NT-501 Cell Therapy for Glaucoma

Overseen By Mariana Nunez, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Stanford University

Must not be taking: Acyclovir, Steroids, Immunosuppressants, Chemotherapy

Disqualifiers: Retinal disease, Cataracts, Diabetes, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 24

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates whether a new cell therapy, NT-501, is safe and effective for individuals with glaucoma, a condition that damages the optic nerve and can lead to vision loss. The study will test the treatment by implanting one or two devices in the eye to assess its impact on visual impairment over 24 months. Participants may qualify if they have glaucoma with some remaining vision, stable eye pressure, and are comfortable undergoing eye surgery. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important glaucoma research.

Will I have to stop taking my current medications?

The trial requires that you stop taking acyclovir and related products before enrolling and throughout the study. If you are on systemic steroids, immunosuppressive medications, or chemotherapy, you cannot participate in the trial.

What prior data suggests that the NT-501 cell therapy is safe for glaucoma patients?

Research has shown that NT-501 cell therapy is safe and well-tolerated for people with glaucoma. Studies have found that the implant does not cause major issues and is generally accepted by the body. One study observed improvements in both the structure and function of patients' eyes. Another study confirmed its likely safety. This suggests the treatment can help without causing significant side effects. For those considering joining a trial, this treatment offers promising safety data. ^{1 2 3 4 5}

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

Researchers are excited about NT-501 for glaucoma because it offers a unique delivery method that continuously releases a therapeutic protein directly in the eye. Unlike standard treatments like eye drops or oral medications, which require frequent administration, NT-501 uses encapsulated cell technology to maintain a steady release of ciliary neurotrophic factor (CNTF) over time. This could potentially provide more consistent protection for the optic nerve and reduce the progression of vision loss. The dual and single implantation approaches allow for flexibility in treatment intensity, catering to different needs of patients. This innovative approach could transform how glaucoma is managed, offering hope for better long-term outcomes.

What evidence suggests that NT-501 cell therapy could be an effective treatment for glaucoma?

Research shows that the NT-501 CNTF implant could be a promising treatment for glaucoma. In this trial, participants will join different treatment arms: one group will receive a dual implantation of two NT-501 devices, another will receive a single implantation of one NT-501 device, and a third will undergo sham implantation with no NT-501 devices. Earlier studies found that patients with primary open-angle glaucoma tolerated the implant well, leading to improvements in both the structure and function of their eyes. The treatment releases a substance that protects and repairs retinal cells, which are essential for vision. Patients experienced better sharpness of vision and improved ability to see contrasts. These positive results suggest that NT-501 might help with vision problems related to glaucoma. ^{1 4 5 6 7}

Who Is on the Research Team?

Jeffrey L Goldberg, MD, PhD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for individuals with stable glaucoma, having an eye pressure (IOP) less than 21 and visual field loss within a specific range. Participants must have some remaining vision (20/200 or better), be able to undergo required tests, and agree to birth control if applicable. Exclusions include those with certain other eye conditions, recent participation in another drug trial, pregnancy, or systemic diseases affecting the eyes.

Inclusion Criteria

Females of childbearing potential must agree to use an effective form of birth control

I am medically fit to undergo all required tests.

Participant's eye pressure must be clinically stable, with IOP <21

Exclusion Criteria

I can follow the study's procedures and attend all visits.

You have had a past occurrence of eye herpes.

I am currently undergoing chemotherapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive NT-501 ECT implants or sham surgery, with follow-up examinations for safety and efficacy

24 months

Initial visit for implantation, followed by periodic visits for 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, with an option for control arm participants to receive implants after 12 months

12 months

Periodic visits

What Are the Treatments Tested in This Trial?

Interventions

• NT-501

Trial Overview The study is testing NT-501 Encapsulated Cell Therapy (ECT), which aims to treat visual impairment due to glaucoma over a period of 24 months. Participants will receive either the NT-501 implants or a sham procedure as a comparison.

How Is the Trial Designed?

Group I: Single Implantation Experimental Treatment 1 Intervention

One NT-501 device will be implanted in the study eye.

Group II: Dual Implantation Experimental Treatment 1 Intervention

Two NT-501 devices will be implanted in the study eye.

Group III: Sham Implantation Placebo Group 1 Intervention

No NT-501 devices will be implanted in the study eye.

NT-501 is already approved in United States for the following indications:

Approved in United States as NT-501 for:

• Glaucoma
• Retinitis pigmentosa
• Age-related macular degeneration

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Published Research Related to This Trial

The study evaluated the safety and tolerability of an encapsulated cell implant delivering ciliary neurotrophic factor (CNTF) in 7 participants with macular telangiectasia type 2 over 36 months, showing no significant adverse effects on visual acuity or dark adaptation.

While there was a temporary reduction in the electroretinogram (ERG) response in some participants at 3 months, all measurements returned to baseline by 12 months, indicating that the treatment was safe and well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ciliary neurotrophic factor for macular telangiectasia type 2: results from a phase 1 safety trial. Chew, EY., Clemons, TE., Peto, T., et al.[2022]

Intraocular administration of ciliary neurotrophic factor (CNTF) via eye drops significantly improved retinal function in diabetic rats, as indicated by larger b-wave amplitudes in electroretinogram tests compared to untreated diabetic rats.

CNTF treatment also prevented structural damage in the retina, such as atrophy of the inner plexiform layer and cavity formation in the pigment epithelium, suggesting its potential as a protective therapy against retinal degeneration in diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical instillation of ciliary neurotrophic factor inhibits retinal degeneration in streptozotocin-induced diabetic rats. Aizu, Y., Katayama, H., Takahama, S., et al.[2019]

Transplantation of human ciliary neurotrophic factor (hCNTF) expressing cells significantly protects retinal ganglion cells (RGCs) from degeneration after optic nerve transection, with higher RGC density observed at multiple time points compared to controls.

The protective effects of hCNTF were evident as early as 5 days post-surgery, maintaining RGC morphology and delaying cell death, indicating its potential as a therapeutic intervention for optic nerve injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Protective effects of transplantation of hCNTF-transfected cell line on axotomy-induced degeneration of retinal ganglion cells]. Li, HM., Lu, SD., Xia, X., et al.[2005]

The NT-501 CNTF intraocular implant was found to be safe and well tolerated in 11 patients with primary open-angle glaucoma, with no serious adverse events reported over 18 months.

Patients with the CNTF implant showed improvements in visual function and retinal structure compared to their fellow eyes, indicating potential neuroprotective effects and supporting further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I NT-501 Ciliary Neurotrophic Factor Implant Trial for Primary Open-Angle Glaucoma: Safety, Neuroprotection, and Neuroenhancement. Goldberg, JL., Beykin, G., Satterfield, KR., et al.[2023]

In a rat model of glaucoma, researchers successfully induced chronic elevated intraocular pressure (IOP) and observed changes in the expression of ciliary neurotrophic factor (CNTF) in the retina over time.

CNTF expression was minimally present in healthy retinas but significantly increased in response to elevated IOP, suggesting a potential role for CNTF in the regeneration of retinal ganglion cells affected by glaucoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression of ciliary neurotrophic factor after induction of ocular hypertension in the retina of rats. Wu, Q., Zhang, M., Song, BW., et al.[2007]

In a Phase I safety trial involving 10 participants, the delivery of ciliary neurotrophic factor (CNTF) via surgically implanted encapsulated cell implants was found to be safe for the human retina, even in cases of severe photoreceptor degeneration.

While the trial was not designed to assess efficacy, three out of seven eyes showed significant improvements in visual acuity, suggesting potential benefits of CNTF treatment for retinal neurodegeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ciliary neurotrophic factor (CNTF) for human retinal degeneration: phase I trial of CNTF delivered by encapsulated cell intraocular implants. Sieving, PA., Caruso, RC., Tao, W., et al.[2022]

Intraocular administration of ciliary neurotrophic factor (CNTF) has shown promise in reducing photoreceptor degeneration and preserving retinal function in animal models of retinal diseases.

The review discusses various delivery methods for CNTF to the retina, emphasizing the need for techniques that ensure sustained release while minimizing harm and overcoming the eye's drug elimination barriers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ciliary neurotrophic factor (CNTF) delivery to retina: an overview of current research advancements. Ghasemi, M., Alizadeh, E., Saei Arezoumand, K., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10183667/

Phase I NT-501 Ciliary Neurotrophic Factor Implant Trial for ... The NT-501 CNTF implant was safe and well tolerated in eyes with POAG. Eyes with the implant demonstrated both structural and functional improvements.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37197702/

Phase I NT-501 Ciliary Neurotrophic Factor Implant Trial for ... The NT-501 CNTF implant was safe and well tolerated in eyes with POAG. Eyes with the implant demonstrated both structural and functional improvements.

3. clinicaltrialsarena.com clinicaltrialsarena.com/analyst-comment/aao-2024-phase-ii-study-cntf/

AAO 2024: Phase II study on the safety of intravitreal NT ... The NT-501 implant exhibited a strong safety profile in glaucoma patients, with encouraging structural improvements that suggest active biological effects and ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01408472

NCT01408472 | NT-501 CNTF Implant for Glaucoma ... Ciliary Neurotrophic Factor (CNTF) has been demonstrated in multiple pre-clinical models to enhance survival and regeneration of retinal ganglion cells, the ...

5. aao.org aao.org/education/editors-choice/cntf-implant-with-neuroprotective-potential-shows-

CNTF implant with neuroprotective potential shows good ... Outcomes. All patients tolerated the NT-501 implant without serious adverse events. Visual acuity and contrast sensitivity demonstrated a mild ...

6. ophthalmologyscience.org ophthalmologyscience.org/article/S2666-9145(23)00030-1/fulltext

Phase I NT-501 Ciliary Neurotrophic Factor Implant Trial for ... Primary outcome was safety through 18 months after implantation assessed by serial eye examinations, structural and functional testing, ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2666914523000301

Phase I NT-501 Ciliary Neurotrophic Factor Implant Trial for ... The NT-501 CNTF implant was safe and well tolerated in eyes with POAG. Eyes with the implant demonstrated both structural and functional improvements ...