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.

Study Overview

• Status: Terminated
• Conditions: Moderate to Severe Allergic Asthma
• Intervention / Treatment: Biological: Placebo; Biological: CYT003

• Study Type: Interventional
• Enrollment (Actual): 365
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czech Republic
  • Kyjov, Czech Republic
    • Cytos Investigator Sites
  • Olomouc, Praha, Tabor, Ostrava, Hradec Kralove, Plzen, Brno, Czech Republic
    • Cytos Investigator Sites
• Germany
  • Bad Woerishofen, Leipzig, Magdeburg, Germany
    • Cytos Investigator Sites
  • Frankfurt aM, Delitzsch, Bonn, Berlin, Ruedersdorf, Germany
    • Cytos Investigator Sites
• Hungary
  • Szazhalombatta, Komaron, Hungary
    • Cytos Investigator Sites
  • Tatabanya, Szombathely, Csorna, Budapest, Balassagyarmat, Hungary
    • Cytos Investigator Sites
• Israel
  • Haifa, Zerifin, Israel
    • Cytos Investigator Sites
  • Rehovot, Petach Tikva, Ramat Gan, Jerusalem, Ashkelon, Afula, Israel
    • Cytos Investigator Sites
• Poland
  • Slupsk, Lodz, Tarnow, Pila, Poznan, Wroclaw, Poland
    • Cytos Investigator Sites
• Russian Federation
  • Ekaterinburg, Russian Federation
    • Cytos Investigator Sites
  • Tomsk,St.Petersburg,Yaroslavl,Novosibirsk,Smolensk,Barnaul, Russian Federation
    • Cytos Investigator Sites
• Ukraine
  • Donetsk, Kharkiv, Kiew, Chernivtsi, Zaporizhzhya, Mykolayiv, Ukraine
    • Cytos Investigator Sites
  • Vinnytsya, Ivano-Frankivsk, Ukraine
    • Cytos Investigator Sites
• United States
  • California
    • Los Angeles, Huntington Beach, San Jose, California, United States
      • Cytos Investigator Sites
    • Walnut Creek, San Diego, Riverside, Fountain Valley, California, United States
      • Cytos Investigator Sites
  • Colorado
    • Colorado Springs, Denver, Colorado, United States
      • Cytos Investigator Sites
  • Connecticut
    • Waterbury, Connecticut, United States
      • Cytos Investigator Sites
  • Florida
    • Miami, Tallahassee, Florida, United States
      • Cytos Investigator Sites
  • Georgia
    • Albany, Georgia, United States
      • Cytos Investigator Sites
  • Indiana
    • South Bend, Indiana, United States
      • Cytos Investigator Sites
  • Louisiana
    • Metairie, Louisiana, United States
      • Cytos Investigator Sites
  • Maine
    • Bangor, Maine, United States
      • Cytos Investigator Sites
  • Maryland
    • Bethesda, Maryland, United States
      • Cytos Investigator Sites
  • Massachusetts
    • North Dartmouth, Massachusetts, United States
      • Cytos Investigator Sites
  • Missouri
    • St. Louis, Missouri, United States
      • Cytos Investigator Sites
  • Nebraska
    • Ohmaha, Bellevue, Nebraska, United States
      • Cytos Investigator Sites
  • New York
    • Rochester, New York, United States
      • Cytos Investigator Sites
  • Ohio
    • Cincinnati, Ohio, United States
      • Cytos Investigator Sites
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • Cytos Investigator Sites
  • Oregon
    • Eugene, Medford, Oregon, United States
      • Cytos Investigator Sites
  • Rhode Island
    • Providence, Warwick, Rhode Island, United States
      • Cytos Investigator Sites
  • South Carolina
    • Spartanburg, Summerville, South Carolina, United States
      • Cytos Investigator Sites
  • Texas
    • San Antonio, Texas, United States
      • Cytos Investigator Sites
  • Virginia
    • Richmond, Virginia, United States
      • Cytos Investigator Sites

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Asthma Control Questionnaire	1 year

Collaborators and Investigators

• Sponsor: Cytos Biotechnology AG
• Investigators: Study Chair: Thomas B Casale, Professor, Creighton University, Omaha (NE)

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: August 23, 2012
• First Submitted That Met QC Criteria: August 27, 2012
• First Posted (Estimate): August 28, 2012

Study Record Updates

• Last Update Posted (Estimate): May 14, 2014
• Last Update Submitted That Met QC Criteria: May 13, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: CYT003-QbG10 12; 2012-003070-39 (EudraCT Number)