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

Lilly

Status and phase: Enrolling; Phase 3

Conditions: Chronic Rhinosinusitis With Nasal Polyps (CRSwNP)

Treatments: Drug: Standard therapy for INCS; Drug: LY3650150; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06338995

18790

J2T-MC-KGBU (Other Identifier)

2023-508760-29-00 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 510 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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510 participants in 3 patient groups, including a placebo group

Lebrikizumab every 2 weeks (Q2W)/ every 4 weeks (Q4W)

Experimental group

Description:

Lebrikizumab will be given as Subcutaneous (SC) injection. Participants will receive background therapy with intranasal corticosteroids (INCS).

Treatment:

Drug: LY3650150

Drug: Standard therapy for INCS

Lebrikizumab Q2W/every 8 weeks (Q8W)

Experimental group

Description:

Lebrikizumab will be given as SC injection. Participants will receive background therapy with INCS.

Treatment:

Drug: LY3650150

Drug: Standard therapy for INCS

Placebo Q2W/Q4W

Placebo Comparator group

Description:

Placebo will be given as SC injection. Participants will receive background therapy with INCS.

Treatment:

Drug: Placebo

Drug: Standard therapy for INCS