NT-501 Cell Therapy for Glaucoma

Overseen by Jeffrey L Goldberg, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Stanford University

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

Disqualifiers: Retinal disease, Cataracts, Diabetes, others

No Placebo Group

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial tests tiny devices that release a protective protein into the eyes of patients with glaucoma-related vision problems. The protein helps protect nerve cells, potentially preventing further vision loss and improving sight.

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 data supports the effectiveness of the NT-501 treatment for glaucoma?

Research shows that ciliary neurotrophic factor (CNTF), a component of NT-501, has been effective in slowing retinal degeneration in animal models and improving visual acuity in some human trials for retinal diseases. Additionally, CNTF has shown potential in stimulating the regeneration of retinal cells in glaucoma models, suggesting it may help protect and enhance vision. ^{1 2 3 4 5}

Is NT-501 Cell Therapy safe for humans?

The NT-501 Cell Therapy, which uses ciliary neurotrophic factor (CNTF) delivered through an encapsulated cell implant, has been shown to be safe in human trials for retinal conditions. In a Phase I trial, it was well-tolerated with minimal side effects, and a similar trial for glaucoma also focused on safety. ^{1 3 4 5 6}

How is the NT-501 treatment for glaucoma different from other treatments?

The NT-501 treatment for glaucoma is unique because it uses an encapsulated cell implant to deliver ciliary neurotrophic factor (CNTF) directly into the eye, which may protect and enhance the function of retinal cells, unlike traditional treatments that primarily focus on lowering eye pressure. ^{1 2 4 5 7}

Research Team

Jeffrey L Goldberg, MD, PhD

Principal Investigator

Stanford University

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• NT-501 (Cell Therapy)

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Dr. Richard A. Miller

Stanford University

Chief Executive Officer since 2023

Stanford University, MD

Dr. Robert Schott

Stanford University

Chief Medical Officer since 2021

University of Michigan, MD

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Ciliary neurotrophic factor (CNTF) for human retinal degeneration: phase I trial of CNTF delivered by encapsulated cell intraocular implants. [2022]

2. China pubmed.ncbi.nlm.nih.gov

Expression of ciliary neurotrophic factor after induction of ocular hypertension in the retina of rats. [2007]

3. England pubmed.ncbi.nlm.nih.gov

Topical instillation of ciliary neurotrophic factor inhibits retinal degeneration in streptozotocin-induced diabetic rats. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Ciliary neurotrophic factor for macular telangiectasia type 2: results from a phase 1 safety trial. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Phase I NT-501 Ciliary Neurotrophic Factor Implant Trial for Primary Open-Angle Glaucoma: Safety, Neuroprotection, and Neuroenhancement. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Ciliary neurotrophic factor (CNTF) delivery to retina: an overview of current research advancements. [2019]

7. China pubmed.ncbi.nlm.nih.gov

[Protective effects of transplantation of hCNTF-transfected cell line on axotomy-induced degeneration of retinal ganglion cells]. [2005]