A Study of Lebrikizumab (LY3650150) in Adult Participants With Chronic Rhinosinusitis and Nasal Polyps Treated With Intranasal Corticosteroids (CONTRAST-NP)

A Multicentre, Randomized, Double-blind, Placebo-controlled, Parallel Group Phase 3 Efficacy and Safety Study of Lebrikizumab/ LY3650150 in Adults With Chronic Rhinosinusitis With Nasal Polyps on a Background Therapy With Intranasal Corticosteroids

The main purpose of this study is to evaluate the efficacy and safety of lebrikizumab in adult participants with chronic rhinosinusitis and nasal polyps treated with intranasal corticosteroids. The study will last about 18 months.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Rhinosinusitis With Nasal Polyps (CRSwNP)
• Intervention / Treatment: Drug: Placebo; Drug: LY3650150; Drug: Standard therapy for INCS

• Study Type: Interventional
• Enrollment (Estimated): 510
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: There may be multiple sites in this clinical trial 1-877-CTLILLY (1-877-285-4559) or; Phone Number: 1-317-615-4559; Email: ClinicalTrials.gov@lilly.com

Study Locations

• United States
  • Louisiana
    • Mandeville, Louisiana, United States, 70448
      • South Louisiana Ear, Nose, Throat & Facial Plastic Surgery - PPDS
      • Principal Investigator: James Connolly
  • Texas
    • McKinney, Texas, United States, 75070-5735
      • Ear Nose and Throat Associates of Texas PA
      • Principal Investigator: Dale Ehmer, Jr.
    • San Antonio, Texas, United States, 78258-3227
      • Alamo ENT Associates
      • Contact: Phone Number: 210-545-0404
      • Principal Investigator: Jeffrey Rosenbloom
  • Virginia
    • Richmond, Virginia, United States, 23235
      • Richmond Ear Nose and Throat
      • Principal Investigator: Michael Armstrong
      • Contact: Phone Number: 804-622-3768

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Physician-diagnosed chronic rhinosinusitis (CRS) with bilateral nasal polyps (NP).
• Prior treatment with systemic corticosteroids (SCS) within the last 2 years (or a medical contraindication or intolerance to SCS), prior surgery for NP, or both.
• Endoscopic bilateral NPS score of at least 5 out of 8, with a minimum score of 2 in each nasal cavity performed at screening and baseline.

• Ongoing symptoms for at least 8 weeks prior to study entry (screening), including:

  1. Nasal congestion with moderate or severe symptom severity (score 2 or 3) at screening and a weekly average severity score of at least 1 (range 0 to 3) at randomization, and
  2. At least one other symptom, such as partial loss of smell (hyposmia), total loss of smell (anosmia), or anterior or posterior rhinorrhea.
• Have concomitant asthma must be stable in the 3 months prior to screening using permitted regular asthma treatment.

Exclusion Criteria:

• Have received a dose of lebrikizumab.
• Have received treatment with any rescue medication and/or have the need for surgery for NP during screening and/or run-in period.
• Allergen immunotherapy (subcutaneous immunotherapy [SCIT]/sublingual immunotherapy [SLIT]) initiated within 6 months prior to screening, that is not on a stable dose (3 months prior to screening) or may require a dose change during study.
• Prior or current biologic treatment for CRSwNP and/or asthma including but not limited to omalizumab, dupilumab, mepolizumab, reslizumab, and benralizumab.

• Have received treatment with any biologic or systemic immunosuppressants for inflammatory disease or autoimmune disease prior to the baseline visit:

  1. B cell-depleting biologics, including rituximab, within 6 months.
  2. other biologics within 5 half-lives (if known) or 8 weeks, whichever is longer.
  3. Systemic immunosuppressants within 4 weeks prior to baseline.
• Have had any sinus intranasal surgery (including nasal polypectomy) within 6 months prior to screening
• Have had prior sino-nasal surgery or sinus surgery changing lateral wall structure of the nose making it difficult to assess endoscopic NPS

• Have a presence of any of the following conditions that may impact the assessment of endpoints at screening or baseline:

  1. Nasal septal deviation occluding at least one nostril.
  2. Antrochoanal polyps.
  3. Acute sinusitis, acute nasal infection, or acute upper respiratory infection.
  4. Ongoing rhinitis medicamentosa.
  5. Presence of another diagnosis associated with NP (ie, eosinophilic granulomatosis with polyangiitis, granulomatosis with polyangiitis, Young's syndrome, primary ciliary dyskinesia, cystic fibrosis).
  6. A nasal cavity tumor (malignant or benign).
  7. Evidence of fungal rhinosinusitis.
• Have anosmia from COVID or any reason other than CRSwNP.
• Participants with forced expiratory volume in 1 second (FEV1) 50% or less (of predicted normal) at screening.
• Female participant who is pregnant, breastfeeding, or is planning to become pregnant, or to breastfeed during the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lebrikizumab every 2 weeks (Q2W)/ every 4 weeks (Q4W); Lebrikizumab will be given as Subcutaneous (SC) injection. Participants will receive background therapy with intranasal corticosteroids (INCS).	Drug: LY3650150; Administered SC.; Drug: Standard therapy for INCS; Administered as intranasal spray.
Experimental: Lebrikizumab Q2W/every 8 weeks (Q8W); Lebrikizumab will be given as SC injection. Participants will receive background therapy with INCS.	Drug: LY3650150; Administered SC.; Drug: Standard therapy for INCS; Administered as intranasal spray.
Placebo Comparator: Placebo Q2W/Q4W; Placebo will be given as SC injection. Participants will receive background therapy with INCS.	Drug: Placebo; Administered SC.; Drug: Standard therapy for INCS; Administered as intranasal spray.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline (CFBL) in Participant Reported Nasal Congestion Score (NCS) Severity	NCS severity is rated by study participants using a 4-point scale (range from 0 to 3), where 0 corresponds to no symptoms and 3 corresponds to severe symptoms. Study participants are asked to record the severity of nasal congestion for the previous 24 hours. This assessment will be collected in the participant eDiary.	Baseline, Week 24
Mean CFBL in Endoscopic Nasal Polyp Score (NPS)	The endoscopic NPS is assessed by a centralized, blinded, independent review of nasal endoscopy video recordings. The total score is the sum of the right and left nasal cavity scores. For each nasal cavity, endoscopic NPS is graded based on polyp size from 0 to 4, where 0 = no polyps and 4 = large polyps.	Baseline, Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in Opacification of Sinuses Measured by the Lund Mackay score (LMK)	Central read on sinus computed tomography (CT) scans for the Lund Mackay score (LMK) will be performed. Review of the CT scans of the right and left frontal sinuses will include the use of a scoring system. The LMK scoring system is a 3-point grading scale where 0 = normal, 1 = partial opacification, and 2 = total opacification. The total score is the sum of the scores from each side and ranges from 0 to 24, where 0 indicates no disease and 24 indicates the most severe disease.	Baseline, Week 24
Mean change in Forced Expiratory Volume in 1 Second (FEV1)	FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation.	Baseline, Week 24
Mean CFBL in Severity of Loss of Smell	Participants will be asked about the severity of loss of smell using a 4-point scale, where 0 corresponds to no symptoms and 3 corresponds to severe symptoms. Study participants are asked to record the severity of loss of smell, for the previous 24 hours. This assessment will be collected in the participant eDiary.	Baseline, Week 24
Mean CFBL in Postnasal Drip	Postnasal drip is rated by study participants using a 4-point scale, where 0 corresponds to no symptoms and 3 corresponds to severe symptoms. Study participants are asked to record the severity of their postnasal drip, at its worst, for the previous 24 hours. This assessment will be collected in the participant eDiary.	Baseline, Week 24

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Estimated): April 10, 2024
• Primary Completion (Estimated): November 22, 2025
• Study Completion (Estimated): October 25, 2026

Study Registration Dates

• First Submitted: March 25, 2024
• First Submitted That Met QC Criteria: March 25, 2024
• First Posted (Actual): April 1, 2024

Study Record Updates

• Last Update Posted (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Pathological Conditions, Anatomical; Paranasal Sinus Diseases; Nose Diseases; Rhinitis; Sinusitis; Nasal Polyps; Polyps; Rhinosinusitis
• Other Study ID Numbers: 18790; J2T-MC-KGBU (Other Identifier: Eli Lilly and Company); 2023-508760-29-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual participant level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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