TNF-α inhibitor tanfanercept (HBM9036) improves signs and symptoms of dry eye in a phase 2 trial in the controlled adverse environment in China

Abstract

Purpose: This study evaluated the clinical safety and efficacy of tanfanercept (HBM9036) ophthalmic solution as a novel treatment for dry eye disease (DED) in a controlled adverse environment (CAE) study conducted in China.

Methods: In a single-center, double-masked, randomized, placebo-controlled study, 100 patients received 0.25% tanfanercept, or placebo, twice daily for eight weeks. A mobile international CAE® DE Model was used for patient selection with a standardized challenge endpoint. Primary efficacy endpoint was fluorescein inferior corneal staining score (ICSS) pre- to post-CAE challenge from baseline. Secondary endpoints included Schirmer's Tear Test, Tear-Film Break-Up Time, Ocular Discomfort Score, Ora Calibra® Ocular Discomfort and 4-Symptom Questionnaire, total corneal staining score (TCSS), and drop comfort. Signs and symptoms were assessed both pre- and post-CAE to evaluate the efficacy of tanfanercept on both environmental and CAE endpoints.

Results: The tanfanercept treatment group showed improvement in ICSS pre- to post-CAE change from baseline scores when compared to placebo (- 0.61 ± 0.11 and - 0.54 ± 0.11, respectively; mean difference = 0.07, p = 0.65). TCSS pre-post-CAE change from baseline scores was also in favor of active when compared to placebo (- 1.03 ± 0.21 and - 0.67 ± 0.21, respectively; mean difference = 0.37, p = 0.23). Schirmer's score improvement was demonstrated in favor of active (1.87 ± 0.62 mm) as compared to placebo (1.28 ± 0.62 mm; mean difference = 0.59 mm, p = 0.50). Change from baseline in mean Tear-Film Break-up Time favored active treatment over placebo (mean difference = 1.21 s, p = 0.45). Notably, the tanfanercept showed more obvious benefits for each DED sign in a subgroup of subjects ≥ 35 years of age. Tanfanercept was well tolerated with no serious adverse events occurring during the study.

Conclusion: Tanfanercept demonstrated improvements in favor of active as compared to placebo in the signs of DED, being safe and well tolerated. These data support further evaluation of tanfanercept for the treatment of DED in China.

Trial registration: This study was retrospectively registered at ClinicalTrials.gov (NCT04092907) on September 17, 2019.

Keywords: Controlled adverse environment; Dry eye disease; TNF-TNFR1 inhibitor; Tanfanercept.

Conflict of interest statement

All authors declare that they have no conflict of interest.

© 2022. The Author(s).

Figures

Fig. 1

Clinical study plan. Subjects were screened for inclusion criteria at Visit 1. During the screening period encompassing Visits 1 and 2, two 90-min exposures to the mobile, international Ora CAE® Dry Eye Model were conducted to determine eligibility to enter into the treatment period of the study. Qualifying subjects who demonstrated potential response to CAE challenge in DED sign and symptom were randomized in a double-masked fashion into one of two treatment arms: 0.25% tanfanercept treatment or placebo treatment. All subjects were instructed to self-administer treatment (active or placebo) BID. At Visits 3 and 4, subjects were not exposed to the CAE but DED signs and symptoms were assessed. At Visits 5 and 6, subjects faced CAE challenge, while DED signs and symptoms were assessed pre-, during (symptom assessments only), and post-challenge

Fig. 2

Subject disposition. In total, 257 subjects were screened at Visit 1. Following 157 screen failures, at Visit 2, 100 subjects were enrolled and randomized in a 1:1 ratio into two treatment arms, 0.25% tanfanercept (active) and placebo, resulting in 50 subjects assigned to each group. During the course of the study, two subjects in the 025% tanfanercept treatment group withdrew due to subject choice (N = 1) and an adverse event (N = 1). The 98 subjects completed the study. Due to major protocol deviations, the per-protocol analysis sets were reduced to 48 subjects in the placebo treatment group and 47 subjects in the 0.25% tanfanercept treatment group

Fig. 3

Change from baseline in pre- to post-CAE ICSS at Visit 6 (Day 57). All subjects in the tanfanercept treatment group showed clinical improvement in change from baseline ICSS when compared to subjects in the placebo treatment group. In a subset of the subjects in the study age 35 years or older, clinical improvements in change from baseline ICSS were further increased compared to placebo

Fig. 4

Change from baseline in pre- to post-CAE TCSS at Visit 6 (Day 57). All subjects in the tanfanercept treatment group showed clinical improvement in change from baseline TCSS when compared to subjects in the placebo treatment group. In a subset of the subjects in the study age 35 years or older, clinical improvements in change from baseline TCSS were further increased compared to placebo

Fig. 5

Change from baseline in Schirmer’s score at Visit 6 (Day 57). All subjects in the tanfanercept treatment group showed clinical improvement in change from baseline Schirmer’s score when compared to subjects in the placebo treatment group. In a subset of the subjects in the study age 35 years or older, clinical improvements in change from baseline Schirmer’s score were further increased compared to placebo

Fig. 6

Ora Calibra® Ocular Discomfort and 4-Symptom Questionnaire Score at Visit 6 (Day 57). Subjects answered the Ora Calibra® Ocular Discomfort and 4-Symptom Questionnaire at each office visit throughout the study. The questionnaire measures ocular discomfort and 4 symptoms of DED: burning, dryness, grittiness, and stinging. There was no consistent improvement in dry eye symptoms for the 0.25% tanfanercept treatment group over placebo treatment group compared to baseline symptom scores measured at Visit 2