Depemokimab

A clinically significant exacerbation is defined as a worsening of asthma requiring the use of systemic corticosteroids.

Moderate exacerbations are defined as clinically significant exacerbations that require treatment with oral/systemic corticosteroids and/or antibiotics. Severe exacerbations are defined as clinically significant exacerbations that require in-patient hospitalization (that is greater than or equal to \[\>=\] 24 hours) or result in death. The frequency of moderate/ severe exacerbations expressed as an annualized rate of moderate or severe exacerbations will be reported.

Mean change from baseline in total mucus plug volume measured at TLC at Week 26 will be assessed.

A HES flare is defined as either: a HES-related clinical manifestation based on a physician documented change in clinical signs or symptoms resulting in the need for the following : An increase in the maintenance systemic corticosteroid dose by at least 10 mg/day (prednisone/prednisolone equivalent) for at least 5 days, and/or an increase in or addition of any cytotoxic and/or immunosuppressive HES therapy. OR 2 or more courses of blinded active oral corticosteroid (OCS) during the intervention period. The frequency of HES flares will be calculated for each participant as the number of unique starting dates for HES flares.

Participants must be in remission at both Weeks 36 and 52.

Total endoscopic nasal polyps (NP) score evaluated the size and extent of nasal polyps via endoscopy. The assessments were performed by central video image recordings of nasal endoscopy. The right and left nostrils were scored from 0 to 4 (0 = No polyps; 1 = Small polyps in the middle meatus not reaching below the inferior border of the middle concha; 2 = Polyps reaching below the lower border of the middle turbinate; 3 = Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle concha; and 4 = Large polyps causing complete obstruction of the inferior meatus). The scores were graded based on NP size, recorded as sum of the right and left nostril scores and ranges from 0 (no polyps) to 8 (large polyps), calculated by summing the scores \[0 to 4\] in each nostril; with higher scores indicating worse status. Baseline was defined as Day 1 value. Change from Baseline = Post-baseline value minus Baseline value.

This endpoint evaluated the change from baseline in the mean nasal obstruction score using a Verbal Response Scale (VRS) from Week 49 through to Week 52. Participants used a VRS to rate nasal obstruction severity, with scores averaged over the specified period to assess treatment impact on nasal obstruction symptoms. Participants were asked to indicate the severity of nasal obstruction at their worst over the last 24 hours using a 4-point VRS, with options of no symptoms, mild symptoms, moderate symptoms, and severe symptoms. This was scored on a scale ranging from 0 (no symptoms) to 3 (severe symptoms), with higher scores indicating worse status. The average of daily scores in 4-weekly intervals were calculated and data are presented for Weeks 49-52. Baseline was defined as the average score from 28 days of electronic diary (eDiary) data collected prior to Day 1. Change from Baseline = Post-baseline value minus Baseline value.

This endpoint evaluated the change from baseline in the mean nasal obstruction score using a Verbal Response Scale (VRS) from Week 49 through to Week 52. Participants used a VRS to rate nasal obstruction severity, with scores averaged over the specified period to assess treatment impact on nasal obstruction symptoms. Participants were asked to indicate the severity of nasal obstruction at their worst over the last 24 hours using a 4-point VRS, with options of no symptoms, mild symptoms, moderate symptoms, and severe symptoms. This was scored on a scale ranging from 0 (no symptoms) to 3 (severe symptoms), with higher scores indicating worse status. Baseline was defined as the average score from 28 days of eDiary data collected prior to Day 1. Change from Baseline = Post-baseline value minus Baseline value.

Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of depemokimab. PK analysis was conducted using standard non-compartmental methods.

Blood samples were collected at indicated time points for PK analysis of depemokimab. PK analysis was conducted using standard non-compartmental methods.

Blood samples were collected from participants at indicated time points and analyzed for AUC(0-Infinity). Pharmacokinetic parameters were calculated by standard non compartmental analysis. As the first dose of depemokimab was administered on Day 1, Week 26 post-dose correlates to Day 1 plus 182 days, that is, Day 183.

Blood samples were collected from participants at indicated time points and analyzed for AUC(0-T). Pharmacokinetic parameters were calculated by standard non compartmental analysis. As the first dose of depemokimab was administered on Day 1, Week 26 post-dose correlates to Day 1 plus 182 days, that is, Day 183.

Blood samples were collected from participants at indicated time points and analyzed for AUC(0-Week 4). Pharmacokinetic parameters were calculated by standard non compartmental analysis. As the first dose of depemokimab was administered on Day 1, Week 4 post-dose correlates to Day 1 plus 28 days, that is, Day 29.

Blood samples were collected from participants at indicated time points and analyzed for AUC(0-Week 12). Pharmacokinetic parameters were calculated by standard non compartmental analysis. As the first dose of depemokimab was administered on Day 1, Week 12 post-dose correlates to Day 1 plus 84 days, that is, Day 85.

Blood samples were collected from participants at indicated time points and analyzed for AUC(0-Week 26). Pharmacokinetic parameters were calculated by standard non compartmental analysis. As the first dose of depemokimab was administered on Day 1, Week 26 post-dose correlates to Day 1 plus 182 days, that is, Day 183.

Blood samples were collected from participants at indicated time points and analyzed for percentage of AUC(0-Infinity) obtained by extrapolation. Pharmacokinetic parameters were calculated by standard non compartmental analysis. As the first dose of depemokimab was administered on Day 1, Week 26 post-dose correlates to Day 1 plus 182 days, that is, Day 183.

Blood samples were collected from participants at indicated time points and analyzed for Tmax. Pharmacokinetic parameters were calculated by standard non compartmental analysis. Tmax was determined directly from the plasma concentration-time data. As the first dose of depemokimab was administered on Day 1, Week 26 post-dose correlates to Day 1 plus 182 days, that is, Day 183.

Blood samples were collected from participants at indicated time points and analyzed for Tlast. Pharmacokinetic parameters were calculated by standard non compartmental analysis. As the first dose of depemokimab was administered on Day 1, Week 26 post-dose correlates to Day 1 plus 182 days, that is, Day 183.

Blood samples were collected from participants at indicated time points and analyzed for Apparent Clearance. Pharmacokinetic parameters were calculated by standard non compartmental analysis. As the first dose of depemokimab was administered on Day 1, Week 26 post-dose correlates to Day 1 plus 182 days, that is, Day 183.

Blood samples were collected from participants at indicated time points and analyzed for apparent volume of distribution. Pharmacokinetic parameters were calculated by standard non compartmental analysis. As the first dose of depemokimab was administered on Day 1, Week 26 post-dose correlates to Day 1 plus 182 days, that is, Day 183.

Blood samples were collected from participants at indicated time points and analyzed for Terminal elimination rate constant. Pharmacokinetic parameters were calculated by standard non compartmental analysis. As the first dose of depemokimab was administered on Day 1, Week 26 post-dose correlates to Day 1 plus 182 days, that is, Day 183.

Blood samples were collected from participants at indicated time points and analyzed for Terminal phase half-life. Pharmacokinetic parameters were calculated by standard non compartmental analysis. As the first dose of depemokimab was administered on Day 1, Week 26 post-dose correlates to Day 1 plus 182 days, that is, Day 183.