Enabling Reductions in Maintenance ICS/LABA Therapy Using As Needed Anti-Inflammatory Reliever for Patients with Severe Eosinophilic Asthma Controlled with Benralizumab: SHAMAL Phase IV Clinical Study

Rationale: Biologics, such as benralizumab, are recommended for add-on treatment of severe, eosinophilic asthma uncontrolled with high-dose inhaled corticosteroids (ICS) and long-acting β₂-agonists (LABA). Severe asthma guidelines recommend stepping down treatment once asthma is well-controlled or once a good clinical response to an add-on asthma biologic has been achieved. However, the efficacy and safety of this practice have not been extensively evaluated.

Methods: SHAMAL is an open-label, parallel-group, active-controlled, multicenter, Phase IV study that will enroll adult patients with severe, eosinophilic asthma receiving high-dose ICS/LABA who have achieved good asthma control: ACQ < 1.5 after > 8 weeks with benralizumab (30 mg subcutaneously according to prescribed label). At enrollment (Visit 1), all patients will switch their previous ICS/LABA maintenance and rescue medications to budesonide/formoterol (400 mg/12 µg [Symbicort^® Turbuhaler]) two puffs twice daily (BID) and a short-acting β₂-agonist (SABA; Ventolin^®) rescue inhaler to be used during the 4- to 8-week run-in period. At Visit 2, patients whose asthma remains well-controlled will be randomized 3 : 1 to either 1) treatment reduction arm (24 – 32 weeks): continue benralizumab 30 mg Q8W and reduce Symbicort maintenance treatment initially SMART (Symbicort maintenance and reliever therapy) 200/6 µg two puffs BID, and then to Symbicort 200/6 µg anti-inflammatory reliever or 2) reference arm (32 weeks): continue benralizumab 30 mg Q8W and Symbicort 400/12 µg 2 puffs BID (plus SABA as needed). The reduction period is followed by a 16-week maintenance period.

Results: The primary endpoint will be the percentage of patients who are able to reduce Symbicort maintenance dose at the end of the reduction period (Week 32) from high-dose to medium-dose Symbicort plus anti-inflammatory reliever, low-dose Symbicort plus anti-inflammatory reliever, or Symbicort anti-inflammatory reliever alone, while maintaining asthma control.

Conclusions: The SHAMAL study aims to demonstrate that severe eosinophilic asthma patients can effectively maintain control by combining use of Benralizumab with the lowest possible inhaled treatment burden using budesonide/formoterol anti-inflammatory reliever.

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Artikel online veröffentlicht:
30. April 2021