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

NCT02375971 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: CRFB002H23012014-003041-10
• Study Type: interventional
• Target: 224
• Locations: 26 countries
• Sites: 86

Brief 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).

Conditions

Retinopathy of Prematurity

Keywords

intravitreal ranibizumab; laser ablation therapy; retinopathy of prematurity; preterm infants; RAINBOW

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Percentage of Participants Requiring Interventions With a Second Modality for ROP at Week 24

  Week 24

• Number of Participants Experiencing an Event, From the First Study Treatment to the Last Study Visit

  Day 1 (after initiation of study treatment) up to study exit (Day 169)

• Percentage of Participants Having Recurrent ROP and Receiving Any Post-baseline Intervention at or Before Week 24

  Week 24

• Percent of Participants With Ocular Adverse Events by Primary System Organ (SOCs) at Week 24

  Week 24

• Mean Change in Ranibizumab Concentration in Pharmacokinetic Serum Samples Over Time at Day 1, Day 15 and Day 29

  Day 1 (Baseline), Day 15 and Day 29

Study Arms (3)

Ranibizumab 0.2 mg

EXPERIMENTAL

1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required

Drug: Ranibizumab

Ranibizumab 0.1 mg

EXPERIMENTAL

1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required

Drug: Ranibizumab

Laser therapy

ACTIVE COMPARATOR

Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed

Procedure: Laser therapy

Interventions

Ranibizumab DRUG

Administered as an intravitreal injection

Ranibizumab 0.1 mg; Ranibizumab 0.2 mg

Laser therapy PROCEDURE

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

Laser therapy

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (86)

Novartis Investigative Site

Loma Linda, California, 92354, United States

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Sacramento, California, 95817, United States

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Aurora, Colorado, 80045, United States

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Chicago, Illinois, 60612, United States

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Louisville, Kentucky, 40208, United States

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Baltimore, Maryland, 21201, United States

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Boston, Massachusetts, 02111, United States

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Ann Arbor, Michigan, 48105, United States

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Rochester, New York, 14642, United States

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Austin, Texas, 78705, United States

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Salt Lake City, Utah, 84132, United States

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Morgantown, West Virginia, 26506, United States

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Graz, A-8036, Austria

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Vienna, 1090, Austria

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Bruges, 8000, Belgium

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Ghent, 9000, Belgium

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Osijek, 31000, Croatia

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Zagreb, 10000, Croatia

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Ostrava Poruba, Czech Republic, 708 52, Czechia

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Praha 4 - Podoli, Czech Republic, 14700, Czechia

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Prague, 12808, Czechia

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Koebenhavn Ø, 2100, Denmark

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Alexandria, 21131, Egypt

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Tallinn, 13419, Estonia

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Amiens, 80054, France

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Marseille, 13915, France

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Bonn, 53127, Germany

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Hanover, 30625, Germany

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Ampelokipoi, GR, 115 27, Greece

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Thessaloniki, GR, 546 29, Greece

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Goudi- Athens, 115 27, Greece

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Budapest, 1125, Hungary

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Debrecen, 4032, Hungary

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Ahmedabad, Gujarat, 380016, India

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Mumbai, Maharashtra, 400 008, India

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Coimbatore, Tamil Nadu, 641014, India

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Madurai, Tamil Nadu, 625020, India

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Vanchiyoor, Thiruvanantapuram, 695035, India

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New Delhi, 110029, India

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Florence, FI, 50139, Italy

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Rome, Lazio, 00168, Italy

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Perugia, PG, 06100, Italy

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Fiumicino, RM, 00054, Italy

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Nagoya, Aichi-ken, 453-8511, Japan

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Nagoya, Aichi-ken, 466 8560, Japan

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Yachiyo, Chiba, 276-8524, Japan

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Fukuoka, Fukuoka, 812-8582, Japan

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Fukuoka, Fukuoka, 814-0180, Japan

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Kurume, Fukuoka, 830-0011, Japan

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Fukushima, Fukushima, 960-1295, Japan

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Sapporo, Hokkaido, Japan

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Zentsujichó, Kagawa-ken, 765-8507, Japan

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Shimajiri-Gun, Okinawa, 901-1303, Japan

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Izumi, Osaka, 594-1101, Japan

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Ohtsu-city, Shiga, 520-2192, Japan

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Fuchū, Tokyo, 183-8561, Japan

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Ōta-ku, Tokyo, 143 8541, Japan

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Setagaya-ku, Tokyo, 157-8535, Japan

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Sumida-ku, Tokyo, 130-8575, Japan

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Toshima-ku, Tokyo, 170-8476, Japan

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Kaunas, LTU, LT-50161, Lithuania

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Kuala Lumpur, Kuala Lumpur, 50586, Malaysia

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Kota Kinabalu, Sabah, 88996, Malaysia

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Querataro, 76090, Mexico

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Bialystok, 15-274, Poland

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Wroclaw, 51-124, Poland

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Brasov, 500025, Romania

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Bucharest, 020395, Romania

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Timișoara, 300041, Romania

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Cheboksary, 428028, Russia

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Kazan', 420012, Russia

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Moscow, 127486, Russia

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Saint Petersburg, 194100, Russia

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Riyadh, 11211, Saudi Arabia

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Bratislava, 833 40, Slovakia

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Taipei, 10002, Taiwan

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Taoyuan District, 33305, Taiwan

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Novartis Investigative Site

Eskişehir, Meselik, 26480, Turkey (Türkiye)

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Novartis Investigative Site

Soguksu / Antalya, Turkey, 07100, Turkey (Türkiye)

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Novartis Investigative Site

Zuhuratbaba / Istanbul, Turkey, 34147, Turkey (Türkiye)

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Novartis Investigative Site

Ankara, 06100, Turkey (Türkiye)

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Novartis Investigative Site

Ankara, 06500, Turkey (Türkiye)

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Novartis Investigative Site

Istanbul, 34140, Turkey (Türkiye)

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Novartis Investigative Site

Manchester, M13 9WL, United Kingdom

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Oxford, OX3 9DU, United Kingdom

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Novartis Investigative Site

Portsmouth, PO6 3LY, United Kingdom

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Related Publications (2)

• Fleck BW, Reynolds JD, Zhu Q, Lepore D, Marlow N, Stahl A, Li J, Weisberger A, Fielder AR; RAINBOW Investigator Group. Time Course of Retinopathy of Prematurity Regression and Reactivation After Treatment with Ranibizumab or Laser in the RAINBOW Trial. Ophthalmol Retina. 2022 Jul;6(7):628-637. doi: 10.1016/j.oret.2022.02.006. Epub 2022 Feb 22.

  PMID: 35202890 DERIVED

• Stahl A, Lepore D, Fielder A, Fleck B, Reynolds JD, Chiang MF, Li J, Liew M, Maier R, Zhu Q, Marlow N. Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): an open-label randomised controlled trial. Lancet. 2019 Oct 26;394(10208):1551-1559. doi: 10.1016/S0140-6736(19)31344-3. Epub 2019 Sep 12.

  PMID: 31522845 DERIVED

MeSH Terms

Conditions

Retinopathy of Prematurity

Interventions

Ranibizumab; Laser Therapy

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics; Ablation Techniques; Surgical Procedures, Operative

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2015
• First Posted: March 3, 2015
• Study Start: December 30, 2015
• Primary Completion: December 14, 2017
• Study Completion: December 14, 2017
• Last Updated: November 14, 2018
• Results First Posted: July 31, 2018

Record last verified: 2018-10

Locations

AU (2); HU (2); DK (1); EG (1); CZ (3); TW (2); US (12); ES (1); RO (3); RU (4); LI (1); BE (2); CR (2); DE (2); JP (17); ME (1); PL (2); SA (1); TU (6); GB (3); MY (2); IT (4); GR (3); SL (1); IN (6); FR (2)