AZD1419 Ph2a Study
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 2

Summary: 
      Ph2a study planned to be run at approximately 16-18 sites in 4 EU countries (Denmark,
      Hungary, Poland and Sweden) enrolling approximately 170 patients to ensure 70 randomized
      patients with eosinophilic, moderate to severe asthma. The patients will receive 13 once
      weekly inhaled doses of the study drug. Treatment is initiated on top of their ICS/LABA
      controller medication, which is then tapered down and withdrawn during a period of 3 weeks
      and during the last 3 weeks of treatment the study drug is given as monotherapy. SABA is used
      as reliever medication during the whole study period. Primary endpoint is Loss of asthma
      control. When the endpoint is met, patients will resume their ICS/LABA, will be followed for
      an additional 4 weeks and will thereafter discontinue the study.
    

Detailed description: 
      Ph2a study planned to be run in approximately 16-18 sites in 4 EU countries (Denmark,
      Hungary, Poland and Sweden) enrolling approximately 170 patients to ensure 70 randomized
      patients with eosinophilic, moderate to severe asthma.

      The study has a withdrawal design.The patients will receive 13 once weekly inhaled doses of
      the study drug (AZD1419 or placebo). Treatment is initiated with 6 doses of the study drug on
      top of their ICS/LABA controller medication. Prior to the 7th dose of the study drug the LABA
      is withdrawn. The following 3 doses are given when ICS is tapered down. Dose 7 is given on
      top of 100% of their ICS, dose 8 is given on top of 50% of the ICS dose, which is then
      tapered down to 25% the following week and withdrawn completely prior to dose 10 of the study
      drug. During the last 3 weeks of treatment (ie last 4 doses), the study drug is given as
      monotherapy. SABA is used as reliever medication during the whole study period. Primary
      endpoint is Loss of asthma control, defined as any of the following criteria: a) An increase
      of ACQ-5 to 1.5 or more b) A reduction of 30% or more in morning peak expiratory flow (PEF)
      from baseline on 2 consecutive days c) At least six additional reliever inhalations of SABA
      in a 24-hour period relative to baseline on 2 consecutive days and d) An exacerbation
      requiring systemic corticosteroids

      When the endpoint is met, patients will resume their regular ICS/LABA controller medication
      and will be followed for an additional 4 weeks, when they do an Early Discontinuation (ED)
      Visit and will thereafter leave the study. For patients not loosing their asthma control, the
      full Observational period is up to week 52, when they will do an End of Treatment Visit
      (EOT). Study procedures are the same on ED and EOT Visits.
    

Intervention name(s): AZD1419; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Inhaled AZD1419 administered at the clinic as once weekly inhalations with the I-neb® device. Start dose is 4 mg and dose adaptation is applied (downtitration to 1mg or uptitration to 8 mg or remain on 4 mg) based on appearance of flu like adverse events; Inhaled Placebo administered at the clinic as once weekly inhalations with the I-neb® device. Start dose is Placebo 4 mg and dose adaptation is applied (downtitration to 1mg or uptitration to 8 mg or remain on 4 mg) based on appearance of flu like adverse events
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: inhaled; TLR9 agonist; withdrawal design; loss of control