Nasal Polyps

This trial (J2T-MC-KGBU) is a pivotal phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial evaluating the efficacy and safety of lebrikizumab compared to PBO in participants with chronic rhinitis (CRS) and bilateral nasal polyps (NPs) who are receiving background treatment with intranasal corticosteroids (INCS). This 72-week trial will assess the efficacy of lebrikizumab in reducing the signs and symptoms of CRS with bilateral NPs. The primary participant group is adults at least 18 years of age. The trial is also open to adolescents at least 12 years of age and weighing at least 40 kg, all of whom will receive lebrikizumab.

250 mg LY3650150 (125 mg/mL) or placebo250 mg LY3650150 (125mg/mL)

LY3650150(Lebrikizumab)
D11AH10000

220
220

250 MG/2 ml
250mg/2mL

Evaluate the efficacy of Lebrikizumab 250 mg Q2W compared to PBO in reducing nasal congestion severity and endoscopic nasal polyp score at week 24 when receiving INCS background treatment.

Adult participants must be 18 years of age or older at the time of consent; have a physician-diagnosed CRS with bilateral NP; have received SCS for CRS or CRSwNP treatment within the past 2 years, or have undergone NP surgery (or both); and have a bilateral endoscopic NPS score of at least 5 (out of 8) at the screening period (first follow-up visit) and the baseline period (third follow-up visit), with a minimum score of 2 for each nasal cavity. Adolescent participants aged 12 to <18 years and weighing ≥40 kg are also permitted to participate at the first follow-up visit. Participants will be excluded if they have already received a dose of Lebrikizumab; are currently participating in any other clinical trial involving an investigational drug or any other type of medical research deemed scientifically or medically incompatible with this trial; have received treatment with an investigational drug within 8 weeks or 5 half-lives (if known) prior to the 3rd follow-up visit (whichever is longer); have a known allergy to any component of Lebrikizumab or its excipients; or have a contraindication to or intolerance to mometasone furoate.

Participants will be ineligible to participate in this trial if they meet any of the following criteria:

1. Have previously received one dose of lebrikizumab.

2. Are currently enrolled in any other clinical trial involving the investigational drug, or any other type of medical research deemed scientifically or medically incompatible with this trial.

3. Have received treatment with the investigational drug within 8 weeks prior to randomization or within 5 half-lives (if known), whichever is longer.

4. Have a known hypersensitivity to any component of lebrikizumab or its excipients.

5. Have a contraindication to or intolerance to mometasone furoate.

6. Have received a leukotriene receptor antagonist within 4 weeks prior to screening (first follow-up visit).

7. Have received any rescue medication during screening and/or the lead-up period and/or require surgery for NP.

8. Initiated allergen immunotherapy (subcutaneous injection immunotherapy [SCIT]/sublingual immunotherapy [SLIT]) within 6 months prior to screening at a non-stable dose (3 months prior to screening [first follow-up visit]), or may require dose changes during the trial.

9. Previously or currently receiving biologic therapy for CRSwNP and/or asthma and/or atopic dermatitis, including but not limited to omalizumab, dupilumab, mepolizumab, reslizumab, and benralizumab.

10. Prior to the baseline follow-up visit (3rd follow-up visit; randomization), treated with any biological or systemic immunosuppressant for an inflammatory disease or autoimmune disease (e.g., rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis).

a. Used B-cell depleting biologics, including rituximab, within 6 months.

b. Previous use of other biologics within 5 half-lives (if known) or 8 weeks (whichever is longer).

c. Received systemic immunosuppressants within 4 weeks prior to the baseline period (3rd follow-up visit).

11. Underwent any intranasal sinus surgery (including nasal polyp removal) within 6 months prior to screening (1st follow-up visit).

12. Previous sinus surgery or sinus surgery altering the lateral nasal wall structure that makes endoscopic NPS assessment difficult.

13. History of severe asthma exacerbation within the past year, with documentation showing SCS use for asthma within the past 12 months.

14. Any of the following conditions that could potentially affect indicator assessment at screening (1st follow-up visit) or the baseline period (3rd follow-up visit):

a. Nasal septum deviation obstructing at least one nostril.

b. Posterior maxillary sinus polyps.

c. Acute sinusitis, acute nasal infection, or acute upper respiratory tract infection.

d. Persistent drug-induced rhinitis.

e. Other diagnoses related to NP (i.e., eosinophilic granulomatosis with polyangiitis, granulomatous polyangiitis, Young's syndrome, primary ciliary dyskinesia, cystic fibrosis).

Note: For adolescents, documentation excluding cystic fibrosis and primary ciliary dyskinesia is required.

f. Nasal cavity tumor (malignant or benign).

g. Evidence of fungal sinusitis.

15. Received any live or live attenuated vaccine (including BCG vaccine or treatment) within 4 weeks prior to the baseline period (3rd follow-up visit), or is scheduled to receive a live attenuated vaccine (or BCG treatment) within 4 weeks during the trial or after receiving the last dose of investigational drug (IP). Note: The following are not considered live vaccines: messenger RNA (RNA) vaccines, vaccines containing inactive viruses, and/or non-replicating viral vector vaccines.

Note: Before enrolling adolescent participants, the trial administrator should assess whether the participants have received the latest immunizations according to local vaccination guidelines. For unvaccinated adolescents, the trial administrator should document the benefit/risk basis for enrolling such participants in the trial.

16. History of human immunodeficiency virus (HIV) infection or HIV serological positivity.

17. Current hepatitis B virus (HBV) infection or chronic infection (i.e., positive for hepatitis B surface antigen [HBsAg] and/or positive for polymerase chain reaction).

18. Current hepatitis C virus (HCV) infection (HCV RNA positive).

19. Known cirrhosis and/or chronic hepatitis of any cause.

20. Diagnosed with active endoparasitic infection or at high risk of developing such infection.

21. A known or suspected history of immunosuppression, as recommended by the trial administrator, including a history of invasive opportunistic infections (e.g., tuberculosis [TB], histoplasmosis, listeriosis, coccidioidomycosis, Pneumocystis jirovecii infection, aspergillosis), even if the infection has resolved; or a history of abnormal frequency, recurrent, or chronic infections.

22. Any of the following infections that occurred within the 3 months prior to screening, or during the screening or induction period:

a. Severe (requiring hospitalization and/or intravenous or equivalent oral antibiotic treatment).

b. Opportunistic (as defined by Winthrop et al 2015).

c. Symptomatic herpes zoster infection that did not resolve at screening. Note: Herpes zoster is considered active and persistent until all blisters have dried and crusted over.

d. Chronic (symptoms, signs, and/or treatment lasting 6 weeks or longer), excluding chronic sinusitis.

e. Recurrent (including but not limited to recurrent cellulitis, chronic osteomyelitis). Note: The medical monitor may, at their discretion, allow the inclusion of participants with only recurrent, mild, and uncomplicated oral and/or genital herpes.

23. An active or acute infection requiring treatment with systemic antibiotics, antiviral drugs, antiparasitic agents, antiprotozoal agents, or antifungal agents within 2 weeks prior to the baseline period (3rd follow-up visit). Note: Participants may be rescreened after infection resolution. If a participant has vaginal or oral candidiasis and is being treated only symptomatically without systemic anti-infective medication, they may be considered for inclusion if they meet other trial eligibility criteria. The inclusion of participants with other uncomplicated localized infections should be discussed with the medical monitor designated by the trial client.

24. A history of malignancy within 5 years prior to screening (excluding basal cell or squamous cell skin cancer and cervical carcinoma in situ that have received appropriate treatment). 25. Any other medical or psychological condition that, according to the trial administrator, may indicate a new and/or poorly understood illness, which could pose an unreasonable risk to the participant's participation in this clinical trial, potentially making participation unreliable or interfering with trial evaluation.

26. A co-existing severe illness that, according to the trial administrator, would adversely affect participation in the trial.

27. Loss of smell due to any cause other than Severe Specific Infectious Pneumonia (COVID-19) or CRSwNP.

28. A recent, incompletely healed nasal piercing that may cause nasal symptoms at screening (first follow-up visit), or a planned new nasal piercing during participation in the trial.

29. At screening (first follow-up visit), the participant's forced expiratory volume in one second (FEV1) is 50% or less of the predicted normal value.

30. Based on the trial administrator's opinion, a clinically significant laboratory abnormality was obtained at screening (first follow-up visit) or (baseline [third follow-up visit]).

31. A female participant who is pregnant, breastfeeding, or intends to become pregnant or breastfeed during participation in this trial.

32. An employee of Eli Lilly and Company, a family member of an Eli Lilly and Company employee, or an employee of any third party participating in this trial whose employee needs to be excluded.

33. A trial administrator, trial center staff member, and/or their immediate family member who is directly related to this trial, where immediate family member is defined as a spouse, parent, child, or sibling, whether by blood or legal adoption.

34. The participant or caregiver is unable or unwilling to participate during the trial, or unwilling to comply with trial restrictions and procedures, including subcutaneous injection of the investigational drug.

35. A history of chronic alcoholism, intravenous drug abuse, or other illicit drug abuse within the two years prior to screening.

36. Deemed by the trial administrator otherwise unsuitable for inclusion in the trial.

You agree to use the investigational drug only as directed by the investigating physician and staff, and to return any unused investigational drug and containers at the end of your participation in the trial or as otherwise directed by the investigating physician.