CYT003-QbG10, a TLR9-agonist, for Treatment of Uncontrolled Moderate to Severe Allergic Asthma

A Randomized, Placebo-Controlled, Phase IIb Dose-Finding Study of CYT003-QbG10, a TLR9-Agonist, in Patients With Moderate to Severe Allergic Asthma Not Sufficiently Controlled on Current Standard Therapy (GINA Steps 3+4)

The purpose of this study is to assess the therapeutic potential and safety/tolerability of study drug (CYT003) at 3 dose levels versus placebo in patients with persistent moderate to severe allergic asthma not sufficiently controlled on current standard controller therapy.

Altogether 360 patients randomized to 4 treatment groups will be included. The study compares three dose strength with placebo. Each patient receives 7 injections of study drug or undistinguishable placebo. Key outcome measures are patient reported parameters on their asthma.

Inclusion Criteria:

• Able and willing to provide written informed consent

• Able and willing to complete all protocol requirements

• Between 18 to 65 years of age

• Presence of persistent asthma for at least 6 months according to GINA 2011 guidelines at step 3 or 4 of treatment who has been on stable controller therapy for at least 4 weeks, and symptoms are not sufficiently controlled with medium to high doses of inhaled corticosteroid (ICS) (>250 to ≤1000 µg/day fluticasone or equivalent) in combination with or without long acting beta agonist (LABA), insufficient control will be based on asthma control questionnaire (ACQ) score ≥1.5 points. Use of stable doses of other controller therapies according to GINA steps 3 and 4 (leukotriene modifiers, sustained release theophylline) are also acceptable, but NOT treatment with anti immunoglobulin E (IgE) antibodies within the past 6 months

• Stable but insufficiently controlled baseline conditions as documented by ACQ ≥1.5 at the screening and the baseline visits.

• Positive skin prick test (SPT) or radioallergosorbent test (RAST) to at least 1 aero-allergen during the screening period

• Forced expiratory volume in one second (FEV1)≥40 to ≤90% of predicted value

• Reversibility of airway obstruction as demonstrated by:

  • FEV1 improvement by >12% , and
  • By ≥200 mL after inhaled β2-agonist (400 µg salbutamol or equivalent). If a subject does not meet reversibility criteria at the screening visit, reversibility may be retested once prior to run-in as long as the test is performed at least 5 days prior to the beginning of the run-in phase

Exclusion Criteria:

• Failure to meet at least 80% compliance with completion of asthma symptoms and medication diaries at the baseline visit, after initial instruction at the screening visit and where necessary additional training at the 2-weeks run-in visit. . An additional maximum 2-weeks training period may be added in such patients.
• Treatment or hospitalization for asthma exacerbation within past 2 months.
• Current use or use of systemic corticosteroids within past 2 months.
• Current smokers.
• Ex-smokers with a smoking history of >10 pack years (1 package per day for 10 years).
• Pregnancy or female planning to become pregnant during the study period.
• Ongoing or planned specific immunotherapy (SIT) during the whole study period or SIT completed within the last 3 years.
• Treatment with IgE antibodies (Xolair®) within past 6 months.
• Use of investigational unapproved drugs within 30 days or within 5 half-lives of the investigational drug, whichever is longer, or planned use during the whole study period.
• Use of investigational biologics within the last 6 months.
• Previous participation in a clinical study with a virus like particle (VLP) Qb-based vaccine.
• Possible dependency of the patient on sponsor and/or investigator.
• Women of child bearing potential