Seasonal allergic rhinitis MedDRA version: 12.0 Level: LLT Classification code 10001723 Term: Allergic rhinitis
Conditions
Interventions
Product Code: VAK694
Pharmaceutical Form: Powder and solvent for solution for infusion
Current Sponsor code: VAK694
Concentration unit: mg milligram(s)
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects must have a history of atopy, defined as a history of seasonal allergic rhinitis for at least 2 years (in relation to the grass pollen allergy season), and evidence of atopy, defined as a positive skin prick test (wheal difference allergen – negative control at least 3 mm) to grass pollen allergen at screening. 2. Male or female subjects aged between 18 and 60 years (inclusive) and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram and laboratory tests. 3. Female subjects must be of non-childbearing potential (women who are postmenopausal or permanently sterilized (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy). Last menstrual bleeding or surgical sterilization procedures (clinical documentation required) must be noted in the Relevant Medical History / Current Medical Conditions section of the CRF. 4. Male subjects must be using two highly effective methods of contraception, (e.g. a barrier method condom or occlusive cap plus spermicide) plus ensure use by the female partner of a second method of contraception. These measures should be in place and males should refrain from fathering a child in the three (3) months following he last study drug administration. 5. Subjects must weigh at least 50 kg with a body mass index (BMI) within the range of 18 to 32 kg/m2 (inclusive). 6. Able to communicate well with the investigator, to understand and comply with the requirements of the study. 7. Subjects must have provided written informed consent prior to study participation. 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
Exclusion criteria: 1. Treatment with intranasal corticosteroids within 28 days prior to the first dose. 2. History of asthma with treatment with inhaled or systemic corticosteroids within 6 months of the first dose. Intermittent treatment with inhaled beta2-agonist therapy permitted. 3. History of chronic obstructive pulmonary disease (COPD). 4. Smokers with a smoking history of > 10 pack/years or anything other than casual smoking during the past year. Urine cotinine levels will be measured during screening and at baseline for all subjects. Active smokers will be defined as any subject who reports regular tobacco use and/or who has a urine cotinine considered positive according to local lab ranges. 5. Use of prescription drugs such as inhaled or oral corticosteroids and leukotriene antagonists within four (4) weeks prior to dosing, and during the study i.e. from screening to end-of-season-1 visit in Season 1 and from baseline through end-of-study visit in Season 2. Use of paracetamol is acceptable, but must be documented in the Concomitant medications / Significant non-drug therapies page of the CRF. Subjects will be allowed to use antihistamine eye drops, antihistamines, inhaled beta2 agonist therapy, and nasal steroids only as rescue medications during the season, as per section 6.6.3, and must not use these treatments on a regular basis during the study. The use of other prescription drugs during the study could be considered and should be discussed between the investigator and Novartis. 6. Participation in any clinical investigation within 4 weeks prior to first dose, or longer in the case of treatment with a drug with a longer half-life. 7. Any exposure to human monoclonal or polyclonal antibodies. 8. Any allergy immunotherapy within 3 year prior to screening. 9. Any prior grass pollen allergy immunotherapy. 10. Donation or loss of 400 mL or more of blood within 12 weeks prior to first dose. 11. Significant illness within two weeks prior to first dose. 12. Recent febrile illness within four weeks prior to first dose. 13. Symptoms of moderate to severe perennial allergic rhinitis. 14. FEV1 < 70% of predicted at screening or baseline. 15. A history of clinically significant ECG or cardiac abnormalities. 16. History of clinically significant drug allergy. A known hypersensitivity to the study drug or drugs similar to the study drug such as monoclonal antibodies. 17. History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result. 18. History of autoimmune disease. 19. Prior history of tuberculosis or a positive test for tuberculosis at screening (differentiated from previous BCG immunization) 20. A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C virus (HCV) test result. 21. History of drug or alcohol abuse within the 12 months prior to first dose or evidence of such abuse as indicated by the laboratory assays conducted during the screening or baseline evaluations. 22. Any active or chronic bacterial, viral, fungal, or parasitic infections 23. History of cancer, other than basal cell carcinoma of the skin 24. Concurrent administ
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Primary end point is the ability of VAK694 to provide sustained suppression of the late phase cutaneous response to allergen as a reflection of long term specific immune tolerance to allergen. ; Main Objective: • To assess the induction of sustained tolerance to allergen when VAK694 with a dosing regimen given every 4 weeks for a total of 4 doses is combined with subcutaneous immunotherapy for the treatment of moderate to severe grass-pollen allergy as measured by the Late Phase Response. • To assess the safety and tolerability of VAK694 when administered in the context of SCIT ; Secondary Objective: • To evaluate the immunomodulatory activity of VAK694 as evidenced by induction of regulatory T cells, down regulation of Th2 cells, decrease in the seasonal rise in allergen-specific IgE, induction of specific antigen-binding neutralizing antibodies (IgG4), and inhibition of facilitated antigen binding (FAB) • To assess the effects of VAK694 combined with SCIT on the symptoms of seasonal allergic rhinitis, measured by the mini-Respiratory Quality of Life Questionnaire (RQLQm) and visual analogue scale (VAS) • To preliminarily assess the ability of VAK694 to reduce the side-effects of SCIT • To preliminarily assess the effects of VAK694 on sustained antibody responses to immunization | — |
Countries
United Kingdom
Outcome results
None listed