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

Inclusion Criteria:

• Physician-diagnosed chronic rhinosinusitis (CRS) with bilateral nasal polyps (NP).

• Prior treatment with systemic corticosteroids (SCS) within the last 2 years (or amedical 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 ineach 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) atscreening and a weekly average severity score of at least 1 (range 0 to 3) atrandomization, and

2. At least one other symptom, such as partial loss of smell (hyposmia), totalloss of smell (anosmia), or anterior or posterior rhinorrhea.

• Have concomitant asthma must be stable in the 3 months prior to screening usingpermitted regular asthma treatment.

Exclusion Criteria:

• Have received a dose of lebrikizumab.

• Have received treatment with any rescue medication and/or have the need for surgeryfor 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 notlimited to omalizumab, dupilumab, mepolizumab, reslizumab, and benralizumab.

• Have received treatment with any biologic or systemic immunosuppressants forinflammatory 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 monthsprior to screening

• Have had prior sino-nasal surgery or sinus surgery changing lateral wall structureof the nose making it difficult to assess endoscopic NPS

• Have a presence of any of the following conditions that may impact the assessment ofendpoints 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, eosinophilicgranulomatosis with polyangiitis, granulomatosis with polyangiitis, Young'ssyndrome, 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 (ofpredicted normal) at screening.

• Female participant who is pregnant, breastfeeding, or is planning to becomepregnant, or to breastfeed during the study.