Retinopathy of Prematurity (ROP)Phase 3RainbowExtNCT02640664
Rainbow Extension Study
A Phase 3 study testing Ranibizumab in people with Retinopathy of Prematurity (ROP), run by Novartis Pharmaceuticals at 73 sites in 24 countries.
Trial 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) Read more about this study
- Who is it for?
- Ages 6 months to 5 years
- Conditions the study is for
- Retinopathy of Prematurity (ROP)
- What is being tested?
- Ranibizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 180 participants
- Where
- 73 sitesin 24 countries
- Study dates
- 16 Jun 2016to 21 Apr 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 5 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
73 sites in 24 countries.
73 sites in 24 countries
Japan16 sites
Novartis Investigative Site
Fuchū, Tokyo, 183-8561
Novartis Investigative Site
Fukuoka, Fukuoka, 812-8582
Novartis Investigative Site
Fukuoka, Fukuoka, 814 0180
Novartis Investigative Site
Izumi, Osaka, 594-1101
Novartis Investigative Site
Kurume, Fukuoka, 830-0011
Novartis Investigative Site
Nagoya, Aichi-ken, 453-8511
Novartis Investigative Site
Nagoya, Aichi-ken, 466 8560
Novartis Investigative Site
Ohtsu-city, Shiga, 520-2192
Novartis Investigative Site
Ōta-ku, Tokyo, 143 8541
Novartis Investigative Site
Sapporo, Hokkaido
Novartis Investigative Site
Setagaya-ku, Tokyo, 157-8535
Novartis Investigative Site
Shimajiri-Gun, Okinawa, 901-1303
Novartis Investigative Site
Sumida-ku, Tokyo, 130-8575
Novartis Investigative Site
Toshima-ku, Tokyo, 170-8476
Novartis Investigative Site
Yachiyo, Chiba, 276-8524
Novartis Investigative Site
Zentsujichó, Kagawa-ken, 765-8507
United States9 sites
Novartis Investigative Site
Ann Arbor, Michigan, 48105
Novartis Investigative Site
Aurora, Colorado, 80045
Novartis Investigative Site
Austin, Texas, 78705
Novartis Investigative Site
Baltimore, Maryland, 21201
Novartis Investigative Site
Chicago, Illinois, 60612
Novartis Investigative Site
Louisville, Kentucky, 40202
Novartis Investigative Site
Morgantown, West Virginia, 26506
Novartis Investigative Site
Rochester, New York, 14642
Novartis Investigative Site
Sacramento, California, 95817
India6 sites
Novartis Investigative Site
Ahmedabad, Gujarat, 380016
Novartis Investigative Site
Coimbatore, Tamil Nadu, 641014
Novartis Investigative Site
Madurai, Tamil Nadu, 625020
Novartis Investigative Site
Mumbai, Maharashtra, 400 008
Novartis Investigative Site
New Delhi, 110029
Novartis Investigative Site
Vanchiyoor, Thiruvanantapuram, 695035
Italy4 sites
Novartis Investigative Site
Fiumicino, RM, 00054
Novartis Investigative Site
Florence, FI, 50139
Novartis Investigative Site
Perugia, PG, 06100
Novartis Investigative Site
Roma, RM, 00168
Russia4 sites
Novartis Investigative Site
Cheboksary, 428028
Novartis Investigative Site
Kazan', 420012
Novartis Investigative Site
Moscow, 127486
Novartis Investigative Site
Saint Petersburg, 194100
Czechia3 sites
Novartis Investigative Site
Ostrava, Poruba, 708 52
Novartis Investigative Site
Prague, 12808
Novartis Investigative Site
Praha 4 - Podoli, Czech Republic, 14700
Greece3 sites
Novartis Investigative Site
Ampelokipoi, GR, 115 27
Novartis Investigative Site
Athens, 115 27
Novartis Investigative Site
Thessaloniki, GR, 564 03
Romania3 sites
Novartis Investigative Site
Brasov, 500025
Novartis Investigative Site
Bucharest, 020395
Novartis Investigative Site
Timișoara, 300041
Turkey (Türkiye)3 sites
Novartis Investigative Site
Istanbul, Bakirkoy, 34140
Novartis Investigative Site
Meselik, Eskişehir, 26480
Novartis Investigative Site
Soguksu / Antalya, Turkey, 07100
Austria2 sites
Novartis Investigative Site
Graz, A-8036
Novartis Investigative Site
Vienna, 1090
Belgium2 sites
Novartis Investigative Site
Bruges, 8000
Novartis Investigative Site
Ghent, 9000
France2 sites
Novartis Investigative Site
Amiens, 80054
Novartis Investigative Site
Marseille, 13915
Hungary2 sites
Novartis Investigative Site
Budapest, 1125
Novartis Investigative Site
Debrecen, 4032
Malaysia2 sites
Novartis Investigative Site
Kota Kinabalu, Sabah, 88996
Novartis Investigative Site
Kuala Lumpur, Kuala Lumpur, 50586
Taiwan2 sites
Novartis Investigative Site
Taipei, 10002
Novartis Investigative Site
Taoyuan, 33305
United Kingdom2 sites
Novartis Investigative Site
Manchester, M13 9WL
Novartis Investigative Site
Portsmouth, PO6 3LY
About this 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
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)
Read the 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.
- Conditions
- Retinopathy of Prematurity (ROP)
- Being tested
- Ranibizumab
- Keywords
- open-label,, long-term,, extension study,, intravitreal ranibizumab,, laser ablation therapy,, retinopathy of prematurity,, preterm infants,, RAINBOW
- Medical subject headings
- Retinopathy of Prematurity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RanibizumabDrug
1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Ranibizumab |
| Laser therapy | No intervention | Laser therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Visual Acuity (VA) of the Better-seeing Eye at the Participant's Fifth Birthday Visit - Comparison Between Treatment Arms
The VA assessment at the child's 5th birthday visit was performed using Early Treatment Diabetic Retinopathy Study (ETDRS) methodology. VA measurements were taken in a sitting position at an initial test distance of 3 meters using Lea Symbols charts. Scores represented the number of optotypes (Lea symbols) the participant identified and ranged from 0 to 100, with higher scores indicating better visual acuity. VA was tested in each eye, using the child's current refractive index. The better-seeing eye was defined as the eye with the higher ETDRS score at the 5th birthday visit. If both eyes had the same ETDRS score, then the right eye was assigned as the better-seeing eye.
Measured: at the participant's fifth birthday visit (maximum 5 years and 4 months post core baseline visit)
Secondary outcomes (24)
Number of Participants With Ocular Adverse Events (AEs) Regardless of Study Treatment or Procedure Relationship by Preferred Term
Number of participants with ocular AEs starting during the core study and ongoing at extension baseline, or starting on/after extension baseline were reported.
Measured: throughout the study, approximately 5 years
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
Number of participants with non-ocular adverse events regardless of study treatment or procedure relationship (greater than or equal to 3% in any arm) by preferred term were reported.
Measured: throughout the study, approximately 5 years
Visual Acuity (VA) of the Worse-seeing Eye at the Participant's Fifth Birthday Visit - Comparison Between Treatment Arms
The VA assessment at the child's 5th birthday visit was performed using Early Treatment Diabetic Retinopathy Study (ETDRS) methodology. VA measurements were taken in a sitting position at an initial test distance of 3 meters using Lea Symbols charts. Scores represented the number of optotypes (Lea symbols) the participant identified and ranged from 0 to 100, with higher scores indicating better visual acuity. VA was tested in each eye, using the child's current refractive index. The worse-seeing eye was the eye with a lower ETDRS score at the 5th birthday visit. If both eyes had the same ETDRS score, then the left eye was assigned as the worse-seeing eye.
Measured: at the participant's fifth birthday visit (maximum 5 years and 4 months post core baseline visit)
Number of Participants With Absence of Active Retinopathy of Prematurity (ROP) at 40 Weeks Post Core Baseline Visit
The absence of active ROP in both eyes is defined by the absence of all of the following features: (1) Vessel dilatation of plus disease in at least 2 quardrants (some persisting tortuosity is allowed), (2) Extra-retina vessels extending from the retina into the vitreous and judged to be a sign of active ROP disease.
Measured: at 40 weeks post core baseline visit
Number of Participants With Absence of Active Retinopathy of Prematurity (ROP) at 52 Weeks Post Core Baseline Visit
The absence of active ROP in both eyes is defined by the absence of all of the following features: (1) Vessel dilatation of plus disease in at least 2 quardrants (some persisting tortuosity is allowed), (2) Extra-retina vessels extending from the retina into the vitreous and judged to be a sign of active ROP disease.
Measured: at 52 weeks post core baseline visit
Number of Participants With Absence of All Ocular Structural Abnormalities at or Before 40 Weeks Post Baseline Visit
The absence of all ocular structural abnormalities is defined by the absence of all of the following fundus features in both eyes at or before the given time point: (1) Substantial temporal retinal vessel dragging causing abnormal structural features/macular Ectopia, (2) Retrolental membrane obscuring the view of the posterior pole, (3) Posterior retinal fold involving the macula, (4) Retinal detachment involving the macula
Measured: at or before 40 weeks post baseline visit
Number of Participants With Absence of All Ocular Structural Abnormalities at or Before the Participant's Fifth Birthday Visit
The absence of all ocular structural abnormalities is defined by the absence of all of the following fundus features in both eyes at or before the given time point: (1) Substantial temporal retinal vessel dragging causing abnormal structural features/macular Ectopia, (2) Retrolental membrane obscuring the view of the posterior pole, (3) Posterior retinal fold involving the macula, (4) Retinal detachment involving the macula
Measured: at or before the participant's fifth birthday visit (up to maximum 5 years and 4 months post core baseline visit)
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before 40 Weeks Post Baseline Visit
Number of participants with absence of each structural abnormality in both eyes at or before the given time point: (1) Substantial temporal retinal vessel dragging causing abnormal structural features/macular Ectopia, (2) Retrolental membrane obscuring the view of the posterior pole, (3) Posterior retinal fold involving the macula, (4) Retinal detachment involving the macula, (5) Retinal detachment not involving the macula, (6) Pre-retinal fibrosis
Measured: at or before 40 weeks post baseline visit
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before the Participant's Fifth Birthday Visit
Number of participants with absence of each structural abnormality in both eyes at or before the given time point: (1) Substantial temporal retinal vessel dragging causing abnormal structural features/macular Ectopia, (2) Retrolental membrane obscuring the view of the posterior pole, (3) Posterior retinal fold involving the macula, (4) Retinal detachment involving the macula, (5) Retinal detachment not involving the macula, (6) Pre-retinal fibrosis, (7) Optic disc pallor, (8) Optic disc swelling, (9) Pigmentary disturbance in the macula, (10) Atrophic changes in the macula
Measured: at or before the participant's fifth birthday visit (up to maximum 5 years and 4 months post core baseline visit)
Number of Participants With Absence of All Ocular Structural Abnormalities at or Before Participant's 2 Years Corrected Age Visit
The absence of all ocular structural abnormalities is defined by the absence of all of the following fundus features in both eyes at or before the given time point: (1) Substantial temporal retinal vessel dragging causing abnormal structural features/macular Ectopia, (2) Retrolental membrane obscuring the view of the posterior pole, (3) Posterior retinal fold involving the macula, (4) Retinal detachment involving the macula
Measured: at or before participant's 2 years corrected age visit (up to 2 years and 4 months post core baseline visit)
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before Participant's 2 Years Corrected Age Visit
Number of participants with absence of each structural abnormality in both eyes at or before the given time point: (1) Substantial temporal retinal vessel dragging causing abnormal structural features/macular Ectopia, (2) Retrolental membrane obscuring the view of the posterior pole, (3) Posterior retinal fold involving the macula, (4) Retinal detachment involving the macula, (5) Retinal detachment not involving the macula, (6) Pre-retinal fibrosis, (7) Optic disc pallor, (8) Optic disc swelling, (9) Pigmentary disturbance in the macula, (10) Atrophic changes in the macula
Measured: at or before participant's 2 years corrected age visit (up to 2 years and 4 months post core baseline visit)
Number of Participants With Recurrence of ROP up to 40 Weeks Post Baseline Visit in the Core Study
Recurrence of ROP was defined as ROP receiving any post-baseline intervention after the 1st study treatment in the core study. In the ranibizumab arms, post-baseline interventions were ranibizumab retreatment or switch to laser. In the laser arm, post-baseline interventions were supplementary laser treatments after 11 days post-baseline, or switch to ranibizumab; supplementary laser treatment within 11 days post-baseline was not counted as recurrence.
Measured: up to 40 weeks post baseline visit in the core study
Number of Participants With Recurrence of ROP up to 52 Weeks Post Baseline Visit in the Core Study
Recurrence of ROP was defined as ROP receiving any post-baseline intervention after the 1st study treatment in the core study. In the ranibizumab arms, post-baseline interventions were ranibizumab retreatment or switch to laser. In the laser arm, post-baseline interventions were supplementary laser treatments after 11 days post-baseline, or switch to ranibizumab; supplementary laser treatment within 11 days post-baseline was not counted as recurrence. Beyond Week 40, participants did not receive any study intervention and no new data was collected after 40 weeks post core baseline visit.
Measured: up to 52 weeks post baseline visit in the core study
Number of Ranibizumab Injections Received Per Participant Over the Whole Safety Observation Period
Number of ranibizumab injections received in the treatment of participants with ROP up to and including 40 weeks post baseline visit in the core study were reported.
Measured: up to and including 40 weeks post baseline visit in the core study
Refraction Status: Summary of Participants at Participant's 2 Years Corrected Age
Summary of participants was reported to evaluate the refraction in each eye at the participant's 2 years corrected age
Measured: at participant's 2 years corrected age (maximum 2 years and 4 months post core baseline visit)
Refraction Status: Summary of Participants at the Participant's Fifth Birthday Visit
Summary of participants was reported to evaluate the refraction in each eye at the participant's 2 years' corrected age
Measured: at the participant's fifth birthday visit (maximum 5 years and 4 months post core baseline visit)
Change From Baseline in Weight
Subject´s weight was reported to evaluate the physical development.
Measured: 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)
Change From Baseline in Head Circumference
Subject´s head circumference was reported to evaluate the physical development.
Measured: Baseline of the core study and at the subject's 2 years' corrected age (maximum 2 years and 4 months post core baseline visit)
Change From Baseline in Sitting Diastolic Blood Pressure
Subject´s Sitting Diastolic Blood Pressure was reported to evaluate the physical development.
Measured: Baseline of the core study and at the subject's 2 years' corrected age (maximum 2 years and 4 months post core baseline visit)
Change From Baseline in Sitting Systolic Blood Pressure
Subject´s Sitting Systolic Blood Pressure was reported to evaluate the physical development.
Measured: Baseline of the core study and at the subject's 2 years' corrected age (maximum 2 years and 4 months post core baseline visit)
Number of Participants With the Summary of Respiratory Function Status
Number of participants with respiratory function status was reported
Measured: at the participants' fifth birthday visit (maximum 5 years and 4 months post core baseline visit)
Number of Participants With Hearing Impairment of Any Type
Number of participants with hearing function status was reported
Measured: at the participants' fifth birthday visit (maximum 5 years and 4 months post core baseline visit)
Duration of Hospitalization
Duration of hospitalization (from birth to first hospital discharge home) was reported to evaluate the health status of the subject
Measured: From baseline of the core study up to 5 years and 4 months post core baseline visit
Weight at the Time of First Hospital Discharge
Weight (gram) at the time of first hospital discharge was reported to evaluate the health status of the subject
Measured: From baseline of the core study up to 5 years and 4 months post core baseline visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2015 (estimated)
- Study start16 Jun 2016
- Primary completion21 Apr 2022
- Study completion21 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Retinopathy of Prematurity (ROP)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 180 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02640664
- Sponsor's protocol ID
- CRFB002H2301E1
- Other IDs
- 2014-004048-36, 2014
- Acronym
- RainbowExt
- Status last verified
- Jan 2023
- First submitted
- 1 Dec 2015
- Last updated
- 13 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Publications
Marlow N, Reynolds JD, Lepore D, Fielder AR, Stahl A, Hao H, Weisberger A, Lodha A, Fleck BW. Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): five-year outcomes of a randomised trial. EClinicalMedicine. 2024 Apr 11;71:102567. doi: 10.1016/j.eclinm.2024.102567. eCollection 2024 May.
PubMed 38638400Marlow 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.
PubMed 34391532
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02640664
- Acronym / sponsor ID
- RainbowExt / CRFB002H2301E1
- Conditions
- Retinopathy of Prematurity (ROP)
- Keywords
- open-label,, long-term,, extension study,, intravitreal ranibizumab,, laser ablation therapy,, retinopathy of prematurity,, preterm infants,, RAINBOW
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 180 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 16 Jun 2016 (actual)
- Primary completion
- 21 Apr 2022 (actual)
- Study completion
- 21 Apr 2022 (actual)
- First posted
- 29 Dec 2015 (estimated)
- Results
- Posted 13 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Ranibizumab 0.2 mg | Experimental | Drug: Ranibizumab1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required |
| Ranibizumab 0.1 mg | Experimental | Drug: Ranibizumab1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required |
| Laser therapy | No intervention | –Laser therapy |
Who may qualify
- Ages
- 6 months to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ranibizumab1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required | Drug | Ranibizumab 0.1 mg, Ranibizumab 0.2 mg |
Primary outcome
Visual Acuity (VA) of the Better-seeing Eye at the Participant's Fifth Birthday Visit - Comparison Between Treatment Arms
Time frame: at the participant's fifth birthday visit (maximum 5 years and 4 months post core baseline visit)
The VA assessment at the child's 5th birthday visit was performed using Early Treatment Diabetic Retinopathy Study (ETDRS) methodology. VA measurements were taken in a sitting position at an initial test distance of 3 meters using Lea Symbols charts. Scores represented the number of optotypes (Lea symbols) the participant identified and ranged from 0 to 100, with higher scores indicating better visual acuity. VA was tested in each eye, using the child's current refractive index. The better-seeing eye was defined as the eye with the higher ETDRS score at the 5th birthday visit. If both eyes had the same ETDRS score, then the right eye was assigned as the better-seeing eye.
24 secondary outcomes
Number of Participants With Ocular Adverse Events (AEs) Regardless of Study Treatment or Procedure Relationship by Preferred Term
Time frame: throughout the study, approximately 5 years
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
Time frame: throughout the study, approximately 5 years
Visual Acuity (VA) of the Worse-seeing Eye at the Participant's Fifth Birthday Visit - Comparison Between Treatment Arms
Time frame: at the participant's fifth birthday visit (maximum 5 years and 4 months post core baseline visit)
Number of Participants With Absence of Active Retinopathy of Prematurity (ROP) at 40 Weeks Post Core Baseline Visit
Time frame: at 40 weeks post core baseline visit
Number of Participants With Absence of Active Retinopathy of Prematurity (ROP) at 52 Weeks Post Core Baseline Visit
Time frame: at 52 weeks post core baseline visit
Number of Participants With Absence of All Ocular Structural Abnormalities at or Before 40 Weeks Post Baseline Visit
Time frame: at or before 40 weeks post baseline visit
Number of Participants With Absence of All Ocular Structural Abnormalities at or Before the Participant's Fifth Birthday Visit
Time frame: at or before the participant's fifth birthday visit (up to maximum 5 years and 4 months post core baseline visit)
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before 40 Weeks Post Baseline Visit
Time frame: at or before 40 weeks post baseline visit
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before the Participant's Fifth Birthday Visit
Time frame: at or before the participant's fifth birthday visit (up to maximum 5 years and 4 months post core baseline visit)
Number of Participants With Absence of All Ocular Structural Abnormalities at or Before Participant's 2 Years Corrected Age Visit
Time frame: at or before participant's 2 years corrected age visit (up to 2 years and 4 months post core baseline visit)
Number of Participants With Absence of Individual Ocular Structural Abnormalities at or Before Participant's 2 Years Corrected Age Visit
Time frame: at or before participant's 2 years corrected age visit (up to 2 years and 4 months post core baseline visit)
Number of Participants With Recurrence of ROP up to 40 Weeks Post Baseline Visit in the Core Study
Time frame: up to 40 weeks post baseline visit in the core study
Number of Participants With Recurrence of ROP up to 52 Weeks Post Baseline Visit in the Core Study
Time frame: up to 52 weeks post baseline visit in the core study
Number of Ranibizumab Injections Received Per Participant Over the Whole Safety Observation Period
Time frame: up to and including 40 weeks post baseline visit in the core study
Refraction Status: Summary of Participants at Participant's 2 Years Corrected Age
Time frame: at participant's 2 years corrected age (maximum 2 years and 4 months post core baseline visit)
Refraction Status: Summary of Participants at the Participant's Fifth Birthday Visit
Time frame: at the participant's fifth birthday visit (maximum 5 years and 4 months post core baseline visit)
Change From Baseline in Weight
Time frame: 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)
Change From Baseline in Head Circumference
Time frame: Baseline of the core study and at the subject's 2 years' corrected age (maximum 2 years and 4 months post core baseline visit)
Change From Baseline in Sitting Diastolic Blood Pressure
Time frame: Baseline of the core study and at the subject's 2 years' corrected age (maximum 2 years and 4 months post core baseline visit)
Change From Baseline in Sitting Systolic Blood Pressure
Time frame: Baseline of the core study and at the subject's 2 years' corrected age (maximum 2 years and 4 months post core baseline visit)
Number of Participants With the Summary of Respiratory Function Status
Time frame: at the participants' fifth birthday visit (maximum 5 years and 4 months post core baseline visit)
Number of Participants With Hearing Impairment of Any Type
Time frame: at the participants' fifth birthday visit (maximum 5 years and 4 months post core baseline visit)
Duration of Hospitalization
Time frame: From baseline of the core study up to 5 years and 4 months post core baseline visit
Weight at the Time of First Hospital Discharge
Time frame: From baseline of the core study up to 5 years and 4 months post core baseline visit
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38638400Marlow N, Reynolds JD, Lepore D, Fielder AR, Stahl A, Hao H, Weisberger A, Lodha A, Fleck BW. Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): five-year outcomes of a randomised trial. EClinicalMedicine. 2024 Apr 11;71:102567. doi: 10.1016/j.eclinm.2024.102567. eCollection 2024 May.
- Derived from this study: PubMed 34391532Marlow 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.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Related trials for Retinopathy of Prematurity (ROP)
RecruitingObservational study
The Correlation Between Red Cell Transfusion and Complications of Prematurity
Retinopathy of Prematurity (ROP), Bronchopulmonary Dysplasia (BPD)
RecruitingObservational study
An Observational Study to Collect Data on How Aflibercept (Eylea) Given Using a Paediatric Dosing Device is Used in Preterm Babies With Retinopathy of Prematurity in the United Kingdom (UK)
Retinopathy of Prematurity, Preterm Infants
RecruitingObservational study
Imaging Retinal Vasculature in Infant Eyes
Retinopathy of Prematurity
RecruitingPhase 1
Safety, PK and PD of FLQ-101 in Premature Neonates
Retinopathy of Prematurity (ROP)
Recruiting
Analyzing Retinal Microanatomy in Retinopathy of Prematurity to Improve Care
Retinopathy of Prematurity (ROP)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
73 sites in 24 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ranibizumab in people with Retinopathy of Prematurity (ROP), run by Novartis Pharmaceuticals at 73 sites in 24 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 73 sites in Japan, United States, India, Italy, Russia and 19 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Visual Acuity (VA) of the Better-seeing Eye at the Participant's Fifth Birthday Visit - Comparison Between Treatment Arms (time frame: at the participant's fifth birthday visit (maximum 5 years and 4 months post core baseline visit)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02640664, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2023.