Clinical trial NCT02640664: Rainbow Extension Study
Official title: RAINBOW Extension Study: an Extension Study to Evaluate the Long Term 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 (ROP)
Keywords: open-label,
long-term,
extension study,
intravitreal ranibizumab,
laser ablation therapy,
retinopathy of prematurity,
preterm infants,
RAINBOW
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-12-29
Enrollment: 180
Sex: ALL
Minimum age (years): 6
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to evaluate the long term efficacy and safety of intravitreal ranibizumab compared with laser ablation therapy in patients who were treated for retinopathy of prematurity (ROP) in the core study CRFB002H2301 (NCT02375971)

Detailed description: This was a multicenter, open-label extension study where the Visual Acuity (VA) assessment at the child's 5th birthday visit was performed. The study had 2 distinct periods (Epochs). Treatment with study ranibizumab (either as retreatment after ranibizumab had already been injected in the same eye or as switch ranibizumab treatment from study laser therapy administered in the core study) was permitted for eligible eyes with recurrence/worsening of ROP up to and including Week 40 from the baseline visit in the core study (Epoch 1). The remainder of the extension study up to the 5th birthday visit (Epoch 2) was observational, with no study treatment planned to be administered.

In the core study, patients were randomized to 1 of the 3 treatment arms (ranibizumab 0.2 mg, ranibizumab 0.1 mg, and laser). Treatment arm assignment and patient identifier in the extension study remained the same as in the core study.

Eligibility criteria: Inclusion Criteria:

* Signed informed consent from parent(s) or legal guardian(s), in compliance with local requirements
* The patient successfully completed the core study H2301, as defined by providing assessments at the Visit 112 (the last scheduled visit in the core study) or, if appropriate, at the last of the additional assessment visits as per protocol in H2301, whichever was latest
* The patient received study treatment in both eyes at baseline of study H2301

Exclusion Criteria:

* Patient had a medical condition or personal circumstance which precluded study participation or compliance with study procedures, as assessed by the Investigator
* Patient had been discontinued from the core study H2301 at any time

Primary outcomes:
measure: Visual Acuity (VA) of the Better-seeing Eye at the Participant's Fifth Birthday Visit - Comparison Between Treatment Arms
timeFrame: at the participant's fifth birthday visit (maximum 5 years and 4 months post core baseline visit)
Secondary outcomes:
measure: Number of Participants With Ocular Adverse Events (AEs) Regardless of Study Treatment or Procedure Relationship by Preferred Term
timeFrame: throughout the study, approximately 5 years
measure: Number of Participants With Non-ocular Adverse Events (AEs) Regardless of Study Treatment or Procedure Relationship (Greater Than or Equal to 3% in Any Arm) by Preferred Term
timeFrame: throughout the study, approximately 5 years
measure: Visual Acuity (VA) of the Worse-seeing Eye at the Participant's Fifth Birthday Visit - Comparison Between Treatment Arms
timeFrame: at the participant's fifth birthday visit (maximum 5 years and 4 months post core baseline visit)
measure: Number of Participants With Absence of Active Retinopathy of Prematurity (ROP) at 40 Weeks Post Core Baseline Visit
timeFrame: at 40 weeks post core baseline visit
measure: Number of Participants With Absence of Active Retinopathy of Prematurity (ROP) at 52 Weeks Post Core Baseline Visit
timeFrame: at 52 weeks post core baseline visit
measure: Number of Participants With Absence of All Ocular Structural Abnormalities at or Before 40 Weeks Post Baseline Visit
timeFrame: at or before 40 weeks post baseline visit
measure: Number of Participants With Absence of All Ocular Structural Abnormalities at or Before the Participant's Fifth Birthday Visit
timeFrame: at or before the participant's fifth birthday visit (up to maximum 5 years and 4 months post core baseline visit)
measure: Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before 40 Weeks Post Baseline Visit
timeFrame: at or before 40 weeks post baseline visit
measure: Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before the Participant's Fifth Birthday Visit
timeFrame: at or before the participant's fifth birthday visit (up to maximum 5 years and 4 months post core baseline visit)
measure: Number of Participants With Absence of All Ocular Structural Abnormalities at or Before Participant's 2 Years Corrected Age Visit
timeFrame: at or before participant's 2 years corrected age visit (up to 2 years and 4 months post core baseline visit)
measure: Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before Participant's 2 Years Corrected Age Visit
timeFrame: at or before participant's 2 years corrected age visit (up to 2 years and 4 months post core baseline visit)
measure: Number of Participants With Recurrence of ROP up to 40 Weeks Post Baseline Visit in the Core Study
timeFrame: up to 40 weeks post baseline visit in the core study
measure: Number of Participants With Recurrence of ROP up to 52 Weeks Post Baseline Visit in the Core Study
timeFrame: up to 52 weeks post baseline visit in the core study
measure: Number of Ranibizumab Injections Received Per Participant Over the Whole Safety Observation Period
timeFrame: up to and including 40 weeks post baseline visit in the core study
measure: Refraction Status: Summary of Participants at Participant's 2 Years Corrected Age
timeFrame: at participant's 2 years corrected age (maximum 2 years and 4 months post core baseline visit)
measure: Refraction Status: Summary of Participants at the Participant's Fifth Birthday Visit
timeFrame: at the participant's fifth birthday visit (maximum 5 years and 4 months post core baseline visit)
measure: Change From Baseline in Weight
timeFrame: Baseline of the core study, at the subject's 2 years' corrected age (maximum 2 years and 4 months post core baseline visit) and at the subjects' fifth birthday (maximum 5 years and 4 months post core baseline visit)
measure: Change From Baseline in Head Circumference
timeFrame: Baseline of the core study and at the subject's 2 years' corrected age (maximum 2 years and 4 months post core baseline visit)
measure: Change From Baseline in Sitting Diastolic Blood Pressure
timeFrame: Baseline of the core study and at the subject's 2 years' corrected age (maximum 2 years and 4 months post core baseline visit)
measure: Change From Baseline in Sitting Systolic Blood Pressure
timeFrame: Baseline of the core study and at the subject's 2 years' corrected age (maximum 2 years and 4 months post core baseline visit)
measure: Number of Participants With the Summary of Respiratory Function Status
timeFrame: at the participants' fifth birthday visit (maximum 5 years and 4 months post core baseline visit)
measure: Number of Participants With Hearing Impairment of Any Type
timeFrame: at the participants' fifth birthday visit (maximum 5 years and 4 months post core baseline visit)
measure: Duration of Hospitalization
timeFrame: From baseline of the core study up to 5 years and 4 months post core baseline visit
measure: Weight at the Time of First Hospital Discharge
timeFrame: From baseline of the core study up to 5 years and 4 months post core baseline visit
Other outcomes:
Locations:
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: 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: 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: Zagreb
country: Croatia
facility: Novartis Investigative Site
city: Praha 4 - Podoli
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Ostrava
country: Czechia
facility: Novartis Investigative Site
state: Poruba
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
country: France
facility: Novartis Investigative Site
city: Marseille
country: France
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: 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: Perugia
country: Italy
facility: Novartis Investigative Site
state: PG
city: Fiumicino
country: Italy
facility: Novartis Investigative Site
state: RM
city: Roma
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: 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: 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: Istanbul
country: Turkey
facility: Novartis Investigative Site
state: Bakirkoy
city: Meselik
country: Turkey
facility: Novartis Investigative Site
state: Eskisehir
city: Soguksu / Antalya
country: Turkey
facility: Novartis Investigative Site
city: Manchester
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: Marlow N, Stahl A, Lepore D, Fielder A, Reynolds JD, Zhu Q, Weisberger A, Stiehl DP, Fleck B; RAINBOW investigators group. 2-year outcomes of ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW extension study): prospective follow-up of an open label, randomised controlled trial. Lancet Child Adolesc Health. 2021 Oct;5(10):698-707. doi: 10.1016/S2352-4642(21)00195-4. Epub 2021 Aug 13.