Clinical and Biological Evaluation of NAAGA Versus Azelastine Eye Drops in Allergic Subjects With Tear Film Dysfunction

NCT06800274 | Completed Phase 4

• 1 other identifier: ASL Napoli 3 sud n. 31/2019
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 1

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.

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)

Outcome Measures

Primary Outcomes (1)

• Improvement in Ocular Surface Disease Index (OSDI) Score from Baseline

  The OSDI is a validated questionnaire used to measure the severity of dry eye disease and its impact on vision-related quality of life. It includes 12 questions divided into three subscales: ocular symptoms, vision-related functions, and environmental triggers. Each item is scored on a scale from 0 ("none of the time") to 4 ("all of the time"). The total OSDI score is calculated on a scale of 0 to 100, with higher scores indicating greater severity. A clinically meaningful change is defined as a decrease of ≥10 points.

  Week 4

Secondary Outcomes (8)

• Improvement in OSDI Score from Baseline

  Week 2

• Changes in Tear Osmolarity from Baseline

  Week 2 and Week 4

• Improvement in Tear Break-Up Time (TBUT) from Baseline

  Week 2 and Week 4

• Improvement in Schirmer's Test 1 Results from Baseline

  Week 2 and Week 4

• Reduction in MMP-9 Positivity from Baseline

  Week 4

Study Arms (2)

NAAGA Group

EXPERIMENTAL

Drug: NAAGA (N-acetyl-aspartyl-glutamate) 49 mg/mL

Azelastine Group

ACTIVE COMPARATOR

Drug: azelastine hydrochloride 0.05%

Interventions

NAAGA (N-acetyl-aspartyl-glutamate) 49 mg/mL DRUG

80 patients were randomly assigned to NAAGA in single dose (49 mg/mL), instilled as 1 drop per eye four times daily for four weeks. Specific diagnostic tests and procedures for dry eye disease were performed at week 0 (baseline), week 2 and week 4.

NAAGA Group

azelastine hydrochloride 0.05% DRUG

54 patients were randomly assigned to azelastine hydrochloride 0.05% instilled as 1 drop per eye 2 times a day in the conjunctival sac for for four weeks. Specific diagnostic tests and procedures for dry eye disease were performed at week 0 (baseline), week 2 and week 4.

Azelastine Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Azienda Ospedaliera OO.RR. S. Giovanni di Dio e Ruggi D'Aragona: lead

Study Sites (1)

Azienda Ospedaliera Universitaria OO.RR. S. Giovanni di Dio e Ruggi D'Aragona

Salerno, Salerno, 84131, Italy

Location

Related Publications (13)

• Suarez-Cortes T, Merino-Inda N, Benitez-Del-Castillo JM. Tear and ocular surface disease biomarkers: A diagnostic and clinical perspective for ocular allergies and dry eye disease. Exp Eye Res. 2022 Aug;221:109121. doi: 10.1016/j.exer.2022.109121. Epub 2022 May 21.

  PMID: 35605673 BACKGROUND

• Shin D, Sang Min J. Comparison of treatment effects between 4.9% N-acetyl-aspartyl glutamic acid and 0.05% cyclosporine A eye drops in dry eye patients. Graefes Arch Clin Exp Ophthalmol. 2022 Oct;260(10):3285-3291. doi: 10.1007/s00417-022-05682-x. Epub 2022 Apr 29.

  PMID: 35486175 BACKGROUND

• Regu VR, Swain RP, Subudhi BB. Drug Delivery for Ocular Allergy: Current Formulation Design Strategies and Future Perspectives. Curr Pharm Des. 2023;29(33):2626-2639. doi: 10.2174/0113816128275375231030115828.

  PMID: 37936454 BACKGROUND

• Leonardi A, Quintieri L, Presa IJ, LLoves JM, Montero J, Benitez-Del-Castillo JM, Leston FJS, Gonzalez-Mancebo E, Asero R, Groblewska A, Kuna P. Allergic Conjunctivitis Management: Update on Ophthalmic Solutions. Curr Allergy Asthma Rep. 2024 Jul;24(7):347-360. doi: 10.1007/s11882-024-01150-0. Epub 2024 Jun 13.

  PMID: 38869807 BACKGROUND

• Kumar N, Feuer W, Lanza NL, Galor A. Seasonal Variation in Dry Eye. Ophthalmology. 2015 Aug;122(8):1727-9. doi: 10.1016/j.ophtha.2015.02.013. Epub 2015 Apr 6. No abstract available.

  PMID: 25912217 BACKGROUND

• Janeczko P, Norris MR, Bielory L. Assessment of receptor affinities of ophthalmic and systemic agents in dry eye disease. Curr Opin Allergy Clin Immunol. 2021 Oct 1;21(5):480-485. doi: 10.1097/ACI.0000000000000773.

  PMID: 34387278 BACKGROUND

• James IG, Campbell LM, Harrison JM, Fell PJ, Ellers-Lenz B, Petzold U. Comparison of the efficacy and tolerability of topically administered azelastine, sodium cromoglycate and placebo in the treatment of seasonal allergic conjunctivitis and rhino-conjunctivitis. Curr Med Res Opin. 2003;19(4):313-20. doi: 10.1185/030079903125001785.

  PMID: 12841924 BACKGROUND

• Jambou D, Lapalus P. Effect of N-acetyl-aspartyl-glutamate (Naaga) on in-vitro leukotriene synthesis by macrophage cell line P388D1. Int J Tissue React. 1990;12(5):273-80.

  PMID: 1983004 BACKGROUND

• Herrero-Vanrell R, Jauregui Presa I, Leceta Bilbao A, Montero-Iruzubieta J. Fundamental Aspects and Relevance of Components in Antihistamine Eye Drops. J Investig Allergol Clin Immunol. 2023 Dec;33(6):431-438. doi: 10.18176/jiaci.0963.

  PMID: 38095492 BACKGROUND

• Goldschmidt PL, Vulliez-Le Normand B, Briquet I, Dray F. Effects of N-acetyl-aspartyl glutamic acid and sodium cromoglycate on leukotriene B4 secretion by human leukocytes. Allergy. 1990 Jul;45(5):363-9. doi: 10.1111/j.1398-9995.1990.tb00512.x.

  PMID: 2165751 BACKGROUND

• Garcia-Queiruga J, Pena-Verdeal H, Sabucedo-Villamarin B, Garcia-Resua C, Giraldez MJ, Yebra-Pimentel E. Temporal Progression of Entry Factors into the Vicious Circle of Dry Eye in Untreated Sufferers. Life (Basel). 2024 Jun 26;14(7):806. doi: 10.3390/life14070806.

  PMID: 39063561 BACKGROUND

• Fukuda K, Kishimoto T, Sumi T, Yamashiro K, Ebihara N. Biologics for allergy: therapeutic potential for ocular allergic diseases and adverse effects on the eye. Allergol Int. 2023 Apr;72(2):234-244. doi: 10.1016/j.alit.2022.09.005. Epub 2022 Nov 1.

  PMID: 36333219 BACKGROUND

• El Fekih L, Khairallah M, Ben Amor H, Mahmoud A, Chiambaretta F, Messaoud R. Successful management of dry eye disease with a new eye drop formulation combining hyaluronic acid, trehalose, and N-acetyl-aspartyl-glutamic acid (NAAGA). J Fr Ophtalmol. 2024 Sep;47(7):104169. doi: 10.1016/j.jfo.2024.104169. Epub 2024 Jun 4.

  PMID: 38838456 BACKGROUND

MeSH Terms

Conditions

Conjunctivitis, Allergic; Dry Eye Syndromes

Interventions

isospaglumic acid

Condition Hierarchy (Ancestors)

Conjunctivitis; Conjunctival Diseases; Eye Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Lacrimal Apparatus Diseases

Study Officials

• Mario Troisi, MD

  Azienda Ospedaliera Universitaria OO.RR. S. Giovanni di Dio e Ruggi D'Aragona, Salerno, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 23, 2025
• First Posted: January 29, 2025
• Study Start: April 21, 2023
• Primary Completion: March 28, 2024
• Study Completion: March 28, 2024
• Last Updated: July 15, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR

Locations

IT (1)