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NCT03019627

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

Completed Phase 2 Results posted Last updated 8 February 2019
What this trial tests

Phase 2 trial testing NGF in Dry Eye in 150 participants. Completed in 31 August 2017.

Timeline
20 January 2017
Primary endpoint
31 August 2017
31 August 2017

Quick facts

Lead sponsorDompé Farmaceutici S.p.A
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment150
Start date20 January 2017
Primary completion31 August 2017
Estimated completion31 August 2017
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Dompé Farmaceutici S.p.A — full company profile →

Who can join

18 and older, any sex, with Dry Eye. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Symptom Assessment in Dry Eye (SANDE) Scores Primary · week 8

Change from baseline with Last Observation Carried Forward (LOCF) imputation. LOCF is a method of imputing missing data in longitudinal studies and tests for difference in mean rates of change in controlled repeated measurements designs with dropouts. The SANDE score is calculated by taking the square root of the product of the frequency of symptoms score and the severity of symptoms score. The SANDE scale ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms.

Frequency
GroupValue95% CI
rhNGF 20μg/mL-38.8± 28.97
Vehicle-34.0± 26.67
Severity
GroupValue95% CI
rhNGF 20μg/mL-32.2± 31.04
Vehicle-31.07± 28.32
SANDE Scores Secondary · Week 4, week 8, week 12

Change from baseline with Last Observation Carried Forward (LOCF) imputation. LOCF is a method of imputing missing data in longitudinal studies and tests for difference in mean rates of change in controlled repeated measurements designs with dropouts. The SANDE score is calculated by taking the square root of the product of the frequency of symptoms score and the severity of symptoms score. The SANDE scale ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms.

Frequency - week 4
GroupValue95% CI
rhNGF 20μg/mL-22.1± 24.08
Vehicle-20.4± 20.66
Frequency - week 8
GroupValue95% CI
rhNGF 20μg/mL-39.6± 28.55
Vehicle-34.6± 27.60
Frequency - week 12
GroupValue95% CI
rhNGF 20μg/mL-44.8± 28.69
Vehicle-28.2± 28.94
Severity - week 4
GroupValue95% CI
rhNGF 20μg/mL-19.9± 25.20
Vehicle-22.2± 24.31
Severity - week 8
GroupValue95% CI
rhNGF 20μg/mL-32.6± 30.64
Vehicle-33.1± 28.30
Severity - week 12
GroupValue95% CI
rhNGF 20μg/mL-38.8± 29.20
Vehicle-24.3± 28.43
Cornea Vital Staining Secondary · week 4, week 8, week 12

Changes from baseline on National Eye Institute (NEI) scale. The NEI/Industry Workshop guidelines were used for grading the scale of corneal and conjunctival damage. The cornea was divided into five sectors (central, superior, inferior, nasal and temporal), each of which was scored on a scale of 0-3, with a maximal total corneal staining score of 15. Both nasally and temporally, the conjunctiva was divided into a superior paralimbal area, an inferior paralimbal area, and a peripheral area with a grading scale of 0-3 and with a maximal total score of 9 for the nasal and temporal conjunctiva (o

week 4
GroupValue95% CI
rhNGF 20μg/mL-3.5± 2.32
Vehicle-3.0± 2.27
week 8
GroupValue95% CI
rhNGF 20μg/mL-4.2± 2.92
Vehicle-4.4± 2.70
week 12
GroupValue95% CI
rhNGF 20μg/mL-4.4± 2.80
Vehicle-5.1± 2.93
Conjunctival Vital Staining Secondary · week 4, week 8, week 12

Changes from baseline on National Eye Institute (NEI) scale. The NEI/Industry Workshop guidelines were used for grading the scale of corneal and conjunctival damage. The cornea was divided into five sectors (central, superior, inferior, nasal and temporal), each of which was scored on a scale of 0-3, with a maximal total corneal staining score of 15. Both nasally and temporally, the conjunctiva was divided into a superior paralimbal area, an inferior paralimbal area, and a peripheral area with a grading scale of 0-3 and with a maximal total score of 9 for the nasal and temporal conjunctiva (o

week 4
GroupValue95% CI
rhNGF 20μg/mL-4.7± 3.94
Vehicle-4.1± 3.45
week 8
GroupValue95% CI
rhNGF 20μg/mL-6.7± 4.16
Vehicle-5.9± 4.07
week 12
GroupValue95% CI
rhNGF 20μg/mL-7.2± 4.23
Vehicle-7.0± 3.90
Change in Tear Film Break-up Time (TFBUT) Secondary · week 4, week 8, week 12

TFBUT was measured by determining the time to tear break-up. The TFBUT was performed after instillation of 5 μL of 2% preservative-free sodium fluorescein solution into the inferior conjunctival cul-de-sac of each eye. The patient was instructed to blink several times to thoroughly mix the fluorescein with the tear film.

week 4
GroupValue95% CI
rhNGF 20μg/mL0.4± 1.68
Vehicle0.8± 1.57
week 8
GroupValue95% CI
rhNGF 20μg/mL0.5± 1.74
Vehicle0.7± 1.89
week 12
GroupValue95% CI
rhNGF 20μg/mL0.5± 2.34
Vehicle0.9± 1.42
Change From Baseline in Wetting Distance Secondary · week 8

The Schirmer test without anesthesia was performed to measure aqueous tear secretion prior to the instillation of any dilating or eye drops

GroupValue95% CI
rhNGF 20μg/mL2.4± 11.41
Vehicle-3.1± 8.66

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected at each time point of the study (ie. Baseline visit, Week 4, Week 8 and ETV or early termination. Reporting threshold: 1%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

rhNGF 20μg/mL
Serious: 5/100 (5%)
Deaths: 0/100
Vehicle
Serious: 0/50 (0%)
Deaths: 0/50

Serious adverse events (5 terms)

ReactionSystemrhNGF 20μg/mLVehicle
DiverticulitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Atrial fibrillationCardiac disorders
ParaesthesiaNervous system disorders
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders
Other adverse events (148 terms — click to expand)

ReactionSystemrhNGF 20μg/mLVehicle
Ocular discomfortEye disorders
Eye painEye disorders
Eye irritationEye disorders
Vision blurredEye disorders
PhotophobiaEye disorders
HeadacheNervous system disorders
Eye dischargeEye disorders
Eye pruritusEye disorders
Eyelid disorderEye disorders
Viral upper respiratory tract infectionInfections and infestations
Eyelid painEye disorders
Eyelid oedemaEye disorders
Dry eyeEye disorders
Eye swellingEye disorders
Lacrimation increasedEye disorders
Ocular hyperaemiaEye disorders
Foreign body sensation in eyesEye disorders
MigraneNervous system disorders
Nasal discomfortRespiratory, thoracic and mediastinal disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
UrticariaSkin and subcutaneous tissue disorders
Seasonal allergyImmune system disorders
BlepharospasmEye disorders
Eyelid margin crustingEye disorders
Abnormal sensation in eyeEye disorders
Eyelid pruritusEye disorders
AsthenopiaEye disorders
Eye allergyEye disorders
visual impairmentEye disorders
ParaesthesiaNervous system disorders
SinusitisInfections and infestations
BronchitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
CoughRespiratory, thoracic and mediastinal disorders
Sinus congestionRespiratory, thoracic and mediastinal disorders
Back painMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Sensation of foreign bodyGeneral disorders
PyrexiaGeneral disorders
abdominal discomfortGastrointestinal disorders

Most-reported serious reactions: Diverticulitis, Upper respiratory tract infection, Atrial fibrillation, Paraesthesia, Chronic obstructive pulmonary disease.

Data from ClinicalTrials.gov NCT03019627 adverse events section.

Sponsor's own description

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: * To assess change from baseline in Symptom Assessment In Dry Eye (SANDE) scores (without imputation), corneal and conjunctival staining according to National Eye Institute (NEI) scale, and in Tear Film Break-up Time (TFBUT) and Schirmer test I, following 4 and 8 weeks of treatment. * To assess change in levels of inflammatory biomarker matrix metallopeptidase 9 (MMP-9) in tears following 8 weeks of treatment. * To assess the incidence and frequency of treatment-emergent adverse events (TEAEs) following 8 weeks of treatment.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Extraocular, periocular, and intraocular routes for sustained drug delivery for glaucoma.
    Kompella UB, Hartman RR, Patil MA. · · 2021 · cited 76× · PMID 32891866 · DOI 10.1016/j.preteyeres.2020.100901
  2. Update On Cenegermin Eye Drops In The Treatment Of Neurotrophic Keratitis.
    Sheha H, Tighe S, Hashem O, Hayashida Y. · · 2019 · cited 61× · PMID 31631965 · DOI 10.2147/opth.s185184
  3. Effect of recombinant human nerve growth factor eye drops in patients with dry eye: a phase IIa, open label, multiple-dose study.
    Sacchetti M, Lambiase A, Schmidl D, Schmetterer L, et al · · 2020 · cited 54× · PMID 30944103 · DOI 10.1136/bjophthalmol-2018-312470
  4. Nerve Growth Factor Biodelivery: A Limiting Step in Moving Toward Extensive Clinical Application?
    Alastra G, Aloe L, Baldassarro VA, Calzà L, et al · · 2021 · cited 32× · PMID 34335170 · DOI 10.3389/fnins.2021.695592
  5. The History of Nerve Growth Factor: From Molecule to Drug
    Gavioli E, Mantelli F, Cesta M, Sacchetti M, et al · · 2024

Verify or expand the search:

Other trials of NGF

Trials testing the same drug.

Other recruiting trials for Dry Eye

Currently open trials in the same condition.

Other Dompé Farmaceutici S.p.A trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing