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

Phase 3

Active, not recruiting

• Conditions: Chronic Sinusitis; Chronic Rhinosinusitis (Diagnosis)
• Interventions: Drug: Sham procedure control; Drug: LYR-210; Other: Background therapy

• Registration Number: NCT05295459
• Lead Sponsor: Lyra Therapeutics

Brief Summary

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

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 Timeline

• Study First Submitted: 2022-03-08
• Study First Submitted QC: 2022-03-16
• Study First Posted: 2022-03-25
• Study Start: 2022-05-13
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-17
• Last Update Posted: 2024-10-21
• Primary Completion: 2025-04-15
• Study Completion: 2025-04-15

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 182

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].

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sham procedure control	Sham procedure control	Single mock administration procedure
Sham procedure control	Background therapy	Single mock administration procedure
LYR-210	Background therapy	Single administration of LYR-210 drug matrix (7500 μg)
LYR-210	LYR-210	Single administration of LYR-210 drug matrix (7500 μg)

Primary Outcome Measures

Name	Time	Method
Change from baseline (CFBL) in the 7-day average composite score of 3 cardinal symptoms (3CS) of nasal blockage/obstruction/congestion, anterior/posterior nasal discharge, and facial pain/pressure at Week 24 in participants without nasal polyps.	Week 24	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.

Secondary Outcome Measures

Name	Time	Method
CFBL in the 7-day average composite score of 3CS at Week 24.	Week 24	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.
CFBL in the 22-item Sino-Nasal Outcome Test (SNOT-22) total score at Week 24.	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.
CFBL in the percent opacification of the bilateral anterior and posterior ethmoids at Week 20, as determined by 3-D volumetric CT analysis.	Week 20	Change from baseline in the 3-D volumetric CT score at Week 20.
Rescue treatment requirement through Week 24.	Week 24	Number and percent of participants requiring rescue treatment through Week 24, this data will be conducted from pooled data from Enlighten 2 and the Enlighten I study.

Trial Locations

Locations (54)

Novak Clinical Trials; 🇺🇸 Tucson, Arizona, United States

Keck School of Medicine at USC Medical Center; 🇺🇸 Arcadia, California, United States

Sensa Health Clinical Research; 🇺🇸 Los Angeles, California, United States

Cedars-Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

University of California - Irvine Medical Center; 🇺🇸 Orange, California, United States

Sacramento Ear Nose and Throat Surgical and Medical Group, Inc; 🇺🇸 Roseville, California, United States

University of California - Davis; 🇺🇸 Sacramento, California, United States

Regional Head & Neck Consulting - SENTA Clinic; 🇺🇸 San Diego, California, United States

Breathe Clear Institute; 🇺🇸 Torrance, California, United States

Colorado ENT and Allergy; 🇺🇸 Colorado Springs, Colorado, United States

Ear, Nose and Throat Associates of South Florida, P.A.; 🇺🇸 Boynton Beach, Florida, United States

ENT and Allergy Associates of Florida - Brandon; 🇺🇸 Brandon, Florida, United States

ENT and Allergy Associates of Florida - Plantation - Dr. Johnson; 🇺🇸 Plantation, Florida, United States

ENT and Allergy Associates of Florida - Plantation - Dr. Wright; 🇺🇸 Plantation, Florida, United States

ENT and Allergy Associates of Florida; 🇺🇸 Port Saint Lucie, Florida, United States

The University of Chicago Medical Center (UCMC); 🇺🇸 Chicago, Illinois, United States

Indiana University; 🇺🇸 Indianapolis, Indiana, United States

University of Kansas Medical Center (KUMC); 🇺🇸 Fairway, Kansas, United States

Tandem Clinical Research; 🇺🇸 Marrero, Louisiana, United States

Massachusetts Eye and Ear Infirmary; 🇺🇸 Boston, Massachusetts, United States

University of Missouri-Columbia; 🇺🇸 Columbia, Missouri, United States

St Louis University; 🇺🇸 Saint Louis, Missouri, United States

ENT and Allergy Associates, LLP - Fifth Avenue New York; 🇺🇸 New York, New York, United States

Columbia University; 🇺🇸 New York, New York, United States

University of Rochester; 🇺🇸 Rochester, New York, United States

ENT and Allergy Associates - White Plains; 🇺🇸 White Plains, New York, United States

Carolina Ear, Nose, & Throat Clinic/CENTRI, Inc.; 🇺🇸 Orangeburg, South Carolina, United States

Houston Methodist Hospital; 🇺🇸 Houston, Texas, United States

ENT Associates of Texas; 🇺🇸 McKinney, Texas, United States

University Hospital Gent; 🇧🇪 Gent, Belgium

Lyra Investigational Site; 🇵🇱 Warszawa, Poland

Universitaire Ziekenhuizen Leuven; 🇧🇪 Leuven, Belgium

University Multiprofile Hospital for Active Treatment; 🇧🇬 Burgas, Bulgaria

UMHAT Kaspela Ltd; 🇧🇬 Plovdiv, Bulgaria

Military Medical Academy Multiprofile Hospital; 🇧🇬 Sofia, Bulgaria

Diagnostic and Consulting Center Mladost - Varna; 🇧🇬 Varna, Bulgaria

HNO Praxis Dr. Andrea Kienle-Gogolok; 🇩🇪 Baden, Germany

HNO Zentrum am Kudamm; 🇩🇪 Berlin, Germany

Universitaetsklinikum Carl Gustav Carus Dresden; 🇩🇪 Dresden, Germany

HNO Landsberg; 🇩🇪 Landsberg, Germany

Universitaetsklinikum Tuebingen; 🇩🇪 Tuebingen, Germany

Semmelweis Egyetem - Nyaksebeszeti Klinika; 🇭🇺 Budapest, Hungary

Budapesti Bajcsy-Zsilinszky Korhaz es Rendelointezet; 🇭🇺 Budapest, Hungary

Szent Imre Korhaz; 🇭🇺 Budapest, Hungary

Eszak-Pesti Centrumkorhaz - Honvedkorhaz; 🇭🇺 Budapest, Hungary

Budapesti Uzsoki Utcai Korhaz; 🇭🇺 Budapest, Hungary

Pecsi Tudomanyegyetem Klinikai Kozpont; 🇭🇺 Pécs, Hungary

Komarom-Esztergom Varmegyei Szent Borbala Korhaz; 🇭🇺 Tatabánya, Hungary

Sleepmedica; 🇵🇱 Białystok, Poland

"Farma-Med." Kujawskie Centrum Medyczne Sp. z o.o.; 🇵🇱 Inowrocław, Poland

Promed P.Lach R.Glowacki Spolka Jawna; 🇵🇱 Krakow, Poland

Velocity Lublin; 🇵🇱 Lublin, Poland

Mazowiecki Szpital Brodnowski Sp. z o.o. - Zespol Oddzialow Otolaryngologii; 🇵🇱 Warszawa, Poland

Panstwowy Instytut Medyczny MSWiA - Klinika Otolaryngologii; 🇵🇱 Wrocław, Poland