CBT-001 Eye Drops for Pterygium

Not currently recruiting at 53 trial locations

Overseen By Abu Abraham, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Cloudbreak Therapeutics, LLC

Disqualifiers: Pterygium removal, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of CBT-001 eye drops (nintedanib ophthalmic formulation) for treating pterygium, a growth on the eye that can cause redness and irritation (conjunctival hyperemia). Researchers are testing two versions of the treatment: a low dose and a high dose, both compared to a placebo (an inactive substance). The goal is to determine if these drops can reduce redness and prevent the growth from worsening over two years. Ideal participants have pterygium and noticeable eye redness but have not undergone surgery to remove it in the past six months. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that CBT-001 eye drops are generally safe. Previous studies indicate that these eye drops, used to treat pterygium (a growth on the eye), are usually well-tolerated. Some side effects, such as diarrhea or changes in liver function, can occur, but they are uncommon when the drops are used in the eyes.

In trials, patients using CBT-001 experienced less eye redness and slower growth of the pterygium. Overall, the safety profile is positive, meaning most people do not encounter serious issues with the treatment. This suggests that CBT-001 is safe for humans, based on the available data. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pterygium?

Unlike the standard treatment options for pterygium, which often involve surgical removal or anti-inflammatory medications, CBT-001 eye drops introduce a novel approach. Researchers are excited about these eye drops because they offer a non-invasive method to potentially reduce the growth of pterygium by targeting the underlying vascular structures. The two dosages being tested, low and high, may provide flexibility in treatment, allowing for personalized care based on the severity of the condition. This treatment could significantly improve patient comfort and outcomes by reducing the need for surgery and its associated risks.

What evidence suggests that CBT-001 eye drops could be effective for pterygium?

Research has shown that CBT-001 eye drops can reduce the growth and redness of pterygium, a tissue growth on the eye. In earlier studies, using CBT-001 at a 0.2% concentration reduced the size and blood vessel growth of pterygium after just four weeks, with benefits persisting even after treatment stopped. Patients tolerated the treatment well. Additionally, animal studies demonstrated that CBT-001 can prevent unwanted blood vessel growth in the eye. These findings suggest that CBT-001 could effectively prevent pterygium from worsening and reduce redness. Participants in this trial will receive either a low or high dose of CBT-001, or a vehicle control as a placebo comparator. ^{3 5 6 7 8}

Who Is on the Research Team?

Bruce A Segal, MD

Principal Investigator

Bruce A. Segal, MD

Are You a Good Fit for This Trial?

This trial is for individuals at least 12 years old with pterygium and good general health. They must have a visual acuity of 20/200 or better in one eye, agree to use contraception if applicable, and not be pregnant or nursing. Excluded are those with uncontrolled diseases like cancer, active ocular infections, significant corneal abnormalities unrelated to pterygium, recent eye surgeries (except for pterygium excision), severe seasonal ocular allergies, history of ocular herpes or trauma.

Inclusion Criteria

Is in good general health as determined by the investigator from medical history and physical examination findings, non-fasting blood analysis within reference range or acceptable to the investigator prior to randomization

I, or my legal guardian, have given written consent to participate.

Subject has a best-corrected visual acuity (BCVA) score equivalent to Snellen acuity of 20/200 or better in at least one eye at Screening and Baseline

Exclusion Criteria

I do not have any eye diseases like macular degeneration.

I have had herpes in my eye before.

I have a disease that is not under control and am receiving treatment for it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CBT-001 eye drops dosed twice daily to evaluate safety and efficacy in reducing conjunctival hyperemia and preventing pterygium progression

12 months

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• CBT-001
• Vehicle

Trial Overview The trial tests the safety and effectiveness of CBT-001 emulsion at two different concentrations (0.1% and 0.2%) against a placebo vehicle. Participants will apply the treatment twice daily for two years to see if it reduces redness and prevents the growth of their pterygium.

How Is the Trial Designed?

Group I: CBT-001 Low Dose Experimental Treatment 1 Intervention

CBT-001 eye drop

Group II: CBT-001 High Dose Experimental Treatment 1 Intervention

CBT-001 eye drop

Group III: Vehicle Placebo Group 1 Intervention

Emulsion eye drop without drug

Who Is Running the Clinical Trial?

Cloudbreak Therapeutics, LLC

Lead Sponsor

Trials

6

Recruited

1,000+

Published Research Related to This Trial

A new nanoparticle depot platform allows for noninvasive, on-demand drug delivery to the eye, significantly reducing the need for uncomfortable intravitreal injections that are typically required every 4-8 weeks.

The light-triggered release of the drug nintedanib from these nanoparticles effectively suppresses choroidal neovascularization in rats without causing any adverse effects on the eye, demonstrating both safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Light-responsive nanoparticle depot to control release of a small molecule angiogenesis inhibitor in the posterior segment of the eye. Huu, VA., Luo, J., Zhu, J., et al.[2018]

The nintedanib nano thermoreversible hydrogel (NNTH) was found to be the most effective treatment for inhibiting corneal neovascularization in rats with alkali burns, outperforming other forms of nintedanib and dexamethasone.

NNTH not only reduced inflammation but also demonstrated a longer duration of drug release, while low concentrations of nintedanib showed minimal cytotoxicity to corneal epithelial cells but effectively inhibited the migration and proangiogenic activity of vascular endothelial cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Nintedanib Nanothermoreversible Hydrogel on Neovascularization in an Ocular Alkali Burn Rat Model. Liu, X., Wu, S., Gong, Y., et al.[2023]

The study developed two types of nanoparticle formulations (αTS-PTX-NLC and αTS-PTX-PEG-NLC) that effectively encapsulate the chemotherapy drug paclitaxel, achieving over 95% entrapment efficiency, which could enhance its delivery for treating retinoblastoma.

Both formulations demonstrated favorable stability and release profiles, with a controlled drug release of 40% over 48 hours, suggesting they could improve ocular bioavailability and reduce systemic toxicity associated with paclitaxel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of α-Tocopherol Succinate-Based Nanostructured Lipid Carriers for Delivery of Paclitaxel. Marathe, S., Shadambikar, G., Mehraj, T., et al.[2023]

Nintedanib effectively inhibits the growth of pterygium cells and induces apoptosis, as evidenced by changes in cell morphology and increased expression of apoptosis-related proteins in cultured human primary pterygium cells.

The mechanism of action involves the inhibition of the FGFR2/ERK pathway, with nintedanib significantly reducing ERK1/2 phosphorylation, indicating its potential as a therapeutic option for treating pterygium.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nintedanib induces apoptosis in human pterygium cells through the FGFR2-ERK signalling pathway. Gong, Y., Liao, YH., Yi, QY., et al.[2023]

Anti-VEGF agents significantly reduce the recurrence rate of pterygium after surgery, with a risk ratio of 0.47 based on a review of 1,096 eyes from 19 randomized controlled trials.

The use of anti-VEGF agents as an adjunct treatment is effective, particularly in White patients, and does not increase the risk of complications compared to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of anti-vascular endothelial growth factor agents in the treatment of primary pterygium. Zhang, B., Dong, X., Sun, Y.[2023]

The newly developed axitinib-loaded nanowafer drug delivery system significantly enhances therapeutic efficacy for treating corneal neovascularization (CNV) compared to traditional topical eye drops, requiring only once-a-day administration instead of twice a day.

The nanowafer is nontoxic and does not interfere with wound healing or epithelial recovery, making it a safer alternative to current eye drop therapies that can cause side effects like glaucoma and cataracts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocular drug delivery nanowafer with enhanced therapeutic efficacy. Yuan, X., Marcano, DC., Shin, CS., et al.[2022]

In a pilot study involving 10 patients (5 treated with ranibizumab and 5 controls), ranibizumab was well tolerated with no reported side effects, indicating its safety for use in treating primary pterygium.

Despite its safety, the study found that a single subconjunctival injection of ranibizumab did not affect the vascularization of pterygium, showing no regression of blood vessels in treated patients compared to controls.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of subconjunctival ranibizumab on primary pterygium: a pilot study. Mandalos, A., Tsakpinis, D., Karayannopoulou, G., et al.[2015]

Nintedanib has been shown to effectively slow the decline in lung function (measured by forced vital capacity) in patients with idiopathic pulmonary fibrosis (IPF), based on data from one phase II and two phase III clinical trials.

While nintedanib is generally safe, with diarrhea being the most common side effect, further research is needed to confirm its impact on mortality and acute exacerbations in specific patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nintedanib for Idiopathic Pulmonary Fibrosis. Tepede, A., Yogaratnam, D.[2022]

In a pilot study involving 10 patients with primary pterygium, a single subconjunctival injection of ranibizumab was found to be well tolerated, with no significant safety concerns reported over a 6-month follow-up period.

While the majority of patients had successful outcomes with intact conjunctival autografts, three recurrences of pterygium were observed, all in patients who received the injection three days prior to surgery, suggesting timing may influence effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of subconjunctival ranibizumab in patients with primary pterygium undergoing pterygium surgery. Galor, A., Yoo, SH., Piccoli, FV., et al.[2015]

In a randomized controlled trial involving 74 pterygium eyes from 66 patients, intralesional injection of bevacizumab significantly reduced symptoms and signs of primary pterygium for at least 6 months, indicating its potential efficacy in treatment.

The study found no significant differences in outcomes between the bevacizumab treatment group and the control group receiving topical antihistamines and vasoconstrictors, suggesting that while bevacizumab may help with symptoms, it does not outperform the control treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of intralesional bevacizumab injection on primary pterygium: preliminary results. Enkvetchakul, O., Thanathanee, O., Rangsin, R., et al.[2022]

The study developed a microemulsion formulation of sunitinib (STB-ME) eye drops that effectively inhibits corneal neovascularization (CNV) through topical application, showing superior efficacy compared to saline and comparable results to dexamethasone.

STB-ME demonstrated enhanced ocular bioavailability, with a 2.47-fold increase in the cornea and a 2.14-fold increase in the conjunctiva, along with sustained drug release, making it a promising treatment option for CNV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preparation of a Sunitinib loaded microemulsion for ocular delivery and evaluation for the treatment of corneal neovascularization in vitro and in vivo. Shi, J., Yang, J., Xu, H., et al.[2023]

In a study involving 21 rabbits, nintedanib was found to significantly reduce corneal neovascularization (NV) compared to both a saline control and Avastin, suggesting it may be a more effective treatment option.

The mechanism of action appears to involve the suppression of key signaling pathways, including VEGF, Akt, and P38 MAPK, which are associated with angiogenesis, indicating nintedanib's potential as a novel therapy for corneal NV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of corneal neovascularization by topical application of nintedanib in rabbit models. Chen, J., Ding, X., Du, W., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11179250/

A Phase IIa Multicenter, Randomized, Vehicle-Controlled ... CBT-001 0.2% decreased pterygia vascularity and lesion length after 4 weeks of dosing with a prolonged effect after dosing. The drug was well tolerated.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38883924/

A Phase IIa Multicenter, Randomized, Vehicle-Controlled, ... CBT-001 0.2% decreased pterygia vascularity and lesion length after 4 weeks of dosing with a prolonged effect after dosing. The drug was well tolerated.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03049852?tab=results

Study Results | Safety and Efficacy of CBT-001 Ophthalmic ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

4. grantome.com grantome.com/grant/NIH/R44-EY028784-03

A Phase 2a Multicenter, Randomized, Vehicle-Controlled ... We have shown that our formulated nintedanib, CBT-001, suppresses cornea neovascularization in a rabbit corneal suture model and causes regression of human ...

5. withpower.com withpower.com/trial/phase-3-pterygium-5-2022-f2cc0

CBT-001 Eye Drops for Pterygium · Info for Participants This trial is testing CBT-001 eye drops to see if they can reduce eye redness and stop tissue growth in people with pterygia. The drops are used regularly ...

6. ophthalmologyscience.org ophthalmologyscience.org/article/S2666-9145(24)00038-1/fulltext

A Phase IIa Multicenter, Randomized, Vehicle-Controlled, ... To evaluate the safety and efficacy of CBT-001, a multitarget tyrosine kinase inhibitor eyedrop, for pterygia.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03049852?term=AREA%5BSponsorSearch%5D(COVERAGE%5BFullMatch%5DEXPANSION%5BNone%5D(%22Cloudbreak%20Therapeutics,%20LLC%22))&rank=6

Safety and Efficacy of CBT-001 Ophthalmic Solution in ... Objectives are to evaluate ocular and systemic safety of CBT-001 in primary or recurrent patients that have moderate to severe pterygium vascularity and to ...

8. clinrol.com clinrol.com/study/NCT05456425

"CBT-001 for Pterygium: Safety & Efficacy" CBT-001, dosed twice daily, effectively reduces conjunctival hyperemia and prevents pterygium progression, with a favorable safety profile.