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
Phase: PHASE3
Conditions: Seasonal Allergic Rhinitis, Rhinoconjunctivitis
Sponsor: Allergy Therapeutics

 
 
Protocol: PQGrass306 
 
 
  
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Allergy Therapeutics (UK) Ltd.: PQGrass306  
Study Protocol 
  
 Status:  
final 
 
Clinical Trial 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  
NCT05540717 
Investigational Product:  
PQ Grass  
Clinical Phase:  
Phase III  
Sponsor:   
Allergy Therapeutics (UK) Ltd.  
Dominion Way  
BN14 8SA  
Worthing  
United Kingdom  
Date: 
June 20, 2023 
  
 
Protocol Title:  

 
 
Protocol: PQGrass306 
 
 
  
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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. 
Short Title:  
Randomised efficacy and safety clinical trial of PQ Grass in subjects with seasonal allergic 
rhinitis and/or rhinoconjunctivitis induced by grass pollen. 
Phase: Phase III 
Sponsor: Allergy Therapeutics (UK) Ltd, Dominion Way, Worthing, West Sussex, BN14 8SA, 
United Kingdom. 
Study centres: The clinical trial will be conducted in the United States of America (US) and in 
5 countries in Europe at approximately 90 clinical trial sites. 15 study sites in total (7 centres in 
the EU and 8 centres in the US).   
 
Rationale: 
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).  
Number of subjects planned:  
The trial will apply an adaptive group sequential design with one interim analysis that will be 
performed on the subjects randomised in Year 1 (N=555). In case the decision is taken to 
progress the study to a second season after the interim analysis, the sample size will be 
recalculated.  
Study period: Estimated first subject enrolled (Q3/2023) and last subject last visit (Q3/2024). 
The end of study (EoS) is defined as the date of the last 6 months telephone follow-up call of 
the last subject in the study. 
 
 

 
 
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Objectives and Endpoints:  
Objectives 
Endpoints 
Primary Efficacy 
To evaluate the efficacy of PQ Grass 
27600 SU in subjects with grass pollen 
induced SAR and/or rhinoconjunctivitis 
based on symptoms and medications.   
• CSMS averaged over the peak GPS.  
Secondary Efficacy 
To evaluate the treatment effect of 
PQ Grass on the CSMS over the entire 
GPS. 
• CSMS averaged over the entire (or truncated) 
GPS. 
To evaluate the quality of life. 
• RQLQ(S) measured within the peak GPS. 
To evaluate the effect of PQ Grass 27600 
SU on IgG4. 
• Serum grass specific IgG4 at Visit 7 
compared to baseline. 
To evaluate the treatment effect of 
PQ Grass 
on 
the 
dSS 
and 
dMS 
components of the CSMS over the GPS. 
• dSS component of the CSMS averaged over 
the peak GPS and entire (or truncated) GPS. 
• dMS component of the CSMS averaged over 
the peak GPS and entire (or truncated) GPS. 
To evaluate the potential of PQ Grass 
27600 SU to reduce symptom burden and 
the need for medication use. 
• The number of well days during the peak 
GPS. 
Safety 
To evaluate the safety and tolerability of 
PQ Grass in subjects with grass pollen 
induced SAR and/or rhinoconjunctivitis. 
• Frequency, severity and relationship of AEs 
to treatment. 
• Frequency of AEs leading to premature 
discontinuation from treatment or clinical 
trial. 
• Frequency of AESI. 
• Changes in clinical laboratory values (serum 
chemistry, haematology and urinalysis) 
between screening and Visit 11. 
• Changes in vital signs at all treatment visits. 
Abbreviation sAE = adverse event; AESI = adverse event of special interest; CSMS = combined symptom and 
medication score; dMS = daily medication score; dSS = daily symptom score; GPS = grass pollen season; Ig = 
immunoglobulin; RQLQ(S) = Rhinoconjunctivitis Quality of Life Questionnaire with standardised activities; SAR 
= seasonal allergic rhinitis; SU = standardised units;  
 
 
 
 

 
 
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Overall Design (Brief Summary): 
This is a 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). 
The trial will have an adaptive group sequential design with one planned interim analysis.  
Subjects will be assigned in a ratio of 1:1 (PQ Grass:Placebo) with treatment course to be 
completed prior to the onset of the grass pollen season (GPS): 
• PQ Grass: 6 injections of PQ Grass (900, 2700, 6000, 6000, 6000, 6000 SU 
sequentially) or 
• Placebo: 6 injections of placebo  
The study includes 4 periods, encompassing 11 visits to the study site and at least 2 follow-up 
telephone calls. Subjects will be provided with enough relief medication to cover them through 
this period by the study site.  
Period 1 (Screening [Visit 1 ± Visit 1a]): This includes the screening visit at which subjects’ 
eligibility for the clinical trial will be assessed.  
Period 2 (Randomisation and treatment [Visit 2 to Visit 7]): At Visit 2, subjects will be 
randomly allocated in a randomisation ratio of 1:1 to the active treatment (PQ Grass) or the 
placebo treatment group and will receive the first injection.  
After Randomization at Visit 2, subjects will thereafter return to the study site at subsequent 
visits during the treatment period (Visit 3 to Visit 7) to receive the remaining injections. The 
average duration of the treatment period will be approximately 16 weeks. 
Treatment with either 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 
will be administered prior to the onset of the GPS.  
Period 3 During the GPS, subjects will record their allergic rhinitis/rhinoconjunctivitis 
symptoms and use of relief medications in an electronic diary (eDiary). The symptom and 
medication scores during the peak GPS and the entire (or truncated) GPS calculated according 
to the European Academy of Allergy and Clinical Immunology (EAACI) recommendations for 
the CSMS (primary endpoint) will be compared between the active and placebo treatment 
groups. The following 4 visits will be performed: 
• Visit 8 (pre-GPS) 
• Visit 9 (≈ onset of GPS) 
• Visit 10 (during GPS) 
• Visit 11 (≈ end of GPS) 

 
 
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Period 4 (Telephone safety follow-up): This consists of safety telephone calls at approximately 
12 weeks and 24 weeks after the last injection to ascertain occurrence of any AEs.  
Target population: Adult (18 to 65 years inclusive) subjects with seasonal allergic rhinitis 
and/or rhinoconjunctivitis due to grass pollen exposure (with or without allergic asthma that is 
well controlled). 
Study treatments, dosage and mode of treatment: 
Active Treatment: 
Each PQ Grass injection will consist of extracts of grass pollen, which are chemically modified 
by treatment with glutaraldehyde and adsorbed to L-tyrosine.  
The injections will be supplied at concentrations of 900, 2700, and 6000 SU per 1.0 milliliter 
(mL) and 50 microgram (µg)/1.0 mL of MPL adjuvant, 2% weight per volume (w/v) L-tyrosine 
and 0.5% (w/v) phenol.  
Reference Therapy: 
Placebo (Buffered saline with L-tyrosine 2% [w/v] and phenol 0.5% [w/v])  
The average duration of treatment will be approximately 11 to 18 weeks.  
Dose/Dose schedule: 
PQ Grass or placebo will be administered during Visits 2 to 7. Visits 2 to 4 will be 
approximately 1 week apart, Visit 5 to 7 will be approximately 4 weeks apart. 
 
Statistical methods 
This is the pivotal Phase III study with PQ Grass. The primary endpoint of the study will be the 
CSMS averaged over the peak GPS. 
The difference in CSMS between PQ Grass and placebo will be evaluated using a linear mixed 
model. Subjects with missing daily CSMS during the peak GPS will be included in the primary 
analysis by using multiple imputation methods to impute missing values on a by-day level.  
The statistical analysis will be performed using a linear mixed model. In the context of the 
adaptive design, a 1-sided testing will be used using group sequential Pocock boundaries chosen 
such that an overall 1 sided type 1 error rate of 2.5% was preserved. 
For the interim analysis after Year 1, the 1-sided p-value was therefore to be compared with α 
= 0.01419 for a statistically significant superiority of the active treatment over placebo.  
The difference between PQ Grass and placebo will be estimated using least squares (LS) means. 
Two-sided appropriate confidence intervals (CIs) for the difference between treatment groups 

 
 
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will be provided. The difference between treatment groups will also be presented in percent 
relative to the LS mean in the placebo group.  
The secondary endpoints will generally be analyzed using a similar statistical approach as the 
primary endpoint. The statistical hypotheses for the key secondary endpoints will only to be 
tested in a confirmatory sense if the analysis of the primary endpoint is statistically significant. 
Multiplicity in the key secondary endpoints will be addressed.  
The frequency, relationship and severity of AEs and frequency of premature discontinuations 
from treatment or study due to AEs will be assessed within each treatment group.  
Adjudication Committee: Yes 
Trial Oversight Committee: Yes 
 
 
 
 
 
 

 
 
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Schedule of activities 
 
 
Period 1 
Screening 
Period 2 
Randomisation and Treatment 
Period 3 ^ 
Pre/During/End of GPS 
Assessments 
Period 4 ^ 
Follow-up 
Visit Number 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9  
V10 
V11 
12w 
after 
last 
injec
tion 
24w 
after 
last 
injec
tion 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
(including asthma 
and allergy history) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Physical 
examination 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
Height and weight 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Mental health status 
assessment 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Skin prick testing 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Spirometry 
X 
 
 
 
 
 
 
 
 
 
 
 
 
PEFR 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
RQLQ(S) 
 
X 
 
 
 
 
 
 
X 
X 
 
 
 
Safety laboratory 
tests 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
Urinalysis 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
Urine pregnancy test 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
IgE, and IgG4  
X 
 
 
 
 
 
X 
 
 
X 
 
 
 
AEs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Randomisation 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Investigational 
drug/placebo 
administration 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
eDiary recording of 
daily 
symptoms/daily 
medication use 
 
 
 
 
 
 
 
X 
 
 
Telephone safety 
follow-up  
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
 
 

 
 
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Main Inclusion criteria 
Subjects will be eligible to be included in the study only if all of the following criteria apply: 
1. Capable of giving signed informed consent  
2. Subject had to be 18 to 65 years of age inclusive, at the time of signing the ICF. 
3. Male or female. 
4. Good general health, as determined by the Investigator, based on a medical evaluation, 
including medical history, physical examination, mental status assessment, and laboratory 
tests.  
5. Positive history of moderate to severe symptoms of SAR/rhinoconjunctivitis ascribed to 
grass (Pooideae) pollen exposure of ≥2 seasons duration 
6. A positive skin prick test (SPT) to histamine (wheals [longest diameter] ≥3 mm) and a 
negative SPT to the negative control (wheal diameter = 0 mm) at Screening. 
7. A positive SPT for grass pollen (wheals [longest diameter] ≥3 mm). 
8. Grass-specific IgE class ≥2 as documented by an ImmunoCAP test at Screening. 
9. FEV1 ≥80% of predicted, with a FEV1/FVC ratio ≥70% and PEFR ≥75% predicted at 
screening. 
 
Main Exclusion criteria  
A subject will be excluded from this study if one or more of the following criteria apply: 
1. Pregnant or lactating subject. 
2. Presence of any medical history of moderate to severe allergy symptoms (verified by a 
positive SPT or positive specific IgE [Class ≥2] at Screening) to any other seasonal 
allergen (other than grass) or perennial allergens. 
3. Moderate to severe symptoms during the 3 years prior to Visit 1 to any other seasonal or 
perennial allergen not tested in the SPT or by specific IgE 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. 
4. Presence of any medical condition that may reduce the ability to survive a serious allergic 
reaction. 
5. Presence of severe or poorly controlled or uncontrolled asthma  
6. Clinical history of type 1 diabetes or poorly controlled type 2 diabetes. 
7. Clinical history of severe systemic reaction or serious systemic reaction in response to 
AIT in the past. 
8. Clinical history of severe or life-threatening anaphylactic reactions to foods, insect venom, 
exercise, drugs, or idiopathic anaphylaxis. 
9. Clinical history of allergy, hypersensitivity or intolerance to the excipients of the 
investigational drug/placebo. 

 
 
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10. 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. 
11. Unable to receive epinephrine therapy (ie, use of epinephrine is contraindicated such as in 
subjects with hyperthyroidism, uncontrolled hypertension, cardiac arrhythmias, closed 
angle glaucoma, or subjects taking other sympathomimetics). 
12. Tyrosine metabolism disorders, especially tyrosinemia, and alkaptonuria. 
13. 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. 
14. 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. 
15. Inability to adhere to the washout periods listed in with respect to Screening and to refrain 
from using the medications indicated until after Visit 11. 
16. Treatment with a preparation containing MPL (eg, Cervarix, Shingrix, Fendrix) within 
2 years prior to Visit 1 and until after completion of Visit 11 (with the exception of the 
investigational drug). 
17. Previous history of epinephrine auto-injector use. 
18. β-blocker medication (local or systemic, including eye drops) for any indication. 
19. Monoamine oxidase inhibitors and tricyclic antidepressants. 
20. Any previous therapy (within the previous 5 years) or current therapy with anti-IgE (eg, 
omalizumab [Xolair]) or anti-interleukins (eg, mepolizumab). 
21. Current or past therapy (within the previous 5 years) with any other immunomodulatory 
biologics. 
22. Unable to refrain from any vaccination (including influenza vaccine and COVID-19 
vaccine) during the clinical trial (unless administered >30 days prior to randomisation). 
23. Participation in a clinical research trial with any investigational drug within 4 weeks of 
Visit 1 or concomitantly with this clinical trial. 
24. Personal, financial or other dependent relationship (eg, employee or immediate relative) 
with the clinical trial site, Sponsor, Sponsor’s representative, or another individual who 
has access to the clinical trial protocol. 
25. Vulnerable subjects or those in judicial or governmental detention, detainment, or 
imprisonment in a public institution.