GlaucomaPhase 1NGF-GlaucomaNCT02855450

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

A Phase 1 study testing rhNGF in people with Glaucoma, run by Dompé Farmaceutici S.p.A at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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. Read more about this study

Who is it for?: Ages 18 to 90 years
Conditions the study is for: Glaucoma
What is being tested?: rhNGF
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 60 participants
Where: 1 siteUnited States
Study dates: Dec 2016to May 2018
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 90 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Show all 20Show fewer

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Byers Eye Institute at Stanford University
Palo Alto, California, 94303

Other trials in United States

About this study

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

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.

Read the 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
Being tested: rhNGF, Vehicle
Medical subject headings: Glaucoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

rhNGFDrug
Also called cenegermin
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.
VehicleDrug
Also called placebo
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.

Study groups in NCT02855450
Study group	Role	What they receive
rhNGF	Experimental	rhNGF (Recombinant Human Nerve Growth Factor) 180 μg/ml eye drops solution Receives: Drug: rhNGF
Vehicle	Placebo comparator	Ophthalmic Placebo solution Receives: Drug: Vehicle

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: At day 56/end of treatment
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.
Measured: Change from baseline to days 7, 28 and 56 (Treatment period), and Day 84 (Follow up)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2016May 2018

First posted4 Aug 2016 (estimated)
Study startDec 2016
Primary completionMay 2018
Study completionMay 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for GlaucomaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 60 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02855450
Sponsor's protocol ID: NGF0314
Acronym: NGF-Glaucoma
Status last verified: Nov 2020
First submitted: 1 Aug 2016
Last updated: 25 Nov 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 34780798

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 25 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02855450
Acronym / sponsor ID: NGF-Glaucoma / NGF0314
Conditions: Glaucoma
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 60 participants (actual)
Lead sponsor: Dompé Farmaceutici S.p.AIndustry (pharma, biotech, devices)
Collaborators: Cromsource
Study start: Dec 2016 (actual)
Primary completion: May 2018 (actual)
Study completion: May 2018 (actual)
First posted: 4 Aug 2016 (estimated)
Results: Posted 25 Nov 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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).

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
rhNGF	Experimental	Drug: rhNGFrhNGF (Recombinant Human Nerve Growth Factor) 180 μg/ml eye drops solution
Vehicle	Placebo comparator	Drug: VehicleOphthalmic Placebo solution

Who may qualify

Ages: 18 to 90 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (20 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
rhNGFAlso: cenegerminRecombinant 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.	Drug	rhNGF
VehicleAlso: placeboOphthalmic 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.	Drug	Vehicle

Primary outcome

Incidence of Events as of Primary Safety Outcomes
Time frame: At day 56/end of treatment
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
Time frame: Change from baseline to days 7, 28 and 56 (Treatment period), and Day 84 (Follow up)
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.

Results and safety

Results posted to the registry on 25 Nov 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
rhNGF	40	35
Vehicle	20	20

Primary outcome: Incidence of Events as of Primary Safety Outcomes

Time frame: At day 56/end of treatment. Number. Unit: Number of events

Measure	rhNGF n = 40	Vehicle n = 20
USPON	0	2
USPON during treatment period	0	0
Intolerance to the drug	6	0
Ocular URAEs	1	1
Local/systemic toxicities	0	0

Population analysed: Safety Set (SAF). The Safety Set includes all randomized subjects who received at least one dose of study medication. This safety population is used in the analysis of all safety endpoints. All analyses based on the SAF are summarized by the treatment received

Primary outcome: Change From Baseline in Visual Analogue Scale (VAS) Ocular Tolerability Score

Time frame: Change from baseline to days 7, 28 and 56 (Treatment period), and Day 84 (Follow up). Mean (Standard Deviation). Unit: score on a scale

Measure	rhNGF n = 40	Vehicle n = 20
Day 7 - primary eye	2.8 (9.09)	-2.1 (5.95)
Day 28 - primary eye	4.0 (11.22)	1.0 (11.85)
Day 56 - primary eye	3.6 (16.08)	-0.9 (6.51)
Day 84 - primary eye	-0.3 (11.81)	0.3 (6.78)
Day 7 - secondary eye	2.1 (9.44)	-1.4 (6.45)
Day 28 - secondary eye	4.6 (13.25)	1.2 (12.16)
Day 56 - secondary eye	4.5 (16.64)	0.6 (10.60)
Day 84 - secondary eye	-0.7 (12.95)	1.5 (10.71)

rhNGF vs Vehicle: Least square means difference: 4.7 (95% CI 0.2 to 9.2), p = 0.040, ANCOVA
rhNGF vs Vehicle: least square mean difference: 2.4 (95% CI -4.1 to 9.0), p = 0.457, ANCOVA
rhNGF vs Vehicle: least square mean difference: 4.0 (95% CI -3.5 to 11.5), p = 0.283, ANCOVA

Population analysed: The Safety Set includes all randomized subjects who received at least one dose of study medication. This safety population is used in the analysis of all safety endpoints. All analyses based on the SAF are summarized by the treatment received. Please note that there were major protocol deviations, so that no complete VAS data was reported during treatment period; for this reason the numbers of participants analyzed per row may differ from the Overall Numbers of Participants.

Adverse events

Time frame: Treatment period: Day 0 (Therapy initiation), Day 7, Day 28, Day 56; Follow-up: Day 84, Day 224. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
rhNGF	3 of 40 (7.5%)	31 of 40 (77.5%)	0 of 40
Vehicle	2 of 20 (10%)	9 of 20 (45%)	0 of 20

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 34780798Beykin 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Jeffrey L Goldberg, MD, PhD principal investigator

, MD, PhD

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing rhNGF in people with Glaucoma, run by Dompé Farmaceutici S.p.A at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Events as of Primary Safety Outcomes (time frame: At day 56/end of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02855450, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2020.