Efficacy and Safety of SUBLIVAC Phleum for Immunotherapy of Grass Pollen-Allergy
Condition: Allergic Rhinitis; Allergic Rhinoconjunctivitis
MeSH terms: Rhinitis; Rhinitis, Allergic
Intervention: SUBLIVAC FIX Phleum Prat.
Intervention description: sublingual daily administration
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Double-blind study
Enrollment: 168.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Sublingual immunotherapy; Dose range finding; Grass pollen; Allergic rhinitis/rhinoconjunctivitis; Immunogenicity

Summary:

      The purpose of this study is to assess safety, tolerability and demonstrate a dose response
      signal using Total Symptom Score (TSS), based on challenges with grass pollen in an
      Environmental Exposure Chamber (EEC), followed by estimation of the minimum effective dose of
      SUBLIVAC FIX Phleum (SP) after 10 months of treatment compared to placebo.

      The study has 4 treatment groups: 3 different doses of SP and placebo will be tested.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subjects who signed informed consent.

          2. Subjects aged ≥18 and ≤65 years at signing of informed consent.

          3. Subjects with at least two-year clinical history of allergic
             rhinitis/rhinoconjunctivitis to grass pollen, with or without concomitant asthma
             (asthma must be controlled).

          4. Subjects with a forced expiratory volume at one second (FEV1) >70% of the predicted
             value as measured during screening or documented within 1 year of study start.

          5. Subjects with a positive skin prick test (SPT) (mean wheal diameter of at least 3 mm
             larger than the negative control; negative control should be <2 mm, histamine control
             should be positive (mean wheal diameter of at least 3 mm larger than the negative
             control)) for grass pollen assessed during screening or a documented positive response
             obtained within 1 year before screening.

          6. Subjects with a grass pollen specific IgE greater than or equal to 0.7 kiloUnits
             (kU)/L assessed during screening or a documented positive result obtained within 1
             year before screening.

          7. Subjects with a TSS of at least 10/24 during baseline EEC challenge (V2) in
             combination with a staff assessed score of at least 2/3 for two objective TSS symptoms
             (i.e. running nose, sneezing or red eyes), during the baseline EEC challenge.

        Exclusion Criteria:

          1. Subjects with (expected) clinically relevant symptoms at the timing of the scheduled
             EEC assessments at Visit 2 and Visit 6 due to concomitant sensitization i.e. positive
             SPT (mean wheal diameter of at least 3 mm larger than the negative control) and a
             history of allergic response to the causative allergen, at the discretion of the
             investigator.

          2. Patients with grass pollen induced asthma.

          3. Subjects who cannot tolerate the Baseline Challenge in the EEC.

          4. Subjects who received immunotherapy (SCIT or SLIT) with grass pollen allergens within
             the past 5 years.

          5. (Ongoing) allergen-specific immunotherapy with any allergen(s) during the study
             period.

          6. Subjects with unsuccessful allergen-specific immunotherapy within the past 5 years
             (e.g., but not limited to, prematurely stopped immunotherapy due to non-compliance,
             AEs or lack of therapeutic effect), at the discretion of the investigator.

          7. Subjects undergoing anti-IgE therapy within the 6 months prior to inclusion and/or
             during the study.

          8. Subjects suffering from severe immune disorders (including auto-immune diseases)
             and/or diseases requiring immunosuppressive drugs.

          9. Subjects suffering from active malignancies or any malignant disease (except for
             localized basal cell cancers of the skin as long as they have been adequately treated
             and no recurrence within 3 months of screening visit) during 5 years prior to
             screening.

         10. Subjects suffering from severe uncontrolled diseases that could increase the risk for
             participating in the study, including but not limited to: cardiovascular
             insufficiency, any severe or unstable lung diseases, endocrine diseases, clinically
             significant renal or hepatic diseases, or haematological disorders at the discretion
             of the Investigator.

         11. Subjects who have active inflammation or infection of the target organs (nose, eyes or
             lower airways) at Visit 1.

         12. Subjects suffering from diseases with a contraindication for the use of adrenaline
             (e.g. hyperthyroidism, glaucoma).

         13. Subjects receiving vaccination within one week before start of therapy or during the
             up-dosing phase.

         14. Subjects receiving treatment with systemic steroids within 4 weeks before visit 1
             and/or during the study.

         15. Subjects receiving treatment with systemic or local β-blockers anytime during the
             study.

         16. Subjects who participated in a clinical study within the last 3 months (e.g. new
             investigational drug or biological) or within the last 30 days (e.g. bio-equivalent
             drug), at the discretion of the Investigator.

         17. Female subjects of child-bearing potential who are pregnant, lactating or using
             inadequate contraceptive measures (adequate contraceptive measures will be: sexual
             abstinence; oral contraceptives, trans dermal patches or depot injection of a
             progestogen drug (starting at least 4 weeks prior to investigational medicinal product
             (IMP) administration); double barrier method: condom or occlusive cap (diaphragm or
             cervical/vault caps) plus spermicidal agent; intrauterine device (IUD), intrauterine
             system (IUS), implant, or vaginal ring (placed at least 4 weeks prior to IMP
             administration); or male partner sterilization (vasectomy with documentation of
             azoospermia) prior to the female subject's entry into trial and is the sole sexual
             partner for that female subject.

         18. Subjects that have a history of alcohol, drug or medication abuse within the past year
             before study start.

         19. Subjects with any clinically relevant abnormal laboratory parameter at screening.

         20. Subjects that lack cooperation or compliance, as judged by the investigator.

         21. Subjects suffering from severe psychiatric, psychological, or neurological disorders.

         22. Subjects who are employees of the sponsor or contract research organisation and/or 1st
             grade relatives or partners of the (principal) investigator.