Efficacy and Safety of LYR-210 for the Treatment of Chronic Rhinosinusitis in Adults (ENLIGHTEN 1)

ENLIGHTEN 1: A Phase III, Randomized, Blinded, Controlled, Parallel-Group Trial to Evaluate the Efficacy and Safety of LYR-210 for the Treatment of Chronic Rhinosinusitis (CRS) in Adults

Multicenter, phase III, randomized, blinded, controlled, parallel group with safety extension phase with crossover or continued treatment.

Study Overview

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

Detailed Description

This is a 52-week, multicenter, phase III, randomized, blinded, controlled, parallel group with a 24-week treatment period followed by a safety extension phase with crossover or continued treatment to evaluate the efficacy and safety of LYR-210 compared with sham control for treatment in adults with CRS.

• Study Type: Interventional
• Enrollment (Actual): 196
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, A-8036
    • Lyra Investigational Site
  • Klagenfurt am Worthersee, Austria, 9020
    • Lyra Investigational Site
  • Linz, Austria, 4010
    • Lyra Investigational Site
  • Wien, Austria, 1090
    • Lyra Investigational Site
• Czechia
  • Brno, Czechia, 656 91
    • Lyra Investigational Site
  • Hradec Králové, Czechia, 500 05
    • Lyra Investigational Site
  • Motol, Czechia, 150 06
    • Lyra Investigational Site
  • Olomouc, Czechia, 77900
    • Lyra Investigational Site
  • Praha, Czechia, 140 59
    • Lyra Investigational Site
• Poland
  • Bydgoszcz, Poland, 85-047
    • Lyra Investigational Site
  • Bydgoszcz, Poland, 85-605
    • Lyra Investigational Site
  • Elbląg, Poland, 82-300
    • Lyra Investigational Site
  • Katowice, Poland, 40-611
    • Lyra Investigational Site
  • Kraków, Poland, 30-033
    • Lyra Investigational Site
  • Kraków, Poland, 31-411
    • Lyra Investigational Site
  • Krosno, Poland, 38-400
    • Lyra Investigational Site
  • Lublin, Poland, 20-362
    • Lyra Investigational Site
  • Nadarzyn, Poland, 05-830
    • Lyra Investigational Site
  • Warszawa, Poland, 00-635
    • Lyra Investigational Site
  • Warszawa, Poland, 04-141
    • Lyra Investigational Site
  • Wrocław, Poland, 53-149
    • Lyra Investigational Site
• Spain
  • Barcelona, Spain, 08003
    • Lyra Investigational Site
  • Barcelona, Spain, 08022
    • Lyra Investigational Site
  • Bilbao, Spain, 48013
    • Lyra Investigational Site
  • Cadiz, Spain, 11407
    • Lyra Investigational Site
  • Granada, Spain, 18014
    • Lyra Investigational Site
  • Madrid, Spain, 28034
    • Lyra Investigational Site
  • Navarro, Spain, 31008
    • Lyra Investigational Site
  • Santander, Spain, 39008
    • Lyra Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-0012
      • Lyra Investigational Site
  • California
    • Escondido, California, United States, 92025
      • Lyra Investigational Site
    • La Mesa, California, United States, 91942
      • Lyra Investigational Site
    • Sacramento, California, United States, 95661
      • Lyra Investigational Site
    • Torrance, California, United States, 90503
      • Lyra Investigational Site
  • Florida
    • Boca Raton, Florida, United States, 33487-5713
      • Lyra Investigational Site
    • Boynton Beach, Florida, United States, 33426
      • Lyra Investigational Site
    • Plantation, Florida, United States, 33324
      • Lyra Investigational Site
    • Port Saint Lucie, Florida, United States, 34952
      • Lyra Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60657
      • Lyra Investigational Site
  • Kentucky
    • Louisville, Kentucky, United States, 40220
      • Lyra Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Lyra Investigational Site
  • New York
    • New Hyde Park, New York, United States, 11042
      • Lyra Investigational Site
    • New York, New York, United States, 10016
      • Lyra Investigational Site
    • New York, New York, United States, 10003
      • Lyra Investigational Site
    • New York, New York, United States, 10029
      • Lyra Investigational Site
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Lyra Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Lyra Investigational Site
    • Spartanburg, South Carolina, United States, 29303
      • Lyra Investigational Site
  • Tennessee
    • Nashville, Tennessee, United States, 37232-8605
      • Lyra Investigational Site
  • Texas
    • Fort Worth, Texas, United States, 76109
      • Lyra Investigational Site
    • Houston, Texas, United States, 77030
      • Lyra Investigational Site
    • Mansfield, Texas, United States, 76063
      • Lyra Investigational Site
    • San Antonio, Texas, United States, 78258
      • Lyra Investigational Site
  • Utah
    • South Ogden, Utah, United States, 84405
      • Lyra Investigational Site
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • 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
• Undergone at least 2 trials of medical treatments in the past
• Mean 3 cardinal symptom (3CS) score
• Bilateral ethmoid disease confirmed on CT
• Has been informed of the nature of the study and provided written informed consent
• Agrees to comply with all study requirements
• If on a waiting list for sinonasal surgery, willing to be removed from list or have surgery date cancelled for the duration of the study.

Exclusion Criteria:

• Inability to tolerate topical anesthesia or endoscopic procedure
• 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	Other: Background Therapy; Daily Saline Irrigation; Drug: Sham procedure control; Sham procedure control

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/each question 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.	24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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/each question 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 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 3-D Volumetric CT Score at Week 20	The percent opacification of the bilateral anterior and posterior ethmoids will be assessed by 3-D volumetric CT analysis at baseline and Week 20. A negative change from Baseline indicates improvement from Baseline.	Week 20
Participants With Rescue Treatments for CRS Through Week 24	This endpoint is descriptively summarized per the prespecified plan. This includes participants that used systemic corticosteroid for any reason as well as participants that were recommended/underwent sinonasal surgery.	Week 24

Collaborators and Investigators

• Sponsor: Lyra Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2022
• Primary Completion (Actual): March 4, 2024
• Study Completion (Actual): September 16, 2024

Study Registration Dates

• First Submitted: January 21, 2022
• First Submitted That Met QC Criteria: January 21, 2022
• First Posted (Actual): February 2, 2022

Study Record Updates

• Last Update Posted (Actual): May 2, 2025
• Last Update Submitted That Met QC Criteria: April 16, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Nose Diseases; Otorhinolaryngologic Diseases; Rhinitis; Paranasal Sinus Diseases; Rhinosinusitis; Sinusitis
• Other Study ID Numbers: LYR-210-2021-004

Drug and device information, study documents

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