CONTRAINDICATIONS
NUCALA should not be administered to patients with a history of hypersensitivity to mepolizumab or excipients in the formulation.

...CONTINUED BELOW

 

DREAM MENSA SIRIUS

 

DREAM (Trial 1)dose-ranging, exacerbation-reduction study"toolbar=yes, scrollbars=yes, resizable=yes, width=400, height=400,top=50, left=50"8

Screening
2 Weeks
Treatment period
52 Weeks
N=621 (randomized 1:1:1:1)
Mepolizumab 750 mg IV (every 4 weeks) + SOC
Mepolizumab 250 mg IV (every 4 weeks) + SOC
Mepolizumab 75 mg IV (every 4 weeks) + SOC
Placebo IV (every 4 weeks) + SOC
Follow-up
4 weeks after the last dose of study medication

SOC=standard of care (regular treatment with high-dose ICS* and at least 1 other controller with or without oral corticosteroids [OCS]).

The only approved dose of NUCALA is 100 mg SC.

*High-dose ICS was defined as ≥880 µg of fluticasone propionate, or the equivalent, per day"toolbar=yes, scrollbars=yes, resizable=yes, width=400, height=400,top=50, left=50"8

Study Description"toolbar=yes, scrollbars=yes, resizable=yes, width=400, height=400,top=50, left=50"8

DREAM established the baseline blood eosinophil enrichment criteria and evaluation of the 100 mg SC dose for the subsequent MENSA and SIRIUS studies.

This 52-week study evaluated the effect of intravenous mepolizumab (75 mg, 250 mg, and 750 mg) on exacerbation rates over 12 months in 616 patients with severe asthma (regular treatment with high-dose ICS and at least one other controller with or without oral corticosteroids); ≥2 exacerbations in past 12 months requiring treatment with oral or systemic corticosteroids; at least 1 of 4 markers of eosinophilic airway inflammation in the previous 12 months: blood eosinophil count ≥300 cells/μL, sputum eosinophil count ≥3%, exhaled nitric oxide concentration ≥50 parts per billion (ppb), or prompt deterioration of asthma control after ≤25% reduction in regular maintenance inhaled corticosteroids/oral corticosteroids.

MENSA (Trial 2)exacerbation-reduction study"toolbar=yes, scrollbars=yes, resizable=yes, width=400, height=400,top=50, left=50"8

Run-in period
Week –1 to –6 all patients given SOC
Treatment period
Week 0 to 32
N=576 (random assignment 1:1:1)
Mepolizumab 75 mg intravenous (IV) and placebo subcutaneous (SC) + SOC
NUCALA and placebo IV + SOC
Placebo IV and placebo SC + SOC

Primary efficacy endpoint measured from Week 0 (baseline) to Exit Visit (Week 32)
Follow-up
4 weeks after the last dose of study medication

SOC=standard of care (regular treatment with high-dose ICS and at least 1 other controller with or without oral corticosteroids).

The only approved dose of NUCALA is 100 mg SC.

Study Description"toolbar=yes, scrollbars=yes, resizable=yes, width=400, height=400,top=50, left=50"8

Design: 32-week study comparing treatment with NUCALA or placebo in 576 patients with severe asthma with an eosinophilic phenotype (identified by blood eosinophil counts ≥150 cells/μL at initiation of treatment [within 6 weeks of dosing] or ≥300 cells/μL in the past 12 months).

Primary endpoint: Frequency of exacerbations.

Secondary endpoint: Included frequency of exacerbations requiring hospitalization and/or emergency department (ED) visits.

Exacerbation definition: Exacerbations of asthma were defined as the worsening of asthma that required use of oral/systemic corticosteroids and/or hospitalization and/or ED visits; for patients requiring maintenance oral/systemic corticosteroids, exacerbations were defined as at least double the existing maintenance dose for at least 3 days.

SIRIUS (Trial 3)oral corticosteroid reduction study"toolbar=yes, scrollbars=yes, resizable=yes, width=400, height=400,top=50, left=50"8

OCS Optimization Phase
–8 to –3 weeks
Induction Phase
4 Weeks
NUCALA + SOC
Placebo SC + SOC
OCS Reduction Phase
Week 4 to 20
NUCALA + SOC every 4 weeks
Placebo SC + SOC every 4 weeks
Maintenance Phase
Week 20 to 24
NUCALA + SOC
Placebo SC + SOC
Primary efficacy endpoint assessed at Week 24 (Exit Visit)
Follow-up§
Week 32

SOC=standard of care (regular treatment with high-dose ICS, OCS equivalent to 5 to 35 mg/day of oral prednisone, and at least 1 other controller).

The OCS Optimization Phase could be extended to 10 weeks if a patient experienced an exacerbation during this phase.
OCS dose titration occurred throughout the Optimization and Reduction Phases of the study.
OCS titration did not necessarily coincide with the visits scheduled for investigational products administration as indicated above.
§ Only patients who did not enter the open-label extension (OLE) study completed the follow-up visit at 12 weeks post last dose.

Study Description"toolbar=yes, scrollbars=yes, resizable=yes, width=400, height=400,top=50, left=50"8

Design: 24-week study comparing treatment with NUCALA or placebo in 135 patients with severe asthma with an eosinophilic phenotype (identified by blood eosinophil counts ≥150 cells/μL at initiation of treatment [within 6 weeks of dosing] or ≥300 cells/μL in the past 12 months) who required daily OCS in addition to regular use of high-dose ICS plus an additional controller.

Primary endpoint: Percent reduction in daily OCS dose (Weeks 20 to 24) while maintaining asthma control.

   818427R0 April 2017