kagawa
Lithuania	Novartis Investigative Site	Kaunas	LTU
Malaysia	Novartis Investigative Site	Kota Kinabalu	Sabah
Malaysia	Novartis Investigative Site	Kuala Lumpur	Wilayah Persekutuan
Mexico	Novartis Investigative Site	Querataro
Poland	Novartis Investigative Site	Bialystok
Poland	Novartis Investigative Site	Wroclaw
Romania	Novartis Investigative Site	Brasov
Romania	Novartis Investigative Site	Bucuresti
Romania	Novartis Investigative Site	Timisoara
Russian Federation	Novartis Investigative Site	Cheboksary
Russian Federation	Novartis Investigative Site	Kazan
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Saint-Petersburg
Saudi Arabia	Novartis Investigative Site	Riyadh
Slovakia	Novartis Investigative Site	Bratislava
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taoyuan
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Eskisehir	Meselik
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Soguksu / Antalya
Turkey	Novartis Investigative Site	Zuhuratbaba / Istanbul
United Kingdom	Novartis Investigative Site	Manchester
United Kingdom	Novartis Investigative Site	Oxford
United Kingdom	Novartis Investigative Site	Portsmouth
United States	Novartis Investigative Site	Ann Arbor	Michigan
United States	Novartis Investigative Site	Aurora	Colorado
United States	Novartis Investigative Site	Austin	Texas
United States	Novartis Investigative Site	Baltimore	Maryland
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Loma Linda	California
United States	Novartis Investigative Site	Louisville	Kentucky
United States	Novartis Investigative Site	Morgantown	West Virginia
United States	Novartis Investigative Site	Rochester	New York
United States	Novartis Investigative Site	Sacramento	California
United States	Novartis Investigative Site	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Croatia,  Czechia,  Denmark,  Egypt,  Estonia,  France,  Germany,  Greece,  Hungary,  India,  Italy,  Japan,  Lithuania,  Malaysia,  Mexico,  Poland,  Romania,  Russian Federation,  Saudi Arabia,  Slovakia,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Week 24
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.	Week 24
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.	Day 1 (after initiation of study treatment) up to study exit (Day 169)
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.	Week 24
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.	Week 24
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.	Day 1 (Baseline), Day 15 and Day 29
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.	Day 1 (Baseline), Day 15 and Day 29
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.	Week 24
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.	Week 24
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.	Baseline, Day 85, Day 169
Secondary	Mean Change From Baseline in Vital Signs (Weight) at Day 85 and Day 169	Body weight was measured. Only descriptive analysis done.	Baseline, Day 85, Day 169
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.	Baseline, Day 85, Day 169