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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Moderate to Severe Allergic Asthma

Intervention / Treatment
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* Biological: CYT003
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>7 weekly/biweekly injections of a placebo buffer | Biological: Placebo<br>* 7 subcutaneous injections, weekly/biweekly within 10 weeks<br>|
| Experimental: CYT003 low dose<br>7 weekly/biweekly injections of CYT003 low dose | Biological: CYT003<br>* 7 subcutaneous injections, weekly/biweekly within 10 weeks<br>|
| Experimental: CYT003 medium dose<br>7 weekly/biweekly injections of CYT003 medium dose | Biological: CYT003<br>* 7 subcutaneous injections, weekly/biweekly within 10 weeks<br>|
| Experimental: CYT003 high dose<br>7 weekly/biweekly injections of CYT003 high dose | Biological: CYT003<br>* 7 subcutaneous injections, weekly/biweekly within 10 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Asthma Control Questionnaire |  | 1 year |