Phase III Study of OT202 in Treating Moderate to Severe Dry Eye

Официальное название

A Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Study to Evaluate the Safety and Efficacy of OT202 Eye Drops in the Treatment of Moderate to Severe Dry Eye

Обзор

This is a multicenter, randomized, double-blind, placebo-controlled Phase III clinical trial, enrolling 842 subjects with moderate to severe dry eye, who will be randomized at a 1:1 ratio to receive either 1% OT202 ophthalmic solution or vehicle control. The trial consists of screening, run-in, 8-week double-blind treatment period, and three long-term safety follow-up cohorts (10 weeks, 28 weeks, and 54 weeks), including 342 subjects for the 10-week follow-up, 350 subjects for the 28-week follow-up, and 150 subjects for the 54-week follow-up. Unblinding will be performed after the completion of double-blind treatment for all subjects, who will then receive open-label 1% OT202 ophthalmic solution uniformly. The co-primary efficacy endpoints are the change from baseline in Total Corneal Fluorescein Staining Score (TCSS) and Visual Analog Scale-Eye Dryness Score (VAS-EDS) at Day 56. Pharmacokinetic assessments will be conducted in 60 of the subjects assigned to the 54-weeks long-term safety follow-up. An interim futility analysis will be performed once approximately 30% of subjects complete the treatment period. Analysis of covariance (ANCOVA) will be utilized for efficacy statistical analyses. The primary objective is to evaluate the efficacy and safety of OT202 ophthalmic solution in the treatment of moderate to severe dry eye.

Вмешательства

• Препарат OT202 conc 1%
  Apply 1-2 drops of OT202 1% solution into the conjunctival sac. three times daily
• Препарат Placebo
  Apply 1-2 drops of placebo solution into the conjunctival sac. three times daily

Первичные конечные точки

• Total Corneal Fluorescein Staining (TCSS) score [Срок оценки: Day 56]
• Total visual analogue scale (VAS)-eye dryness score (EDS) score [Срок оценки: Day 56]

Вторичные конечные точки (5)

• Symptom assessment in dry eye (SANDE) scores [Срок оценки: Day 56]
• Ocular surface disease index (OSDI) scores [Срок оценки: Day 56]
• Corneal staining scores [Срок оценки: Day 14\Day 28\Day 56]
• Tear film break-up time (TFBUT) [Срок оценки: Day 14\Day 28\Day 56]
• Schirmer I test [Срок оценки: Day 14\Day 28\Day 56]

Критерии участия

Критерии включения

• 30 to 75 years of age (inclusive) at the time of signing the ICF, either sex or ethnic group.
• With history of dry eye for at least 6 months prior to screening, and history of use or willingness to use eye drops for the treatment of dry eye within 6 months prior to screening.
• Binocular BCVA ≥ 0.25 decimals (standard logarithmic visual acuity chart) at Screening and Baseline.
• At least one eye (the same eye) meets all the following criteria at screening and baseline:

• 5 ≤ TCSS ≤ 15, with individual corneal region staining ≤ 3
• Eye dryness score (EDS) ≥ 40 points in VAS
• TFBUT ≤ 5 seconds
• 1 mm/5 min ≤ Schirmer I test (without surface anesthesia) ≤ 10 mm/5 min
• Must be able to understand and sign the ICF approved by Independent Ethics Committee (EC).
• Willing and able to conduct protocol-required study visits, follow study guidelines, and take study drug as instructed.

Критерии исключения

• Patients who have previously participated in a Phase I or Phase II clinical study of OT202
• With contraindication or hypersensitivity to the study drug (OT202 and excipients) or diagnostic reagents (fluorescein sodium, lissamine green, etc.).
• During the screening period and baseline period, any eye with ocular active inflammation or structural abnormalities that may affect the trial assessment, including but not limited to trichiasis, blepharospasm, blepharitis, meibomitis, severe meibomian gland dysfunction(diagnosed according to the Expert Consensus on the Diagnosis and Treatment of Meibomian Gland Dysfunction in China (2023)), bulbar conjunctival laxity, keratitis, recurrent corneal erosion, allergic conjunctivitis, iritis, anterior chamber inflammation, known retinal detachment, diabetic retinopathy, or history of any progressive retinal disease.
• With history of possible or confirmed ocular infection (bacterial, viral, or fungal) or ocular herpes (simple or zoster) in either eye, as determined by the patient's medical history and/or at the screening and baseline examinations.
• Those with intraocular pressure (non-contact tonometry) greater than 21 mmHg or less than 8 mmHg or diagnosed with glaucoma at screening and baseline, or those with ocular hypertension who underwent intraocular pressure reduction therapy, and those with a history or suspicion of glaucoma.
• Those with any systemic disease are expected to potentially affect the study results. It includes but is not limited to Sjögren syndrome, Stevens-Johnson syndrome, rheumatoid arthritis, graft versus host disease, systemic lupus erythematosus, scleroderma, sarcoidosis, herpes, acne, rosacea, etc.
• Those who cannot stop using any ocular medication or treatment during the clinical trial.
• Those with recent clinically relevant history (e.g., hepatic, renal impairment) within 6 months prior to screening or current severe, unstable, or uncontrolled cardiovascular, pulmonary, hepatic, renal, autoimmune, and other relevant systemic diseases (e.g., severe chronic obstructive pulmonary disease, arrhythmia, significant heart failure, uncontrolled hypertension, type 2 diabetes mellitus), as assessed by the investigator.
• Those on a chronic, systemic medication regimen used for less than 1 month at screening and baseline or with dose changed within 1 month (including initiation of new medication and discontinuation).
• Those who have used any prohibited medications (topical ocular, systemic, and/or injectable medications) during the specified period prior to screening. These medications are also prohibited during the study. However, if a subject has a prohibited medication at screening, it needs to be stopped and washed out according to the washout period specified below, which can be included in the wash-out period. The minimum reasonable washout period for prohibited medications is as follows:

• Systemic and local immunosuppressant and immunotherapy (such as cyclosporine eye drops, tacrolimus eye drops, etc.): 60 days;
• Corticosteroids (any route): 14 days;
• Systemic or ocular topical mast cell stabilizers, antihistamines, antihistamines/mast cell stabilizer combination, vasoconstrictors, monoamine oxidase inhibitors: 7 days;
• Other topical ophthalmic preparations (including artificial tears): 3 days;
• Medications known to cause ocular dryness (e.g., anticholinergics, serotonin reuptake inhibitors, beta-blockers, diuretics, etc.): 14 days.

Note: Non-periocular, low-potency, over-the-counter corticosteroid topical skin creams are allowed for use in the study (e.g., hydrocortisone butyrate cream/ointment).

• Those who wore corneal contact lenses within 7 days prior to screening or required them during the study.
• Those who underwent meibomian gland massage or moist chamber therapy within 7 days prior to screening, or non-drug therapies for dry eye such as intense pulsed light therapy, thermal pulsation therapy, etc., within the previous 6 months before screening.
• Those who previously underwent dry eye surgery such as tear duct embolization (current tear duct embolization status or punctal plug use in the past 6 months) or amniotic membrane transplantation.
• Those who underwent ocular surface surgery (e.g., LASIK excimer laser in situ keratomileusis) within 12 months prior to screening or intraocular surgery within 6 months prior to screening in either eye, as determined by the subject's medical history and/or examination, or anticipated ocular surgery during the study.
• Those who use other investigational products or devices within 3 months prior to screening or concurrently during the study.
• Non-compliance with drug administration (< 80% or > 120%) during the introduction period.
• Females of childbearing potential who are currently pregnant, or have a positive pregnancy test result, or plan to get pregnant during the study, or are currently breastfeeding, or do not agree to use appropriate contraception methods to avoid pregnancy during the study period up to 1 month after the last dose of study drug.
• Males who do not agree to use one or more acceptable effective contraception methods during the study period up to 1 month after the last dose of study drug.
• Any condition or situation that, in the opinion of the investigator, may pose a safety risk to the subject in the trial or may interfere with the conduct of the study, or the investigator believes that the subject may not be able to complete or comply with the requirements of the study (due to administrative reasons or otherwise).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 49 центров

• The First Affiliated Hospital of Bengbu Medical University — Bengbu
• The Second Affiliated Hospital of Anhui Medical University — Хэфэй
• Peking University People's Hospital — Пекин
• Peking Union Medical College Hospital — Пекин
• Chongqing Aier Eye Hospital — Чунцин
• The First Affiliated Hospital of Fujian Medical University — Фучжоу
• Xiamen Eye Center Affiliated to Xiamen University — Xiamen
• Zhongshan Ophthalmic Center, Sun Yat-sen University — Гуанчжоу
• … и ещё 41 центр

Идентификаторы

NCT: NCT07740564 · OT202-03-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗