Clinical trial NCT02375971: RAINBOW Study: RAnibizumab Compared With Laser Therapy for the Treatment of INfants BOrn Prematurely With Retinopathy of Prematurity
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Retinopathy of Prematurity
Keywords: intravitreal ranibizumab
laser ablation therapy
retinopathy of prematurity
preterm infants
RAINBOW
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-03-03
Enrollment: 224
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Detailed 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).

Eligibility criteria: 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)

Primary outcomes:
measure: Percentage of Participants With Absence of Active ROP and Absence of Unfavorable Structural Outcomes in Both Eyes at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants Requiring Interventions With a Second Modality for ROP at Week 24
timeFrame: Week 24
measure: Number of Participants Experiencing an Event, From the First Study Treatment to the Last Study Visit
timeFrame: Day 1 (after initiation of study treatment) up to study exit (Day 169)
measure: Percentage of Participants Having Recurrent ROP and Receiving Any Post-baseline Intervention at or Before Week 24
timeFrame: Week 24
measure: Percent of Participants With Ocular Adverse Events by Primary System Organ (SOCs) at Week 24
timeFrame: Week 24
measure: Mean Change in Ranibizumab Concentration in Pharmacokinetic Serum Samples Over Time at Day 1, Day 15 and Day 29
timeFrame: Day 1 (Baseline), Day 15 and Day 29
measure: Mean Change in Vascular Endothelial Growth Factor (VEGF) Levels Over Time at Day 1, Day 15 and Day 29
timeFrame: Day 1 (Baseline), Day 15 and Day 29
measure: Total Number of Ranibizumab Injections Received at Week 24
timeFrame: Week 24
measure: Percent of Participants With Non-Ocular Adverse Events by Primary System Organ (SOCs) at Week 24
timeFrame: Week 24
measure: Mean Change From Baseline in Vital Signs (Body Length, Head Circumference and Knee to Heel Length) at Day 85 and Day 169
timeFrame: Baseline, Day 85, Day 169
measure: Mean Change From Baseline in Vital Signs (Weight) at Day 85 and Day 169
timeFrame: Baseline, Day 85, Day 169
measure: Mean Change From Baseline in Vital Signs (Sitting Blood Pressure) at Day 85 and Day 169
timeFrame: Baseline, Day 85, Day 169
Other outcomes:
Locations:
city: Loma Linda
country: United States
facility: Novartis Investigative Site
state: California
city: Sacramento
country: United States
facility: Novartis Investigative Site
state: California
city: Aurora
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Chicago
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Louisville
country: United States
facility: Novartis Investigative Site
state: Kentucky
city: Baltimore
country: United States
facility: Novartis Investigative Site
state: Maryland
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Rochester
country: United States
facility: Novartis Investigative Site
state: New York
city: Austin
country: United States
facility: Novartis Investigative Site
state: Texas
city: Salt Lake City
country: United States
facility: Novartis Investigative Site
state: Utah
city: Morgantown
country: United States
facility: Novartis Investigative Site
state: West Virginia
city: Graz
country: Austria
facility: Novartis Investigative Site
city: Vienna
country: Austria
facility: Novartis Investigative Site
city: Brugge
country: Belgium
facility: Novartis Investigative Site
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Osijek
country: Croatia
facility: Novartis Investigative Site
city: Zagreb
country: Croatia
facility: Novartis Investigative Site
city: Ostrava Poruba
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Praha 4 - Podoli
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Praha
country: Czechia
facility: Novartis Investigative Site
city: Koebenhavn Ø
country: Denmark
facility: Novartis Investigative Site
city: Alexandria
country: Egypt
facility: Novartis Investigative Site
city: Tallinn
country: Estonia
facility: Novartis Investigative Site
city: Amiens Cedex 1
country: France
facility: Novartis Investigative Site
city: Marseille
country: France
facility: Novartis Investigative Site
city: Bonn
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Ampelokipi
country: Greece
facility: Novartis Investigative Site
state: GR
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
state: GR
city: Goudi- Athens
country: Greece
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Ahmedabad
country: India
facility: Novartis Investigative Site
state: Gujarat
city: Mumbai
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Coimbatore
country: India
facility: Novartis Investigative Site
state: Tamil Nadu
city: Madurai
country: India
facility: Novartis Investigative Site
state: Tamil Nadu
city: Vanchiyoor
country: India
facility: Novartis Investigative Site
state: Thiruvanantapuram
city: New Delhi
country: India
facility: Novartis Investigative Site
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Roma
country: Italy
facility: Novartis Investigative Site
state: Lazio
city: Perugia
country: Italy
facility: Novartis Investigative Site
state: PG
city: Fiumicino
country: Italy
facility: Novartis Investigative Site
state: RM
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Yachiyo-city
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Fukuoka city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Fukuoka-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Kurume city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Fukushima-city
country: Japan
facility: Novartis Investigative Site
state: Fukushima
city: Sapporo-city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Zentsuji-city
country: Japan
facility: Novartis Investigative Site
state: Kagawa
city: Shimajiri-Gun
country: Japan
facility: Novartis Investigative Site
state: Okinawa
city: Izumi-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Ohtsu-city
country: Japan
facility: Novartis Investigative Site
state: Shiga
city: Fuchu-city
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Ota-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Setagaya-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Sumida-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Toshima-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Kaunas
country: Lithuania
facility: Novartis Investigative Site
state: LTU
city: Kota Kinabalu
country: Malaysia
facility: Novartis Investigative Site
state: Sabah
city: Kuala Lumpur
country: Malaysia
facility: Novartis Investigative Site
state: Wilayah Persekutuan
city: Querataro
country: Mexico
facility: Novartis Investigative Site
city: Bialystok
country: Poland
facility: Novartis Investigative Site
city: Wroclaw
country: Poland
facility: Novartis Investigative Site
city: Brasov
country: Romania
facility: Novartis Investigative Site
city: Bucuresti
country: Romania
facility: Novartis Investigative Site
city: Timisoara
country: Romania
facility: Novartis Investigative Site
city: Cheboksary
country: Russian Federation
facility: Novartis Investigative Site
city: Kazan
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Saint-Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Riyadh
country: Saudi Arabia
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taoyuan
country: Taiwan
facility: Novartis Investigative Site
city: Eskisehir
country: Turkey
facility: Novartis Investigative Site
state: Meselik
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Soguksu / Antalya
country: Turkey
facility: Novartis Investigative Site
city: Zuhuratbaba / Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
city: Oxford
country: United Kingdom
facility: Novartis Investigative Site
city: Portsmouth
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.