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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Glaucoma

Intervention / Treatment
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* Drug: rhNGF
* Drug: Vehicle


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rhNGF<br>rhNGF (Recombinant Human Nerve Growth Factor) 180 μg/ml eye drops solution | Drug: rhNGF<br>* 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.<br>* Other names: cenegermin;|
| Placebo Comparator: Vehicle<br>Ophthalmic Placebo solution | Drug: Vehicle<br>* 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.<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | Change from baseline to days 7, 28 and 56 (Treatment period), and Day 84 (Follow up) |