Neurotrophins, a science-driven excellence

Dompé farmaceutici is a leader in the research and development of innovative solutions utilizing manufactured neurotrophins for more than a decade. Neurotrophins are a family of proteins that induce the survival, development, and function of nerve cells. Nerve growth factor1 2 3 (NGF) is the first discovered member of the neurotrophin family 4. NGF, a protein naturally produced by ocular tissue, is an essential neurotrophin that induces proliferation, migration, and differentiation of corneal epithelial cells which is important in maintaining corneal integrity, sensory innervation, and overall function. NGF is often viewed as the prototype for all neurotrophins. 5 6

The discovery of NGF earned Rita Levi Montalcini and Stanley Cohen the Nobel Prize7 in 1986. Therapeutic development began 24 years later with Dompé’s acquisition of the rights for the development, production, and marketing of rhNGF in 2010. Today, our expertise in the science behind neurotrophins is driving the evolution of our research programs to evaluate potential applications of rhNGF to various ocular and systemic conditions.

Neurotrophic keratitis

NK is a degenerative disease of the cornea caused by trigeminal nerve damage, which if left untreated, can lead to loss of corneal sensitivity, corneal epithelium breakdown, and even corneal perforation. The interaction between corneal nerves, epithelial cells/keratocytes, and the lacrimal gland mediates corneal homeostasis which is vital for optimal corneal health. Despite increasing awareness of NK as a distinct clinical entity, its management continued to be challenged by the lack of approved treatments, that specifically targets the root pathogenesis of NK.

Our researchers were the first in the world to develop an innovative method to produce the first topical biologic for the treatment of NK. In recognition of the groundbreaking research leading to the development of cenegermin-bkbj (rhNGF), in 2018 the FDA granted the treatment "Breakthrough Therapy Designation" and, during the registration process, conferred it a "Fast Track" and "Priority Review" status.

Scientific evidence on the role of endogenous NGF in ocular surface homeostasis informed our focus on the applicability of neurotrophins as a treatment for neurotrophic keratitis.

Important Safety Information

WARNINGS AND PRECAUTIONS

Use with Contact Lens

Patients should remove contact lenses before applying OXERVATE and wait 15 minutes after instillation of the dose before reinsertion.

Eye Discomfort

OXERVATE may cause mild to moderate eye discomfort such as eye pain during treatment. The patient should be advised to contact their doctor if a more serious eye reaction occurs.

ADVERSE REACTIONS

The most common adverse reactions (incidence >5%) are eye pain, ocular hyperemia, eye inflammation and increased lacrimation.

INDICATION

OXERVATE® (cenegermin-bkbj) ophthalmic solution 0.002% (20 mcg/mL) is indicated for the treatment of neurotrophic keratitis.

To report ADVERSE REACTIONS, contact Dompé U.S. Inc. at 1-833-366-7387 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch<... complete information on the safety and efficacy of OXERVATE, please see full Prescribing Information.

Sjögren's

Sjögren’s disease is a chronic autoimmune disease involving many organs and systems in the body and is most commonly presenting with severe dryness of mucosal membranes due to lymphocytic infiltration of the exocrine glands, primarily in the mouth and eyes 8.

Sjögren’s Dry Eye Disease occurs as a result of damage to the lacrimal glands by the immune system. Dry eye associated with Sjögren’s is often more severe than in patients who do not have underlying Sjögren’s9 . In a survey of Sjögren’s patients, dry eye was a recurring frequent symptom experienced by this patient group (92%) 10 . Sjögren’s Dry Eye Disease is a progressive condition that may have a negative impact on the quality of life of affected patients11 12 .

If left untreated, it can lead to long-term consequences such as punctate epithelial erosions, nonhealing corneal ulcers, perforation, and scarring 13 . Neurosensory abnormalities have been recognized by Dry Eye Workshop II as playing an etiological role in dry eye disease, and manifestations of dry eyes from Sjögren’s patients may correlate with a loss of neural regulation of ocular function 14. This evidence has inspired Dompé to invest in research in investigating rhNGF as a potentially novel approach to managing dry eye in patients with Sjögren’s.

The Scientific Development Ahead

At Dompé we believe that research into the neurotrophin family of proteins is still in its infancy. This is why we believe that our dedication to eye care is only the first step. Our ambition is to identify and produce new and effective drug development in different therapeutic indications to offer patients new options for treatment in areas of high unmet medical need.

Neurotrophins pipeline

Recombinant Human Nerve Growth Factor (rhNGF)

INN (International Non-proprietary Name): Cenegermin
phase III

The Nerve Growth Factor (NGF) is a polypeptide essential for the survival and growth of sympathetic and sensory neurons and for differentiation of neurons in the central nervous system. The protein is highly conserved across species, with human NGF (hNGF) and murine NGF (mNGF) sharing 90% homology in amino-acid sequence of mature protein.

NGF binds two distinct classes of receptors:

1) tropomyosin receptor kinase A (TrkA), a transmembrane tyrosine kinase that is also known as high-affinity NGF receptor, and

2) low affinity NGF receptor (p75 LNGFR), also called p75 neurotrophin receptor (p75NTR).

NGF and its receptors are expressed, in addition to the other compartments, both in the anterior and the posterior segment of the eye, and play a crucial role in the physiopathology of several ocular diseases.

On going Clinical studies
NGF0221

Study to Evaluate Safety and Efficacy of Cenegermin (Oxervate) 20 mcg/mL vs Vehicle, in Patients With Sjögren's Dry Eye

NGF0121

Study to Evaluate Safety and Efficacy of Oxervate® Ophthalmic Solution vs Vehicle in Severe Sjögren's Dry Eye Disease

NGF0120

Study to Evaluate OXERVATE™ in Patients With Stage 1 Neurotrophic Keratitis (DEFENDO)

Completed Clinical studies
NGF0112

Study to Evaluate Safety, Tolerability and Pharmacokinetics of rhNGF Eye Drops in Healthy Volunteers

NGF0213

Safety and Efficacy of rhNGF Eye Drops at Different Doses in Patients With Dry Eye

NGF0212

Evaluation of Safety and Efficacy of rhNGF in Patients With Stage 2 and 3 Neurotrophic Keratitis. (REPARO)

NGF0113

A Dose Ranging Study to Evaluate the Safety and Potential Efficacy of rhNGF in Patients With Retinitis Pigmentosa (RP) (Lumos)

NGF0214

Evaluation of Efficacy of 20 µg/ml rhNGF New Formulation (With Anti-oxidant) in Patients With Stage 2 and 3 NK

NGF0216

An 8-week Study to Evaluate Safety and Efficacy of NGF Eye Drops Solution Versus Vehicle in Patients With Dry Eye

NEMO

Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema (NEMO)

NGF0314

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

NGF0116

A 8 Weeks Study to Evaluate Efficacy & Safety of rhNGF vs Vehicle in Patients After Cataract and Refractive Surgery

NGF0117

Study to Evaluate Safety, Tolerability & PK of rhNGF in Healthy Volunteers

NGF0118

A Study to Evaluate Safety and Efficacy of rhNGF Eye Solution vs Vehicle in Patients With Moderate to Severe Dry Eye

Neurotrophins publications

International Journal of Molecular Sciences March 2022

MicroRNAs Expression in response to rhNGF in Epithelial Corneal Cells: Focus on Neurotrophin Signaling Pathway

Chiara Compagnoni, Veronica Zelli, Andrea Bianchi, Antinisca Di Marco, Roberta Capelli, Davide Vecchiotti, Laura Brandolini, Anna Maria Cimini, Francesca Zazzeroni, Marcello Allegretti, Edoardo Alesse and Alessandra Tessitore.

Frontiers in Pharmacology March 2022

Intravitreal administration of rhNGF enhances regenerative processes in a zebrafish model of retinal degeneration

Pasquale Cocchiaro, Vincenzo Di Donato, Davide Rubbini, Rodolfo Mastropasqua, Marcello Allegretti, Flavio Mantelli, Andrea Aramini and Laura Brandolini.

Orphanet Journal of Rare Diseases February 2022

Eight months follow-up of corneal nerves and sensitivity after treatment with cenegermin for neurotrophic keratopathy

Emilio Pedrotti, Erika Bonacci, Chiara Chierego, Alessandra De Gregorio, Tiziano Cozzini, Tommaso Brighenti, Grazia Caldarella, Giovanlorenzo Pastore, Adriano Fasolo & Giorgio Marchini

Orphanet Journal of Rare Diseases February 2022

Long-term clinical efficacy of topical treatment with recombinant human nerve growth factor in neurotrophic keratopathy: a novel cure for a rare degenerative corneal disease?

Alice Bruscolini, Marco Marenco, Giuseppe Maria Albanese, Alessandro Lambiase & Marta Sacchetti

Frontiers in Pharmacology January 2022

Recombinant Human Nerve Growth Factor (Cenegermin)–Driven Corneal Wound Healing Process: An Evidence-Based Analysis

Chiara Bonzano, Sara Olivari, Carlo Alberto Cutolo, Angelo Macrì, Daniele Sindaco, Davide Borroni, Elisabetta Bonzano and Carlo Enrico Traverso.

Graefe's Archive for Clinical and Experimental Ophthalmology October 2021

Long-term clinical outcome and satisfaction survey in patients with neurotrophic keratopathy after treatment with cenegermin eye drops or amniotic membrane transplantation

Marta Sacchetti, Chiara Komaiha, Alice Bruscolini, Giuseppe Maria Albanese, Marco Marenco, Rossella Anna Maria Colabelli Gisoldi, Augusto Pocobelli, Alessandro Lambiase.

Journal of patient-reported outcomes May 2020

Development of the Neurotrophic Keratopathy Questionnaire: Qualitative Research

L.T. Murray

Nature February 2020

Topical recombinant human Nerve growth factor (rh-NGF) is neuroprotective to retinal ganglion cells by targeting secondary degeneration

Guo, L., Davis, B.M., Ravindran, N. et al.

The British journal of ophthalmology January 2020

Effect of Recombinant Human Nerve Growth Factor Eye Drops in Patients With Dry Eye: A Phase IIa, Open Label, Multiple-Dose Study

M Sacchetti et al.

Ophthalmology January 2020

Topical Recombinant Human Nerve Growth Factor (Cenegermin) for Neurotrophic Keratopathy: A Multicenter Randomized Vehicle-Controlled Pivotal Trial

SC Pflugfelder et al.

Investigative Ophthalmology and Visual Science August 2019

Effect of topical recombinant human nerve growth factor (cenegermin) on corneal sensitivity in patients with neurotrophic keratitis

Massaro-Giordano M et al.

Value in Health October 2018

Impact of Cenegermin on the quality of life in neurotrophic keratopathy

Value in Health

Ophthalmology September 2018

Phase II Randomized, Double-Masked, Vehicle-Controlled Trial of Recombinant Human Nerve Growth Factor for Neurotrophic Keratitis

S. Bonini et al.

Ophthalmology September 2018

Phase I Trial of Recombinant Human Nerve Growth Factor for Neurotrophic Keratitis

Bonini et al.

Current eye research July 2017

Recombinant Human Nerve Growth Factor Treatment Promotes Photoreceptor Survival in the Retinas of Rats With Retinitis Pigmentosa

M Sacchetti et al.

The ocular surface January 2017

A Two-Week, Randomized, Double-masked Study to Evaluate Safety and Efficacy of Lubricin (150 μg/mL) Eye Drops Versus Sodium Hyaluronate (HA) 0.18% Eye Drops (Vismed®) in Patients With Moderate Dry Eye Disease

A Lambiase et al.

Investigative ophthalmology & visual science September 2014

NK1 Receptor Antagonists as a New Treatment for Corneal Neovascularization

F Bignami et al.

Biodrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy June 2014

Safety and pharmacokinetics of escalating doses of human recombinant nerve growth factor eye drops in a double-masked, randomized clinical trial

MP Ferrari et al.

Investigative Ophthalmology and Visual Science April 2014

Phase I/II dose-ranging, randomized clinical trial of recombinant human nerve growth factor in the treatment of neurotrophic keratitis: Preliminary results

Sinigaglia F. et al.

Investigative Ophthalmology and Visual Science June 2013

Phase I, randomized, double-masked, vehicle-controlled study to evaluate safety, tolerability and pharmacokinetics of recombinant human nerve growth factor eye drops in healthy volunteers

Buggage R. et al.

PNAS, Proceedings of the National Academy of Sciences August 2009

Experimental and clinical evidence of neuroprotection by nerve growth factor eye drops: Implications for glaucoma

Alessandro Lambiase, Luigi Aloe, Marco Centofanti, Vincenzo Parisi, Flavio Mantelli, Valeria Colafrancesco, Gian Luca Manni, Massimo Gilberto Bucci, Stefano Bonini and Rita Levi Montalcini

The New England Journal of Medicine April 1998

Topical Treatment with Nerve Growth Factor for Neurotrophic Keratitis

Stefano Bonini, Alessandro Lambiase, Paolo Rama, Giancarlo Caprioglio, Luigi Aloe

The New England Journal of Medicine April 1998

Topical treatment with Nerve Growth Factor for Corneal Neurotrophic Ulcers.

Alessandro Lambiase, Paolo Rama, Stefano Bonini, Giancarlo Caprioglio and Luigi Aloe

Neurotrophins stories

NGF0221

Study to Evaluate Safety and Efficacy of Cenegermin (Oxervate) 20 mcg/mL vs Vehicle, in Patients With Sjögren's Dry Eye

Brief summary

The study objective is to assess the efficacy and safety of cenegermin (rhNGF) ophthalmic solution at 20 mcg/mL concentration administered three times daily for 4 weeks in patients with severe Sjögren's dry eye disease who are under chronic treatment with topical Cyclosporine A.

detailed description

This is a 4 week phase III, multicenter, double-masked, vehicle-controlled study to evaluate safety and efficacy of cenegermin ophthalmic solution at 20 mcg/mL solution versus vehicle, in patients with severe Sjögren's dry eye disease.

During the screening all procedures for inclusion will be performed. From the day of screening the patients will stop any kind of further treatment, except CsA and commercially available preservative free artificial tears provided by Sponsor for a period of 7 days and 9 days. At the end of the washout period , patients meeting the entry criteria for this study will be randomized 1:1 and treated for 4 weeks with either cenegermin ophthalmic solution 20 mcg/mL TID or vehicle TID.

In addition to topical CsA eye drops (both groups will continue with topical CsA eye drops, or other topical ophthalmic treatment of the same class), during the 4 weeks of masked treatment only the administration of IMP is allowed. During the follow up period, the patient can administer additional artificial tear eye drops, provided by Sponsor, only if strictly needed, and must document in the patient's diary the number of additional drops administered for each eye. Patients will then be followed up for efficacy and safety endpoints until week 16 and for safety endpoints until week 24. The total duration of the study is 25 weeks including 1 week of screening.

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NGF0121

Study to Evaluate Safety and Efficacy of Oxervate® Ophthalmic Solution vs Vehicle in Severe Sjögren's Dry Eye Disease

Brief summary

The study objective is to assess the efficacy and safety of cenegermin (rhNGF) ophthalmic solution at 20 mcg/mL concentration administered three times daily for 4 weeks in patients with severe Sjögren's dry eye disease.

detailed description

This is a 4 week phase III, multicenter, double-masked, vehicle-controlled study to evaluate safety and efficacy of cenegermin ophthalmic solution at 20 mcg/mL solution versus vehicle, in patients with severe Sjögren's dry eye disease. During the screening all procedures for inclusion will be performed. From the day of screening the patients will stop any kind of further treatment, except commercially available preservative free artificial tears provided by Sponsor.

At the end of the wash out period, patients meeting the entry criteria for this study will be randomized 1:1 and treated for 4 weeks with either cenegermin ophthalmic solution 20 mcg/mL TID or vehicle TID. During the 4 weeks of masked treatment only the administration of IMP is allowed.

During the follow up period, the patient can administer additional artificial tear eye drops, provided by Sponsor, only if strictly needed, and must document in the patient's diary the number of additional drops administered for each eye.

Patients will then be followed up for efficacy and safety endpoints until week 16 and for safety endpoints until week 24.

The total duration of the study is 25 weeks including 1 week of screening.

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NGF0112

Study to Evaluate Safety, Tolerability and Pharmacokinetics of rhNGF Eye Drops in Healthy Volunteers

Brief summary

The primary objective of this study is to assess the safety and tolerability of single and multiple ascending doses of rhNGF when administered as eye drops in healthy subjects

detailed description

This is a Phase I, randomised, double-masked, placebo-controlled eye drops administration study of rh-NGF in healthy male and female subjects.

This study consists of a single ascending dose part (part 0 one drop single application). Then single ascending dose part (part A; one drop three times a day) and a multiple ascending dose part (part B; one drop three times a day for five days). All parts of the study will consist of 3 ascending dose levels.

In order to support the dose escalation MAD phase from Covance, Basel to Covance, Leeds, an additional cohort (0M) will be conducted at Covance, Leeds at the same dose level as cohort 1M to ensure a degree of consistency between the two sites, i.e. that no dose escalation stopping criteria were met at either site.

In Part 0, each ascending dose cohort will include 3 subjects treated with one dose of rh-NGF.

In part A, each ascending dose cohort will include 6 subjects treated with rh-NGF and 2 with placebo.

In part B, each ascending dose cohort will include 9 subjects treated with rh-NGF drug and 3 with placebo, in addition to cohort 0M, which will include 3 subjects treated with rh-NGF and 1 with placebo

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NGF0120

Study to Evaluate OXERVATE™ in Patients With Stage 1 Neurotrophic Keratitis (DEFENDO)

Brief summary

This study is to evaluate the safety and efficacy of OXERVATE™ 0.002% (20 mcg/mL) cenegermin-bkbj ophthalmic solution in patients with Stage 1 neurotrophic keratitis (NK).

detailed description

An 8-week, Multicenter, Open Label, Prospective Study With 24 Weeks of Follow-up to Evaluate Safety and Efficacy of OXERVATE™ 0.002% (20 mcg/mL) Cenegermin-bkbj Ophthalmic Solution in Patients With Stage 1 Neurotrophic Keratitis (NK)

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NGF0213

Safety and Efficacy of rhNGF Eye Drops at Different Doses in Patients With Dry Eye

Brief summary

The primary objective of this study was to assess the efficacy and safety of different doses of rhNGF when administered as eye drops to patients with dry eye.

detailed description

This is an open-label study evaluating safety and efficacy of recombinant human nerve growth factor (rhNGF) eye drops at different doses in patients with Dry Eye

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NGF0212

Evaluation of Safety and Efficacy of rhNGF in Patients With Stage 2 and 3 Neurotrophic Keratitis. (REPARO)

Brief summary

This study is aimed at assessing the safety and the efficacy of two dose regimens of recombinant human nerve growth factor (rhNGF) eye drops solution compared to vehicle for inducing a complete healing of stage 2 (persistent epithelial defect) and 3 (corneal ulcer) neurotrophic keratitis

detailed description

The primary objective of this study is to assess the safety and the efficacy of two dose regimens (10 µg/ml or 20 µg/ml 6 times a day) of recombinant human nerve growth factor (rhNGF) eye drops solution compared to vehicle for inducing a complete healing of stage 2 (persistent epithelial defect) and 3 (corneal ulcer) neurotrophic keratitis (NK) as measured by the Reading Center evaluating the clinical pictures of corneal fluorescein staining.

Secondary objectives of the study are to assess the duration of complete healing, improvement in visual acuity and improvement in corneal sensitivity following treatment with rhNGF eye drops solution

This is a combined phase I/II study. The phase I and II segments of the study will be conducted as an 8 week, randomized, double-masked, vehicle controlled, parallel group study (referred to as the controlled treatment period) followed by a 48 or 56 week follow-up period The design of the phase I and phase II segments of the study are identical with the exception that in the phase I segment of the study the randomization scheme is different and patients will be followed with additional safety assessments and blood samples for PK (pharmacokinetic) profiling In the ascending dose Phase I segment of the study two doses of rhNGF 10 and 20 µg/ml will be evaluated in a sequential manner

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NGF0113

A Dose Ranging Study to Evaluate the Safety and Potential Efficacy of rhNGF in Patients With Retinitis Pigmentosa (RP) (Lumos)

Brief summary

The primary objective of the study is to assess the safety and tolerability of two dose regimens of recombinant human nerve growth factor (rhNGF) eye drops solution administered over 6 months versus a vehicle control in patients with typical retinitis pigmentosa. The secondary objective of this study is to attempt to show a dose response by assessing the potential efficacy of the rhNGF dose regimens for improving or slowing the deterioration of visual function outcomes at 3 and 6 months. During a 6 month follow-up period patients will be monitored to determine if there is evidence of a persistent biological effect after discontinuation of the study treatment.

detailed description

This is a 24-week phase Ib/II, multicenter, randomized, double-masked, vehicle controlled, parallel-group, dose-ranging study with a 24-week follow-up period to evaluate the safety and potential efficacy of two doses (60 μg/ml and 180 μg/ml) of recombinant human nerve growth factor (rhNGF) eye drops solution versus vehicle in patients with typical retinitis pigmentosa (RP).

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NGF0214

Evaluation of Efficacy of 20 µg/ml rhNGF New Formulation (With Anti-oxidant) in Patients With Stage 2 and 3 NK

Brief summary

Brief Summary:

The primary objective of this study is to evaluate the efficacy of 20 µg/ml 6 times a day of rhNGF eye drops solution (formulation containing anti-oxidant) compared to vehicle (formulation containing anti-oxidant) given 6 times a day. The evaluation of efficacy is intended as:

detailed description

An 8-week phase II, multicenter, randomized, double-masked, vehicle-controlled, parallel group study with a 24 or 32 week follow-up period to evaluate the efficacy of a formulation containing anti-oxidant of recombinant human nerve growth factor (rhNGF) in 20 μg/ml, eye drops solution versus vehicle containing anti-oxidant in patients with Stage 2 and 3 Neurotrophic Keratitis. The primary objective was to evaluate the efficacy of 20 μg/ml 6 times a day of recombinant human nerve growth factor (rhNGF) containing anti-oxidant, eye drops solution compared to vehicle (formulation containing anti-oxidant) given 6 times a day in inducing a complete healing of stage 2 (PED) and 3 (corneal ulcer) NK as measured by the central reading center, evaluating the clinical pictures of corneal fluorescein staining.

Secondary objectives were to assess the duration of complete healing, improvement in visual acuity and improvement in corneal sensitivity, and percentage of patients achieving complete corneal clearing defined as complete absence of staining on the modified Oxford Scale.

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NGF0216

An 8-week Study to Evaluate Safety and Efficacy of NGF Eye Drops Solution Versus Vehicle in Patients With Dry Eye

Brief summary

The primary objective of this study was to assess the efficacy and safety of rhNGF when administered as eye drops to patients with dry eye

The secondary objectives of this study were:

detailed description

The proposed phase II study is a single-center, randomized, double-masked, parallel-arm, vehicle-controlled trial, designed to evaluate the safety and efficacy of Recombinant Human Nerve Growth Factor (rhNGF) eye drops at 20 μg/ml concentration administered six times daily for 8 weeks in patients with dry eye. After confirmation of inclusion and exclusion criteria all eligible patients will be randomized at 2:1 ratio to rhNGF or vehicle control treatment with 8 weeks of study treatments administration with 4 weeks Follow-up.

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NEMO

Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema (NEMO)

Brief summary

This study aims at investigating the therapeutic potential of recombinant human Nerve Growth Factor ( rhNGF ) eye drops treatment in patients with Retinitis Pigmentosa (RP) associated with cystoid macular edema (CME) in a phase II, randomized, double-masked, controlled clinical trial.

detailed description

This study aims at investigating the therapeutic potential of recombinant human Nerve Growth Factor ( rhNGF ) eye drops treatment in patients with Retinitis Pigmentosa (RP) associated with cystoid macular edema (CME) in a phase II, randomized, double-masked, controlled clinical trial.

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NGF0314

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

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.

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NGF0116

A 8 Weeks Study to Evaluate Efficacy & Safety of rhNGF vs Vehicle in Patients After Cataract and Refractive Surgery

Brief summary

The primary objective of this exploratory study is to assess preliminary efficacy and safety of rhNGF when administered as eye drops to patients after cataract and refractive surgery.

The main criteria for evaluation were:

detailed description

The proposed phase II study is a single-centre, randomized, double masked, parallel arm, vehicle-controlled trial, designed to evaluate the preliminary efficacy and safety of rhNGF eye drops at 20 µg/ml concentration administered six times daily for 8 weeks in patients who underwent cataract and corneal refractive surgery, both known to damage the corneal sensory nerve plexus.

After confirmation of inclusion and exclusion criteria all eligible patients will be randomized at 2:1 ratio to rhNGF or vehicle control treatment with 8 weeks of study treatments administration with 4 weeks Follow-up.

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NGF0117

Study to Evaluate Safety, Tolerability & PK of rhNGF in Healthy Volunteers

Brief summary

The primary objective of this study is to assess the safety and tolerability of a single short-term and a multiple dose scheme of rhNGF when administered as eye drops in healthy subjects of Japanese ethnicity.

The secondary objective of this study is to assess the pharmacokinetics of single and multiple doses of rhNGF when administered as eye drops in healthy subjects of Japanese ethnicity.

detailed description

This is a Phase I, randomized, double-masked, placebo-controlled eye drops administration study of rhNGF in healthy male and female subjects of Japanese Ethnicity to evaluate the Safety, Tolerability and Pharmacokinetics of Recombinant Human Nerve Growth Factor Eye Drops (rhNGF 20 μg/mL -formulation containing L-methionine as excipient) versus vehicle (vehicle control containing L-methionine as excipient) in Healthy Male and Female Volunteers of Japanese Ethnicity. The IMP was administered in the study Eye with the following scheme:

Day 1: One drop instilled into study eye (35 μL, corresponding to 0.70 μg of rhNGF).

Day 2, 3, 4, 5, 6: One drop six times a day (every 2h) into study eye (210 μL, corresponding to 4.20 μg of rhNGF).

Total dose in the study eye will be 31 drops (1085 μL, equivalent to 21.7 μg rhNGF) over 6 days.

The reference product (vehicle) was administered in the study eye with the following scheme:

Day 1: One drop instilled into study eye (35 μL, corresponding to 0 μg of rhNGF].

Day 2, 3, 4, 5, 6: One drop six times a day (every 2h) into study eye (210 μL, corresponding to 0 μg of rhNGF).

A total dose of placebo vehicle in the study eye will be 31 drops (1085 μL, 0 μg rhNGF) over 6 days.

For the Fellow (Non-Study) Eye for all subjects, the scheme was the following:

Day 1: One drop instilled into a fellow eye (35 μL, corresponding to 0 μg of rhNGF).

Day 2, 3, 4, 5, 6: One drop six times a day (every 2h) into a fellow eye (210 μL, corresponding to 0 μg of rhNGF).

A total dose of placebo vehicle in the fellow eye will be 31 drops (1085 μL, 0 μg rhNGF) over 6 days.

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NGF0118

A Study to Evaluate Safety and Efficacy of rhNGF Eye Solution vs Vehicle in Patients With Moderate to Severe Dry Eye

Brief summary

The primary objective of this study is to assess the efficacy and safety of rhNGF eye drops at 20 μg/ml concentration administered two or three times daily for 4 weeks in patients with moderate to severe dry eye. The trial is designed to perform dose ranging.

detailed description

This is a 4 weeks, Phase II, multicenter, randomized, double-masked, vehicle-controlled, parallel group study with 12 weeks of follow-up to evaluate safety and efficacy of recombinant human Nerve Growth Factor (rhNGF) eye drops solution versus vehicle, in patients with moderate to severe dry eye (DE).

Test product is rhNGF 20 μg/ml; reference product is vehicle. Test and reference will be instilled in both eyes according to the following scheme:

Group 1: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours, e.g. 7:00 am, 02:00 pm; 09:00 pm).

Group 2: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours, e.g. 7:00 am, 02:00 pm; 09:00 pm).

NB: rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.

Group 3: vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours, e.g. 7:00 am, 02:00 pm; 09:00 pm).

Randomization 1:1:1 of 300 patients to rhNGF eye drops solution 20 μg/ml TID (100 patients) or rhNGF eye drops solution 20 μg/ml BID + vehicle eye drop SID (100 patients) or vehicle eye drops solution (100 patients) TID for 4 weeks.

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