NCX 470 for Glaucoma

(Whistler Trial)

Overseen By Siobhan Garbutt, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Nicox Ophthalmics, Inc.

Disqualifiers: Narrow angles, Ocular disease, Uncontrolled disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new eye drop called NCX 470, a nitric oxide-donating bimatoprost prostaglandin analog, to assess its effect on the liquid in the eye, which influences eye pressure. The study compares NCX 470 with a placebo to better understand its impact. It targets individuals without glaucoma who may have high eye pressure. Those with higher-than-normal eye pressure but without glaucoma or other serious eye issues might be suitable for this trial. As a Phase 2/3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to advancing eye care.

Do I need to stop my current medications to join the trial?

The trial information does not specify if 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 NCX 470 is likely to be safe for humans?

Research has shown that NCX 470, an eye drop that releases nitric oxide, is generally safe for patients. Studies have found it effectively reduces high eye pressure in individuals with open-angle glaucoma or ocular hypertension. Importantly, these studies did not identify any new safety concerns with its use.

In trials, researchers compared NCX 470 to latanoprost, a common glaucoma medication. Results indicated that NCX 470 not only matched but also outperformed latanoprost in lowering eye pressure. Additionally, no new safety issues emerged with NCX 470 over time. This suggests that the treatment is generally safe based on current evidence. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for glaucoma work by reducing eye pressure, often using drugs like prostaglandin analogs or beta-blockers. But NCX 470 takes a different approach, combining a nitric oxide-donating prostaglandin analog. This combination not only reduces intraocular pressure but also enhances blood flow to the optic nerve, which could protect against glaucoma damage. Researchers are excited about its potential to work faster and more effectively than standard treatments, possibly showing results in just a few days with once-daily dosing.

What evidence suggests that NCX 470 might be an effective treatment for glaucoma?

Research has shown that NCX 470 effectively lowers eye pressure, crucial for treating conditions like glaucoma. In studies, NCX 470 0.1% reduced eye pressure more effectively than latanoprost, a common treatment, achieving reductions of 7.9 to 10.0 mmHg compared to 7.1 to 9.8 mmHg with latanoprost. This trial will test NCX 470 0.1% against a placebo to further evaluate its effectiveness and safety. Additionally, patients tolerated it well, which is important for long-term use. Overall, these findings suggest that NCX 470 could be a promising option for managing high eye pressure and open-angle glaucoma. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults over 18 years old, of any gender, who do not have glaucoma but may have ocular hypertension (OHT) with eye pressure between 16 and 28 mmHg. It's not suitable for people already diagnosed with glaucoma.

Inclusion Criteria

I do not have glaucoma.

Your eye pressure is between 16 and 28 mmHg.

My gender does not exclude me from this trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive NCX 470 0.1% or placebo, one drop in the randomized eye once a day for 8 days

8 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NCX 470

Trial Overview

The study tests NCX 470 ophthalmic solution against a placebo to see how it affects the fluid dynamics in the eyes of healthy volunteers or those with high eye pressure but no glaucoma.

How Is the Trial Designed?

Group I: NCX 470 0.1% Active Control 1 Intervention

NCX 470 0.1% - one drop in the randomized eye once a day for 8 days

Group II: Placebo Placebo Group 1 Intervention

Artificial tears - one drop in the randomized eye once a day for 8 days

Who Is Running the Clinical Trial?

Nicox Ophthalmics, Inc.

Lead Sponsor

Trials

7

Recruited

2,800+

Published Research Related to This Trial

In a study of 94 black patients with open-angle glaucoma or ocular hypertension, both bimatoprost 0.03% and travoprost 0.004% significantly lowered intraocular pressure (IOP), but bimatoprost was more effective, with 85% of patients achieving at least a 20% reduction in IOP compared to 68% for travoprost.

Bimatoprost also resulted in a higher percentage of patients experiencing greater than 40% IOP reduction (31.9% vs. 20.9% for travoprost), while both treatments had similar safety profiles with no serious adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing bimatoprost and travoprost in black Americans. Noecker, RJ., Earl, ML., Mundorf, TK., et al.[2022]

Prostaglandin analogs like bimatoprost, latanoprost, and travoprost are effective and well-tolerated treatments for reducing intraocular pressure in patients with open-angle glaucoma and ocular hypertension, offering an alternative for those who do not respond to standard treatments.

These medications are at least as effective as the commonly used beta-blocker timolol, and while they can be combined with other treatments, more research is needed to determine the best combinations and to assess any differences in efficacy among the prostaglandin analogs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostaglandin analog treatment of glaucoma and ocular hypertension. Alexander, CL., Miller, SJ., Abel, SR.[2018]

NCX 139, a new compound combining latanoprost amide and a nitric oxide (NO) donor, significantly lowered intraocular pressure (IOP) in both rabbit and dog models of ocular hypertension, demonstrating its potential as an effective treatment for glaucoma.

In contrast to its des-nitro analog, NCX 139 showed a notable NO-mediated vascular relaxant effect and was more effective in reducing IOP compared to standard treatments like bimatoprost and latanoprost, particularly in hypertensive conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A dual acting compound with latanoprost amide and nitric oxide releasing properties, shows ocular hypotensive effects in rabbits and dogs. Impagnatiello, F., Borghi, V., Gale, DC., et al.[2018]

NCX 470, a new compound combining bimatoprost with nitric oxide, significantly lowers intraocular pressure (IOP) more effectively than bimatoprost alone in three animal models, including rabbits, monkeys, and dogs.

The enhanced IOP-lowering effect of NCX 470 is attributed to its dual action on the PGF2α and NO/cGMP signaling pathways, demonstrating its potential as a superior treatment for glaucoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraocular Pressure-Lowering Activity of NCX 470, a Novel Nitric Oxide-Donating Bimatoprost in Preclinical Models. Impagnatiello, F., Toris, CB., Batugo, M., et al.[2015]

Latanoprostene bunod (LBN) and NCX 470 are novel glaucoma treatments that combine prostaglandin analogs with nitric oxide (NO) donors, showing greater intraocular pressure (IOP) reduction compared to traditional treatments like latanoprost and timolol in clinical settings.

LBN demonstrated superior IOP-lowering efficacy in patients, while NCX 470 was more effective than bimatoprost in animal models, highlighting the potential of NO-donating therapies in managing ocular hypertension and glaucoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostaglandin analogues and nitric oxide contribution in the treatment of ocular hypertension and glaucoma. Impagnatiello, F., Bastia, E., Almirante, N., et al.[2023]

NCX 470 (0.1%) significantly reduced intraocular pressure (IOP) more effectively than Lumigan® (bimatoprost, 0.01%) in both single and repeated dosing studies involving Beagle dogs, with average IOP decreases of -6.06 mmHg for NCX 470 compared to -3.60 mmHg for Lumigan.

The enhanced IOP-lowering effect of NCX 470 is attributed to its ability to increase aqueous humor outflow facility and uveoscleral outflow, without altering aqueous flow, as demonstrated in non-human primates and 3D human trabecular meshwork constructs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NCX 470 Reduces Intraocular Pressure More Effectively Than Lumigan in Dogs and Enhances Conventional and Uveoscleral Outflow in Non-Human Primates and Human Trabecular Meshwork/Schlemm's Canal Constructs. Galli, C., Bastia, E., Hubatsch, DA., et al.[2023]

NCX 470, a nitric oxide-donating bimatoprost, effectively reversed increases in intraocular pressure (IOP) and improved ocular blood flow and retinal function in a rabbit model of ischemia/reperfusion, indicating its potential for enhancing ocular health.

The treatment not only lowered IOP but also restored retinal responses and reduced oxidative stress markers, suggesting that NCX 470 may improve retinal physiology through mechanisms beyond just lowering IOP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NCX 470 Restores Ocular Hemodynamics and Retinal Cell Physiology After ET-1-Induced Ischemia/Reperfusion Injury of Optic Nerve and Retina in Rabbits. Bastia, E., Sgambellone, S., Lucarini, L., et al.[2022]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38499140/

A Randomized, Controlled Comparison of NCX 470 ...

The NO-donating prostaglandin analogue NCX 470 0.1% was well-tolerated and lowered IOP more than latanoprost in subjects with OAG or OHT at all 6 time points.

2.

nicox.com

nicox.com/wp-content/uploads/EN_NCX470DenaliToplineAugust2025_PR_FINAL.pdf

Nicox Announces Positive Results from the NCX 470 ...

NCX 470, Nicox's lead clinical product candidate, is a novel NO-donating bimatoprost eye drop being developed for the lowering of IOP in ...

3.

ophthalmologytimes.com

ophthalmologytimes.com/view/nicox-releases-topline-data-from-phase-3-denali-trial-of-ncx-470-in-open-angle-glaucoma-or-ocular-hypertension-patients

Nicox releases topline data from phase 3 Denali trial ...

The IOP lowering effect from baseline was 7.9 to 10.0 mmHg for NCX 470 0.1% vs. 7.1 to 9.8 mmHg for latanoprost 0.005%. This was measured as a ...

4.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1551714424003136

A phase 3 adaptive dose selection trial of NCX 470, a nitric ...

NCX 470 demonstrated dose-dependent reductions in mean diurnal IOP at day 28 that were non-inferior to latanoprost 0.005 % at all three doses and superior to ...

5.

appliedclinicaltrialsonline.com

appliedclinicaltrialsonline.com/view/ncx-470-glaucoma-strong-intraocular-pressure-reductions

NCX 470 Meets Phase III Goal in Glaucoma With Strong ...

The Denali trial confirmed non-inferiority of NCX 470 to latanoprost in lowering intraocular pressure, with consistent efficacy, favorable ...

6.

firstwordpharma.com

firstwordpharma.com/story/6229530

Nicox's NCX 470 Demonstrates Sustained Efficacy through ...

NCX 470 maintained robust IOP reduction during this period with no additional safety signals seen. New Drug Applications (NDAs) for NCX 470 are ...