Clinical trial NCT06800274: Clinical and Biological Evaluation of NAAGA Versus Azelastine Eye Drops in Allergic Subjects With Tear Film Dysfunction
Official title: A Randomized, Single-Blind Clinical Investigation to Compare the Efficacy and Safety of N-Acetyl-Aspartyl-Glutamate (NAAGA) Versus Azelastine Eye Drops in Patients With Allergic Conjunctivitis Associated With Tear Film Dysfunction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Allergic Conjunctivitis
Dry Eye Disease (DED)
Keywords: allergic conjunctivitis
dry eye disease (DED)
tear film dysfunction
azelastine
antihistamine eye drops
N acetyl-aspartyl glutamic acid (NAAGA)
Lead sponsor: Azienda Ospedaliera OO.RR. S. Giovanni di Dio e Ruggi D'Aragona
Sponsor class: OTHER
First posted: 2025-01-29
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized, single-blind study aims to compare the efficacy and safety of N-acetyl-aspartyl-glutamate (NAAGA) and azelastine hydrochloride eye drops in patients with allergic conjunctivitis associated with tear film dysfunction. A total of 134 atopic patients with mild-to-moderate tear film dysfunction were included. Participants were randomly assigned to receive either NAAGA (49 mg/mL, four times daily) or azelastine (0.05%, twice daily) for four weeks. The primary endpoint is the change in Ocular Surface Disease Index (OSDI) scores from baseline to week 4. Secondary endpoints include tear osmolarity, Schirmer test results, tear break-up time (TBUT), MMP-9 levels, and corneal staining scores. This study seeks to provide evidence for the tailored management of allergic conjunctivitis and tear film dysfunction.

Detailed description: There is limited but growing evidence in the literature regarding the effectiveness of N-acetyl-aspartyl-glutamate (NAAGA) in managing allergic conjunctivitis, particularly in patients with concomitant tear film dysfunction. NAAGA is a neuropeptide with dual activity as a mast cell stabilizer and anti-inflammatory agent, reducing histamine release and mitigating inflammatory cascades such as leukotriene production and complement activation. These mechanisms address both the allergic and inflammatory components of ocular surface diseases. Despite its promising therapeutic potential, studies directly comparing NAAGA to other treatments, particularly H1 receptor antagonists like azelastine, remain scarce.

In previous studies, NAAGA has demonstrated efficacy in reducing ocular surface inflammation, improving tear film stability, and alleviating symptoms of dry eye disease (DED). It has been reported a significant reduction in inflammatory markers, such as HLA-DR expression, and improvement in tear break-up time (TBUT) and Ocular Surface Disease Index (OSDI) scores in patients treated with NAAGA. Another investigation comparing NAAGA to cyclosporine A noted faster symptom relief and fewer adverse effects with NAAGA, highlighting its tolerability and potential for broader application. However, the literature lacks robust, head-to-head comparisons of NAAGA with second-generation antihistamines, such as azelastine, in the context of allergic conjunctivitis with tear film dysfunction.

Based on this background, this randomized, single-blind trial is designed to compare the efficacy and safety of NAAGA (49 mg/mL) with azelastine hydrochloride (0.05%) in treating patients with mild-to-moderate allergic conjunctivitis associated with tear film dysfunction. Both treatments target key mechanisms of disease but differ in their primary mode of action. NAAGA offers dual anti-inflammatory and mast cell-stabilizing effects, while azelastine acts predominantly as an H1 receptor antagonist with additional mast cell stabilization.

The primary objective of this study is to demonstrate that NAAGA is non-inferior to azelastine in improving symptoms and clinical parameters of allergic conjunctivitis associated with tear film dysfunction. Specifically, the study will evaluate changes in the Ocular Surface Disease Index (OSDI) score over four weeks of treatment. Secondary objectives include assessing changes in tear osmolarity, TBUT, Schirmer test results, MMP-9 levels, and corneal staining scores, as well as patient-reported symptoms of ocular discomfort.

This trial will include 134 patients with atopy and mild-to-moderate tear film dysfunction, randomized to receive either NAAGA eye drops (administered four times daily) or azelastine eye drops (administered twice daily) for four weeks. Both groups will undergo comprehensive evaluations, including the OSDI questionnaire, tear osmolarity testing, Schirmer I test, TBUT measurement, MMP-9 assessment, and fluorescein staining of the ocular surface. Patient-reported discomfort will be tracked through weekly diaries.

The investigation is expected to provide critical insights into the comparative efficacy and safety of NAAGA and azelastine in this patient population. NAAGA's dual-action profile may offer broader therapeutic benefits, particularly in addressing inflammation-driven tear film instability and ocular surface damage. Results from this study could inform clinical decision-making and support the development of more targeted, personalized treatments for patients with allergic conjunctivitis and tear film dysfunction.

Eligibility criteria: Inclusion Criteria:

* Adults (≥18 years) with atopy confirmed by skin prick tests, elevated specific IgE levels, or Prist result \>100 kU/L.
* Mild-to-moderate tear film dysfunction defined by OSDI scores ≥13 and at least one diagnostic abnormality (TBUT \<10 sec, Schirmer I test \<10 mm, CLEK score for corneal staining \>1, or tear osmolarity \>308 mOsm/L).

Exclusion Criteria:

* Severe ocular surface disorders
* Unilateral dry eye syndrome.
* Recent ocular surgery (within 3 months) or refractive surgery (within 6 months).

  . - Active ocular infections.
* Previous herpetic keratitis.
* Systemic or topic therapies with steroids in the last three months.
* Local therapies in the last 14 days.

Primary outcomes:
measure: Improvement in Ocular Surface Disease Index (OSDI) Score from Baseline
timeFrame: Week 4
Secondary outcomes:
measure: Improvement in OSDI Score from Baseline
timeFrame: Week 2
measure: Changes in Tear Osmolarity from Baseline
timeFrame: Week 2 and Week 4
measure: Improvement in Tear Break-Up Time (TBUT) from Baseline
timeFrame: Week 2 and Week 4
measure: Improvement in Schirmer's Test 1 Results from Baseline
timeFrame: Week 2 and Week 4
measure: Reduction in MMP-9 Positivity from Baseline
timeFrame: Week 4
measure: Improvement in Corneal Staining Scores
timeFrame: Week 4
measure: Patient-Reported Changes in Ocular Discomfort
timeFrame: Week 4
measure: Incidence of Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Week 4
Other outcomes:
Locations:
city: Salerno
country: Italy
facility: Azienda Ospedaliera OO.RR. S. Giovanni di Dio e Ruggi D'Aragona
Study officials:
References:
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