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: Active, not recruiting
• 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. Each symptom is rated on a 4-point (0-3) scale where 0=absent symptoms and 3=severe symptoms. The composite score of 3CS is the sum of the three cardinal symptom scores.	24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CFBL in the 7-day average CS score of nasal blockage/obstruction/congestion at Week 24	Nasal blockage/obstruction/congestion is one of the 3 cardinal symptoms. Each symptom is rated on a 4-point (0-3) scale where 0=absent symptoms and 3=severe symptoms.	Week 24
CFBL in the 7-day average CS score of anterior/posterior nasal discharge at Week 24	Anterior/posterior nasal discharge is one of the 3 cardinal symptoms. Each symptom is rated on a 4-point (0-3) scale where 0=absent symptoms and 3=severe symptoms.	Week 24
CFBL in the 7-day average CS score of facial pain/pressure at Week 24	Facial pain/pressure is one of the 3 cardinal symptoms. Each symptom is rated on a 4-point (0-3) scale where 0=absent symptoms and 3=severe 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 24		Week 24
Number and percent of participants requiring rescue treatment through Week 24		Week 24

Collaborators and Investigators

• Sponsor: Lyra Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2022
• Primary Completion (Estimated): March 15, 2024
• Study Completion (Estimated): September 15, 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): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Paranasal Sinus Diseases; Nose Diseases; 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