Efficacy and Safety of LYR-210 for the Treatment of Chronic Rhinosinusitis in Adults (ENLIGHTEN 2)

ENLIGHTEN 2: A Phase III, Randomized, Blinded, Controlled, Parallel-Group Trial to Evaluate the Efficacy and Safety of LYR-210 for the Treatment of Chronic Rhinosinusitis in Adults

Multicenter, phase III, randomized, blinded, controlled, parallel group.

Study Overview

• Status: Completed
• Conditions: Chronic Sinusitis; Chronic Rhinosinusitis (Diagnosis)
• Intervention / Treatment: Drug: LYR-210; Drug: Sham procedure control; Other: Background therapy

Detailed Description

This is a 24-week, multicenter, phase III, randomized, blinded, controlled, parallel group with a 24-week treatment period to evaluate the efficacy and safety of LYR-210 compared with sham control for treatment in adults with CRS.

• Study Type: Interventional
• Enrollment (Actual): 182
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Ghent, Belgium
    • University Hospital Gent
  • Leuven, Belgium
    • Universitaire Ziekenhuizen Leuven
• Bulgaria
  • Burgas, Bulgaria
    • University Multiprofile Hospital for Active Treatment
  • Plovdiv, Bulgaria
    • UMHAT Kaspela Ltd
  • Sofia, Bulgaria
    • Military Medical Academy Multiprofile Hospital
  • Varna, Bulgaria
    • Diagnostic and Consulting Center Mladost - Varna
• Germany
  • Baden, Germany, 76669
    • HNO Praxis Dr. Andrea Kienle-Gogolok
  • Berlin, Germany
    • HNO Zentrum am Kudamm
  • Dresden, Germany
    • Universitaetsklinikum Carl Gustav Carus Dresden
  • Landsberg, Germany
    • HNO Landsberg
  • Tübingen, Germany
    • Universitaetsklinikum Tuebingen
• Hungary
  • Budapest, Hungary, 1115
    • Szent Imre Korhaz
  • Budapest, Hungary, 1145
    • Budapesti Uzsoki Utcai Korhaz
  • Budapest, Hungary, 1134
    • Észak-Pesti Centrumkórház - Honvédkórház
  • Budapest, Hungary, 1106
    • Budapesti Bajcsy-Zsilinszky Korhaz es Rendelointezet
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem - Nyaksebeszeti Klinika
  • Nyíregyháza, Hungary
    • Lyra Investigational Site
  • Pécs, Hungary
    • Pécsi Tudományegyetem Klinikai Központ
  • Tatabánya, Hungary
    • Komarom-Esztergom Varmegyei Szent Borbala Korhaz
• Poland
  • Bialystok, Poland
    • Sleepmedica
  • Inowrocław, Poland
    • "Farma-Med." Kujawskie Centrum Medyczne Sp. z o.o.
  • Krakow, Poland, 31-411
    • Promed P.Lach R.Glowacki Spolka Jawna
  • Lublin, Poland, 20-362
    • Velocity Lublin
  • Warsaw, Poland, 02-507
    • Mazowiecki Szpital Brodnowski Sp. z o.o. - Zespol Oddzialow Otolaryngologii
  • Warsaw, Poland, 03-242
    • Lyra Investigational Site
  • Wroclaw, Poland, 53-149
    • Panstwowy Instytut Medyczny MSWiA - Klinika Otolaryngologii
• United States
  • Arizona
    • Tucson, Arizona, United States, 85741
      • Novak Clinical Trials
  • California
    • Arcadia, California, United States, 91007
      • Keck School of Medicine at USC Medical Center
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90006
      • Sensa Health Clinical Research
    • Orange, California, United States, 92868
      • University of California - Irvine Medical Center
    • Roseville, California, United States, 95661
      • Sacramento Ear Nose and Throat Surgical and Medical Group, Inc
    • Sacramento, California, United States, 95817
      • University of California - Davis
    • San Diego, California, United States, 92108
      • Regional Head & Neck Consulting - SENTA Clinic
    • Torrance, California, United States, 90503
      • Breathe Clear Institute
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Colorado ENT and Allergy
  • Florida
    • Boynton Beach, Florida, United States, 33426
      • Ear, Nose and Throat Associates of South Florida, P.A.
    • Brandon, Florida, United States, 33511
      • ENT and Allergy Associates of Florida - Brandon
    • Plantation, Florida, United States, 33324
      • ENT and Allergy Associates of Florida - Plantation - Dr. Johnson
    • Plantation, Florida, United States, 33324
      • ENT and Allergy Associates of Florida - Plantation - Dr. Wright
    • Port Saint Lucie, Florida, United States, 34952
      • ENT and Allergy Associates of Florida
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medical Center (UCMC)
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas Medical Center (KUMC)
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts Eye and Ear Infirmary
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri-Columbia
    • St Louis, Missouri, United States, 63104
      • St Louis University
  • New York
    • New York, New York, United States, 10032
      • Columbia University
    • New York, New York, United States, 10016
      • ENT and Allergy Associates, LLP - Fifth Avenue New York
    • Rochester, New York, United States, 14642
      • University of Rochester
    • White Plains, New York, United States, 10605
      • ENT and Allergy Associates - White Plains
  • South Carolina
    • Orangeburg, South Carolina, United States, 29118
      • Carolina Ear, Nose, & Throat Clinic/CENTRI, Inc.
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • McKinney, Texas, United States, 75070
      • ENT Associates of Texas
  • Utah
    • Ogden, Utah, United States, 84405
      • Lyra Investigational Site
  • Virginia
    • Richmond, Virginia, United States, 23235
      • Lyra Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18
• Diagnosed as having CRS
• Bilateral ethmoid disease confirmed on CT
• Mean 3 cardinal symptom (3CS) score
• Undergone at least 2 trials of medical treatments in the past
• Has been informed of the nature of the study and provided written informed consent
• Agrees to comply with all study requirements
• If currently on a waiting list for sinonasal surgery, willing to be removed from the waiting list or have preplanned surgery date cancelled for the duration of the study. [Note: this does not preclude a participant from receiving or being recommended for sinonasal surgery as rescue treatment during the study].

Exclusion Criteria:

• Inability to tolerate topical anesthesia
• Previous nasal surgery
• Presence of nasal polyp grade 2 or higher
• Seasonal allergic rhinitis
• Perennial rhinitis with symptoms that are well controlled by regular use of intranasal corticosteroids
• Severe asthma
• History or clinical evidence or suspicion of invasive fungal sinusitis, allergic fungal rhinosinusitis, atrophic rhinitis, or odontogenic sinusitis
• Obstruction preventing proper placement and retention of LYR-210 as seen on endoscopy
• Anatomic variation that, in the opinion of the investigator, would adversely impact placement of LYR-210 as seen on CT
• Known history of hypersensitivity or intolerance to corticosteroids
• Known history of hypothalamic pituitary adrenal axial dysfunction
• Previous pituitary or adrenal surgery
• Dental procedure/implant on maxillary dentition within 4 weeks of the Screening visit.
• Past or present acute or chronic intracranial or orbital complications of CRS
• History or diagnosis (in either eye) of glaucoma or ocular hypertension
• Past or present functional vision in only 1 eye
• Past, present, or planned organ transplant or chemotherapy with immunosuppression
• Currently positive for COVID-19 or residual sinonasal symptoms from a previous COVID-19 infection
• Pregnant or breast feeding. Females of child-bearing potential must test negative for pregnancy at the time of screening
• Evidence of disease or condition expected to compromise survival or ability to complete follow-up assessments
• Currently participating in an investigational drug or device study
• Determined by the investigator as not suitable to be enrolled

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LYR-210; Single administration of LYR-210 drug matrix (7500 μg)	Drug: LYR-210; LYR-210 drug matrix (mometasone furoate); Other: Background therapy; Daily Saline Irrigation
Sham Comparator: Sham procedure control; Single mock administration procedure	Drug: Sham procedure control; Sham procedure control; Other: Background therapy; Daily Saline Irrigation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline (CFBL) in the 7-day Average Composite Score of 3 Cardinal Symptoms (3CS) in Participants Without Nasal Polyps	The 3CS are nasal blockage/obstruction/congestion, anterior/posterior nasal discharge, and facial pain/pressure. The diary is completed daily by study participants throughout the study. Each symptom is rated on a 4-point (0-3) scale where 0= none/absent symptoms, 1=mild symptoms, 2=moderate symptoms, and 3=severe symptoms. The composite score of 3CS is the sum of the three cardinal symptom scores. The 3CS total score ranges from 0-9, with higher scores indicating worse symptoms.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CFBL in the 22-item Sino-Nasal Outcome Test (SNOT-22) Total Score at Week 24	The SNOT-22 questionnaire is a 22-item disease-specific quality of life instrument. Each symptom is scored on a 6-point scale where 0 = no problem and 5 = problem as bad as it can be. The total SNOT-22 score is the sum of the 22 items and can range from 0 to 110 with higher scores indicating worse symptoms.	Week 24
CFBL in the 7-day Average Composite Score of 3CS in All Participants at Week 24	The 3CS are nasal blockage/obstruction/congestion, anterior/posterior nasal discharge, and facial pain/pressure. The diary is completed daily by study participants throughout the study. Each symptom is rated on a 4-point (0-3) scale where 0= none/absent symptoms, 1=mild symptoms, 2=moderate symptoms, and 3=severe symptoms. The composite score of 3CS is the sum of the three cardinal symptom scores. The 3CS total score ranges from 0-9, with higher scores indicating worse symptoms.	Week 24
CFBL in the 3-D Volumetric CT Score at Week 20	Change from baseline in the percent opacification of the bilateral anterior and posterior ethmoids at Week 20, as determined by 3-D volumetric CT analysis. 3-D volumetric scoring involves evaluations of each slice of 3-D coronal CT sequences and summing of all the slices to create a volumetric score ranging from 0% to 100%. A negative change from Baseline indicates improvement from Baseline.	Week 20
Rescue Treatment Requirement Through Week 24	Number and percent of participants requiring rescue treatment (systemic corticosteroid for any reason or participants that were recommended/underwent sinonasal surgery) through Week 24.	Week 24

Collaborators and Investigators

• Sponsor: Lyra Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2022
• Primary Completion (Actual): April 2, 2025
• Study Completion (Actual): April 2, 2025

Study Registration Dates

• First Submitted: March 8, 2022
• First Submitted That Met QC Criteria: March 16, 2022
• First Posted (Actual): March 25, 2022

Study Record Updates

• Last Update Posted (Actual): February 19, 2026
• Last Update Submitted That Met QC Criteria: January 31, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease
• Other Study ID Numbers: LYR-210-2021-005

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No