June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Phase I/II randomized, double-masked, vehicle-controlled trial of recombinant human nerve growth factor (rhNGF) eye drops in stage 2/3 neurotrophic keratitis
Author Affiliations & Notes
  • Flavio Mantelli
    Ophthalmology, Dompé farmaceutici SpA, Milan, Italy
  • Marcello Allegretti
    Ophthalmology, Dompé farmaceutici SpA, Milan, Italy
  • Wendy Chao
    Ophthalmology, Dompé farmaceutici SpA, Milan, Italy
  • Isabella Filatori
    Ophthalmology, Dompé farmaceutici SpA, Milan, Italy
  • Paolo Battigello
    Ophthalmology, Dompé farmaceutici SpA, Milan, Italy
  • Valentina Vaja
    Ophthalmology, Dompé farmaceutici SpA, Milan, Italy
  • Jennifer Goodman
    Ophthalmology, Dompé farmaceutici SpA, Milan, Italy
  • Francesco Sinigaglia
    Ophthalmology, Dompé farmaceutici SpA, Milan, Italy
  • Footnotes
    Commercial Relationships   Flavio Mantelli, Dompé farmaceutici SpA (E); Marcello Allegretti, Dompé farmaceutici SpA (E); Wendy Chao, Dompé farmaceutici SpA (E); Isabella Filatori, Dompé farmaceutici SpA (E); Paolo Battigello, Dompé farmaceutici SpA (E); Valentina Vaja, Dompé farmaceutici SpA (E); Jennifer Goodman, Dompé farmaceutici SpA (E); Francesco Sinigaglia, Dompé farmaceutici SpA (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1172. doi:
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      Flavio Mantelli, Marcello Allegretti, Wendy Chao, Isabella Filatori, Paolo Battigello, Valentina Vaja, Jennifer Goodman, Francesco Sinigaglia; Phase I/II randomized, double-masked, vehicle-controlled trial of recombinant human nerve growth factor (rhNGF) eye drops in stage 2/3 neurotrophic keratitis. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1172.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Neurotrophic keratitis (NK), a rare degenerative corneal disease, lacks effective therapies. As the underlying pathology is damage to the trigeminal nerve and loss of corneal innervation, treatment with nerve growth factor (NGF) is surmised to promote healing of moderate (stage 2) to severe (stage 3) NK.

Methods : A Phase I/II multicenter, randomized, double-masked, vehicle-controlled trial compared safety and efficacy of recombinant human NGF (rhNGF) eye drops (10 or 20 μg/ml) vs vehicle, 6 drops/day for 8 weeks, in patients with NK stage 2 (persistent epithelial defect) or 3 (ulcer). Phase I assessed safety in 18 patients randomized 7:7:4 to rhNGF 10 μg/ml, 20 μg/ml or vehicle. Phase II assessed safety and efficacy in 156 patients randomized 1:1:1 to rhNGF 10 μg/ml, 20 μg/ml or vehicle. Complete corneal healing (<0.5mm corneal fluorescein staining) was assessed at week 4 (primary efficacy endpoint) and week 8 (secondary endpoint). Complete absence of staining (0mm in the corneal lesion area and no persistent residual staining elsewhere) was analyzed post hoc. Missing values were imputed using the last observation carried forward.

Results : Table 1 summarizes the efficacy analyses. At week 4, 19.6% of patients receiving vehicle healed completely vs 54.9% receiving rhNGF 10 μg/ml (Δ35.3%; 97.06% confidence interval [CI] 15.88–54.71; P<0.001) and 58.0% receiving rhNGF 20 μg/ml (Δ38.4%; 97.06% CI 18.96–57.83; P<0.001). At week 8, 43.1% of patients receiving vehicle healed completely vs 74.5% receiving rhNGF 10 μg/ml (Δ31.4%; 97.06% CI 11.25–51.49; P<0.001) and 74.0% receiving rhNGF 20 μg/ml (Δ30.9%; 97.06% CI 10.60–51.13, P<0.002). Exploratory comparison of differences between rhNGF doses was not significant at week 4 or 8. Post hoc analysis of complete absence of staining at weeks 4 and 8 (Table 2) maintained statistically significant differences between rhNGF and vehicle groups and showed consistently higher percentages in the rhNGF 20 μg/ml group. rhNGF was well tolerated; adverse effects were mostly local, mild and transient.

Conclusions : rhNGF is safe and more effective than vehicle in promoting healing of stage 2/3 NK.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 

Table 1. Analysis of complete corneal healing (<0.5mm fluorescein staining)

Table 1. Analysis of complete corneal healing (<0.5mm fluorescein staining)

 

Table 2. Post hoc analysis of complete absence of staining (0mm staining in the corneal lesion area; no persistent residual staining elsewhere)

Table 2. Post hoc analysis of complete absence of staining (0mm staining in the corneal lesion area; no persistent residual staining elsewhere)

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