Study to Evaluate Safety and Efficacy of rhNGF Eye Drops Solution Versus Vehicle in Patients With Glaucoma

NCT ID: NCT02855450

Last Updated: 2020-11-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-31
• Study Completion Date: 2018-05-31

Brief Summary

The primary objective of the study is to assess the safety and tolerability of a 180μg/ml TID dose regimen of recombinant human nerve growth factor (rhNGF) eye drop solution administered over 8 weeks versus a vehicle control in patients with progressive primary open-angle glaucoma despite IOP control.

The secondary objectives are to measure the changes in BCDVA, visual field, ERG and structural changes in ganglion cell layer and nerve fiber layer thickness measured by optical coherence tomography. The secondary outcomes will be examined at 1, 4 and 8 weeks of therapy, and at 4 and 24 weeks after cessation of therapy (Week 12 visit and Week 32 visit), and will include functional assessments to investigate evidence of a persistent biological effect after discontinuation of the study treatment.

Detailed Description

This is an 8 Week phase Ib, monocentric, randomized, double-masked, vehicle controlled, parallel groups, study with a 24 Week follow-up period to evaluate the safety and potential efficacy of a 180 μg/ml recombinant human nerve growth factor (rhNGF) eye drops solution versus vehicle in 60 study participants with chronic primary open angle glaucoma.

Participants may qualify with either progressive optic neuropathy despite maximal current therapy (i.e. IOP reduction), or with stabilized IOP but diminished vision (central or peripheral).

Participants with a qualifying eye will be randomized 2:1 to topical recombinant human nerve growth factor (rhNGF) therapy or vehicle placebo control. Examinations for safety and efficacy will occur one week following initiation of therapy, and at 4, 8, 12 and 32 weeks.

All participants in either arm will be followed clinically at 4 weeks after cessation of therapy.

Conditions

Glaucoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

rhNGF

rhNGF (Recombinant Human Nerve Growth Factor) 180 μg/ml eye drops solution

Group Type: EXPERIMENTAL

rhNGF

Intervention Type: DRUG

Recombinant Human Nerve Growth Factor 180μg/ml (one 35 μl drop equals to 6.30 μg of rhNGF) reconstituted solution three times a day (TID) for 8 weeks of treatment.

Vehicle

Ophthalmic Placebo solution

Group Type: PLACEBO_COMPARATOR

Vehicle

Intervention Type: DRUG

Ophthalmic Placebo solution of the same composition as the test product with the exception of rhNGF reconstituted solution times a day (TID) for 8 weeks of treatment.

Interventions

rhNGF

Recombinant Human Nerve Growth Factor 180μg/ml (one 35 μl drop equals to 6.30 μg of rhNGF) reconstituted solution three times a day (TID) for 8 weeks of treatment.

Intervention Type: DRUG

Vehicle

Ophthalmic Placebo solution of the same composition as the test product with the exception of rhNGF reconstituted solution times a day (TID) for 8 weeks of treatment.

Intervention Type: DRUG

Other Intervention Names

cenegermin; placebo

Eligibility Criteria

Inclusion Criteria

1. Patients 18 years of age or older. Participant must understand and sign the informed consent. If the participant's vision is impaired to the point where he/she cannot read the informed consent document, the document will be read to the participant in its entirety.

2. Participant's clinical diagnosis must be consistent with glaucoma characterized by the following features: a) clinical evidence of progressive RGC dysfunction and degeneration using visual field and/or a structural modality. There must be at least 3 reliable visual fields within 14 months prior to entering into the study; b) residual visual field preservation in at least 1 quadrant.

3. Participant must be medically able to undergo the testing required in the flowsheet of exam procedures.

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

Exclusion Criteria

1. Participant has another optic nerve or retinal degenerative disease or co-morbidity causing significant vision loss, irrespective of whether it is currently treated or untreated, that could limit the possibility of visual recovery.

2. Participant is blind in one eye.

3. Participant has a requirement of acyclovir and/or related products during study duration. 4- Participant has evidence of corneal opacification or lack of optical clarity.

4. Participant has evidence of corneal opacification or lack of optical clarity.

5. Participant has undergone lens removal in the last 3 months, with or without intra-ocular lens implantation, or has undergone intra-ocular lens replacement within 3 months, or has undergone any other ocular surgery within 9 months prior to initiation of study drug.

6. Participant is receiving systemic steroids or other immunosuppressive medications.

7. Participant is currently participating in or has within the last 3 months participated in any other clinical trial of a non-clinically approved drug by ocular or systemic administration.

8. Participant has uveitis or other ocular inflammatory disease.

9. Participant has diabetic macular edema.

10. Participant has a history of ocular herpes zoster.

11. Participant is on chemotherapy.

12. Participant has a history of malignancy, not counting basal cell carcinomas, UNLESS it was treated successfully 2 years prior to inclusion in the trial.

13. Known hypersensitivity to one of the components of the study or procedural medications.

14. History of drug, medication or alcohol abuse or addiction.

15. Females of childbearing potential (those who are not surgically sterilized or post- menopausal for at least 1 year) are excluded from participation in the study if they meet any one of the following conditions:

1. are currently pregnant or,

2. have a positive result on the urine pregnancy test at the Screening/Baseline Visit or,

3. intend to become pregnant during the study treatment period or,

4. are breast-feeding or,

5. not willing to use highly effective birth control measures, such as: Hormonal contraceptives - oral, implanted, transdermal, or injected and/or mechanical barrier methods - spermicide in conjunction with a barrier such as a condom or diaphragm or IUD during the entire course of and 30 days after the study treatment periods.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cromsource

INDUSTRY

Sponsor Role: collaborator

Dompé Farmaceutici S.p.A

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffrey L Goldberg, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

, MD, PhD

Locations

Byers Eye Institute at Stanford University

Palo Alto, California, United States

Countries

United States

References

Beykin G, Stell L, Halim MS, Nunez M, Popova L, Nguyen BT, Groth SL, Dennis A, Li Z, Atkins M, Khavari T, Wang SY, Chang R, Fisher AC, Sepah YJ, Goldberg JL. Phase 1b Randomized Controlled Study of Short Course Topical Recombinant Human Nerve Growth Factor (rhNGF) for Neuroenhancement in Glaucoma: Safety, Tolerability, and Efficacy Measure Outcomes. Am J Ophthalmol. 2022 Feb;234:223-234. doi: 10.1016/j.ajo.2021.11.002. Epub 2021 Nov 13.

Reference Type: DERIVED

PMID: 34780798 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

NGF0314

Identifier Type: -

Identifier Source: org_study_id