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

Primary Purpose

Glaucoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
rhNGF
Vehicle
Sponsored by
Dompé Farmaceutici S.p.A
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glaucoma

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Byers Eye Institute at Stanford University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

rhNGF

Vehicle

Arm Description

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

Ophthalmic Placebo solution

Outcomes

Primary Outcome Measures

Incidence of Events as of Primary Safety Outcomes
Unexpected Severe Progression Of Optic Neuropathy (USPON) is a composed parameter which required at least 28 single evaluations; it occurred if the subject answered Yes to any of the following 4 questions on unexpected severe progression: Best Corrected Distance Visual Acuity (BCDVA): 'Yes' for at least one treated eye at any Follow-Up Visit after first study drug dose Humphrey Visual Field (HVF): 'Yes' for at least one treated eye in at least one assessment during treatment or follow-up period Electroretinography (ERG): 'Yes' for at least one treated eye at any Follow-Up Visit after first study drug dose Optical Coherence tomography (OCT): 'Yes' for at least one treated eye at any Follow-Up Visit after first study drug dose Intolerance and allergy to the drug was identified based on preferred term of treatment-emergent adverse events. URAEs are unexpected related AE affecting ocular function. Local/systemic toxicities were identified via the AE form
Change From Baseline in Visual Analogue Scale (VAS) Ocular Tolerability Score
A ocular tolerability score was determined using a 100 mm VAS on which 0 meant No symptoms and 100 meant the Worst possible discomfort. The patients subjectively evaluated their ocular symptoms (foreign body sensation, burning or stinging, itching, pain, sticky feeling, blurred vision and photophobia) using the VAS giving the value they were feeling from none to an extreme value. The ocular symptoms were evaluated by the patients through the scale. Only "overall" values for primary eye and secondary eye are reported here under. An eye was considered as Primary eye, if the eye was treated and the investigator considered this eye as qualifying eye. If both eyes were considered as qualifying eye, the right eye was chosen. The other eye was then considered as Secondary eye, if the eye was treated.

Secondary Outcome Measures

Full Information

First Posted
August 1, 2016
Last Updated
November 24, 2020
Sponsor
Dompé Farmaceutici S.p.A
Collaborators
Cromsource
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1. Study Identification

Unique Protocol Identification Number
NCT02855450
Brief Title
Study to Evaluate Safety and Efficacy of rhNGF Eye Drops Solution Versus Vehicle in Patients With Glaucoma
Acronym
NGF-Glaucoma
Official Title
An 8 Week Phase Ib, Monocentric, Randomized, Double-masked, Parallel Groups, Study With a 24 Week Follow-up to Evaluate Safety and Potential Efficacy of a 180 μg/ml rhNGF Eye Drops Solution Vs Vehicle in Patients With Glaucoma
Study Type
Interventional

2. Study Status

Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
December 2016 (Actual)
Primary Completion Date
May 2018 (Actual)
Study Completion Date
May 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Dompé Farmaceutici S.p.A
Collaborators
Cromsource

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glaucoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
rhNGF
Arm Type
Experimental
Arm Description
rhNGF (Recombinant Human Nerve Growth Factor) 180 μg/ml eye drops solution
Arm Title
Vehicle
Arm Type
Placebo Comparator
Arm Description
Ophthalmic Placebo solution
Intervention Type
Drug
Intervention Name(s)
rhNGF
Other Intervention Name(s)
cenegermin
Intervention Description
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
Intervention Name(s)
Vehicle
Other Intervention Name(s)
placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence of Events as of Primary Safety Outcomes
Description
Unexpected Severe Progression Of Optic Neuropathy (USPON) is a composed parameter which required at least 28 single evaluations; it occurred if the subject answered Yes to any of the following 4 questions on unexpected severe progression: Best Corrected Distance Visual Acuity (BCDVA): 'Yes' for at least one treated eye at any Follow-Up Visit after first study drug dose Humphrey Visual Field (HVF): 'Yes' for at least one treated eye in at least one assessment during treatment or follow-up period Electroretinography (ERG): 'Yes' for at least one treated eye at any Follow-Up Visit after first study drug dose Optical Coherence tomography (OCT): 'Yes' for at least one treated eye at any Follow-Up Visit after first study drug dose Intolerance and allergy to the drug was identified based on preferred term of treatment-emergent adverse events. URAEs are unexpected related AE affecting ocular function. Local/systemic toxicities were identified via the AE form
Time Frame
At day 56/end of treatment
Title
Change From Baseline in Visual Analogue Scale (VAS) Ocular Tolerability Score
Description
A ocular tolerability score was determined using a 100 mm VAS on which 0 meant No symptoms and 100 meant the Worst possible discomfort. The patients subjectively evaluated their ocular symptoms (foreign body sensation, burning or stinging, itching, pain, sticky feeling, blurred vision and photophobia) using the VAS giving the value they were feeling from none to an extreme value. The ocular symptoms were evaluated by the patients through the scale. Only "overall" values for primary eye and secondary eye are reported here under. An eye was considered as Primary eye, if the eye was treated and the investigator considered this eye as qualifying eye. If both eyes were considered as qualifying eye, the right eye was chosen. The other eye was then considered as Secondary eye, if the eye was treated.
Time Frame
Change from baseline to days 7, 28 and 56 (Treatment period), and Day 84 (Follow up)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. 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. Participant must be medically able to undergo the testing required in the flowsheet of exam procedures. Females of childbearing potential must agree to use an effective form of birth control. Exclusion Criteria: 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. Participant is blind in one eye. 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. Participant has evidence of corneal opacification or lack of optical clarity. 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. Participant is receiving systemic steroids or other immunosuppressive medications. 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. Participant has uveitis or other ocular inflammatory disease. Participant has diabetic macular edema. Participant has a history of ocular herpes zoster. Participant is on chemotherapy. Participant has a history of malignancy, not counting basal cell carcinomas, UNLESS it was treated successfully 2 years prior to inclusion in the trial. Known hypersensitivity to one of the components of the study or procedural medications. History of drug, medication or alcohol abuse or addiction. 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: are currently pregnant or, have a positive result on the urine pregnancy test at the Screening/Baseline Visit or, intend to become pregnant during the study treatment period or, are breast-feeding or, 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey L Goldberg, MD, PhD
Organizational Affiliation
, MD, PhD
Official's Role
Principal Investigator
Facility Information:
Facility Name
Byers Eye Institute at Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94303
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34780798
Citation
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. Erratum In: Am J Ophthalmol. 2022 Oct;242:254.
Results Reference
derived

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

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