A Phase IIb study to identify the best dose of test drug CYT003-QbG10 versus placebo, in patients with moderate to severe allergic asthma not sufficiently controlled on current standard treatment.
- Conditions
- Allergic AsthmaMedDRA version: 16.1Level: LLTClassification code 10001705Term: Allergic asthmaSystem Organ Class: 100000004855Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2012-003070-39-HU
- Lead Sponsor
- Cytos Biotechnology AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 360
Each patient must meet the following criteria to be enrolled in this study. Note: All potential patients will sign an informed consent form (ICF) (Visit Scr/R1) before performing any study procedures.
1.Able and willing to provide written informed consent
2.Able and willing to complete all protocol requirements
3.Between 18 to 65 years of age
4.Persistent asthma with all of the following:
•Present for at least 6 months according to GINA 2011 guidelines at Step 3 or 4 of treatment
•Stable doses of controller therapy for at least 4 weeks prior to signing the ICF
•Symptoms are not sufficiently controlled with medium to high doses of ICS (>250 to =1000 µg/day fluticasone or equivalent) in combination with or without LABA.
•Asthma control questionnaire (ACQ) score =1.5.
Note: Use of stable doses of other controller therapies according to GINA Steps 3 and 4 (leukotriene modifiers, sustained-release theophylline) are also acceptable provided doses are stable for 4 weeks prior to signing the ICF. Treatment with anti immunoglobulin E (IgE) antibodies (Xolair®) within the past 6 months will not be allowed (see exclusion criterion 18)
5.Stable but insufficiently controlled baseline conditions as documented by ACQ =1.5 at the screening and the baseline visits.
6.Positive skin prick test (SPT) or radioallergosorbent test (RAST) to at least 1 aero-allergen during the screening visit
7.Forced expiratory volume in one second (FEV1) =40 to =90% of predicted value
8.Reversibility of airway obstruction as demonstrated by:
•FEV1 improvement of =12% , and
•FEV1 improvement of =200 mL after inhaled ß2-agonist (400 µg salbutamol or equivalent).
If a patient does not meet reversibility criteria at the screening visit, reversibility can be retested once prior to run-in visit R2. Reversibility testing should occur after at least 6 hours of short-acting ß2-agonist (SABA) withhold and at least 12 hours of LABA withhold. Reversibility can be performed after a longer LABA withhold at the discretion of the principal investigator.
9.Patients meeting the contraception requirements detailed in the contraception requirements section.
Contraception Requirements
Male patients who can father a child & Female patients of childbearing potential must agree to use 2 highly effective methods of contraception with their female partners. Contraception must include at least 1 barrier method
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 360
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Patients meeting any of the following criteria will be excluded from the study. Note: Any patient who fails during the screening visit may rescreen once with approval of the medical monitor.
1.Failure to meet at least 80% compliance of use of the patient e-diary/PEF meter (AM3) at baseline visit, after initial instructions at the screening visit and, where necessary, additional training at the R2 run-in visit. The 80% AM3 compliance will be calculated over the 10 days prior to and including the morning session of BL/T1. A scheduled AM3 session will be considered to be compliant if a complete set of answers and at least 1 PEF measurement is available.
2.Treatment or hospitalization for asthma exacerbation within past 2 months prior to signing the ICF. Patients who have an exacerbation during the screening visit/run-in period will be considered screen failures.
3.Current use or use of systemic corticosteroids within past 2 months prior to signing the ICF.
4.Current smokers.
5.Ex-smokers with a smoking history of >10 pack years (e.g., 1 pack per day for 10 years).
6.Major surgery within 4 weeks prior to enrollment or anticipated within the 12-week treatment period that might impact study procedures (e.g., spirometry)
7.Presence or history of clinically relevant cardiovascular, renal, pulmonary, endocrine, autoimmune, dermatological, neurological, psychiatric, or ocular disease as judged by the investigator.
8.Any malignancy within the previous 5 years except completely excised and cured squamous carcinoma of the uterine cervix, cutaneous basal cell carcinoma or squamous cell carcinoma
9.Presence of suspicious lymphadenopathy or splenomegaly on physical examination.
10.Confirmed or suspected current infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
11.Presence of active infectious disease as judged by the investigator.
12.Active autoimmune diseases or prior diagnosis of autoimmune disease including but not limited to rheumatoid arthritis, lupus, and colitis ulcerosa.
13.Pregnancy (based on positive urine test at screening visit) or lactation.
14.Female planning to become pregnant during the study period.
15.Patients with any history of abuse of alcohol or other recreational drugs.
16.Ongoing or planned specific immunotherapy (SIT) during the whole study period or SIT completed within the last 3 years.
17.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.
18.Use of investigational or approved biologics including IgE antibodies (Xolair®) within the last 6 months.
19.Previous participation in a clinical study with a virus-like particle (VLP) recombinantly expressed virus capsid shell (Qb)-based vaccine.
20.Possible dependency of the patient on sponsor and/or investigator.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this study is to assess the therapeutic potential and safety/tolerability of QbG10 at 3 dose levels versus placebo in patients with persistent moderate to severe allergic asthma not sufficiently controlled on current standard inhaled corticosteroids (ICS) with or without long-acting ß2 agonist (±LABA) therapy (Global Initiative for Asthma [GINA] steps 3 and 4) ;Secondary Objective: not applicable;Primary end point(s): •Change from baseline in ACQ score ;Timepoint(s) of evaluation of this end point: at Week 12
- Secondary Outcome Measures
Name Time Method Secondary end point(s): •FEV1 (pre- and post-bronchodilator)<br>•MiniAQLQ<br>•Daytime/nighttime symptoms, use of reliever medication (SABA) and morning and evening PEF as self-reported by patients in e-diaries<br>•Number of and time to asthma exacerbations <br>•Additional exploratory analyses of the clinical state of patients may use information captured from diaries or eCRF such as:<br>•An increase in the use of SABA defined as at least a doubling of the number of puffs from baseline (baseline will be defined as the average puffs per day over the last 10 days prior to the baseline visit [BL/T1]), or as an increase to 8 or more puffs of SABA over a 24 hour period<br>•A 30% decrease from baseline (baseline will be defined as the average of best morning PEF values over the last 10 days prior to the baseline visit [BL/T1]) in PEF provided that the decrease persists for 2 or more consecutive days<br>