Clinical trial NCT01673672: CYT003-QbG10, a TLR9-agonist, for Treatment of Uncontrolled Moderate to Severe Allergic Asthma
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Moderate to Severe Allergic Asthma
Lead sponsor: Cytos Biotechnology AG
Sponsor class: INDUSTRY
First posted: 2012-08-28
Enrollment: 365
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Asthma Control Questionnaire
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles, Huntington Beach, San Jose
country: United States
facility: Cytos Investigator Sites
state: California
city: Walnut Creek, San Diego, Riverside, Fountain Valley
country: United States
facility: Cytos Investigator Sites
state: California
city: Colorado Springs, Denver
country: United States
facility: Cytos Investigator Sites
state: Colorado
city: Waterbury
country: United States
facility: Cytos Investigator Sites
state: Connecticut
city: Miami, Tallahassee
country: United States
facility: Cytos Investigator Sites
state: Florida
city: Albany
country: United States
facility: Cytos Investigator Sites
state: Georgia
city: South Bend
country: United States
facility: Cytos Investigator Sites
state: Indiana
city: Metairie
country: United States
facility: Cytos Investigator Sites
state: Louisiana
city: Bangor
country: United States
facility: Cytos Investigator Sites
state: Maine
city: Bethesda
country: United States
facility: Cytos Investigator Sites
state: Maryland
city: North Dartmouth
country: United States
facility: Cytos Investigator Sites
state: Massachusetts
city: St. Louis
country: United States
facility: Cytos Investigator Sites
state: Missouri
city: Ohmaha, Bellevue
country: United States
facility: Cytos Investigator Sites
state: Nebraska
city: Rochester
country: United States
facility: Cytos Investigator Sites
state: New York
city: Cincinnati
country: United States
facility: Cytos Investigator Sites
state: Ohio
city: Oklahoma City
country: United States
facility: Cytos Investigator Sites
state: Oklahoma
city: Eugene, Medford
country: United States
facility: Cytos Investigator Sites
state: Oregon
city: Providence, Warwick
country: United States
facility: Cytos Investigator Sites
state: Rhode Island
city: Spartanburg, Summerville
country: United States
facility: Cytos Investigator Sites
state: South Carolina
city: San Antonio
country: United States
facility: Cytos Investigator Sites
state: Texas
city: Richmond
country: United States
facility: Cytos Investigator Sites
state: Virginia
city: Kyjov
country: Czech Republic
facility: Cytos Investigator Sites
city: Olomouc, Praha, Tabor, Ostrava, Hradec Kralove, Plzen, Brno
country: Czech Republic
facility: Cytos Investigator Sites
city: Bad Woerishofen, Leipzig, Magdeburg
country: Germany
facility: Cytos Investigator Sites
city: Frankfurt aM, Delitzsch, Bonn, Berlin, Ruedersdorf
country: Germany
facility: Cytos Investigator Sites
city: Szazhalombatta, Komaron
country: Hungary
facility: Cytos Investigator Sites
city: Tatabanya, Szombathely, Csorna, Budapest, Balassagyarmat
country: Hungary
facility: Cytos Investigator Sites
city: Haifa, Zerifin
country: Israel
facility: Cytos Investigator Sites
city: Rehovot, Petach Tikva, Ramat Gan, Jerusalem, Ashkelon, Afula
country: Israel
facility: Cytos Investigator Sites
city: Slupsk, Lodz, Tarnow, Pila, Poznan, Wroclaw
country: Poland
facility: Cytos Investigator Sites
city: Ekaterinburg
country: Russian Federation
facility: Cytos Investigator Sites
city: Tomsk,St.Petersburg,Yaroslavl,Novosibirsk,Smolensk,Barnaul
country: Russian Federation
facility: Cytos Investigator Sites
city: Donetsk, Kharkiv, Kiew, Chernivtsi, Zaporizhzhya, Mykolayiv
country: Ukraine
facility: Cytos Investigator Sites
city: Vinnytsya, Ivano-Frankivsk
country: Ukraine
facility: Cytos Investigator Sites
Study officials:
affiliation: Creighton University, Omaha (NE)
name: Thomas B Casale, Professor
role: STUDY_CHAIR
References: