Safety and pharmacokinetics of escalating doses of recombinant human nerve growth factor eye drops (HT006.2.2) in healthy subjects.

BACKGROUND

HT006.2.2 is a kind of recombinant human nerve growth factor (rhNGF) eye drop with the potential to treat neurotrophic keratitis.

OBJECTIVE

To evaluate the safety, immunogenicity, and pharmacokinetic (PK) characteristics of HT006.2.2 eye drops in Chinese healthy volunteers.

METHODS

This study was divided into three parts. In Part A (single-dose) and Part B (multi-dose), four dose groups were per-specified: 5 µg/mL, 20 µg/mL, 60 µg/mL and 120 µg/mL. Each dose group comprised eight subjects randomized in a 3:1 ratio to receive the HT006.2.2 or placebo. Serum samples were collected for systemic PK analysis and anti-drug antibody (ADA) detection. The Part C comprised two single-dose groups (20 µg/mL and 60 µg/mL), and tear samples were collected at preset time points for tear fluid PK analysis. The drug mass per gram of tears (unit: µg/g) was calculated and used as the drug concentration to recalculate the PK parameters. Safety was evaluated via vital signs monitoring, 12-lead electrocardiogram, clinical laboratory tests, and ophthalmologic assessments (ocular symptoms and signs, slit-lamp microscopy, corneal fluorescein sodium staining, intraocular pressure measurement, and best-corrected visual acuity). Adverse events were collected following the initial administration of the investigational drug and were defined as treatment-emergent adverse events (TEAEs).

RESULTS

This study enrolled a total of 163 subjects, with 161 receiving the medication and completing the study as planned. HT006.2.2 showed favorable tolerance across both single-dose and multiple-dose parts. At the highest dose of 120 µg/mL, no maximum tolerated dose (MTD) was reached. No discernible dose-response relationship was identified in the incidence of TEAEs across dosage groups, with the total TEAE rate in HT006.2.2 groups remaining non-exceeding that of the placebo group. Ocular TEAEs included corneal vital dye staining, eye itching, eye pain, conjunctival hyperemia, and decreased visual acuity. In addition, no HT006.2.2 or ADA was detected in the peripheral blood of healthy subjects. Tear fluid PK analysis of HT006.2.2 (20 µg/mL) showed time to peak concentration (Tmax) of 0.17 h, mean peak concentration (Cmax) of 3.63 ± 2.06 µg/g, elimination half-life (t1/2) of 4.21 h.

CONCLUSIONS

HT006.2.2 eye drops exhibited favorable safety in Chinese healthy subjects, with localized ocular distribution, no systemic exposure, and no detectable ADAs. These findings support the continuation of clinical development for HT006.2.2 in China.