An Exploratory Study of PQ Grass 27600 SU

Allergy Therapeutics119 enrolled

Overview

PQGrass309 is aimed at exploring the expected average treatment effect of PQ Grass 27600 SU cumulative dose on symptom and medication score in a field setting. The study will enrol adult subjects with seasonal allergic rhinitis and/or rhinoconjunctivitis (SAR) induced by grass pollen exposure.

PQGrass309 is a randomised, double-blind, placebo-controlled exploratory study to explore the efficacy and safety of PQ Grass 27600 SU in subjects with seasonal allergic rhinitis and/or rhinoconjunctivitis (SAR) induced by grass pollen exposure. The study is expected to be conducted in the United States (US) and the European Union (EU). The aim of this exploratory field study is to explore amongst others the following: * The efficacy and safety (up to 6 months following treatment) of a cumulative dose of 27600 standardised units (SU) of PQ Grass in the treatment of grass pollen allergy. * The expected average treatment effect on combined symptom and medication score.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

119

Conditions

Rhinitis, Allergic, Seasonal

Interventions

PQ GrassBIOLOGICAL

Suspension for injection

Active PlaceboDRUG

Suspension for injection

Standard PlaceboDRUG

Solution for injection

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: \- Informed Consent 1. Capable of giving signed informed consent and demonstrates willingness to comply with the requirements and restrictions listed in the ICF and study protocol and to attend required study visits. 2. Subject who has signed and dated the ICF. \- Age: 3. 18 to 65 years of age inclusive, at the time of signing the ICF. \- Sex / Contraceptive requirements: 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) or females of childbearing potential who agree to comply with the contraceptive requirements of the study protocol. \- Subjects and general health characteristics: 6. Good general health, as determined by the investigator, based on a medical evaluation, including medical history, physical examination, 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 study procedures. 7. Positive history of moderate to severe symptoms of seasonal allergic rhinitis and/or rhinoconjunctivitis ascribed to grass (Pooideae) pollen exposure that required repeated use of antihistamines, nasal corticosteroids, and/or leukotriene modifiers for relief of symptoms during the last 2 consecutive seasons prior to the study, 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 \[GINA, 2020\]). 8. A positive SPT for grass pollen (wheals \[longest diameter\] ≥3 mm and histamine ≥3 mm) and a negative SPT to the negative control (wheal diameter =0) at screening. 9. Grass specific IgE class ≥2 as documented by an ImmunoCAP test at screening. 10. FEV1 ≥80% of predicted, with a FEV1/FVC ratio ≥70% and (PEFR) ≥75% predicted at screening. 11. Subjects who have no suspicion or symptoms of SARS-CoV-2 infection (as assessed by the investigator) or who have had no contact with a confirmed case of COVID-19 in the past 2 weeks prior to screening and randomisation. Exclusion Criteria (include amongst others): \- Medical conditions: 1. Pregnant or lactating subject. 2. Moderate to severe allergy symptoms during the screening and treatment periods, and/or GPS caused by perennial allergens or seasonal allergens (other than grass) as verified by medical history and positive SPT. Exception: screening, treatment and collection of eDiary data can 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). 3. Subjects with a positive SPT at US and EU sites in regions with relevant southern grass (Bahia grass, Bermuda grass or Johnson grass) exposure. 4. Moderate to severe symptoms during the 3 years prior to Visit 1 to another seasonal or perennial allergen not tested in the SPT that cannot be avoided during the study and the symptoms of which may interfere with administration of treatment and /or impact the data collected, as determined by the investigator. 5. Presence of any medical condition that may reduce the ability to survive a serious allergic reaction. 6. History of autoimmune disease including Hashimoto's thyroiditis or other immunological disorder or other diseases (including, but not limited to, malignancy, cardiovascular, gastro-intestinal, hepatic, renal, hematological, 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 study treatment. 7. Presence of severe or uncontrolled or partly controlled asthma as defined in the GINA guidelines (GINA 2020) or asthma that requires more than a daily dose above 400 mcg of inhaled budesonide or equivalent. 8. Emergency room visit or hospitalisation for asthma in the 12 months prior to screening and randomisation or any history of a life-threatening asthma attack. 9. Presence of non-atopic rhinitis and/or rhino-sinusitis (with or without polyps). 10. Presence of nasal polyps and/or chronic sinusitis. 11. Presence of any acute or chronic ocular disorder, other than allergic conjunctivitis, which could interfere with the evaluation of CPT. 12. Eye surgery within the past 6 months. 13. Presence of any skin conditions (e.g. skin abnormalities, tattoos) which might interfere with the interpretation of the SPT results. 14. Clinical history of Type I diabetes. Subjects with well-controlled Type II diabetes will be allowed to participate at the discretion of the investigator. 15. Any acute infection (including upper respiratory tract infections in the 14 days prior to Visit 2), which in the opinion of the investigator may pose a safety risk to the subject. 16. Clinical history of severe or serious systemic reaction in response to AIT treatment in the past. 17. Clinical history of severe or life-threatening anaphylactic reactions to foods, insect venom, exercise, drugs or idiopathic anaphylaxis. 18. Clinical history of allergy, hypersensitivity or intolerance to the excipients of the IMP. 19. Tyrosine metabolism disorders, especially tyrosinemia and alkaptonuria. \- Prior/concomitant therapy: 20. History of any allergen SIT. 21. Inability to adhere to the washout periods for Prohibited Medications/Therapies with respect to Visit 1/1a and to refrain from using the medications indicated until after Visit 15. 22. Treatment with a preparation containing MPL (e.g., Cervarix, Shingrix, Fendrix) within 2 years prior to Visit 1 and until after completion of Visit 15 (with the exception of the IMP). 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 sympathomimetic). 24. Previous history of epinephrine device use. 25. β-blocker medication (including eye drops), for any indication. 26. Monoamine oxidase inhibitors and tricyclic antidepressants. (Tricyclic antidepressants should be avoided at least 2 weeks prior to screening). 27. Any previous therapy (within 12 months prior to screening) or current therapy with anti IgE (e.g., Xolair) or anti-interleukins (e.g., mepolizumab) or any other therapy with a biologic agent. 28. Unable to refrain from any vaccination (including influenza and any potential vaccine for COVID-19) during the study (unless administered more than 30 days prior to randomisation). Please note: Emergency vaccinations (e.g., tetanus due to injury) can be administered at any time. 29. Current or past therapy (within the previous 5 years) with immunosuppressant drugs or immunomodulatory biologics. Other exclusions 30. Clinical history of drug or alcohol abuse which, in the investigator's opinion, could interfere with the subject's ability to participate in the study. 31. Participation in a clinical research trial with any IMP within 4 weeks of Visit 1 or concomitantly with this study 32. Personal, financial or other dependent relationship (e.g., employee or immediate relative) with the study site, Sponsor, Sponsor's representative, or another individual who has access to the study protocol. 33. Vulnerable subjects or those in judicial or governmental detention, detainment or imprisonment in a public institution. 34. Subjects likely to have prolonged periods of absence (e.g., business or personal travel) during the GPS defined as: * Absence of 22 days or more in similar or mixed geographic regions as determined by the investigator, with no single trip in a similar geographical region exceeding 14 days and no single trip in a non-similar geographical region exceeding 7 days, * Absence of 15 days or more in non-similar geographic regions as determined by the investigator, with no single trip exceeding 7 days. 35. Have changed residence between geographical regions since the last GPS. Exception: the old and new residences are in the same or similar geographical region as determined by the investigator.

Locations (14)

Allergy and Asthma Associates of Bluegrass

Lexington, Kentucky, United States

Chesapeake Clinical Research, Inc.

White Marsh, Maryland, United States

Atlantic Research Center, LLC

Outcomes

Primary Outcomes

CSMS (Combined Symptom and Medication Score) Averaged Over the Peak Grass Pollen Season (GPS)

The daily CSMS is calculated as the sum of the daily Symptom Score (dSS) and the daily Medication Score (dMS). The dSS component of the CSMS is calculated as the sum of 6 individual symptom (2 conjunctival and 4 nasal) scores, each with a range of 0 to 3 points and divided by 6, and therefore has a total range between 0 and 3. The dMS is a score assigned according to the step of relief medication used in a day (from 0: no relief medication to 3: oral corticosteroids with step and step 2 medications). The daily CSMS has a range between 0 and 6. The average CSMS over the peak GPS will be calculated as sum of the daily CSMS within the peak GPS divided by the number of days of the peak GPS where the CSMS has been collected. Higher values in the scale represent worse outcomes.

Time frame: Measures collected approximately over 2-5 weeks (peak GPS). The exact time frame depended on the GPS start and end dates for each region (depending on pollen detection), therefore, a specific week from baseline can not be estimated globally.

Secondary Outcomes

CSMS Averaged Over the Entire (or Truncated) GPS

The daily CSMS is calculated as the sum of the daily Symptom Score (dSS) and the daily Medication Score (dMS). The dSS component of the CSMS is calculated as the sum of 6 individual symptom (2 conjunctival and 4 nasal) scores, each with a range of 0 to 3 points and divided by 6, and therefore has a total range between 0 and 3. The dMS is a score assigned according to the step of relief medication used in a day (from 0: no relief medication to 3: oral corticosteroids with step and step 2 medications). The daily CSMS has a range between 0 and 6. The average CSMS over the entire (or truncated) GPS will be calculated as sum of the daily CSMS within the peak GPS divided by the number of days of the GPS where the CSMS has been collected. Higher values in the scale represent worse outcomes.

Time frame: Measures collected approximately over 10 weeks (entire/truncated GPS). The exact time frame depended on the GPS start and end dates for each region (depending on pollen detection), therefore, a specific week from baseline can not be estimated globally.

Data from ClinicalTrials.gov

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Ocean Township, New Jersey, United States

Smith Allergy & Asthma Specialists

Cortland, New York, United States

Corning Center for Clinical Research

Horseheads, New York, United States

Allergy Partners of Western North Carolina

Asheville, North Carolina, United States

Bernstein Clinical Research Center, LLC

Cincinnati, Ohio, United States

Allergy Asthma & Sinus Center, S.C.

Greenfield, Wisconsin, United States

Universitatsmedizin Berlin - Charite Campus Mitte - Allergie Centrum Charite

Berlin, Germany

Universitätsklinikum Carl Gustav Carus an der TU Dresden

Dresden, Germany

...and 4 more locations

Total Combined Score (TCS) Averaged Over the Peak GPS

The daily TCS was the sum of the dSS and dMS calculated from the data recorded in the eDiary. For the dSS 6 individual symptoms were assessed: conjunctival symptoms (2 items) and nasal symptoms (4 items). Each item was scored on a 4-point severity scale (0 = no symptoms, 3 = severe symptoms). The dSS was calculated as the sum of the scores for the 6 indicidual symptoms, ranging from 0 to 18. For the dMS was rated on a scale from 0 to 20, depending on the relief medication use. Higher scores in TCS are related to worse outcomes.

TCS Averaged Over Entire (or Truncated) GPS

The daily TCS was the sum of the dSS and dMS calculated from the data recorded in the eDiary. For the dSS 6 individual symptoms were assessed: conjunctival symptoms (2 items) and nasal symptoms (4 items). Each item was scored on a 4-point severity scale (0 = no symptoms, 3 = severe symptoms). The dSS was calculated as the sum of the scores for the 6 indicidual symptoms, ranging from 0 to 18. The dMS was rated on a scale from 0 to 20, depending on the relief medication use: Score = 0, No relief medication used = 0 up to Score 20 = use of oral corticosteroids. Higher scores in TCS are related to worse outcomes.

Daily Symptom Score (dSS) of the CSMS Averaged Over the Peak and Entire (or Truncated) GPS

The dSS component of the CSMS was calculated as the sum of 6 individual symptom (2 conjunctival and 4 nasal) scores, each with a range of 0 to 3 points and divided by 6, and therefore has a total range between 0 and 3. Higher scores are related to worse outcomes.

Time frame: Measures collected approximately over 2-5 weeks (peak GPS) or 10 weeks (entire/truncated GPS). The exact time frame depended on the GPS start and end dates for each region (depending on pollen detection).

Daily Medication Score (dMS) of the CSMS Averaged Over the Peak and Entire (or Truncated) GPS

dMS of the CSMS consists on a score with a range from 0 to 3: 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. Higher scores are related to worse outcomes.

dSS of the TCS Averaged Over the Peak GPS and Entire (or Truncated) GPS

The dSS of the TCS is calculated as the sum of the scores (0-No symptoms to 3-Severe symptoms) for the 6 individual symptoms (i.e. ranging from 0 to 18). Higher scores are related to worse outcomes.

dMS of the TCS Averaged Over the Peak GPS and Entire (or Truncated) GPS

The dMS of the TCS was rated on a scale from 0 to 20 depending on the use of relief medication: Score = 0, No relief medication used = 0 up to Score 20 = use of oral corticosteroids. Higher values are related to worse outcomes.

Correlation Between TSS During CPT, CSMS, TCS, dSS (for CSMS and TCS) and dMS (for CSMS and TCS) Over the Peak and Entire (or Truncated) GPS for Subjects With a Positive CPT at Baseline.

Variables evaluated for correlation: * Average combined score medication (CSMS) over the peak GPS or entire/truncated GPS * Average Total combined score (TCS) over the peak GPS or entire/truncated GPS * dSS (daily symptom score) of CSMS (CSMS.dSS) over the peak GPS or entire/truncated GPS * dMS (daily medication score) of CSMS (CSMS-dMS) over the peak GPS or entire/truncated GPS * dSS of TCS (TCS-dSS) over the peak or entire/truncated GPS * dMS of TCS (TCS-dMS) over the peak or entire/truncated GPS * Change from baseline in Total symptom score (TSS) during CPT (Conjunctival provocation test) The correlation between the above variables were explored using linear regression models. Outcomes are presented as Mean Squared Errors, representing the strength of the correlation, CI numbers not available. Low values represent stronger correlation between the two variables.

Number of Well Days and Severe Days During the Peak and Entire (or Truncated) GPS.

A "well day" was defined based on CSMS as a day with: * No use of relief medication on the particular day, * And a total symptom score ≤2 out of 18 A "severe day" was based on CSMS and defined as a day with a symptom score of 3 in any of the 6 rhinitis/rhinoconjunctivitis symptoms. The probability of a well day or a severe day was analyzed using data on a by-day level per subject using generalized estimating equation (GEE) or similar approaches as appropriate. Well days and severe days were assessed during the peak GPS and entire (or truncated) GPS.

Serum Ig Responses (Change in Total IgE and Grass-specific IgE From Baseline to Visit 12 and Visit 15)

Immunological measurements (total IgE and grass-specific IgE) and their changes between screening and post-treatment were analyzed descriptively. The change from baseline in immunoglobulin measurements was additionally analyzed using analysis of covariance (ANCOVA), including treatment groups and with baseline as covariate.

Time frame: Baseline (Visit 2), Visit 12 (2 weeks before start of the GPS) and visit 15 (end of the GPS). The exact time frame depended on the GPS start and end dates for each region, and visit 15 was usually in the range between 24 and 32 weeks after screening

Change in Serum Ig Responses (Change in Grass-specific IgG4 From Baseline to Visit 12 and Visit 15)

Immunological measurements (grass-specific IgG4) and their changes between screening and post-treatment were analyzed descriptively. The change from baseline in immunoglobulin measurements was additionally analyzed using analysis of covariance (ANCOVA), including treatment groups and with baseline as covariate.

RQLQ(S) During the Peak GPS

Rhinoconjunctivitis quality of life was assessed using the Rhinoconjunctivitis Quality of Life Questionnaire with Standardised Activities (RQLQ\[S\]). The RQLQ(S) comprises 28 questions in 7 domains (activity limitation, sleep problems, nose symptoms, eye symptoms, non-nose/eye symptoms, practical problems, and emotional function). Each question is scored on a scale from 0 to 6. Score is calculated as a mean of the 28 responses, with a range from 0 to 6. Higher scores are related with worse outcomes.

Time frame: Measures were collected approximately over 2-5 weeks (peak GPS). The exact time frame depended on the GPS start and end dates for each region (depending on pollen detection), therefore, a specific week from baseline can not be estimated globally.

Frequency, Severity and Relationship of AEs to Treatment

Number of subjects with at least one event of the specified AE type. The frequency, relationship and severity of AEs will be assessed within each treatment group. Note: TEAE (treatment emergent adverse events) are reported in the Adverse Event section.

Time frame: Up to 1 year

Frequency of AEs Leading to Premature Discontinuation From Treatment or Study

Number of participants who prematurely discontinued from treatment or study due to AEs.

Time frame: Up to 1 year

Frequency of AESI

Number of participants with Adverse events of special interest (AESI). Suspected AESIs in this study were defined as signs and symptoms indicative of new-onset auto-immune or neuroinflammatory disorders.

Time frame: Up to 1 year

Number of Participants With Changes in Serum Chemistry Between Screening and Visit 15

Alert ranges were defined for laboratory values (Glucose, Sodium, Uric acid, Urea, Potassium, Calcium, Creatinine, Chloride, Total protein, Phosphorus, Cholesterol, Albumin, Total Bilirubin, Alkaline phosphatase, LDH, AST, ALT, GGT, CRP) lying outside the normal range to a clinically relevant degree. Shift tables comparing the values at baseline to the values at the final visit were created for each variable.

Time frame: At Screening (Visit 1) and at the end of pollen season (Visit 15). The exact time frame depended on the GPS start and end dates for each region, however, visit 15 usually ranged between week 24 and week 32 from screening

Number of Participants With Changes in Hematology Between Screening and Visit 15

Alert ranges were defined for laboratory values (Haemoglobin, haematocrit, total WBC and differentials, total RBC, RBC indices, and platelet count) lying outside the normal range to a clinically relevant degree. Shift tables comparing the values at baseline to the values at the final visit were created for each urinalysis parameter.

Number of Participants With Changes in Urinalysis Between Screening and Visit 15

pH, Protein, Glucose, Ketones, Bilirubin, Blood, Nitrite, Urobilinogen, Leukocytes were determined in urine. Alert ranges were defined for laboratory values lying outside the normal range to a clinically relevant degree. Shift tables comparing the values at baseline to the values at the final visit were created for each urinalysis parameter.

Baseline and Changes in PEFR (Only in Subjects With Past or Current Asthma) at All Treatment Visits

PEFR - peak expiratory flow rate. Baseline measure of PEFR was performed in all subjects. Only in subjects with past or current asthma, PEFR was performed at Visits 2 (baseline) to 11, prior to and approximately 30 to 60 minutes following study drug administration. At Visit 1 (screening), the PEFR should be ≥75% predicted for subjects to be eligible for the study. Note that the exact time frame for each visit depended on the GPS start and end dates for each region (depending on pollen detection), therefore, a specific week from baseline can not be estimated globally.

Time frame: At baseline (Visit [V]2) only for all subjects, and also at V3 (V2 +~1 week [wk]), V4 (V3+~1wk), V5 (V4+~4wk), V6 (V5+~3wk), V7 (V6+~1wk), V8 (V7+~1wk), V9 (V8+~1wk), V10 (V9+~1wk) and V11 (~3-7wk before GPS) for subjects with past or current asthma

Changes in Vital Signs (Body Temperature) Between Baseline and All Treatment Visits

Body temperature was measured after the subject has been in the supine position for at least 5 minutes at all visits: Visit 1 to Visit 15. At Visits 2 (baseline) to 11, vital sign measurements were performed before and 30 to 60 minutes following study drug administration. Changes in temperature values reported only post-injection. All vital signs-related information will be listed by subject, visit and timepoint. The exact time frame for each visit depended on the GPS start and end dates for each region (depending on pollen detection), therefore, a specific week from baseline can not be estimated globally.