A proof of concept study of the effects of QAX576 (an interleukin-13 monoclonal antibody) on allergic inflammation following out of allergy season repeated nasal allergen challenge in subjects with seasonal allergic rhinitis sensitive to Timothy grass pollen.

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-003403-13-DE
• Date of registration: 03/09/2007
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A proof of concept study of the effects of QAX576 (an interleukin-13 monoclonal antibody) on allergic inflammation following out of allergy season repeated nasal allergen challenge in subjects with seasonal allergic rhinitis sensitive to Timothy grass pollen.
• Scientific title: A proof of concept study of the effects of QAX576 (an interleukin-13 monoclonal antibody) on allergic inflammation following out of allergy season repeated nasal allergen challenge in subjects with seasonal allergic rhinitis sensitive to Timothy grass pollen.
• Date of first enrolment: 19/12/2007
• Target sample size: 42
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-003403-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: open label active calibrator group If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Germany, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Healthy, male and female, non-smoking subjects, aged 18 to 55 years inclusive, with a history of allergic rhinitis consistent with Timothy grass pollen allergy. They must show:
• a positive skin prick test to Timothy grass pollen (wheal difference Timothy grass
pollen – negative control = 3 mm) at or within the 12 months preceding the screening visit and
• pre nasal allergen challenge TNSS = 3 at screening
• demonstrate symptomatic worsening (TNSS =4 point rise) within 30 minutes after
nasal allergen challenge
• ability to participate in repeated nasal lavages and nasal filter paper assessments at screening.
2. Body Mass Index (BMI) must be within the range of 18 to 30 kg/m2. Subjects must weigh between 50 and 100 kg (inclusive) to participate in this study.
3. Be otherwise healthy with no health problems that may jeopardize the subjects
participating in the study, absence of history of other significant allergies.
4. Only post-menopausal and surgically sterilized female subjects are allowed to participate in this study. Post-menopausal women must have no regular menstrual bleeding for at least 1 year prior to inclusion and menopause will be confirmed by a plasma FSH > 40 IU/L. Surgically sterilized, female subjects must have had the procedure performed at least 6 months prior to screening and the procedure must be supported with clinical documentation made available to sponsor and noted in the Relevant Medical History / Current Medical Conditions section of the CRF.
5. Male subjects must be using 2 methods of contraception, i.e., spermicidal gel plus condom, for the entire duration of the study, up to Study Completion visit (i.e., refrain from fathering a child in the six (6) months following last study drug administration).
6. Able to communicate well with the Investigator, to understand and comply with the requirements of the study. Understand and sign the written informed consent.
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
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Presence of any structural nasal abnormalities or nasal polyps on examination, a history of frequent nose bleeding, recent nasal surgery or recent (within 8 weeks prior to screening visit) or recent (four weeks) or ongoing upper or lower respiratory tract infection.
2. Smokers (use of tobacco products in the previous 3 months). Urine cotinine levels will be measured during screening and at baseline on Day 1 for all subjects. Smokers will be defined as any subject who reports tobacco use or has a urine cotinine greater than 500 ng/mL.
3. Presence of any respiratory disease other than a history of mild intermittent asthma not requiring regular treatment and associated with normal lung function (FEV1 = 80% predicted at screening after 6 hour short-acting bronchodilator washout).
4. Inability to perform spirometry or spirometry-induced airflow limitation.
5. Use of any prescription drugs within 4 weeks prior to dosing or OTC drugs within 14 days prior to dosing (particularly oral, inhaled, nasal or injectable corticosteroids, decongestants, anti-histamines, medications with anti-inflammatory effects, any other nasally applied medication) within four (4) weeks prior dosing. Paracetamol is acceptable, but must be documented in the Concomitant medications / Significant non-drug therapies page of the CRF. As required’ short-acting bronchodilator treatment for mild intermittent asthma is acceptable, but must be documented in the Concomitant medications / Significant non-drug therapies page of the CRF. Use of multivitamin and/or mineral preparations, if taken before, to be avoided since the screening visit.
6. If the subject gives a history of having received immunotherapy in the past 3 years as therapy or as part of a clinical trial..
7. History or presence of any surgical or medical condition which, in the opinion of the
investigator, may jeopardize the subject in case of participation in the study.
8. Significant illness within two weeks prior to dosing.
9. A past medical history of clinically significant ECG abnormalities.
10. History of autonomic dysfunction (e.g., history of fainting, orthostatic hypotension).
11. History of clinically significant drug allergy. A known hypersensitivity to the study drug or drugs similar to the study drug.
12. Donation or loss of 400 mL or more of blood within 8 weeks prior to first dosing, or longer if required by local regulation.
13. History of immunodeficiency diseases, including a positive HIV test result.
14. A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result.
15. History of drug or alcohol abuse within the 12 months prior to dosing or evidence of such abuse as indicated by the laboratory assays conducted during the screening evaluations.
16. History or laboratory evidence of acute or chronic renal insufficiency or abnormal liver function.
17. History of clinical schistosomiasis, or stool examination positive for ova or parasites, or travel within the preceding 6 months to an area with endemic schistosomiasis, including but not limited to Southeast and Southwest Asia and Africa.
18. Any planned travel to endemic areas within 6 months following end of study.
19. If blood absolute eosinophil count at screening =350 cells/mm3, subjects may be included in the study only after active parasitic infection is ruled out as the etiology of eosinophilia.
20. History of exposure to human therapeutic antibodies, immunoglobulins or other plasma products.
21. Pregnant or lactating female su

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Seasonal allergic rhinitis
MedDRA version: 9.1 Level: LLT Classification code 10001723 Term: Allergic rhinitis

Intervention(s)

Product Code: QAX576
Pharmaceutical Form: Powder for solution for infusion
Current Sponsor code: QAX576
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 6-
Pharmaceutical form of the placebo: Powder for solution for infusion
Route of administration of the placebo: Parenteral use (Noncurrent)

Trade Name: Flutide® Nasal
0,05 mg Suspension
Pharmaceutical Form: Nasal spray*
INN or Proposed INN: Fluticason-17-propionat
CAS Number: 80474-14-2
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Main Objective: To assess the ability of QAX576 to inhibit inflammation from nasal allergen exposure (Timothy Grass Pollen) as assessed by Th2-associated cytokines in nasal secretions.

Secondary Objective: • Assess the ability of QAX576 to inhibit eosinophils infiltration into nasal fluids after allergen challenge
• Assess the ability of QAX576 to block allergen induced allergic rhinitis as measured by total nasal symptom scores (TNSS)
• Assess if pharmacokinetics of plasma QAX576 in subjects with seasonal allergic rhinitis differ from pharmacokinetic in healthy volunteers
• Determine if IL-13 production in subjects with allergic rhinitis correlates with the degree of response to allergen challenge
•To perform exploratory pharmacogenetic assessments to examine whether individual genetic variation in genes relating allergic disease correlate with systemic levels of allergic mediators.

Primary end point(s): The primary analysis will be the analysis of IL-5 concentrations from the nasal filter adsorption 6 h post nasal allergen challenge on Day 8 and Day 15. The log transformed IL-5 levels from the QAX576 and Placebo group will be analyzed using a mixed model with fixed effects for treatment (QAX576, Placebo), day (Day 8, Day 15), treatment*day interaction and a random effect for subject. The log transformed IL-5 concentration from the nasal filter adsorption 6 h post the last pre-dose nasal allergen challenge will be included in the model as a covariate for baseline adjustment.

Estimates for the treatment contrasts “QAX576 – Placebo” on Day 8 and Day 15 will be provided together with 90% confidence intervals.
The primary contrasts are the “QAX576 – Placebo” differences on Day 8 and 15 which will be tested for statistical significance using one sided t-tests at the multiplicity adjusted 10% alpha level. Since there are two primary contrast, p-values will be adjusted for multiplicity using the method based on the simulated distribution of the maximum of the two t-statistics (Westfall, Young 1993).

Secondary ID(s)

CQAX576A2104