Neurotrophic Keratitis
Conditions
Keywords
STSP-0902, Ophthalmic Solution, Neurotrophic Keratitis
Brief summary
This is a Phase II, double-blind, placebo-controlled study to evaluate the safety and efficacy of STSP-0902 ophthalmic solution in patients with neurotrophic keratitis (NK). The study plans to enroll 48 patients with Mackie Stage 2 or 3 NK affecting one or both eyes. Eligible subjects will be randomized 1:1:1 into three dosing groups. Each dosing group will follow a drug-placebo allocation (12 active: 4 placebo). Treatment involves topical ocular administration for 8 weeks. Subjects who are not healed after the 8 weeks of masked treatment period will be permitted to receive standard of care during the follow-up period
Interventions
Eye drop, 3 times daily for 8 weeks
Eye drop, 3 or 6 times daily for 8 weeks
Sponsors
Staidson (Beijing) Biopharmaceuticals Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female patients aged between 18 to 85 years (inclusive). 2. Diagnosed with NK in one or both eyes, with the study eye classified as Mackie Stage 2 (PED) or Stage 3 (corneal ulcer), and with a maximum corneal defect diameter ≥2 mm. 3. Reduced or absent corneal sensitivity in the defect area and at least 1 adjacent corneal quadrant, confirmed by: ≤40 mm using the aesthesiometer or cotton swab test demonstrating marked reduction or absence of corneal sensitivity. 4. NK duration \>2 weeks in the study eye, as confirmed by the investigator based on medical history. 5. No improvement in the study eye for ≥7 days prior to randomization. 6. Effective non-pharmacological contraception used by the subject (and partner, if applicable) throughout the trial and for 3 months after the last dose, with no plans for pregnancy or gamete donation. 7. Voluntarily sign informed consent, with willingness and ability to comply with study procedures, follow-ups, and assessments.
Exclusion criteria
1. Any eye with corneal stromal ulceration involving \>1/3 of corneal thickness or at risk of corneal melting/perforation. 2. Active infection (bacterial, viral, fungal, amoebic, chlamydial) in any eye, or active ocular inflammation unrelated to NK. 3. Study eye with other ocular diseases requiring topical medication apart from the prescribed adjunctive treatments during the trial. 4. Bilateral vision loss severely impacting daily life, as assessed by the investigator. 5. Study eye with Schirmer I test ≤3 mm/5 minutes. 6. Severe lagophthalmos, eyelid margin disease, or meibomian gland dysfunction in the study eye that may impair corneal healing or trial outcomes. 7. Study eye with any surgery within 3 months prior to randomization (including corneal/non-corneal surgeries affecting trial assessments, except surgeries related to NK etiology), or planned ocular surgery during the trial. 8. Study eye with prior surgical intervention for NK (e.g., tarsorrhaphy, conjunctival flap) that may confound efficacy assessments, or amniotic membrane transplantation within 6 weeks prior to randomization. 9. Study eye with botulinum toxin injections to the levator muscle within 3 months prior to randomization or planned during the trial. 10. Requirement to wear contact lenses during the trial. 11. History of inefficacy or poor response to nerve growth factor (NGF) eye drops in any eye. 12. Use of autologous serum eye drops, deproteinized calf blood extracts, or other growth factor-containing ocular medications in the study eye(s) planned during the trial. 13. Use of NSAIDs, or corticosteroids in the study eye within 1 week prior to randomization or planned during the trial. 14. Use of neurotoxic drugs (e.g., antipsychotics, antiepileptics, antihistamines) or systemic immunosuppressants within 4 weeks prior to randomization or planned during the trial, excluding those who have been using it stably for at least 4 weeks before enrollment. 15. Poorly controlled systemic or ocular conditions (e.g., diabetic retinopathy, uveitis, autoimmune diseases, malignancies, psychiatric disorders) that may confound efficacy assessments or compliance, as judged by the investigator. 16. Known hypersensitivity to the study drug, its excipients, or components of trial-related ophthalmic tests (e.g., fluorescein). 17. History of drug abuse or alcohol dependence. 18. Participation in another interventional trial (drugs, devices, or vaccines) within 3 months prior to randomization or planned during this trial. 19. Female subjects who are pregnant, breastfeeding, or test positive for serum pregnancy; or who are failure to use effective contraception for 2 weeks prior to screening, during the trial, or for 3 months post-dosing. 20. Difficulty administering eye drops, venous blood sampling, or history of needle phobia/vasovagal syncope. 21. Any other condition deemed unsuitable for trial participation by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events | Screening to Week 10 | Number of participants with ocular and systemic adverse events as assessed by CTCAE v5.0. |
| Ocular Symptoms and Signs | Screening to Week 10 | Number of subjects with clinically significant changes in ocular symptoms and signs. |
| Intraocular Pressure (IOP) Measurements | Screening to Week 10 | Change in IOP is measured using a non-contact tonometer (In cases requiring precise IOP evaluation, a contact tonometer may be used). |
| Slit-Lamp Examinations | Screening to Week 10 | Number of subjects with clinically significant changes detected by slit-lamp microscope. The slit lamp examinations will encompass the eyelids, conjunctiva, cornea, anterior chamber, aqueous humor, iris, lens, and other relevant ocular structures. |
| Optical Coherence Tomography (OCT) Results | Screening to Week 10 | Proportion of corneal thickness affected by the stromal ulceration, as evaluated by the investigator. |
| Clinically Significant Changes in Vital Signs | Screening to Week 10 | Vital signs include body temperature in ℃, pulse rate in bpm, respiration rate in breaths/ minute, and blood pressure in mmHg. |
| Clinically Significant Changes in Physical Examinations | Screening to Week 10 | Physical examinations include assessments of general status, skin and mucous membranes, lymph nodes, head and neck, chest, abdomen, musculoskeletal system, spine/extremities, nervous system, and additional regions as clinically indicated. |
| Clinically Significant Changes in 12-Lead ECGs | Screening to Week 10 | Parameters measured: Heart rate in bpm, P-R interval in ms, QRS duration in ms, QT interval in ms, QTc interval in ms. |
| Clinically Significant Laboratory Abnormalities | Screening to Week 10 | Blood samples will be collected for hematology, blood biochemistry and coagulation function. Urine sample will be collected for and urinalysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Corneal Healing | Baseline to Week 10 | Percentage of subjects achieving corneal healing assessed via corneal fluorescein staining by the investigator |
| Corneal Sensitivity | Baseline to Week 10 | Evaluation of sensation in corneal quadrants using the aesthesiometer |
| Patients with Deterioration | Baseline to Week 10 | Percentage of Subjects with Disease Deterioration |
| Best Corrected Visual Acuity (BCVA) | Baseline to Week 8 | Change in BCVA from Baseline |
| Tear Secretion | Baseline to Week 8 | Change in Tear Secretion from Baseline as evaluated via Schirmer I test |
| Visual Quality of Life Assessed Using the NEI-VFQ-25 | Baseline to Week 8 | VFQ-25 is a questionnaire composed of 25 vision-targeted questions assessing 11 vision-related constructs, along with a single-item question to rate general health. Original responses from the questionnaire are recoded to a scale ranging from 0 to 100, where a higher score indicates better visual function. Each question corresponds to one of the 12 sub-scales and scores for each sub-scale are calculated by averaging its constituent questions. The overall composite score is generated by averaging the 11 vision-specific sub-scales, excluding the general health item. |
| STSP-0902 concentration | Baseline to Week 10 | Measurement of STSP-0902 in plasma after drug administration |
| Incidence of positive detection of anti-STSP-0902 antibodies | Baseline to Week 10 | Measurement of anti-drug antibody (ADA) to STSP-0902 in plasma after drug administration |
Countries
China
Contacts
CONTACTWanchun Huai
PRINCIPAL_INVESTIGATORWeiyun Shi, Ph.D
Shandong First Medical University Affiliated Eye Hospital
PRINCIPAL_INVESTIGATORTing Wang, Ph.D
Shandong First Medical University Affiliated Eye Hospital
Outcome results
None listed