Bevacizumab for Retinopathy of Prematurity

(ROP4 Trial)

Not currently recruiting at 36 trial locations

Overseen By Brooke P Fimbel

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Jaeb Center for Health Research

Disqualifiers: Previous ROP treatment, Stage 4/5 ROP, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Immediate

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether two different doses of bevacizumab, a medication injected into the eye, can effectively treat type 1 retinopathy of prematurity (ROP), a severe eye condition in premature infants. The study targets babies with type 1 ROP in zone I, the most serious form affecting the central retina. Eligible infants should weigh less than 1251 grams at birth and have been diagnosed with type 1 ROP in zone I within the past two days. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important early findings.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using bevacizumab as an eye injection is generally safe for treating retinopathy of prematurity (ROP). One study on babies with ROP found that bevacizumab worked well and was well-tolerated, with no major safety concerns.

Compared to similar treatments, bevacizumab often required fewer follow-up treatments, indicating effective results without additional issues. Importantly, studies reviewed have reported no severe side effects, which reassures those considering this treatment.

The FDA has also approved bevacizumab for other eye conditions, supporting its overall safety. While this trial continues to collect more data, existing studies provide strong evidence that bevacizumab is a safe choice for treating ROP. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about bevacizumab for retinopathy of prematurity (ROP) because it offers a targeted approach by inhibiting vascular endothelial growth factor (VEGF), which is crucial in the abnormal blood vessel growth seen in ROP. Unlike the standard treatments, such as laser therapy that can damage retinal tissue, bevacizumab is administered as an intravitreal injection, potentially preserving more of the infant's vision. Additionally, with two different dosage options—0.063 mg and 0.25 mg—researchers hope to find the most effective and safest dose, offering more tailored treatment options for affected infants.

What evidence suggests that bevacizumab might be an effective treatment for retinopathy of prematurity?

Research has shown that bevacizumab effectively treats retinopathy of prematurity (ROP), a serious eye condition in premature babies. One study found that 85.13% of eyes with ROP improved after a bevacizumab injection, with the most severe cases (zone I stage 3+) showing a 100% improvement. Another study demonstrated that even a low dose of 0.03 mg effectively treated type 1 ROP in all tested eyes. In this trial, participants will receive either a 0.063 mg or 0.25 mg dose of bevacizumab, potentially offering promising treatment options for severe ROP cases. ^{4 6 7 8 9}

Who Is on the Research Team?

David K Wallace, MD, MPH

Principal Investigator

Vanderbilt University

Are You a Good Fit for This Trial?

This trial is for premature babies with a birth weight under 1251 grams who have been newly diagnosed with severe type of retinopathy (eye disease) in zone I. Babies can't participate if they have other significant eye problems, previous ROP treatments, active infections around the eye, advanced stages of ROP, or if they cannot receive treatment within two days of diagnosis.

Inclusion Criteria

I was recently diagnosed with a specific eye condition in the past 2 days.

My birth weight was less than 1251 grams.

Exclusion Criteria

I have been treated for retinopathy of prematurity before.

Opacity that precludes an adequate view of the retina

My eye condition is at stage 4 or 5 ROP.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 days

Treatment

Participants receive a single intravitreal injection of either 0.063 mg or 0.25 mg of bevacizumab in one or both eyes

Immediate

1 visit (in-person)

Initial Follow-up

Study exams to monitor treatment success and safety at 1 day, 4 days, 1, 2, 3, and 4 weeks post-treatment

4 weeks

Multiple visits (in-person)

Extended Follow-up

Additional study exams to assess long-term outcomes at 2 and 4 months post-treatment, and at adjusted age 6 and 12 months

12 months

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab

Trial Overview

The study is testing low doses of Bevacizumab (0.063 mg and 0.25mg) to see if it's effective for treating severe retinopathy in very young infants. It will also look at how well the retina's blood vessels develop after treatment compared to standard doses.

How Is the Trial Designed?

Group I: Bevacizumab- 0.25 mg Experimental Treatment 1 Intervention

Participants will receive a single intravitreal injection of 0.25 mg of bevacizumab in one or both eyes following enrollment into the study. The injection/s should be given as soon as possible but no later than 2 days after the diagnosis of type 1 ROP meeting all of the inclusion criteria and none of the exclusion criteria.

Group II: Bevacizumab- 0.063 mg Experimental Treatment 1 Intervention

Participants will receive a single intravitreal injection of 0.063 mg of bevacizumab in one or both eyes following enrollment into the study. The injection/s should be given as soon as possible but no later than 2 days after the diagnosis of type 1 ROP meeting all of the inclusion criteria and none of the exclusion criteria.

Bevacizumab is already approved in European Union, United States, Japan, Canada for the following indications:

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Who Is Running the Clinical Trial?

Jaeb Center for Health Research

Lead Sponsor

Trials

162

Recruited

36,200+

National Eye Institute (NEI)

Collaborator

Trials

572

Recruited

1,320,000+

Pediatric Eye Disease Investigator Group

Collaborator

Trials

20

Recruited

4,800+

Published Research Related to This Trial

Intravitreal injection of bevacizumab is a safe and effective treatment for aggressive posterior retinopathy of prematurity (APROP), as demonstrated in a case involving a premature infant with significant retinal improvements after treatment.

While tissue contraction can occur as a side effect, localized tractional retinal detachment can be effectively managed with lens-sparing vitrectomy, allowing for successful retinal reattachment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive effect of intravitreal bevacizumab prior to lens-sparing vitrectomy in aggressive posterior retinopathy of prematurity: a case report. Sun, HJ., Choi, KS., Lee, SJ.[2021]

A systematic review of 9 studies involving 77 eyes of 48 infants revealed significant variability in the off-label use of bevacizumab for treating retinopathy of prematurity (ROP), with doses ranging from 0.4 to 1.25 mg, and 0.75 mg being the most common.

The review highlighted the need for further randomized controlled trials to determine the optimal timing, frequency, and dosage of bevacizumab, while also emphasizing the importance of monitoring for potential systemic complications and long-term effects in infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic analysis of the off-label use of bevacizumab for severe retinopathy of prematurity. Micieli, JA., Surkont, M., Smith, AF.[2022]

Intravitreal bevacizumab (Avastin) was used as a salvage treatment for progressive retinopathy of prematurity (ROP) in three patients, showing stabilization of the disease despite previous laser therapy.

The treatment allowed for improved visibility and management of ROP, enabling further laser treatment when necessary, indicating its potential efficacy in difficult cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Off-label use of intravitreal bevacizumab (Avastin) for salvage treatment in progressive threshold retinopathy of prematurity. Lalwani, GA., Berrocal, AM., Murray, TG., et al.[2015]

In a study involving 24 eyes from 13 infants with severe retinopathy of prematurity (ROP), intraocular bevacizumab treatment led to regression of new blood vessels in all cases, demonstrating its efficacy in managing this condition.

While many eyes experienced vision salvage and no serious neurodevelopmental issues were noted over a mean follow-up of 30.7 months, there were significant adverse events, including retinal detachment and hepatic dysfunction, highlighting the need for careful monitoring when using this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious adverse events and visual outcomes of rescue therapy using adjunct bevacizumab to laser and surgery for retinopathy of prematurity. The Indian Twin Cities Retinopathy of Prematurity Screening database Report number 5. Jalali, S., Balakrishnan, D., Zeynalova, Z., et al.[2016]

Avastin (bevacizumab) therapy shows promise as a more effective treatment for retinopathy of prematurity (ROP) with potentially fewer complications, especially in severe cases where traditional LASER therapy has poor outcomes.

Current clinical trials are exploring the use of Avastin alone for acute vision-threatening ROP and in combination with LASER therapy for recurrent cases, indicating a shift towards less destructive treatment methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antivascular endothelial growth factor for retinopathy of prematurity. Mintz-Hittner, HA., Best, LM.[2022]

In a study involving 12 eyes of 7 premature infants with type 1 retinopathy of prematurity, a single intravitreal injection of bevacizumab (Avastin) led to complete regression of the disease without the need for further treatment.

The infants treated had a mean weight of 846.57 grams and a mean gestational age of 25.57 weeks, indicating that bevacizumab is a promising therapy for this vulnerable population, although more research is needed to establish its role compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of type 1 retinopathy of prematurity with intravitreal bevacizumab (Avastin). Dorta, P., Kychenthal, A.[2022]

Infants with treatment-warranted retinopathy of prematurity (TW-ROP) who received intravitreal bevacizumab (IVB) injections had significantly fewer diagnoses and readmissions compared to those treated with diode laser photocoagulation (DLP), suggesting better immediate outcomes with IVB.

At an average follow-up of 20 months, there was no significant difference in neurodevelopmental delay between the two treatment groups, indicating that systemic morbidity may be similar for both IVB and DLP treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Intravitreal Bevacizumab and Diode Laser Photocoagulation for Treatment-Warranted Retinopathy of Prematurity. Chen, TA., Schachar, IH., Moshfeghi, DM.[2019]

A premature infant born at 26 weeks was successfully treated for severe retinopathy of prematurity with bevacizumab, leading to complete resolution of the disease.

Bevacizumab is an effective and cost-efficient treatment option for retinopathy of prematurity, which can be administered easily by ophthalmologists without specialized equipment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal bevacizumab for the treatment of retinopathy of prematurity: a case report. Flavahan, PW., Lavy, TE., Wykes, W.[2015]

In a case series of 11 premature infants with moderate to severe stage 3 retinopathy of prematurity (ROP), treatment with a single intravitreal injection of bevacizumab was safe and effective, with no complications reported.

All 22 eyes treated showed successful outcomes without any retinal detachment or other ocular abnormalities, suggesting that bevacizumab could be a promising alternative to laser therapy for ROP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal injection of bevacizumab (avastin) for treatment of stage 3 retinopathy of prematurity in zone I or posterior zone II. Mintz-Hittner, HA., Kuffel, RR.[2022]

Intravitreal bevacizumab (Avastin) was found to enter the systemic circulation and cause long-lasting changes in lung matrix metalloproteinases (MMPs) and their inhibitors in neonatal rats, suggesting potential systemic effects beyond its local application.

The treatment with Avastin led to increased levels of MMP-2 and MMP-9 in the lungs of rats exposed to hyperoxia and intermittent hypoxia, which may contribute to impaired lung development and conditions like bronchopulmonary dysplasia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal bevacizumab alters type IV collagenases and exacerbates arrested alveologenesis in the neonatal rat lungs. Valencia, AM., Cai, CL., Tan, J., et al.[2019]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4600496/

Outcomes and Prognostic Factors of Intravitreal ...

One week after the bevacizumab injection, ROP regressed in 63 eyes (85.13%), with a statistically significant higher rate in zone I stage 3+ ROP (100%), as ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00622726

Study Details | NCT00622726 | Bevacizumab Eliminates ...

This study enrolled 150 confirmed cases of vision threatening ROP which have definite plus disease [ranging from Early Treatment for Retinopathy of Prematurity, ...

3.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1007374

Efficacy of Intravitreal Bevacizumab for Stage 3+ ...

The primary ocular outcome was recurrence of retinopathy of prematurity in one or both eyes requiring retreatment before 54 weeks' postmenstrual ...

4.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/32324197/

Short-term Outcomes After Very Low-Dose Intravitreous ...

These data suggest that 0.004 mg may be the lowest dose of bevacizumab effective for ROP. Further investigation is warranted to confirm effectiveness.

5.

ophthalmologyretina.org

ophthalmologyretina.org/article/S2468-6530(25)00061-2/fulltext

Low-Dose Bevacizumab 0.03 mg for Treatment of Type 1 ...

The outcomes achieved in 123 eyes in clinical practice using a 0.03-mg dose of IVB confirm that this dose is effective for treatment of ROP; all 123 eyes (100%) ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8784485/

Ocular and Systemic Results of Intravitreal Bevacizumab ...

The aim of this study was to evaluate the effectiveness and safety of an intravitreal bevacizumab injection (IVB) in the treatment of retinopathy of prematurity ...

7.

nature.com

nature.com/articles/s41433-025-03735-z

Comparing safety and efficacy of Bevacizumab ...

Bevacizumab showed a significantly delayed reactivation, while Ranibizumab and its biosimilar Razumab were comparable. Data from clinical trials.

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S2162098923005406

Intravitreal Bevacizumab in Retinopathy of Prematurity

This article is aimed to review and summarize the indications, outcomes and safety profiles regarding the use of intravitreal bevacizumab in patients with ...

9.

aao.org

aao.org/education/editors-choice/common-anti-vegf-agents-appear-to-have-similar-saf

Common Anti-VEGF Agents Appear to Have Similar Safety ...

This study provides real-world data comparing 3 commonly used anti-VEGF agents for ROP treatment. Bevacizumab showed lower retreatment rates than the other two ...