Efficacy and Safety of PQ Grass in Subjects With Seasonal Allergic Rhinitis and/or Rhinoconjunctivitis Induced by Grass Pollen

Seasonal Allergic Rhinitis Clinical Trial

Official title:

A Randomised, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Efficacy and Safety of PQ Grass in Subjects With Seasonal Allergic Rhinitis and/or Rhinoconjunctivitis Induced by Grass Pollen Exposure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05540717
• Other study ID #: PQGrass306
• Secondary ID: 2019-001517-16
• Status: Completed
• Phase: Phase 3
• Start date: October 11, 2022
• Est. completion date: November 1, 2023

Study information

• Verified date: January 2024
• Source: Allergy Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The PQGrass306 (G306) clinical trial is the pivotal Phase III efficacy clinical trial of PQ Grass. The aim of the G306 pivotal clinical trial is to confirm the efficacy and safety of the optimal effective dose of PQ Grass 27600 SU. This will be determined through the measurements of the effect of PQ Grass on the symptoms of seasonal allergic rhinitis (SAR)/rhinoconjunctivitis and the use of relief medications to control these symptoms during the peak grass pollen season (GPS).

Description:

Multi-centre, randomised, parallel group, double-blind, placebo-controlled clinical trial to confirm the efficacy and safety of the optimal effective dose of PQ Grass (27600 SU). Randomized study subjects, in a randomisation ratio of 1:1, will receive either treatment with 6 injections of active treatment (900, 2700, 6000, 6000, 6000 and 6000 SU sequentially) to achieve a cumulative nominal dose of 27600 SU, or 6 injections of placebo prior to the onset of the grass pollen season (GPS). The aim of the study is to confirm the efficacy and safety of the optimal effective dose of the PQ Grass 27600 SU dose. Efficacy will be determined through the measurements of the effect of PQ Grass on the symptoms of seasonal allergic rhinitis (SAR)/rhinoconjunctivitis and the use of relief medications to control these symptoms during the peak GPS.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 858
• Est. completion date: November 1, 2023
• Est. primary completion date: November 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the ICF (informed consent form) and in this clinical trial protocol and to attend required clinical trial visits.

2. Subject who has a signed and dated ICF.

3. Subject must be 18 to 65 years of age inclusive, at the time of signing the ICF.

4. Male or female.

5. Female subjects who are not of childbearing potential (defined as at least 12 months natural spontaneous amenorrhoea, or at least 6 weeks following surgical menopause/permanent sterilisation [hysterectomy, bilateral oophorectomy and bilateral salpingectomy]) or females of childbearing potential who agree to comply with the contraceptive requirements of the clinical trial protocol.

6. Good general health, as determined by the Investigator, based on a medical evaluation, including medical history, physical examination, mental status assessment and laboratory tests. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator agrees that the finding is unlikely to introduce additional risk factors and will not interfere with the clinical trial procedures.

7. Positive history of moderate to severe symptoms of SAR/rhinoconjunctivitis ascribed to grass (Pooideae) pollen exposure of at least 2 seasons duration, despite having received allergy pharmacotherapy (e.g., antihistamines, nasal corticosteroids, leukotriene modifiers, etc.) during the last 2 consecutive grass pollen seasons prior to the clinical trial, confirmed by subject records. Please note: Subjects with asthma may be included, but the asthma must be well controlled (according to current Global Initiative for Asthma [GINA] guidelines [GINA 2022]).

8. A positive SPT (skin prick test) to histamine (wheals [longest diameter] =3 mm) and a negative SPT to the negative control (wheal diameter = 0 mm) at screening.

9. A positive SPT for grass pollen (wheals [longest diameter] =3 mm).

10. Grass specific IgE (immunoglobulin E) class =2 as documented by an ImmunoCAP test at screening.

11. Forced expiratory volume in one second (FEV1) =70% of predicted, with a FEV1/forced vital capacity (FVC) ratio >75% and PEFR (peak expiratory flow rate) =70% of predicted at screening.

Exclusion Criteria:

1. Pregnant or lactating subject.

2. Presence of any medical history of moderate to severe allergy symptoms (verified by a positive SPT at screening or positive specific IgE [=2] at screening) to any other seasonal allergen (other than grass) or perennial allergens. Exception: Period 1, Period 2 and Period 3 of the entire clinical trial will be conducted outside of the pollen season(s) of concern or perennial allergies are irrelevant due to avoidance measures (e.g., cats and dog allergy). Subjects with mild allergy symptoms (only) to any other allergen apart from grass may be included at the discretion of the Investigator. In countries in Europe where Bermuda grass is present, any medical history of moderate to severe allergy symptoms to Bermuda grass (verified by a positive SPT or positive specific IgE [Class =2]), will also represent a reason for exclusion as it will not be possible to conduct Period 1, Period 2 and Period 3 of the entire clinical trial outside of Bermuda grass pollen season. Albeit Bermuda grass being commonly defined as a grass, it belongs to the Poaceae family, while the sentence (other than grass) in Exclusion criterion #2 refers to grass of Pooideae subfamily (as defined in Inclusion criterion #7).

3. Subjects at US clinical trial sites in regions where southern grasses (Bahia grass, Bermuda grass or Johnson grass) are the dominant grasses and the main cause of grass allergy symptoms with a positive SPT to any of the 3 grasses (irrespective of the severity of symptoms).

4. Moderate to severe symptoms during the 3 years prior to Visit 1 to any other seasonal or perennial allergen not tested in the SPT done at screening that cannot be avoided during the Period 1 to Period 3 of the clinical trial and the symptoms of which may interfere with administration of treatment and/or impact the data collected.

5. Presence of any medical condition that may reduce the ability to survive a serious allergic reaction.

6. Presence of active systemic autoimmune disorder, systemic autoimmune disorders in remission or active organ specific autoimmune disorder.

7. Presence of active malignant neoplasia, severe cardiovascular disease (e.g., coronary artery disease, cardiac insufficiency, etc.), pulmonary insufficiency, severe psychiatric disorders or primary and secondary immunodeficiencies.

8. History of any other immunological disorder or other diseases (including, but not limited cardiovascular [including uncontrolled or inadequately controlled hypertension], gastro-intestinal, hepatic, renal, haematological, neurological, endocrine or pulmonary disease) that in the opinion of the Investigator may pose a safety risk or compromise the interpretation of efficacy of the clinical trial treatment.

9. Presence of severe or poorly controlled or uncontrolled asthma as defined by at least

1 of the following criteria:

1. Severe asthma (as per the current GINA guidelines [GINA, 2022]).

2. Uncontrolled or poorly controlled asthma as per the current GINA guidelines (GINA, 2022).

3. Asthma that requires more than a daily dose above 800 µg of inhaled budesonide (or clinically comparable inhaled corticosteroid) as per the current GINA guidelines (GINA, 2022).

4. History of 2 or more systemic corticosteroid courses within 6 months of screening or Visit 2 or 1 course of systemic corticosteroids within 3 months of screening or Visit 2 to treat asthma.

5. Prior intubation/mechanical ventilation for asthma.

6. Emergency room visit or hospitalisation for asthma in the 12 months prior to screening or Visit 2.

7. Any history of a life-threatening asthma attack.

8. FEV1 <70% of predicted or FEV1/FVC =75% or PEFR <70% of predicted with or without controller medications at screening or Visit 2.

10. Presence non-atopic rhinitis and/or rhino-sinusitis (with or without polyps).

11. Presence of nasal polyps and/or chronic sinusitis.

12. Presence of any acute or chronic ocular disorder, other than allergic conjunctivitis.

13. Eye surgery within the past 6 months.

14. Presence of any skin conditions (e.g., skin abnormalities, tattoos etc.), which might interfere with the interpretation of the SPT results.

15. Clinical history of Type I diabetes or poorly controlled Type II diabetes.

16. Moderate to severe upper or lower respiratory infections requiring medication within 14 days before screening (Visit 1) or Visit 2.

17. Presence of acute or chronic infection, fever or inflammation at screening or Visit 2.

18. Clinical history of severe systemic reaction or serious systemic reaction in response to AIT (allergen immunotherapy) in the past.

19. Clinical history of severe or life-threatening anaphylactic reactions to foods, insect venom, exercise, drugs or idiopathic anaphylaxis.

20. Clinical history of allergy, hypersensitivity or intolerance to the excipients of the investigational drug/placebo.

21. Clinical history of allergy, hypersensitivity or intolerance to the relief medications (for relief of allergy symptoms during Period 3) provided for use in this clinical trial.

22. Clinical history of hereditary angioedema.

23. Unable to receive epinephrine therapy (i.e., use of epinephrine is contraindicated such as in subjects with hyperthyroidism, uncontrolled hypertension, cardiac arrhythmias, closed angle glaucoma or subjects taking other sympathomimetics).

24. Tyrosine metabolism disorders, especially tyrosinemia and alkaptonuria.

25. Clinical history of drug or alcohol abuse, which, in the Investigator's opinion, could interfere with the subject's ability to participate in the clinical trial.

26. Subjects who have suspicion or symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (as assessed by the Investigator) or who have had unprotected contact with a confirmed case of COVID-19 (coronavirus disease 2019) in the 2 weeks prior to screening or Visit 2 (based on the Investigator's discretion).

27. Subjects who were hospitalised for COVID-19 within 6 months prior to screening or Visit 2.

28. Any history of AIT for grass pollen allergy in the past or history of AIT for any other type of allergy (excluding food allergy) in the past 5 years.

29. Inability to adhere to the washout periods listed in the protocol, with respect to screening and to refrain from using the medications indicated until after Visit 11.

30. Treatment with a preparation containing MPL (monophosphoryl lipid-A) (e.g., Cervarix, Shingrix, Fendrix) within 2 years prior to Visit 1 and until after completion of Visit 11 (with the exception of the investigational drug).

31. Previous history of epinephrine auto-injector use.

32. ß-blocker medication (local or systemic, including eye drops) for any indication.

33. Monoamine oxidase inhibitors and tricyclic antidepressants. Please note: Tricyclic antidepressants should be avoided at least 2 weeks prior to screening.

34. Any previous therapy (within the previous 5 years) or current therapy with anti IgE (e.g., omalizumab [Xolair]) or anti-interleukins (e.g., mepolizumab).

35. Current or past therapy (within the previous 5 years) with any other immunomodulatory biologics.

36. Unable to refrain from any vaccination (including influenza vaccine and COVID-19 vaccine) during the clinical trial (unless administered >30 days prior to randomisation). Please note: Emergency vaccinations (e.g., tetanus due to injury) can be administered at any time. Booster vaccinations (only) for COVID-19 can be administered during the clinical trial apart from during the treatment period. There should be at least 14 days interval from the last administration of the investigational drug/placebo prior to administration of a COVID-19 booster injection.

37. Participation in a clinical research trial with any investigational drug within 4 weeks of Visit 1 or concomitantly with this clinical trial. Please note: The period of exclusion begins at the time of the last visit of the prior clinical research trial. Subjects consented and screened, but not dosed in the prior clinical research trial are not excluded.

38. Personal, financial or other dependent relationship (e.g., employee or immediate relative) with the clinical trial site, Sponsor, Sponsor's representative, or another individual who has access to the clinical trial protocol.

39. Vulnerable subjects or those in judicial or governmental detention, detainment or imprisonment in a public institution.

40. Subjects likely to have prolonged periods of absence (e.g., business or personal

travel) during the GPS defined as:

• Absence of a total of 22 days or more in similar geographical regions (as determined by the Investigator), with no single trip in a similar geographical region exceeding 14 days.
• Absence of a total of 15 days or more in non-similar geographic regions (as determined by the Investigator), with no single trip in a non-similar geographical region exceeding 7 days.

41. Have changed residence to a different geographical region(s) since the last GPS. Exception: The old and new residences are in the same or similar geographical region as determined by the Investigator.

Related Conditions & MeSH terms

• Conjunctivitis
• Rhinitis
• Rhinitis, Allergic
• Rhinitis, Allergic, Seasonal
• Rhinoconjunctivitis
• Seasonal Allergic Rhinitis

Intervention

Biological:
• PQ Grass
Suspension for Injection
• Placebo
Solution for injection

Locations

Country	Name	City	State
Austria	Medizinische Universitaet Innsbruck - Universitatsklinik fuer Dermatologie, Venerologie und Allergologie	Innsbruck
Austria	Bezirkskrankenhaus Kufstein	Kufstein
Austria	Ambulatorium für Allergie und klinische Immunologie AAKI	Wien
Austria	Medizinische Universitat Wien (Medical University of Vienna)	Wien
Czechia	Fakultní nemocnice u sv. Anny v Brne	Brno
Czechia	MUDr. Jana Poloniová - alergologie a klinická imunologie	Ceské Budejovice
Czechia	Alergopraktik, s.r.o.	Jablonec Nad Nisou
Czechia	Alergologie a imunologie MUDr. Hofstetr	Jihlava
Czechia	Alergoimuno s.r.o.	Ostrava-Hrabuvka
Czechia	ACREDULA BENEDICTA s.r.o.	Pardubice
Czechia	Fakultní nemocnice Plzen	Plzen
Czechia	KASMED, s.r.o.	Tábor
Czechia	MUJ ALERGOLOG s.r.o.	Trutnov
Germany	CIMS Studienzentrum Bamberg, GmbH	Bamberg
Germany	Charité - Universitaetsmedizin Berlin Klinik fuer Dermatologie, Venerologie und Allergologie/ Abteilung Allergologie und Immunologie	Berlin
Germany	Praxis Dr. Petra El-Naib	Chemnitz
Germany	HNO-Praxis Dr. Udo Schaefer	Dresden
Germany	Klinische Forschung Dresden GmbH	Dresden
Germany	Praxis fuer HNO und Allergologie	Dresden
Germany	Universitaetsklinikum Carl Gustav Carus an der TU Dresden	Dresden
Germany	RKM740 Hals-Nasen-Ohrenheilkunde	Duesseldorf
Germany	HNO-Praxis Dr. Uta Thieme	Duisburg
Germany	Gemeinschaftspraxis Ruhr	Essen
Germany	Medizentrum Essen Borbeck	Essen
Germany	Medaimun GmbH	Frankfurt am Main
Germany	medicoKIT GmbH	Goch
Germany	Hamburger Institut für Therapieforschung GmbH	Hamburg
Germany	Klinische Forschung Hamburg GmbH	Hamburg
Germany	Velocity Clinical Research Hamburg	Hamburg
Germany	Praxis Dres. med. Florian Heimlich und Angelika Witzel-Heimlich	Heidelberg
Germany	HNO-Praxis Landsberg	Landsberg
Germany	Praxis fuer Pneumologie und Allergologie	Leipzig
Germany	Sektion Rhinologie/Allergologie Klinik fuer HNO-Heilkunde, UKGM - Marburg	Marburg
Germany	Beldio Research GmbH	Memmingen
Germany	Facharztpraxis Dr. med. Jan-Christof Bohn	Mittweida
Germany	Ballenberger, Freytag, Wenisch Institut fuer klinische Forschung GmbH	Neu Isenburg
Germany	Studienzentrum Maerkisch-Oderland	Neuenhagen
Germany	KliFOs - Klinische Forschung Osnabrueck	Osnabrück
Germany	Studienzentrum Dr. Sabine Lassmann	Saalfeld
Germany	Klinische Forschung Schwerin GmbH	Schwerin
Germany	Klinikum Stuttgart - Krankenhaus Bad Cannstatt (KBC) - Frauenklinik	Stuttgart
Germany	Dres. med. Josef und Wilma Grosskopf	Wallerfing
Hungary	Gróf Tisza István Kórház Rendelointézet MEDIDOCUMENT Kereskedelmi és Szolgáltató Betéti Társaság	Berettyóújfalu
Hungary	Clinexpert Kft	Budapest
Hungary	HiTech Medical Kft.	Budapest
Hungary	Pecsi Tudomanyegyetem Altalanos Orvostudomanyi Kar	Pécs
Poland	Allergy Clinic Homeo Medicus	Bialystok
Poland	Prywatny Gabinet Internistyczno - Alergologiczny	Bialystok
Poland	Centrum Medyczne Czestochowa - PRATIA - PPDS	Czestochowa
Poland	Centrum Medyczne Pratia Katowice	Katowice
Poland	Specjalistyczna Praktyka Lekarska dr n. med. Joanna Orlicz-Widawska	Katowice
Poland	ETG Kielce	Kielce
Poland	Centrum Nowoczesnych Terapii Dobry Lekarz Sp. z o.o.	Kraków
Poland	Krakowskie Centrum Medyczne	Kraków
Poland	Malopolskie Centrum Alergologii	Kraków
Poland	ETG Lódz	Lódz
Poland	Uniwersytecki Szpital Kliniczny im. Barlickiego, Poradnia alergologii i chorob pluc	Lódz
Poland	Clinical Best Solutions Sp. Z O.O. Spólka Komandytowa	Lublin
Poland	Centrum Alergologii Teresa Hofman Sp. z o.o.	Poznan
Poland	Specjalistyczna Przychodnia Lekarska ALERGO-MED Sp. z.o.o.	Poznan
Poland	EMED Centrum Uslug Medycznych Ewa Smialek	Rzeszów
Poland	ETG Skierniewice	Skierniewice
Poland	ALERGO-MED Specjalistyczna Przychodnia Lekarska Sp. z.o.o	Tarnów
Poland	Specjalistyczne Centrum Medyczne Centermed Sp. z o.o.	Tarnów
Poland	IRMED Irena Wojciechowska	Warszawa
Poland	WK Medical Service Sp. z o.o.	Warszawa
Poland	"ALL-MED" Specjalistyczna Opieka Medyczna, Medyczny Instytut Badawczy	Wroclaw
Poland	Michal Bogacki - DOBROSTAN	Wroclaw
Poland	Niepubliczny Zaklad Opieki Zdrowotnej Przychodnia Lekarska Hipokrates Sp. z o.o.	Zabrze
United States	Northern Light Allergy and Immunology	Bangor	Maine
United States	Paul A. Shapero M.D.	Bangor	Maine
United States	Nebraska Medical Research Institute, The Asthma & Allergy Center	Bellevue	Nebraska
United States	Bellingham Asthma Allergy and Immunology Clinic	Bellingham	Washington
United States	Allergy & Asthma Specialists	Blue Bell	Pennsylvania
United States	IMMUNOe Research Centers	Centennial	Colorado
United States	Allergy Asthma and Immunology Research Institute	Charlotte	North Carolina
United States	Bernstein Clinical Research Center, LLC	Cincinnati	Ohio
United States	Cincinnati Allergy and Asthma Center	Cincinnati	Ohio
United States	Clinical Research of The Ozarks Inc - Warrensburg	Columbia	Missouri
United States	Optimed Research Ltd	Columbus	Ohio
United States	Velocity Clinical Research Denver	Denver	Colorado
United States	Lysosomal Rare Disorders Research & Treatment Center	Fairfax	Virginia
United States	Velocity Clinical Research, Inc	Grants Pass	Oregon
United States	Allergy, Asthma & Sinus Center, S.C.	Greenfield	Wisconsin
United States	Parikh Institute for Research LLC	Highland Park	New Jersey
United States	Allergy and Asthma Associates of Bluegrass	Lexington	Kentucky
United States	Allergy Partners of Central Kentucky	Lexington	Kentucky
United States	Family Allergy Asthma Research Institute	Louisville	Kentucky
United States	University of Wisconsin Clinical Science Center	Madison	Wisconsin
United States	Velocity Clinical Research - Medford - ERN - PPDS	Medford	Oregon
United States	Montana Medical Research	Missoula	Montana
United States	Allergy Associate of Utah	Murray	Utah
United States	Eastern Virginia Medical School	Norfolk	Virginia
United States	Atlantic Research Center LLC	Ocean City	New Jersey
United States	Oklahoma Institute of Allergy and Asthma Clinical Research, LLC - CRN - PPDS	Oklahoma City	Oklahoma
United States	Allergy & Asthma Specialists PSC	Owensboro	Kentucky
United States	Allergy and Clinical Immunology Associates	Pittsburgh	Pennsylvania
United States	Northwest Research Center	Portland	Oregon
United States	Weiss Medical	Riverdale	New Jersey
United States	Toledo Institute of Clinical Research Inc	Toledo	Ohio
United States	Chesapeake Clinical Research Inc	White Marsh	Maryland
United States	Respiratory Medicine Research Institute of Michigan	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Allergy Therapeutics

Countries where clinical trial is conducted

United States,  Austria,  Czechia,  Germany,  Hungary,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Combined symptom and medication score (CSMS) averaged over the peak grass pollen season (GPS)	6 individual symptoms assessed in a 4 point severity scale (0-No symptoms to 3-Severe symptoms) and combined with relief medication use assessed using a 4 point severity scale (0=No relief medication, 1=anti-histamine use, 2=nasal corticosteroid use, and 3=oral corticosteroid use).	Approximately 2-5 weeks
Secondary	Serum grass specific IgG4 (immunoglobulin G4) at Visit 7 compared to baseline.		Approximately 16-22 weeks
Secondary	The number of well days during the peak GPS.		Approximately 10 weeks. Duration of the Peak Grass pollen season (GPS) to be determined as per pollen counts within the GPS
Secondary	Rhinoconjunctivitis Quality of Life Questionnaire with standardised activities (RQLQ(S)) measured within the peak GPS	Rhinoconjunctivitis quality of life questionnaire with standardised activities - RQLQ(S).; 7-point scale (0 = not impaired at all - 6 = severely impaired). Scoring available: higher scores reflect lower quality of life.	Up to approximately 6 months
Secondary	Frequency, severity and relationship of AEs (adverse event) to treatment		Up to 1 year
Secondary	Frequency of AEs leading to premature discontinuation from treatment or clinical trial		Up to 1 year
Secondary	Frequency of AESI (adverse events of special interest)		Up to 1 year
Secondary	Changes in serum chemistry values between screening and Visit 11	Including sodium, potassium and chloride concentration (mmol/L)	8 months approximately
Secondary	Changes in serum chemistry values between screening and Visit 11	Including glucose, uric acid, urea, phosphorus and cholesterol concentration (mmol/L)	8 months approximately
Secondary	Changes in serum chemistry values between screening and Visit 11	Including calcium, creatinine and total bilirubin concentration (µmol/L)	8 months approximately
Secondary	Changes in serum chemistry values between screening and Visit 11	Including total protein and albumin concentration (g/L)	8 months approximately
Secondary	Changes in serum chemistry values between screening and Visit 11	Including alkaline phosphatase, LDH (lactate dehydrogenase), AST (aspartate aminotransferase), ALT (alanine aminotransferase) and GGT (gamma-glutamyl transferase) (U/L)	8 months approximately
Secondary	Changes in serum chemistry values between screening and Visit 11	Including CRP (C-reactive protein) (mg/L)	8 months approximately
Secondary	Changes in haematology values between screening and Visit 11	Including total RBC (red blood cells) and differential (10^12/L)	8 months approximately
Secondary	Changes in haematology values between screening and Visit 11	Including total WBC (white blood cells) and differential and platelet count (10^9/L)	8 months approximately
Secondary	Changes in haematology values between screening and Visit 11 - Haemoglobin	Haemoglobin concentration	8 months approximately
Secondary	Changes in clinical laboratory values (urinalysis) between screening and Visit 11	Urinalysis (using a urine dip-stick) pH - Results will be assessed by the investigators as clinical significant or not	8 months approximately
Secondary	Changes in clinical laboratory values (urinalysis) between screening and Visit 11	Urinalysis (using a urine dip-stick) protein, glucose, bilirubin, blood and leukocytes - Results will show zero, traces, +1, +2, +3, +4 Note: Microscopic examination will be conducted if protein, leukocytes and/or blood are detected. If needed, microscopic examination will include WBC, RBC, casts, and bacteria.	8 months approximately
Secondary	Changes in clinical laboratory values (urinalysis) between screening and Visit 11	Urinalysis (using a urine dip-stick) Ketones, nitrite, urobilinogen - Results will show negative or positive Note: Microscopic examination will be conducted if nitrite are detected. If needed, microscopic examination will include WBC, RBC, casts, and bacteria.	8 months approximately
Secondary	Changes in vital signs at all treatment visits	Systolic and diastolic blood pressure	7 months approximately
Secondary	Combined symptom and medication score (CSMS) averaged over the entire (or truncated) grass pollen season (GPS)	6 individual symptoms assessed in a 4 point severity scale (0-No symptoms to 3-Severe symptoms) and combined with relief medication use assessed using a 4 point severity scale (0=No relief medication, 1=anti-histamine use, 2=nasal corticosteroid use, and 3=oral corticosteroid use)	Time Frame: Approximately 10 weeks
Secondary	Daily symptom score (dSS) component of the CSMS averaged over the peak GPS and entire (or truncated) GPS	Sum of the scores (0-No symptoms to 3-Severe symptoms) for the 6 individual symptoms assessed in CSMS divided by 6	Time Frame: Time Frame: Approximately 10 weeks. Duration of the Peak Grass pollen season (GPS) to be determined as per pollen counts within the GPS
Secondary	Daily medication score (dMS) component of the CSMS averaged over the peak GPS and entire (or truncated) GPS	Score 0 (no relief medication) to 3 (highest step relief medication) per day; based on at least 1 dose of the medication of the highest step taken that day	Time Frame: Approximately 10 weeks. Duration of the Peak Grass pollen season (GPS) to be determined as per pollen counts within the GPS