A Randomized, Double-blind, Placebo-controlled, Multi-center Study of the Efficacy and Safety of STG320 Sublingual Tablets of House Dust Mite (HDM) Allergen Extracts in Adults and Adolescents With HDM-associated Allergic Rhinitis
Phase: PHASE3
Conditions: Rhinitis, Allergic, Perennial, House Dust Mite Allergy
Sponsor: Stallergenes Greer

CONFIDENTIAL 
STALLERGENES 
Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 1 of 123 
 
PROTOCOL SL75.14 
VERSION 7.0 – 05 October 2017 
 
A randomized, double-blind, placebo-controlled, multi-center study of the efficacy and 
safety of STG320 sublingual tablets of house  
dust mite (HDM) allergen extracts in adults and adolescents with HDM-associated 
allergic rhinitis 
 
 
Sponsor: STALLERGENES 
6 rue Alexis de Tocqueville 
92160 Antony 
FRANCE 
 
STG320 Sublingual Tablet of Dermatophagoides pteronyssinus and  
Dermatophagoides farinae Allergen Extracts 
IND Number: 16252 
EudraCT Number: 2014-004223-46 
 
 
 
The confidential information in this document is provided to you as an Investigator, a 
potential Investigator or consultant, for review by you, your staff and applicable review 
committee(s). It is understood that the information will not be disclosed to any third 
party without written authorization from the Sponsor, except to the extent necessary to 
obtain informed consent from those persons to whom the investigational product may be 
administered, or their legally acceptable representative(s) 
ClinicalTrials.gov ID: NCT02443805 
 
Confidential/Proprietary Information 

CONFIDENTIAL 
STALLERGENES 
Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 2 of 123 
 
1. SIGNATURE PAGE 
For STALLERGENES: 
Martine Le Gall 
Senior Medical Director 
___________________________________ 
Date and Signature 
Isabelle Douville 
Clinical Project Manager 
___________________________________ 
Date and Signature 
Shahin Gharakhanian 
Interim Global Head of Clinical Development 
and Medical Affairs 
___________________________________ 
Date and Signature 
Coordinating Investigators: 
Prof Pascal Demoly 
Département de Pneumologie et Addictologie 
Hôpital Arnaud de Villeneuve 
Montpellier, France 
___________________________________ 
Date and Signature 
Prof Thomas B. Casale 
Division of Allergy and Immunology 
University of South Florida 
Tampa, FL (United States of America) 
___________________________________ 
Date and Signature 
For the study center: 
By my signature below, I hereby attest that I have read, discussed and understood the background 
information concerning the investigational product. I have read and discussed this Protocol (study 
code SL75.14) and agree to carry out the study as set out therein. I agree that the study shall be 
conducted in compliance with ICH Good Clinical Practice (GCP) standards, the Code of Federal 
Regulations on Good Clinical Practice and all applicable regulatory requirements. I accept my 
obligations relating to the principles that have their origin in the Declaration of Helsinki and 
specifically to Independent Ethics Committee (IEC)/Institutional Review Committee (IRB), 
Informed Consent, and also my obligations to the Sponsor, or contracted representatives, as far as 
safety reporting, providing data, allowing monitoring, auditing, inspection by domestic and foreign 
Regulatory Authorities and quality control visits are concerned. 
In addition, I have been informed that certain Regulatory Authorities require the Sponsor to obtain 
and supply details about the investigator’s ownership interest in the Sponsor or the study drug and 
more generally about his/her financial ties with the Sponsor. 

CONFIDENTIAL 
STALLERGENES 
Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 3 of 123 
 
STALLERGENES will use and disclose the information solely for the purpose of complying with 
regulatory requirements. 
Hence, I: 
- 
agree to supply STALLERGENES with any information regarding ownership interest and 
financial ties (including those of my spouse and dependent children) 
- 
agree to promptly update this information if any relevant changes occur during the course of 
the study and for one year following completion of the study, and 
- 
agree that STALLERGENES may disclose this information about such ownership interests and 
financial ties to Regulatory Authorities. 
 
Obligations of confidentiality are accepted by both parties. 
 
Investigator:  
 
 
 
 
 
Name: ____________________ 
 
 
 
 
Study Site number: _______________ 
 
Date: ____________________ 
 
 
 
 
 
Signature: 

CONFIDENTIAL 
STALLERGENES 
Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 4 of 123 
 
2. TABLE OF CONTENTS 
 
1. 
SIGNATURE PAGE 
2 
2. 
TABLE OF CONTENTS 
4 
3. 
GENERAL INFORMATION 
8 
3.1 
Investigator 
8 
3.2 
Sponsor 
8 
3.3 
Contract Research Organization (including Central Laboratory) 
8 
3.4 
Other Providers 
8 
3.5 
Protocol Summary 
10 
3.6 
Flow Chart 
26 
3.7 
Study Schematic Diagram 
29 
3.8 
List of Abbreviations 
30 
4. 
BACKGROUND INFORMATION 
33 
4.1 
Scientific Background 
33 
4.2 
Investigational Product 
34 
4.3 
Non-Clinical Studies 
35 
4.3.1 
Pharmacology 
35 
4.3.2 
Pharmacokinetics 
35 
4.3.3 
Toxicology 
35 
4.4 
Clinical Development 
35 
4.4.1 
STALLERGENES - Sponsored Studies 
36 
4.4.2 
Studies Conducted by STALLERGENES Partner Company (Shionogi and Co., Ltd) 
37 
4.5 
Study Rationale 
37 
4.6 
Good Clinical Practices Statement 
38 
5. 
STUDY OBJECTIVES AND PURPOSE 
39 
5.1 
Primary Objective 
39 
5.2 
Secondary Objectives 
39 
5.2.1 
Efficacy of STG320 during the Primary Evaluation Period (Month 12) 
39 
5.2.2 
Efficacy of STG320 during the Secondary Evaluation Periods (Months 3, 6 and 9) 
40 
5.2.3 
Effect of STG320 at the End of the Treatment 
40 
5.3 
Exploratory Objectives 
40 
5.4 
Safety Objectives 
41 
6. 
STUDY DESIGN 
41 
6.1 
Type/Design 
41 
6.2 
Number of Patients and Study Sites 
42 
6.3 
Measures to Minimize Bias 
42 
6.3.1 
Randomization 
42 
6.3.2 
Blinding 
42 
6.4 
Study Duration 
43 
7. 
SELECTION AND WITHDRAWAL OF PATIENTS 
43 
7.1 
Inclusion Criteria 
43 
7.2 
Exclusion Criteria 
44 
7.3 
Inclusion Criterion at the end of the run-in/baseline evaluation period 
46 
7.4 
Patient Withdrawal 
46 
7.4.1 
Withdrawal Criteria 
47 
7.4.2 
Patient Replacement Policy 
47 
8. 
TREATMENT OF PATIENT (INVESTIGATIONAL PRODUCTS AND CONCOMITANT 
MEDICATIONS) 
47 
8.1 
Study Investigational Products 
47 
8.1.1 
Description of Investigational Products 
47 
8.1.2 
Packaging 
48 

CONFIDENTIAL 
STALLERGENES 
Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 5 of 123 
 
8.1.3 
Labeling 
49 
8.1.4 
Storage Requirements 
49 
8.1.5 
Investigational Product Dispensation 
49 
8.1.6 
Monitoring of Patient Compliance 
50 
8.1.7 
Investigational Products (IP) Accountability 
50 
8.2 
Concomitant Treatments and Rescue Medications 
50 
8.2.1 
Concomitant Treatments 
50 
8.2.2 
Rescue Medications 
51 
8.2.3 
Epinephrine Auto-Injector 
52 
8.2.3.1 
Special Warnings and Precautions 
52 
8.2.3.2 
Safety and Emergency Procedures 
52 
8.2.4 
Prohibited Concomitant Treatments (Medications and Therapies) 
53 
8.2.4.1 
Prohibited Treatments During the Screening Phase 
53 
8.2.4.2 
Prohibited Concomitant AR Treatments During Run-in and Treatment Phase 
54 
8.2.5 
Maintenance Asthma Therapy (When Used) 
54 
9. 
STUDY PROCEDURES 
55 
9.1 
Patient Identifier 
55 
9.2 
Description of Procedures 
55 
9.2.1 
Informed Consent Form 
55 
9.2.2 
Inclusion and Exclusion Criteria 
55 
9.2.3 
Medical and Allergy History 
55 
9.2.4 
Demographic Data, Height and Weight 
55 
9.2.5 
Prior and Concomitant Medication 
55 
9.2.6 
Physical Examination and Vital Signs 
56 
9.2.7 
Skin Prick Test 
56 
9.2.8 
Spirometry 
56 
9.2.9 
Classification of Asthma Status 
57 
9.2.10 
Blood sampling 
57 
9.2.11 
Dust sampling 
57 
9.2.12 
Pregnancy Test 
58 
9.2.13 
IVRS/IWRS 
58 
9.2.14 
Dispensation and Use of the Electronic Diary (e-diary) 
58 
9.2.15 
Standardized Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ(S)≥12) 
59 
9.2.16 
Global Rating of Change Questionnaire 
59 
9.2.17 
Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment Questions: 
Allergy Specific (WPAI + CIQ: AS) 
60 
9.2.18 
EQ-5D-5L Generic Health-Related Quality of Life 
60 
9.2.19 
HDM Avoidance Measures Questionnaire 
61 
9.2.20 
Adverse Events/Concomitant Medication Card 
61 
9.3 
Visit by Visit Description 
61 
9.3.1 
Visit 1 (Selection Visit) 
61 
9.3.2 
Visit 2 (Run-in period Visit) 
62 
9.3.3 
Visit 3 (Randomization Visit) 
63 
9.3.4 
Visit 4 (Month 1 Visit) 
64 
9.3.5 
Visit 5 (Month 3 Visit) 
65 
9.3.6 
Visit 6 (Month 6 Visit) 
66 
9.3.7 
Visit 7 (Month 9 Visit) 
66 
9.3.8 
Visit 8 (Month 11 Visit) 
67 
9.3.9 
Visit 9 (Month 12, End of Treatment Visit) 
68 
9.3.10 
Visit 10 (Post-Treatment Follow-Up Visit) 
69 
9.3.11 
Early Termination Visit 
69 
9.4 
Other Supplies 
69 

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STALLERGENES 
Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 6 of 123 
 
9.4.1 
Rescue Medication (Section 8.2.2 “Rescue Medications”) 
69 
9.4.2 
Skin Prick Test Kits (Section 9.2.7 “Skin Prick Test”) 
69 
9.4.3 
Blood Sampling Kits (Section 9.2.10 “Blood sampling”) 
70 
9.4.4 
Dust Sampling Kits (Section 9.2.11 “Dust Sampling”) 
70 
9.4.5 
Pregnancy Tests (Section 9.2.12 “Pregnancy Test”) 
70 
10. 
ASSESSMENT OF EFFICACY 
70 
10.1 
Primary Efficacy Variable 
70 
10.2 
Secondary Efficacy Variables 
71 
10.2.1 
Rhinitis Total Symptom Score (RTSS) 
71 
10.2.2 
Rescue Medication Score (RMS) 
71 
10.2.3 
Adjusted Symptom Score (ASS) 
71 
10.2.4 
Combined Symptom and MedicationScore (CSMS) 
72 
10.2.5 
Total Ocular Symptom Score (TOSS) 
72 
10.2.6 
Rhinoconjunctivitis Total Symptom Score (RCTSS) 
72 
10.2.7 
Six Individual Rhinoconjunctivitis Symptom Scores (RSSs) 
72 
10.2.8 
Rhinoconjunctivitis Rescue Medication Usage 
72 
10.2.9 
Visual Analogue Scale (VAS) 
73 
10.2.10 
Proportion of Symptom-Controlled Days (PSCD) 
73 
10.2.11 
Proportion of Not-Controlled Days (PNCD) 
73 
10.2.12 
Controlled patients (CP) 
73 
10.2.13 
Standardized Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ(S)≥12) scores 
73 
10.2.14 
EQ-5D-5L Generic Health-Related Quality of Life Questionnaire 
74 
10.2.15 
Global Rating of Change Score (GRCS) 
74 
10.3 
Other Variables 
74 
10.3.1 
Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment Questions: 
Allergy Specific (WPAI + CIQ: AS) 
74 
10.3.2 
Immunological Markers (IgE and IgG4) 
74 
10.4 
Exploratory Variables 
74 
10.4.1 
Candidate Biomarkers 
74 
10.5 
Baseline Characteristics 
74 
10.6 
Methods and Timing for Assessing, Recording, and Analyzing the Efficacy Variables 
75 
11. 
ASSESSMENT OF SAFETY 
75 
11.1 
Specifications of Safety Variables 
75 
11.2 
Methods and Timing for Assessing, Recording, and Analyzing the Safety Variables 
75 
11.3 
Adverse Events 
76 
11.3.1 
Definitions 
76 
11.3.1.1 
Adverse Event 
76 
11.3.1.2 
Serious Adverse Event 
79 
11.3.1.3 
Pre-defined Adverse Event of Special Interest 
79 
11.3.2 
Reporting 
80 
11.3.2.1 
Reporting of AE 
80 
11.3.2.2 
Reporting of SAE and Serious AESI 
80 
11.4 
Unblinding 
81 
11.5 
Overdose 
81 
11.6 
Pregnancy 
82 
11.7 
Management of Adverse Events and Patient Discontinuation from Study 
82 
11.7.1 
Adverse Event Necessitating Temporary Discontinuation of the IP 
82 
11.7.2 
Patient Discontinuation from Study 
82 
11.7.3 
Management of Adverse Events 
83 
11.8 
Independent Data Safety Monitoring Board Review 
83 
12. 
STATISTICS 
83 
12.1 
Determination of Sample Size 
84 

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STALLERGENES 
Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 7 of 123 
 
12.2 
Definition of Clinical Relevance of the Efficacy Results 
85 
12.3 
Determination of Study Population for Analysis 
85 
12.4 
Handling of Missing and Incomplete Data 
86 
12.5 
Efficacy analyses 
87 
12.5.1 
Evaluation Periods 
87 
12.5.2 
Primary Efficacy Analysis 
87 
12.5.3 
Secondary Efficacy Analyses 
88 
12.6 
Other Analyses 
89 
12.7 
Exploratory Analyses 
89 
12.8 
Safety Analyses 
89 
12.9 
Baseline Evaluation 
91 
12.10 
Prior and Concomitant Medication Usage Evaluation 
91 
12.11 
Subject Disposition 
91 
12.12 
Compliance with the Investigational Product in the Treatment Period 
92 
12.13 
Criteria for Unblinding the Results 
92 
13. 
ETHICS 
92 
13.1 
Approval 
92 
13.2 
Patient Informed Consent / Assent 
93 
13.2.1 
Information 
93 
13.2.2 
Informed Consent / Assent 
94 
13.3 
Patient Confidentiality 
94 
13.4 
Informing the General Practitioner 
94 
14. 
STUDY MANAGEMENT AND ADMINISTRATION 
95 
14.1 
Monitoring 
95 
14.2 
Direct Access to Source Data/Documents 
95 
14.3 
Audit and Inspection 
96 
14.4 
Electronic Case Report Forms (e-CRFs) 
96 
14.5 
Adherence to Protocol 
96 
14.6 
Termination of the Study 
97 
14.7 
Stopping Rules for the study 
97 
14.8 
Investigator Site File 
97 
14.9 
Data Handling and Record Keeping 
98 
14.10 
Clinical Study Report 
98 
14.11 
Patient Insurance 
98 
14.12 
Publication and Presentation Policy 
99 
14.13 
Archiving and Data Retention 
99 
14.14 
Allocation of Responsibilities 
99 
14.15 
Curriculum Vitae 
99 
14.16 
fisher Form 1572 (Statement of Investigator – Mandatory for US) 
100 
14.17 
Financial Disclosure 
100 
15. 
REFERENCES 
101 
16. 
APPENDICES 
105 
 

CONFIDENTIAL 
STALLERGENES 
Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 8 of 123 
 
3. GENERAL INFORMATION 
3.1 
Investigator 
The complete and updated list of Investigators is maintained in the Trial Master File (TMF). 
3.2 
Sponsor 
STALLERGENES 
6 rue Alexis de Tocqueville 
92160 Antony 
FRANCE 
Contact Persons 
Isabelle Douville 
Clinical Project Manager 
Tel: +33 (0)1 55 59 28 03 
Fax: +33 (0)1 55 59 20 68 
Email: idouville@stallergenes.com 
Martine Le Gall 
Senior Medical Director 
Tel: +33 (0)1 55 59 25 56 
Fax: +33 (0)1 55 59 20 68 
Email: mlegall@stallergenes.com 
3.3 
Contract Research Organization (including Central Laboratory) 
Quintiles Inc 
4820 Emperor Boulevard 
Durham, NC 27703 
USA 
Tel: +1 919 998 2000 
3.4 
Other Providers 
Fisher Clinical Services 
Thermo Fisher Scientific 
Steinbühlweg 69 
4123 Allschwil 
Switzerland 
Tel: +41 61 485 2300 
 

CONFIDENTIAL 
STALLERGENES 
Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 9 of 123 
 
CRF Health 
Brook House - 3rd Floor 
229-243 Shepherds Bush Road 
Hammersmith 
London, W6 7AN 
United Kingdom 
Tel: +44 208 222 7460 
 
Indoor Biotechnologies Inc 
1216 Harris Street, Green Park 
Charlottesville, VA 22903 
USA 
Tel: +1 434 984 2304 
 
 
 
 

CONFIDENTIAL 
STALLERGENES 
Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 10 of 123 
 
3.5 
Protocol Summary  
Study number: 
SL75.14 
Title of the study: 
A randomized, double-blind, placebo-controlled, multi-center study of the efficacy and safety  
of STG320 sublingual tablets of house dust mite (HDM) allergen extracts in adults and 
adolescents with HDM-associated allergic rhinitis. 
Study objectives: 
To assess the efficacy and safety of 12 months of treatment with 300 IR of STG320 sublingual 
tablets compared with placebo in adults and adolescents with HDM-associated allergic rhinitis 
(AR). 
Primary objective:  
To evaluate the efficacy of STG320 sublingual tablets at a daily dosage of 300 IR when 
administered for 12 months to adults and adolescents with HDM-associated AR.  
The primary efficacy variable will be the average Total Combined Score (TCS), calculated for 
each patient as the average of the non-missing daily TCSs during the primary evaluation period 
(i.e., the last 4 weeks of treatment). The daily TCS (scale 0-15) is the sum of the subject’s daily 
Rhinitis Total Symptom Score (RTSS, scale 0-12) and daily Rescue Medication Score (RMS, 
scale 0-3). 
Secondary objectives:  
1) To assess the efficacy of STG320 sublingual tablets at the dosage of 300 IR as evaluated by 
the following secondary efficacy variables during the primary evaluation period: 
• Rhinitis Total Symptom Score (RTSS): itchy nose, sneezing, runny nose, blocked nose  
• Rescue Medication Score (RMS)  
• Adjusted Symptom Score (ASS) 
• Combined Symptom and Medication Score (CSMS) 
• Total Ocular Symptom Score (TOSS): itchy/red eyes and watery eyes  
• Rhinoconjunctivitis Total Symptom Score (RCTSS): four rhinitis symptom scores and 
two ocular symptom scores 
• Individual Rhinoconjunctivitis Symptom Scores (RSSs): itchy nose, sneezing, runny 
nose, blocked nose, itchy/red eyes and watery eyes 
• Rhinoconjunctivitis rescue medication use, overall and by type of treatment 

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STALLERGENES 
Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 11 of 123 
 
• Overall assessment of allergic rhinitis symptoms by a Visual Analogue Scale (VAS) 
(ranging 0-100) 
• Proportion of Symptom Controlled Days (PSCD), Proportion of Not-Controlled Days 
(PNCD) and Controlled Patients (CP) 
• Overall Standardized Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ(S)≥12) 
and RQLQ(S)≥12 domains  
• Health questionnaire EQ-5D-5L  
• Global Rating of Change Score (GRCS) (15-point Likert scale) 
2) Rhinoconjunctivitis symptom evaluation and rescue medication use will also be evaluated 
during the 2-week secondary evaluation periods (i.e., assessment to be started 2 weeks 
before the relevant visit at month 3, month 6 and month 9). The following endpoints will be 
assessed: 
• TCS 
• RTSS 
• RMS 
• ASS 
• CSMS 
• TOSS  
• RCTSS 
• RSSs 
• Rhinoconjunctivitis rescue medication use, overall and by type of treatment 
• Overall assessment of allergic rhinitis symptoms by a Visual Analogue Scale (VAS) 
3) To assess the effect of STG320 on other variables at the end of the treatment: 
• Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment 
Questions: Allergy Specific (WPAI + CIQ: AS) 
• Immunological markers: D. pte and D. far-specific serum IgE and IgG4 
Exploratory objectives: 
• To assess the impact of HDM exposure level on the efficacy results 
• To measure the levels of candidate serum and RNA biomarkers before and after study 
treatment to evaluate the correlation between these biomarkers and the clinical response 
to STG320 (serum and RNA banking wherever permitted by local regulations) 

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STALLERGENES 
Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 12 of 123 
 
Safety objectives: 
To assess the safety of 12 months of treatment with STG320 at the daily dose of 300 IR. The 
safety assessments include adverse events (AEs), Adverse Events of Special Interest (AESI) 
(anaphylaxis, severe laryngopharyngeal disorders, autoimmune disorders and eosinophilic 
esophagitis), vital signs and routine safety laboratory tests. 
Methodology:  
This is a randomized, double-blind, placebo-controlled, phase III study with two parallel arms 
in patients with house dust mite (HDM)-associated allergic rhinitis (AR). 
The study consists of a screening phase (1 to 6 months), a treatment phase (12 months) and a 
post-treatment follow-up phase (2 weeks).  
Study Type/Phase: III 
Inclusion Criteria 
The patient must fulfill the following inclusion criteria to be eligible for the study: 
1. Have house dust mite (HDM)-associated allergic rhinitis (AR) (with or without asthma) 
for at least 1 year based on the presence of: 
• Symptoms for 4 or more consecutive weeks in the previous year and for at least 
4 days per week during those weeks. 
• Symptoms requiring regular intake of symptomatic treatment(s). 
• Symptoms evaluated as “troublesome” by the patients or impairing their daily 
activities, leisure or sport, school or work or involving sleep disturbance. 
2. Have given signed informed consent to participate, after having been informed of the 
nature and aims of the study, in accordance with local regulation and requirements. 
3. Male or female outpatients 12 to 65 years of age.  
4. Sensitized to D. pteronyssinus (D. pte) and/or D. farinae (D. far) defined as skin prick 
test wheal diameter at least 5 mm greater than the negative control and HDM-specific 
serum IgE ≥3.5 kU/L. 
5. Willing to and capable of completing the e-diary, study questionnaires and scales. 
Exclusion Criteria 
If a patient meets any of the following criteria, s/he cannot participate in this study: 
1. A history of rhinitis, rhinoconjunctivitis or asthma to allergens other than HDM, likely 
to result in rhinitis symptoms during the baseline and primary evaluation periods.  

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STALLERGENES 
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Protocol version 7.0 – 05 October 2017 – Page 13 of 123 
 
Specifically, when the following are present: 
• documented sensitization (positive Skin Prick Test [wheal diameter at least 5 mm 
greater than the negative control] or allergen specific serum IgE >3.5kU/L) and 
history of clinically relevant symptoms to allergen(s) other than HDM 
• anticipated exposure to such allergen(s) during the baseline and primary 
evaluation periods 
For example, the following patients are to be excluded:  
- 
patients sensitized to cat or dog allergens and regularly exposed to these animals 
- 
patients sensitized to perennial allergens, such as aspergillus, cladosporium, 
alternaria, cockroach 
- 
patients sensitized to seasonal allergens such as parietaria, ragweed or mugwort, if 
these allergens are endemic in the region during the baseline and primary evaluation 
periods 
2. Any diagnosed nasal (other than HDM allergic rhinitis) or oral disease that could 
interfere with the efficacy or safety assessments, such as nasal polyposis, recurrent 
chronic rhino-sinusitis (at least 2 isolated episodes per year in the 2 previous years, each 
episode lasting more than 8 weeks) or a history of chronic oral inflammation or current 
active oral inflammation from any etiology (e.g., oral lichen planus, oral ulceration or 
oral mycosis) and/or oral wounds. 
3. Recent nasal surgery (i.e., within the previous 6 months). 
4. Partly controlled or uncontrolled asthma defined in the Global Initiative for Asthma 
2014 guidelines (GINA 2014) as the presence of daytime asthma symptoms more than 
twice/week or nocturnal symptoms/awakening or need for reliever/rescue treatment 
more than twice/week or FEV1 <80% of predicted or personal best value.  
5. Asthma therapies consistent with GINA treatment Step 3, Step 4 and Step 5 i.e., the 
preferred controller medication consists of inhaled corticosteroid (ICS) combined with 
long-acting beta (β)-2 agonist (LABA) according to GINA classification 2014 (refer to 
Appendix II for the full details of other controller options). 
Eligible asthmatic patients will be those with asthma controlled by treatment(s) 
consistent with GINA 2014 treatment Steps 1 or 2 [i.e., reliever treatment with as needed 
short acting β2-agonist with or without controller treatment consisting of low dose 
inhaled corticosteroid (i.e., <400 g of budesonide/day or equivalent dose of other 
corticosteroid) or leukotriene receptor antagonist or low dose theophylline]. 
6. Experienced a life-threatening asthma attack or an asthma exacerbation that resulted in 
Intensive Care Unit (ICU) hospitalization. 
7. Requiring continuous treatment with systemic corticosteroids for any indication. 
8. Requiring continuous treatment with β-blockers or with Monoamine Oxidase Inhibitors 

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STALLERGENES 
Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 14 of 123 
 
(MAOIs). 
9. Received an immunosuppressive treatment within 3 months prior to screening. 
10. Received allergen immunotherapy (AIT) by any route: 
- 
for house dust mites: AIT for more than 1 month within the 5 years before screening  
- 
for other allergen(s): ongoing or recently stopped (within 6 months) AIT. 
11. Any history of anaphylaxis after previous allergen immunotherapy, exposure to 
allergen(s) or of unknown cause.  
12. A history of hypersensitivity to STG320 or its excipients or contraindication to the use 
of rescue medications (i.e., antihistamines and corticosteroids). 
13. Female with positive urine pregnancy test or lactating or expecting to conceive within 
the duration of the study. 
14. Sexually active female of child-bearing potential without medically accepted 
contraceptive method: hormonal birth control (orally, injectable or by implant, for at 
least 2 months before enrollment), intrauterine device, male condom or diaphragm used 
with spermicide, monogamous relationship with a vasectomised partner. Women are 
considered not to have childbearing potential prior to menarche or at least 2 years after 
menopause or if they have had a bilateral tubal ligation or a total hysterectomy or 
bilateral oophorectomy or ovariectomy.  
15. Unable or unwilling to comply with the study protocol requirements, including those 
who anticipate significant changes in their daily environment in relation to HDM 
exposure or who are likely to travel for extended periods of time during the main 
efficacy assessment period.  
16. Patients with past or current disease(s) which, as judged by the Investigator, may affect 
the patient’s participation in or the outcome of this study. These diseases include, but 
are not limited to, cardiovascular disease, malignancy, active tuberculosis, hepatic 
disease, renal disease, hematologic disease, neurologic or psychiatric disease, severe 
autoimmune disorder, immunodeficiency or immunologic disease and endocrine 
disease. 
17. Patients with a history of eosinophilic esophagitis or with current severe or persistent 
gastroesophageal symptoms including dysphagia or chest pain. 
18. Contraindications to allergen specific immunotherapy. 
19. Patients with history of drug or alcohol abuse. 
20. Participation in any clinical study within 30 days prior to the selection visit. 
21. Possible dependency of the patient on sponsor or investigators/subinvestigators or study 
personnel. 

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Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 15 of 123 
 
Patients who fulfill all of the above inclusion criteria and none of the exclusion criteria will be 
eligible for the 5-week placebo run-in period. During this period, patients will take placebo 
tablets (single-blind) and will score their HDM-associated allergic rhinoconjunctivitis 
symptoms and record rescue medication usage on a daily basis. The last 4 weeks will be used 
as the baseline evaluation period. 
 
Inclusion Criterion at the end of the run-in/baseline evaluation period 
Only patients who fulfill the following criterion will be eligible for randomization: 
1. Patients with an average TCS 5 (on a scale of 0 to 15) over the baseline evaluation 
period.  
Study period (planned): 
 
Study Duration:   
June 2015 to June 2018 
Time Schedule: 
First patient first visit: 
June 2015  
Screening Phase: 
June 2015 to April 2016 and from 
 
September 2016 to June 2017 
Baseline Evaluation Period:  
September 2015 to May 2016 and from 
 
September 2016 to July 2017 
Randomization Period: 
October 2015 to May 2016 and from 
 
October 2016 to July 2017 
Last patient last treatment:  
June 2018 (projected) 
Last patient last visit:  
June 2018 (projected) 
Number of patients (planned):  
Approximately 3,500 patients will be screened to randomize 1,740 patients (i.e., 870 patients 
randomized in each treatment group). 
Number of centers (planned):  
Approximately 150-190 study centers in the United States of America, Canada, Europe, Israel 
and Russia are expected to participate. 
 

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Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 16 of 123 
 
Investigational product: (dose, mode of administration) 
Investigational product: STG320 - Sublingual tablet of house dust mites allergen extracts 
(Dermatophagoides pteronyssinus and Dermatophagoides farinae) 
Doses: 300 IR 
Mode of administration: STG320 is administered sublingually. 
Two treatment steps: 
 
1) Initiation Period: 
During the initiation phase, patients randomized to the active treatment group will take 1 tablet 
of 100 IR on Day 1, and 2 tablets of 100 IR to be taken simultaneously on Day 2.  
 
2) Maintenance Period: 
From the 3rd day until the end of the Treatment Phase (approximately 12 months, with a 
minimum of 10 months), patients will take 1 tablet of 300 IR per day. 
Reference product: 
Reference product: placebo tablets matching the 100 IR dose in the initiation phase [100 IR 
placebo (P100)] and placebo tablets matching the 300 IR dose during the maintenance phase 
[300 IR placebo (P300)]. 
Mode of administration: Placebo STG320 is administered sublingually. 
1) Initiation Period: 
During the initiation phase, patients randomized to the placebo treatment group will take 
1 tablet of 100 IR placebo (P100) on Day 1, and 2 tablets of 100 IR placebo (P100) to be taken 
simultaneously on Day 2.  
2) Maintenance Period: 
From the 3rd day until the end of the Treatment Phase (approximately 12 months, with a 
minimum of 10 months), patients will take 1 tablet of 300 IR placebo (P300) per day. 
Study duration per patient: 
The total duration of the study for an individual patient will be between 14 and 20 months, 
including a 1 to 6 month screening phase (including a run-in period of 5 weeks), a treatment 
phase of approximately 12 months and a post-treatment follow-up phase of 2 weeks. 
In total, 10 visits will be conducted: 2 screening visits, 1 randomization visit, 6 regular follow-
up visits (Months 1, 3, 6, 9, 11 and 12) and 1 post-treatment visit (Month 12.5). 
Evaluation periods 
The evaluation periods will be defined as follows: 

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STALLERGENES 
Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 17 of 123 
 
- 
Baseline evaluation period: last 4 weeks of the 5-week run-in period 
- 
Interim evaluation periods: 2 weeks every 3 months after randomization (i.e., Month 3, 
Month 6 and Month 9), 
- 
Primary evaluation period: 4 weeks prior to the end of the treatment period  
Criteria for evaluation: 
Primary Efficacy Variable: Total Combined Score 
The primary efficacy variable will be the average Total Combined Score (TCS). The average 
TCS is calculated for each patient as the average of the non-missing daily TCSs. 
The daily TCS (scale 0-15) is the sum of the patient’s daily Rhinitis Total Symptom Score 
(RTSS, scale 0-12) and daily Rescue Medication Score (RMS, scale 0-3).  
The RTSS is defined as the sum of the four rhinitis symptom scores (i.e., itchy nose, sneezing, 
runny nose, and blocked nose) evaluated daily by the patient. The patient assessment will 
address symptom intensity over the previous 24 hours and will be performed at the same time 
every morning, using a 4-point scale (0 = no symptoms; 1 = mild symptoms (symptom clearly 
present, but minimal awareness; easily tolerated), 2 = moderate symptoms (definite awareness 
of symptom that is bothersome but tolerable), 3 = severe symptoms (symptom that is hard to 
tolerate; causes interference with activities of daily living and/or sleeping).  
If any of the four individual rhinitis symptoms for a given day is missing, then the RTSS for 
that day will be considered missing. 
The RMS is based on the assumptions that an intranasal corticosteroid is more effective than 
an antihistamine and an oral corticosteroid is more effective than an intranasal corticosteroid, 
leading to a derived ordinal scale: 0=absent, 1=oral associated or not with topical (ocular drops) 
non-sedative H1 antihistamine (H1A), 2=intranasal corticosteroids (INS) with or without oral 
or topical (ocular drops) H1 antihistamine, 3=oral corticosteroids with or without INS or oral 
or topical (ocular drops) H1 antihistamine.  
If rescue medication data for a given day are missing, then the RMS for that day will be 
considered missing. 
Secondary Variables 
• Rhinitis Total Symptom Score (RTSS, scale 0-12).  
• Rescue Medication Score (RMS, scale 0-3). 
• Adjusted Symptom Score (ASS, scale 0-12). This score is derived from the daily RTSSs, 
after adjustment for the patient's rescue medication use. 
• Combined Symptom and Medication Score (CSMS, scale 0-6). The CSMS is derived from 
RTSS and RMS. 
 

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• Total Ocular Symptom Score (TOSS, scale 0-6). The TOSS is calculated as the sum of 
individual scores for itchy/red eyes and watery eyes.  
• Rhinoconjunctivitis Total Symptom Score (RCTSS, scale 0-18). The RCTSS is calculated 
as the sum of the four rhinitis symptom scores and the two ocular symptom scores. 
• Each of the six individual Rhinoconjunctivitis Symptom Scores (RSSs, each scored on a 
scale of 0-3): itchy nose, sneezing, runny nose, blocked nose, itchy/red eyes and watery eyes 
• Rhinoconjunctivitis rescue medication use, overall and by type of treatment 
• Visual Analogue Scale (VAS) assessing the intensity of the allergic rhinitis symptoms 
(ranging from 0 = absence of symptoms to 100 = very severe symptoms). 
• Proportion of Symptom-Controlled Days (PSCD) defined for each patient during the 
evaluation periods as: 
- 
PSCD2-0: Proportion of days with RTSS ≤2 and no rescue medication used  
• Proportion of Not-Controlled Days (PNCD) defined for each patient during the evaluation 
periods as the proportion of days with: 
- 
At least one individual rhinitis symptom score = 2 and RMS>0, or 
- 
At least two individual rhinitis symptom scores = 2 whatever the RMS, or 
- 
At least one individual rhinitis symptom score = 3 whatever the RMS 
• Controlled patients (CP) as follows: 
- 
CP752-0: Patients with at least 75% of the days with RTSS ≤2 and no rescue medication 
used (controlled for at least three quarters of the evaluation periods) 
• Overall Standardized Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ(S)≥12) 
score and RQLQ(S)≥12 domain scores 
The RQLQ(S)≥12 consists of 28 questions, divided into 7 domains (activities, sleep, non-
nose/eye symptoms, practical problems, nasal symptoms, eye symptoms and emotions), 
each question being evaluated on a 7-point Likert scale (lower being better). 
• EQ-5D-5L 
EQ-5D-5L describes the patient’s health state using 5 questions and a VAS score. 
• Global Rating of Change Score (GRCS): questionnaire assessing treatment efficacy by the 
patient compared to the baseline evaluation period (15-point Likert scale) 
Other variables 
• Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment 
Questions: Allergy Specific (WPAI + CIQ: AS) 
• Immunological markers: D. pte and D. far-specific serum IgE and IgG4 
 

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Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 19 of 123 
 
Exploratory variables 
• Candidate serum and RNA biomarkers 
Safety variables: 
Adverse events, Adverse Events of Special Interest (AESI) including anaphylaxis, severe 
laryngopharyngeal disorders, autoimmune disorders and eosinophilic esophagitis, assessment 
of routine laboratory safety tests, physical examinations and vital signs. 
Study Conduct: 
Screening Phase: 
Visit 1 (Selection Visit):  
Study patient information and informed consent form signature, demographics/ height/ weight, 
medical history, and prior and concomitant medication use, diagnosis of asthma and its 
treatment, FEV1 for all patients (i.e., whether asthmatic or not), physical examination and SPT 
for HDM and other allergens, urine pregnancy test for all female patients of childbearing 
potential. 
Testing of blood laboratory parameters and immunologic markers in patients with positive SPT. 
Sampling for serum and RNA banking wherever permitted by local regulations. 
Visit 2 (Run-in period Visit):  
Patients meeting all the selection criteria will enter a single-blind placebo run-in period of 
5 weeks (including the baseline evaluation period). This 5-week period is to be selected based 
on the patient’s history of HDM-related rhinitis symptoms and the investigator’s knowledge of 
the peak season for HDM in the area. During this 5-week period, patients will take 1 placebo 
tablet sublingually each day. Rescue medications as treatment for symptoms of allergic 
rhinoconjunctivitis will be provided with instructions for their use. Patients will score their 
rhinoconjunctivitis symptoms and rescue medication use in an electronic diary (e-diary) daily 
for 5 weeks.  
Treatment Phase: 
Visit 3 (Randomization Visit): 
This Visit is to be performed within the 7 days following the 5-week run-in period. Patients 
with an average TCS 5/15 over the baseline evaluation period will be included in the treatment 
phase of the study. FEV1 will be performed only on asthmatic patients. The patients will be 
randomized and assigned to one of the two treatment groups. Patients will be re-supplied with 
rescue medications as treatment for symptoms of allergic rhinoconjunctivitis if necessary, and 
reminded of instructions for their use. Patients will be asked to complete the RQLQ(S)≥12, EQ-
5D-5L, and WPAI + CIQ: AS questionnaires prior to the first dose administration. The first 
dose of study treatment will be administered in the doctor’s office and the patient will be 
monitored for at least 30 minutes thereafter. 
 

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Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 20 of 123 
 
Dust sampling kits will be supplied to the patients to collect a dust sample at their residence. 
The dust samples will be centrally assayed for HDM load. 
 
During the treatment phase, patients will be scheduled for visits 1 month after randomization 
(Visit 4) and every 3 months thereafter (Visits 5 to 7).  
In order to prevent missing data, patients who discontinued the treatment before the first interim 
evaluation period (i.e., before 3 months of treatment) will be asked to continue the study 
(without study treatment) until Visit 5 (i.e., until the end of the first interim evaluation period). 
Patients will be asked to score their rhinoconjunctivitis symptoms and rescue medication use 
on the e-diary during the first interim evaluation period.  
Visit 4 (Month 1): 
This Visit is to be performed 30 days ± 4 days after Visit 3. Treatment compliance and adverse 
event occurrence will be evaluated and recorded. Any potential issues or questions will be 
addressed. If necessary, additional training will be provided.  
Visits 5 to 7 (Months 3, 6, and 9):  
Visits 5, 6 and 7 are to be performed 90 days, 180 days and 270 days ± 7 days after Visit 3, 
respectively. Patients will be instructed to record their rhinoconjunctivitis symptoms and rescue 
medication use on the e-diary daily for a period of 2 weeks before each relevant visit scheduled 
after 3, 6 and 9 months of treatment. Patients will also evaluate the overall severity of the rhinitis 
symptoms on the VAS, on a weekly basis. Visits will be scheduled at the end of the 2-week 
evaluation period, or as close as possible thereafter.  
Visit 8 (Month 11): 
This Visit is to be performed 323 to 330 days after Visit 3. For patients who enter the study in 
late winter or spring (from February to June), this visit can be anticipated, but should not be 
earlier than 270 days after Visit 3. Patients will be instructed to start recording their 
rhinoconjunctivitis symptoms and rescue medication use daily using the e-diary and continue 
the daily recording for 4 weeks after this visit. This 4-week period will represent the primary 
evaluation period and should be performed one year later close to the 4 weeks of the baseline 
evaluation period. Over this 4-week period, patients will also evaluate the overall severity of 
the rhinitis symptoms on the VAS, on a weekly basis. 
Visit 9 (Month 12): 
This visit will be held at the end of the treatment period, 360 to 367 days after Visit 3. For 
patients who enter the study in late winter or spring (from February to June), this visit can be 
anticipated, but should not be earlier than 300 days after Visit 3. Patients will be questioned 
about any HDM avoidance measures implemented since the study start. RQLQ(S)≥12, EQ-5D-
5L, Global Rating of Change Questionnaire, WPAI + CIQ: AS questionnaires, blood testing 
and sampling for serum and RNA banking will be performed. FEV1 will be performed only on 
asthmatic patients. 
 
 

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Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 21 of 123 
 
Post-treatment follow-up Phase: 
Visit 10: 
The post-treatment follow-up visit will be held 14 days ± 7 days after Visit 9. 
Adverse events and use of concomitant medications will be recorded at all visits. 
 
In the context of the study, a Data Safety Monitoring Board (DSMB) will regularly review 
cumulative safety data to monitor overall study safety. 
Statistical methods:  
Determination of Sample Size 
The primary endpoint is the average TCS defined, for each patient, as the average of the non-
missing daily TCSs over the last four weeks prior to the end of the treatment period. 
As recommended by the US Food and Drug Administration (FDA), the clinical relevance of 
the efficacy results on the primary endpoint is pre-defined as follows [Nelson et al.,2017]: 
• The relative difference of the TCS versus placebo should be ‐15%, and  
• The upper bound of the 95% CI of the TCS relative difference versus placebo should be 
‐10% 
In the European study VO57.07 [Bergmann et al., 2014] conducted in 509 patients, the analysis 
of the average TCS showed a placebo mean of 3.65 and a relative mean difference of ‐17% 
between groups with a 95% CI of [‐30% ; ‐3%]. The Coefficient of Variation (CV) was of 67% 
in the placebo group and 77% in the active group. 
Based on this 95% CI (i.e., [‐30% ; ‐3%]), an expected  relative difference versus placebo of 
-20% was considered as a possible and reasonable value for the true relative difference between 
both groups. Besides, a CV of 75% was assumed to account for a possible higher variability of 
the data in this international study (i.e., North America, Europe, Israel and Russia). 
Thus, assuming a two-sided nominal level of significance of 5%, a relative difference versus 
placebo of ‐20%, a placebo mean of 3.65, and a CV of 75%, simulations were performed based 
on 5,000 samples and showed that 739 evaluable patients per treatment group were sufficient 
to achieve a power of around 80% so as to fulfill both requirements (estimated relative 
difference versus placebo ≤‐15% and upper bound of the 95% CI ≤‐10%). 
Of note, with the same assumptions and 739 evaluable patients per treatment group, the power 
of detecting a significant difference between both groups is greater than 99%.   
Assuming a drop-out rate of 15% during the study, a total of 1,740 randomized patients 
(870 patients per group) will be required to ensure that 1,478 patients are included in the 
primary efficacy analysis. The screen failure rate is estimated at 50%, leading to a planned total 
number of screened patients of 3,480. 
 

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STALLERGENES 
Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 22 of 123 
 
Determination of Study Populations for Analyses 
Analysis Sets 
• Safety Set: 
The Safety Set will include all randomized patients who received at least one dose of the 
investigational product (IP). 
All safety analyses will use the Safety Set. 
• Full Analysis Set (FAS): 
In order to be as close as possible to the Intent-To-Treat (ITT) principle, the Full Analysis Set 
will include all randomized patients who received at least one dose of the IP and have at least 
one primary efficacy evaluation during the treatment period (i.e., at least one day with a valid 
TCS during one of the evaluation periods). 
The FAS will be the primary analysis set for all efficacy analyses (primary, secondary, 
exploratory and other analyses). 
• Per Protocol Set (PPS): 
The Per Protocol Set will include all patients in the FAS who complied with the study protocol 
without any major protocol deviations and had at least 14 days with a valid TCS during the 
primary evaluation period. 
The primary efficacy analysis will be replicated in the PPS. 
The definition of protocol deviations (minor or major) will be specified in the Statistical 
Analysis Plan (SAP). The classification of the protocol deviations as minor or major will be 
performed during the Data Review Meeting (DRM) before unblinding of the data.  
 
Primary Efficacy Analysis: 
The primary variable, the average TCS, will be summarized descriptively. The square root of 
the average TCS will be analyzed in the FAS during the primary evaluation period using an 
Analysis of Covariance (ANCOVA) with treatment group as main effect and pooled center, the 
square root of the baseline average TCS, age class (adolescent, adult), gender, asthma status 
(presence/absence) and sensitization status (mono-/poly-sensitized) as covariates. 
Patients in the FAS having no efficacy evaluation during the primary period (i.e., no valid 
assessment) will not be part of the primary analysis. They will be included in the sensitivity 
analyses to assess the robustness of the primary analysis with regard to missing data. Sensitivity 
analyses will include Pattern-Mixture Models (PMMs) with reference-based imputation 
methods, a Mixed Model with Repeated Measures (MMRM) for the four evaluation periods 
and an analysis of the average TCS during the primary period using the Last Observation 
Carried Forward (LOCF) method. 

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Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 23 of 123 
 
The primary efficacy analysis will be repeated in the PPS as a supportive analysis. 
The average TCS will also be analyzed in the FAS during the primary evaluation period using 
a Wilcoxon rank-sum test (non-parametric method). This analysis will be provided as a 
supportive analysis to check the consistency of results. 
A point estimate and 95% Confidence Interval (CI) for the difference in means between the 
active treatment group and placebo will be calculated (primary analysis, sensitivity and 
supportive analyses). These results will also be expressed as relative difference (%) and relevant 
95% CI compared to the placebo group. 
Clinical Relevance of the Efficacy Results 
As recommended by the US Food and Drug Administration (FDA), the clinical relevance of 
the results on the primary endpoint is pre-defined as follows [Nelson et al.,2017]: 
• 
The relative difference of the TCS versus placebo should be -15%, and  
• 
The upper bound of the 95% confidence interval of the TCS relative difference versus 
placebo should be -10% 
Based on historical data obtained with STG320 in study VO57.07 [Bergmann et al.,2014], it is 
expected that the baseline average Total Combined Score (TCS) will be close to 7. Thus, a 
clinically meaningful effect of 15% in a given patient with an initial TCS of 7 would correspond 
to an improvement of about 1 point (15% of 7 is 1.08). More specifically, this threshold may 
be illustrated using e.g., the two following clinical cases:  
• With an initial TCS of 7 and a constant RM intake, the patient will benefit from a 
symptom improvement of 1 point corresponding to a change of one severity class in one 
symptom e.g., from “severe” to “moderate”  
• With an initial TCS of 7 and a stable symptom severity, the patient will experience a 
decrease of one step in RM intake e.g., s/he will stop the intranasal corticosteroids (from 
step 2: intranasal corticosteroids with or without antihistamine to step 1: antihistamine) 
or s/he will not take rescue medication anymore (from step 1: antihistamine to no rescue 
medication) 
This clinical benefit is expected to last all year round as HDM allergic rhinitis induces perennial 
symptoms. 
Secondary Efficacy Analyses: 
Secondary efficacy analyses will be conducted in the FAS.  
In order to control the overall type I error and to draw robust conclusions with regard to the 
key secondary endpoints, a step-down sequential closed testing procedure will be applied on 
six secondary endpoints which will be tested in the following order: 
• 
1. Rhinitis Total Symptom Score (RTSS) during the primary evaluation period 

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Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 24 of 123 
 
• 
2. Overall score of Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) at the 
end of the treatment period 
• 
3. Rhinoconjunctivitis Total Symptom Score (RCTSS) during the primary evaluation 
period 
• 
4. Blocked nose symptom score during the primary evaluation period 
• 
5. Proportion of Symptom-Controlled Days (PSCD, proportion of days with RTSS≤2 
and no rescue medication use) during the primary evaluation period 
• 
6. Rescue Medication Score (RMS) during the primary evaluation period 
The average RTSS, RMS, ASS, CSMS, TOSS, RCTSS and each of the six average individual 
RSSs (calculated as the average of the non-missing daily scores) during the primary evaluation 
period will be analyzed similarly to the average TCS using the corresponding baseline scores 
(except PPS analysis and sensitivity analyses). They will be summarized descriptively during 
each evaluation period. 
The proportions of days with rescue medication intake will be summarized descriptively, 
overall and for each rescue medication category, and analyzed using a Wilcoxon rank-sum test 
at each evaluation period. 
The PSCD2-0 and PNCD will be summarized descriptively and analyzed using a Wilcoxon rank-
sum test at the end of the treatment. 
The CP752-0 will be summarized descriptively and analyzed using a χ2 test at the end of the 
treatment. 
The average VAS score (calculated as the average of the non-missing weekly scores), the 
overall RQLQ(S)≥12 score and RQLQ(S)≥12 scores by domain will be analyzed similarly to 
the primary efficacy variable using the corresponding baseline scores (except PPS analysis and 
sensitivity analyses). 
The EQ-5D-5L health profile (5 questions) and EQ-5D-5L VAS score will be summarized 
descriptively. 
The GRCS will be analyzed by means of a Cochran Mantel-Haenszel test (row mean score 
statistic) using pooled centers as a stratification variable. The proportions of improved patients 
will be compared between groups using a ² test or Fisher exact test. 
Other analyses 
The WPAI + CIQ: AS scores will be summarized descriptively. Percentage of impairment for 
each score will be calculated and described. 
Immunological markers (D. pte- and D. far-specific serum IgE and IgG4) before and after 
treatment as well as the fold-changes (i.e., the ratio after treatment to before treatment) will be 
summarized descriptively. 

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STALLERGENES 
Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 25 of 123 
 
Exploratory analyses 
Exploratory variables will be summarized descriptively. 
Efficacy analyses will be performed by subgroup of HDM exposure level. 
Correlation between candidate serum and RNA biomarkers and clinical response will be 
investigated. 
Safety Analyses 
Safety data will be summarized in the Safety Set by treatment group using descriptive statistics: 
continuous variables by summary statistics and categorical variables by absolute and relative 
frequencies. 

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STALLERGENES 
Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 26 of 123 
 
3.6 
Flow Chart  

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STALLERGENES 
Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 27 of 123 
 
Study Assessments 
Screening Phase 
Treatment Phase 
Post Treatment 
Follow-up Phase 
Visit 1 
Selection 
Visit 2  
Run-in 
Visit 3 
Randomization 
= Visit 2 
+5 weeks 
(+0 to 7 days) 
Visit 4 
1 mo FU 
 = Visit 3 
+30 days 
(±4 days) 
Visit 5 
3 mo FU 
= Visit 3 
+90 days 
(±7 days) 
Visit 6 
6 mo FU 
= Visit 3 
+180 days 
(±7 days) 
Visit 7 
9 mo FU 
= Visit 3 
+270 days 
(±7 days)  
Visit 8 
11 mo FU 
= Visit 3 
+323 to 
330 days  
Visit 9 
12 mo FU 
= Visit 3 
+360 to 
367 days  
Visit 10 
2 wk post treat. 
= Visit 9 
+14 days 
(±7 days)  
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Patient eligibility 
X 
X 
X 
 
 
 
 
 
 
 
Medical history, demographics and Prior 
and Concomitant medication 
X 
 
 
 
 
 
 
 
 
 
HDM avoidance measures questionnaire* 
 
 
 
 
 
 
 
 
X 
 
FEV1  
X 
 
X*** 
 
 
 
 
 
X*** 
 
Physical examination (incl. vital signs)* 
X 
 
 
 
 
 
 
 
X 
 
Skin prick test (SPT) 
X 
 
 
 
 
 
 
 
 
 
Dust sampling at patient’s home 
 
 
X 
 
 
 
 
 
 
 
Safety laboratory tests* 
X 
 
 
 
 
 
 
 
X 
 
Immunological markers (IgE, IgG4) and 
serum and RNA banking* 
X 
 
 
 
 
 
 
 
X 
 
Pregnancy test (urine) 
X 
 
X 
 
 
 
 
 
 
 
Dispensing of placebo tablets for the run-
in phase 
 
X 
 
 
 
 
 
 
 
 
Randomization 
 
 
X 
 
 
 
 
 
 
 
Dispensing of investigational product 
 
 
X 
 
X 
X 
X 
 
 
 
Dispensing of rescue medication 
 
X 
X 
X 
X 
X 
X 
X 
 
 
Dispensing of epinephrine auto-injector 
 
 
X 
 
 
 
 
 
 
 

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Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 28 of 123 
 
Rhinoconjunctivitis Symptoms and 
Rescue medication use (e-diary) on a 
daily basis** 
 
X 
1+4 w 
 
 
X 
2 w† 
X 
2 w† 
X 
2 w† 
 
 
X 
4 w‡ 
 
VAS (e-diary) on a weekly basis** 
 
X 
 
 
X 
X 
X 
 
X 
 
RQLQ(S)≥12* 
 
 
X 
 
 
 
 
 
X 
 
Global Rating of Change Questionnaires* 
 
 
 
 
 
 
 
 
X 
 
WPAI + CIQ: AS and EQ-5D-5L Health 
Survey* 
 
 
X 
 
 
 
 
 
X 
 
Adverse events* and concomitant 
medication* 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
*: performed at Early Termination Visit in case of premature withdrawal; **: patients having discontinued the treatment before the first interim evaluation period 
will be asked to continue the study (without study treatment) and score their rhinoconjunctivitis symptoms and RM use until Visit 5 ***: FEV1 only repeated on 
asthmatic patients at Visit 3 and at the end of study treatment or at early termination visit; †: patients will be asked to record their rhinoconjunctivitis symptoms and 
RM use for 2 weeks before Visit 5, Visit 6 and Visit 7; ‡: patients will be asked to record their rhinoconjunctivitis symptoms and RM use during the 4 weeks from 
Visit 8 to Visit 9. 
Notes:  
Immunological markers: Serum IgE and IgG4 specific for D. pte and D. far allergens should be tested in patients with positive SPT at Visit 1. Testing should be 
repeated at Visit 9. 
Safety Laboratory Tests: Hematology: hemoglobin, hematocrit, red blood cells (RBC), platelets, white blood cells (WBC), differential count (neutrophils, 
basophils, eosinophils, monocytes, lymphocytes) and Biochemistry: glucose, creatinine, sodium, potassium, chloride, bilirubin (direct, indirect, total), ASAT 
(SGOT), ALAT (SGPT), GGT, performed at Visits 1 and 9. 
E-diary: An electronic diary (e-diary) will be dispensed to patients at Visit 2. Patients will be asked to bring back the device to the study site at each visit. Patient 
will assess rhinoconjunctivitis symptoms and rescue medication usage daily at the same time after awakening.  
Epinephrine auto-injector: At Visit 3, patients will be supplied with an epinephrine auto-injector and they will be instructed when and how to use it. At each 
subsequent visit until Visit 9, the Investigator will check if the patient has used this device. If the previously dispensed device has been lost or used for an AE that 
does not require the patient’s withdrawal from the study, a new auto-injector will be dispensed.  
Visit 8 and Visit 9 dates: For patients who enter the study in late winter or spring (from February to June), Visit 8 and Visit 9 will be anticipated when needed, but 
should not be earlier than 270 and 300 days after Visit 3, respectively.  
 

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Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 29 of 123 
 
3.7 
Study Schematic Diagram  
 
Screening Phase
Selection 
FU
Placebo
2w
2w
2w
4w
Selection
1w
300IR
Select.
Rand.
1 M
3 M
6 M
9 M
11 M
12 M
V1
V2
V3
V4   
V5
V6
V7
V8
V9 V10
Placebo 5 weeks
Treatment 12 months
Run-In period
Treatment Phase
Patient Selection
Baseline 
evaluation
4w
Prim Eval Period

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3.8 
List of Abbreviations  
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
AIT 
Allergen Immunotherapy 
ALAT (SGPT) 
Alanine Aminotransferase 
ANCOVA 
Analysis of Covariance 
AR 
Allergic Rhinitis 
ASAT (SGOT) 
Aspartate Aminotransferase 
ASS 
Adjusted Symptom Score 
ATC 
Anatomical Therapeutic Chemical 
ATS/ERS 
American Thoracic Society/European Respiratory Society 
CI 
Confidence Interval 
CP 
Controlled Patient 
CPMP  
Committee for Proprietary Medicinal Products 
CRO 
Contract Research Organization 
CSMS 
Combined Score and Medication Score 
CV 
Coefficient of Variation 
D. far 
Dermatophagoides farinae 
D. pte 
Dermatophagoides pteronyssinus 
DRM 
Data Review Meeting 
DSMB 
Data Safety Monitoring Board 
e-CRF 
Electronic Case Report Form 
e-diary 
Electronic Diary 
EGD 
Esophagogastroduodenoscopy 
EoE 
Eosinophilic Esophagitis 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
FEV1 
Forced Expiratory Volume in one second 
GCP 
Good Clinical Practice 

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GGT 
Gamma Glutamyl Transferase 
GINA 
Global Initiative for Asthma 
GP 
General Practitioner 
GRCS 
Global Rating of Change Score 
HDM 
House Dust Mites 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
ICS 
Inhaled Corticosteroid 
ICU 
Intensive Care Unit 
Ig 
Immunoglobulin 
IP 
Investigational Product 
IR 
Index of Reactivity 
ITT 
Intention-To-Treat 
IVRS/IWRS 
Interactive Voice/Web Response System  
LABA 
Long-Acting Beta(ß)2-Agonist 
LS 
Least Square 
LOCF 
Last Observation Carried Forward 
MAOI 
Monoamine Oxidase Inhibitor 
MedDRA 
Medical Dictionary for Regulatory Activities 
µg 
Microgram 
MMRM 
Mixed Model with Repeated Measures 
PMM 
Pattern Mixture Model 
PNCD 
Proportion of Not-Controlled Days 
PPS 
Per Protocol Set 
PSCD 
Proportion of Symptom-Controlled Day 
PT 
Preferred Term 
RBC 
Red Blood Cells 
RCTSS 
Rhinoconjunctivitis Total Symptom Score 
RM 
Rescue Medication 
RMS 
Rescue Medication Score 

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RNA 
Ribonucleic Acid 
RQLQ(S)≥12 
Standardized Rhinoconjunctivitis Quality of Life Questionnaire for 
Subjects ≥12 Years of Age 
RSS 
Rhinoconjunctivitis Symptom Score 
RTSS 
Rhinitis Total Symptom Score 
SABA 
Short-Acting Beta(ß)2-Agonist 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SCIT 
Subcutaneous Immunotherapy 
SD 
Standard Deviation 
SLIT 
Sublingual Immunotherapy 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SPT 
Skin Prick Test 
TCS 
Total Combined Score 
TEAE 
Treatment-Emergent Adverse Event 
TMF 
Trial Master File 
TOSS 
Total Ocular Symptom Score 
USA 
United States of America 
VAS 
Visual Analog Scale 
WBC 
White Blood Cell 
WPAI + CIQ: AS 
Work Productivity and Activity Impairment Questionnaire plus 
Classroom Impairment Questions: Allergy Specific 
 

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4. BACKGROUND INFORMATION 
4.1 
Scientific Background 
Allergy is one of the most common diseases in the world. Untreated or inadequately treated Allergy 
Rhinitis (AR) can cause sleep disturbance, daytime fatigue and somnolence [Leger et al.,2006] as 
well as depressed mood, irritability, behavioral problems [Meltzer,2001; Hankin et al.,2010] or 
impaired social functioning [Meltzer,2001]. There are also significant indirect costs associated with 
this condition including absenteeism from work or school and decreased productivity when at work 
[Blaiss,2007]. 
Using a conservative estimate, AR occurs in over 500 million people around the world [Bousquet 
et al.,2008]. Sneezing, congestion, clear rhinorrhoea and nasal pruritus are the key symptoms 
characterizing the disease. It is estimated that AR affects up to 60 million people in the United 
States (US), and its prevalence is increasing. Despite a reported prevalence ranging from 10 to 30% 
in adults and up to 40% in children [Warner et al.,2006], AR is frequently under-recognized, 
misdiagnosed, and ineffectively treated [Meltzer et al.,2012]. The prevalence peaks in childhood 
and adolescence and decreases in the elderly. It has been established that the patholophysiogical 
mechanisms of rhinitis contribute to the development of asthma in a large number of patients 
[Rowe-Jones,1997]. The risk for AR patients in developing asthma is three times higher than 
among the general population (10% versus 3.6%), confirming the hypothesis that rhinitis is often 
the first step in the natural history of asthma [Rachelefsky,1999]. 
Allergens such as cat and dog dander, cockroach and house dust mite are associated with perennial 
rhinitis while allergies to grass, weeds, and tree pollens are characterized by seasonal rhinitis 
symptoms.  
Mites consist of a large taxonomic subclass, named Acarina. Among them, Dermatophagoides 
pteronyssinus and Dermatophagoides farinae are the main species involved in AR in Europe and 
North America [Platts-Mills and Weck,1989].The most important habitat for Dermatophagoides 
mites is in bedding (mattress and bed clothes), where the food is supplied as human scales and 
where the temperature is ideal. Overstuffed furniture, carpets and unlaundered clothing are also 
important habitats [Mosbech,1985]. 
Current treatment options are allergen avoidance, symptomatic therapy, and specific 
immunotherapy. Allergen avoidance is often virtually impossible. Symptomatic treatments include 
antihistamines, intranasal corticosteroids, chromones and leukotriene modifiers. These treatments 
provide temporary relief from allergy symptoms but are not effective in all patients and do not have 
a disease-modifying effect [Nathan,2007]. In addition, pharmacotherapy may be associated with 
significant side effects such as sedative and anticholinergic effects for antihistamines, dryness and 
epistaxis for intranasal corticosteroids and neuropsychiatric reactions for leukotriene modifiers 
[Byrne et al.,2012; Fernández-Caldas,2013]. 
Allergen immunotherapy is the only therapy available that acts on the main cause of the allergic 
reaction by modifying or down-regulating the immune response to allergens. 

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Allergen-specific subcutaneous immunotherapy (SCIT) is the oldest route of administration used 
to desensitize patients and is still a recommended therapeutic option for subjects with AR [Cox et 
al.,2011]. However, despite its long use history, only 5% of the US population with AR, asthma, 
or both benefit from this treatment [Cox,2008]. Its use is limited by the risk of near-fatal or fatal 
anaphylaxis as well as the discomfort and inconvenience of frequent injections [Bernstein et 
al.,2004; Amin et al.,2006; Nelson,2007]. 
Allergen-specific sublingual immunotherapy (SLIT) is an alternative to SCIT with similar efficacy 
[Canonica et al.,2009; Cox et al.,2011; Canonica et al.,2014]. The favorable safety profile of SLIT 
and its convenience are likely factors for the substantial and growing increase in its use 
[Nelson,2007; Cox and Jacobsen,2009]. The Allergic Rhinitis and its Impact on Asthma (ARIA) 
2008 Update [Bousquet et al.,2008] and its 2010 revision [Brozek et al.,2010] provide recent expert 
guidance in this therapeutic area. These reviews indicate that SLIT may be used for the treatment 
of subjects with mite allergy. In addition, recent Cochrane reviews [Radulovic et al.,2010; Lin et 
al.,2013] confirm that SLIT is a viable alternative to SCIT with a significantly lower risk profile 
and little difference in overall efficacy. 
STALLERGENES is developing a sublingual immunotherapy (SLIT) tablet of HDM allergen 
extracts (STG320 HDM sublingual tablets) containing standardized allergen extracts from both 
Dermatophagoides pteronyssinus (D. pte) and Dermatophagoides farinae (D. far). The efficacy 
and safety of STG320 tablets at daily doses of 300IR and 500IR have been demonstrated in adults 
and adolescents with AR.  
 
The purpose of the present study is to confirm the efficacy and safety of STG320 sublingual tablets 
at the daily dose of 300IR in adults and adolescents with HDM-associated AR. 
4.2 
Investigational Product 
The Investigational Product (IP) is STG320 HDM sublingual tablet containing extracts of 
Dermatophagoides pteronyssinus (D. pte) and Dermatophagoides farinae (D. far) [active 
substance]. 
STG320 is obtained by extracting, purifiying, freeze-drying and sieving of the genuine allergen 
sources. These drug substances are obtained separately from both D. pte and D. far and then mixed 
together in a 50:50 immunological activity ratio (expressed in IR). The mixture is processed by 
direct compression to obtain the sublingual tablets of HDM allergen extracts. 
The allergen preparation potency unit used by STALLERGENES is defined as Index of Reactivity 
or "IR" [Hrabina et al.,2007; Wahn et al.,2009]. The titer of an allergen extract corresponds to 100 
IR/mL when, in a skin prick test performed with the STALLERGENES skin prick test device (i.e., 
the Stallerpoint®), in 30 subjects sensitized to the allergen in question, the extract produces a wheal 
measuring 7 mm in diameter (geometric mean). Skin reactivity in these subjects is simultaneously 
demonstrated by a positive response to a prick-test with 9% codeine phosphate or 10 mg/mL 
histamine dihydrochloride. 

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The IP is further described in Section 8.1 “Study Investigational Products” and in the Investigator’s 
Brochure (Version 10 dated 11 June 2014). 
4.3 
Non-Clinical Studies 
Detailed information on the non-clinical experience with STG320 can be found in the 
Investigator’s Brochure. A summary of this information is provided below. 
4.3.1 
Pharmacology 
Published animal studies demonstrate the alleviation or prevention of type-I hypersensitivity 
reactions upon allergen re-challenge of sensitized animals following repeated administration of 
allergens. To strengthen these experimental results and to extend them to the mite extracts 
manufactured at STALLERGENES, freeze-dried extracts of D. pte/D. far were tested in a murine 
model of chronic HDM-induced asthma. The study results demonstrated that the freeze-dried 
extracts of D. pte/D. far are efficacious as a sublingual immunotherapy vaccine in the murine 
model [Study DS/ST/09/234 – refer to the STG320 Investigator Brochure]. 
4.3.2 
Pharmacokinetics 
No animal pharmacokinetics data have been generated with the mite extracts. The lack of relevance 
of pharmacokinetic data can be explained as follows: 
- 
By the sublingual-swallow route, the proteolytic digestion in the gastrointestinal tract is 
assumed to be the predominant fate of mite extracts, as they consist mostly of proteins and 
glycoproteins. The extent of systemic absorption of the mite extracts is unknown but is 
assumed to be negligible. 
- 
Based on our knowledge of the mechanism of action of SLIT, the pharmacological effect of 
the mite extracts included in the tablets is not related to plasma allergen levels but to the 
capture of allergens by dendritic cells within the sublingual mucosa and transport to draining 
lymph nodes. 
4.3.3 
Toxicology  
Repeat-dose oral (gavage) and subcutaneous administration of freeze-dried extracts of D. pte and 
D. far in rats were well tolerated. No evidence of treatment-related toxicity was noted after doses 
of up to 2,500 IR/kg/day administered for 26 weeks. 
4.4 
Clinical Development 
STALLERGENES is conducting a multinational clinical development program with STG320 for 
the treatment of HDM-associated AR. To date, seven clinical studies evaluating the sublingual 
tablet for this indication have been conducted: five by STALLERGENES and two by Shionogi & 
Co., Ltd.  

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4.4.1 
STALLERGENES - Sponsored Studies 
Studies in Adults 
• Phase I Study VO36.04F in adults [aged 18 to 50 years] 
This phase I, randomized, double-blind, placebo-controlled single-center study in 31 adults (18-50 
years old) with perennial AR caused by sensitization to house-dust mites assessed the safety and 
tolerability of four STG320 dose regimens with 10 days of administration: two incremental dose 
regimens up to 500 IR and constant dose regimens at 500 IR or 300 IR. 
STG320 was generally well tolerated at doses up to 500 IR. It was concluded that a dose escalation 
period could reduce the incidence and severity of application site reactions. 
• Phase II/III Study VO57.07 in adults [aged 18 to 50 years] 
This natural field, randomized, double-blind, placebo-controlled, multi-center study was conducted 
in adults with HDM-related AR to assess the efficacy and safety of STG320 at the 300 IR and 500 
IR doses. The study included a 12 month treatment period (Year 1) and a 12 month treatment free 
follow-up period (Year 2). 509 patients were enrolled, 427 completed the first year, and 397 
completed the second year. Statistically significant differences between the 300 IR group and the 
500 IR group compared to placebo on the primary endpoint were demonstrated during the Year 1 
primary evaluation period. The difference between the two active treatment groups was not 
statistically significant. Efficacy was maintained during the treatment-free follow-up year (Year 
2). The overall safety profile of the two doses was favorable with no appreciable differences in 
tolerability between them. No anaphylaxis or autoimmune disorders were reported. No unexpected 
risk was identified [Bergmann et al.,2014]. 
• Phase II Study VO67.10 Environmental Exposure Chamber in adults [aged 18 to 55 
years] 
This randomized, double-blind, placebo-controlled, multi-center, dose ranging study, performed in 
an Environmental Exposure Chamber, was conducted in Canada in 355 adults with HDM-related 
AR. It evaluated the efficacy, safety and tolerability of 100 IR, 300 IR and 500 IR administered 
once daily for 6 months. A dose effect was observed on the primary efficacy endpoint. The 
reduction in symptom severity was limited with the 100 IR dose (19.8%), but larger with the 300 IR 
(28.8%) and the 500 IR doses (33.2%). The overall safety profile was consistent with that observed 
in previous studies. 
Studies in Children and Adolescents 
• Phase III Study VO64.08 in children and adolescents [aged 5 to 17 years] 
This natural field, randomized, double-blind, placebo-controlled, multi-center study was conducted 
in Europe in children and adolescents with HDM-associated AR to assess the safety and efficacy 
of STG320 at the 300 IR dose. Overall, 471 patients (241 in the 300 IR group and 230 in the 
placebo group) were randomized.  
This study was initially designed to include 24 months of treatment (i.e., 12 months of treatment 
in Year 1 and 6 months of treatment in each of Year 2 and Year 3) and 22 months of treatment-free 

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follow-up. While all patients met the study inclusion criteria (i.e., clinical history, positive prick 
skin test, positive HDM-specific serum IgE, and the presence of symptoms at baseline), they 
reported minimal symptoms post-randomization. Therefore, the efficacy of the investigational 
product could not be assessed. Accordingly, the Data Safety Monitoring Board of independent 
external experts recommended the early termination of the study “for futility”, before the patients 
started the second treatment period. These findings underscore the need for additional diagnostic 
criteria in future pediatric studies to ensure the enrollment of patients with HDM-driven AR. 
The safety profile of the 300 IR dose of STG320 in children and adolescents was consistent with 
that observed in previous studies in adults. Patients with asthma showed a similar safety profile as 
those without asthma. 
• Phase I Study VO73.13 in adolescents [aged 12 to 17 years] 
This randomized, double-blind, placebo-controlled, single-center study (Canada) assessed the 
safety and tolerability of 3 dose-regimens, 500 IR, 1000 IR and 1500 IR of STG320 sublingual 
tablets evaluated over a treatment period of 10 consecutive days in 37 adolescents with HDM-
associated AR. The three doses were well tolerated. The overall safety profile was consistent with 
that observed in previous studies with the 300 IR and 500 IR doses in adults, adolescents and 
children. 
4.4.2 
Studies Conducted by STALLERGENES Partner Company (Shionogi and Co., Ltd) 
• Phase I Study 1109D1711 in adults [aged 20 to 39 years] 
This randomized, double-blind, placebo-controlled, single-center study (Japan) assessed the safety 
of three doses (100 IR, 300 IR and 500 IR) of STG320 versus placebo in 36 adults with HDM-
associated perennial allergic rhinitis treated for 14 days. All doses were well tolerated. 
• Phase II/III Study 1207D1731 in adolescents and adults [aged 12 to 64 years] 
This natural field, randomized, double-blind, placebo-controlled, multi-center (Japan) study was 
conducted in adolescents and adults with HDM-related AR to assess the efficacy and safety of 
STG320 at the doses of 300 IR and 500 IR over a 12 month treatment period.  
968 patients (181 adolescents) were enrolled and 853 patients (159 adolescents) completed the 12-
month treatment phase. Statistically significant differences between both the 500 IR group and the 
300 IR group compared to placebo on the primary endpoint were demonstrated. A subgroup 
analysis in adolescents (age category: ≥12 to <18) showed statistically significant differences 
between both 500 IR and 300 IR compared to placebo on the primary efficacy endpoint.  
The safety profile was consistent with that observed in studies conducted in Europe and Canada.  
4.5 
Study Rationale 
Up to 09 June 2015, 1,571 patients (1,182 adults, 261 adolescents and 128 children) with HDM-
associated AR have been exposed to STG320 (doses from 100 IR to 1500 IR) in the rhinitis 
development program.  

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Overall, the results of the natural field and environmental exposure chamber studies demonstrate 
that the 500 IR and 300 IR doses of STG320 are similarly efficacious in treating adults with HDM-
induced AR. 
A favorable safety and tolerability profile has been observed for all tested doses. No deaths were 
reported. There were no reports of anaphylactic shock, anaphylaxis, or Intensive Care Unit (ICU) 
admission and no use of epinephrine. The most frequent adverse reactions were application site 
reactions such as oral pruritus and throat irritation. Most were of mild or moderate intensity and 
were mainly reported during the first weeks of treatment. Drug-related adverse events (AEs) 
leading to premature discontinuation were more frequent in active treatment groups compared to 
placebo. 
Based on the totality of the efficacy and safety data, the development of the 300 IR dose of STG320 
will be pursued.  
This randomized, double-blind, placebo-controlled study is designed to confirm the efficacy and 
safety of the 300 IR dose of STG320 in adolescents and adults (12-65 years of age) with HDM-
associated AR. Treatment will be administered daily for 12 months. Patients will be selected on 
the basis of a clinical history consistent with HDM-associated AR, positive skin prick test and the 
presence of HDM-specific serum IgE. To better enable the identification of patients whose 
symptoms are driven by HDM allergy, evidence of HDM-exposure has been added as an inclusion 
criterion.  
4.6 
Good Clinical Practices Statement  
The present study will be conducted in accordance with: 
- 
This protocol 
- 
International Conference on Harmonization: ICH E6 Note for Guidance on Good Clinical 
Practice [CPMP/ICH/135/95] 
- 
International Conference on Harmonization: ICH E11 Clinical Investigation of Medicinal 
Products in the Paediatric Population [CPMP/ICH/2711/99] 
- 
Code of Federal Regulations on Good Clinical Practice, Title 21 – Parts 50, 54, 56, 312, 314) 
and  
- 
The principles that have their origin in the Declaration of Helsinki 
- 
Applicable local laws and regulations 
 

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5. STUDY OBJECTIVES AND PURPOSE 
This study is designed to assess the efficacy and safety of 12 months of treatment with 300 IR of 
STG320 sublingual tablets compared with placebo in adults and adolescents with house dust mite 
(HDM)-associated allergic rhinitis (AR). 
5.1 
Primary Objective  
The primary objective of this study is to evaluate the efficacy of STG320 sublingual tablets at a 
daily dosage of 300 IR when administered for 12 months to adults and adolescents with HDM-
associated AR.  
The primary efficacy variable will be the average Total Combined Score (TCS), calculated for each 
patient as the average of the non-missing daily TCSs during the primary evaluation period (i.e., the 
last 4 weeks of treatment). The daily TCS (scale 0-15) is the sum of the patient’s daily Rhinitis 
Total Symptom Score (RTSS, scale 0-12) and daily Rescue Medication Score (RMS, scale 0-3). 
5.2 
Secondary Objectives 
5.2.1 
Efficacy of STG320 during the Primary Evaluation Period (Month 12) 
To assess the efficacy of STG320 sublingual tablets at the dosage of 300 IR as evaluated by the 
following secondary efficacy variables during the primary evaluation period 
• Rhinitis Total Symptom Score (RTSS).  
• Rescue Medication Score (RMS) 
• Adjusted Symptom Score (ASS, scale 0-12). This score is derived from the daily RTSSs, after 
adjustment for the patient's rescue medication use. 
• Combined Symptom and Medication Score (CSMS, scale 0-6). The CSMS is derived from 
RTSS and RMS. 
• Total Ocular Symptom Score (TOSS, scale 0-6). The TOSS is calculated as the sum of 
individual scores for itchy/red eyes and watery eyes.  
• Rhinoconjunctivitis Total Symptom Score (RCTSS). The RCTSS is calculated as the sum of 
the four rhinitis symptom scores and the two ocular symptom scores. 
• Each of the six individual Rhinoconjunctivitis Symptom Scores (RSSs, each scored on a scale 
of 0-3): itchy nose, sneezing, runny nose, blocked nose, itchy/red eyes and watery eyes. 
• Rhinoconjunctivitis rescue medication use, overall and by type of treatment.  
• Visual Analogue Scale (VAS) assessing the intensity of the allergic rhinitis symptoms (ranging 
from 0 = absence of symptoms to 100 = very severe symptoms). 

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• Proportion of Symptom-controlled Days (PSCD), Proportion of Not-Controlled Days (PNCD) 
and Controlled Patients (CP) 
• Overall Standardized Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ(S)≥12) and 
RQLQ(S)≥12 domains.  
• Health questionnaire EQ-5D-5L  
• Global Rating of Change Score (GRCS) (15-point Likert scale) 
5.2.2 
Efficacy of STG320 during the Secondary Evaluation Periods (Months 3, 6 and 9) 
Rhinoconjunctivitis symptom evaluation and rescue medication use will also be evaluated during 
the 2-week secondary evaluation periods (i.e., assessment to be started 2 weeks before the relevant 
visits at Month 3, Month 6 and Month 9). The following endpoints will be assessed: 
• TCS 
• RTSS 
• RMS 
• ASS 
• CSMS 
• TOSS  
• RCTSS 
• RSSs 
• Rhinoconjunctivitis rescue medication use, overall and by type of treatment 
• Overall assessment of allergic rhinitis symptoms by a Visual Analogue Scale (VAS) 
5.2.3 
Effect of STG320 at the End of the Treatment 
To assess the effect of STG320 compared to placebo on other variables at the end of the treatment 
• Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment 
Questions: Allergy Specific (WPAI + CIQ: AS) 
• Immunological markers: D. pte- and D. far-specific serum IgE and IgG4 
5.3 
Exploratory Objectives  
To assess the impact of HDM exposure level on the efficacy results. 
To measure the levels of candidate serum and RNA biomarkers before and after study treatment to 
evaluate the correlation between these biomarkers and the clinical response to STG320. 

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5.4 
Safety Objectives  
To assess the safety of 12 months of treatment with STG320 at the daily dose of 300 IR. The safety 
assessments include adverse events (AEs), Adverse Events of Special Interest (AESI) (anaphylaxis, 
severe laryngopharyngeal disorders, autoimmune disorders and eosinophilic esophagitis), vital 
signs and routine safety laboratory tests. 
6. STUDY DESIGN 
6.1 
Type/Design 
This is a randomized, double-blind, placebo-controlled, phase III study with two parallel arms to 
be conducted in patients with HDM-associated allergic rhinitis consisting of a 1 to 6 month 
screening phase (including a run-in period of 5 weeks), a treatment phase of approximately 
12 months and post-treatment follow-up phase of 2 weeks. 
Male or female patients aged 12 to 65 years (inclusive) with HDM-related allergic rhinitis for at 
least one year requiring regular intake of symptomatic treatments will be randomized to one of two 
treatment groups. 
In addition to the patients’ history, the diagnosis will be confirmed by the positivity of Skin Prick 
Test (SPT) with HDM allergen and the presence of HDM-specific IgE. An assessment of the HDM 
load in the patient’s residence collected dust will also be performed before randomization.  
Overall, each patient is to attend 10 visits. Visits 1 will involve screening for eligibility. Visit 2 
will start the run-in phase. Visit 3 to Visit 9 will comprise the treatment phase and Visit 10 will 
involve the post-treatment follow-up phase. 
Screening Phase (Visit 1 and Visit 2) 
• Selection Visit (Visit 1) 
At Visit 1, the first screen will be performed to assess patient’s eligibility for the study.  
• Run-in period (Visit 2) 
At Visit 2, patients still meeting all of the inclusion and none of the exclusion criteria, except the 
criteria assessed on the baseline TCS, will enter a single-blind placebo run-in period of 5 weeks. 
The selected period will be individualized based on the patient’s history of previous HDM-related 
rhinitis symptoms (i.e., the period during which the patient is reported to be the most symptomatic). 
During this period, patients will take 1 placebo tablet sublingually each day. Rescue medications 
as treatment for symptoms of allergic rhinitis to HDM will be provided with instructions for their 
use. Patients will record their rhinoconjunctivitis symptoms and rescue medication use in an 
electronic diary (e-diary) daily and will assess the intensity of the AR symptoms on a Visual 
Analogue Scale (VAS) weekly for 5 weeks. 
An average TCS 5 (scale 0 to 15) during the four last weeks of the run-in period will serve as an 
ultimate inclusion criterion for the selection of patients for randomization. 

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For those patients who meet this inclusion criterion, these 4 weeks will also serve as the baseline 
evaluation period. 
Treatment Phase (Visits 3-9) 
At Visit 3, eligible patients will be randomized 1:1 to either active treatment or placebo. The first 
dose of study treatment will be administered at the study site and the patient will be monitored for 
at least 30 minutes thereafter. Subsequent doses are to be taken at home, daily, at the same time in 
the morning, for a period of approximately 12 months with a minimum of 10 months. Interim 
efficacy assessments will be performed at Month 3, 6, and 9 after randomization (Visits 5-7). The 
primary efficacy evaluation period (from Visit 8 to Visit 9) will be during the same 4 weeks of the 
year as those of the baseline evaluation period or as close as possible to these weeks. 
A limited shortening of the 12-month treatment phase should be considered when necessary in 
patients who enter the study in late winter or spring (from February to June), in order to adapt and 
to avoid possibly less favorable conditions for mite exposure in late winter/spring and to prevent 
confounding symptoms due to pollens in case of early pollination in the following year. The 
purpose of this relative flexibility in planning the treatment duration for those patients is to ensure 
the primary efficacy evaluation is performed when conditions are optimal for such evaluation. 
Post-Treatment Follow-Up Phase (Visit 10) 
Patients will attend a follow-up visit, 2 weeks after the administration of their last IP dose. 
6.2 
Number of Patients and Study Sites 
It is planned to screen approximately 3,500 patients in order to randomize 1,740 (i.e., 870 patients 
randomized in each treatment group). Approximately 150-190 centers from the United States of 
America (USA), Canada, Europe, Israel and Russia are expected to participate.  
6.3 
Measures to Minimize Bias 
6.3.1 
Randomization 
All patients will receive a screening number via an Interactive Web/Voice Response System 
(IVRS/IWRS).  
A computer-generated randomization list with stratification by study site will be prepared by a 
different statistician from the biostatisticians in charge of the study data analyses.  
A copy of the complete randomization list will be provided to the IVRS/IWRS responsible person 
and to the company contracted to package the investigational product.  
6.3.2 
Blinding 
During the run-in period, patients will receive placebo tablets. All efforts are to be taken by study 
site personnel to not reveal to the patients the placebo nature of the tablets and maintain the single 
blind. 

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After randomization and throughout the study treatment and post-treatment phases, the study is 
designed as a double-blind study. Therefore, during the treatment phase, patients, investigators and 
site staff, and all study staff will be blinded as to treatment group assignment. The investigational 
products (i.e., active and placebo tablets) will be the same with respect to appearance and taste. 
Labeling and packaging will also be identical. 
Under normal circumstances, the treatment blind must be maintained. In the case of medical 
emergency in which knowledge of the treatment allocation is considered by the Investigator as 
critical in managing the patient’s condition, the Investigator will utilize IVRS/IWRS and use the 
unblinding functions. In case of technical issues with the IVRS/IWRS system, the Investigator will 
contact either the responsible person from the Pharmacovigilance department or the primary CRO 
designee to unblind the patient.  
If the blind is broken, the date, the reason for breaking the blind, and the person doing so is to be 
recorded on the source document, and in the appropriate e-CRF page, and STALLERGENES or 
its representative must be notified immediately. 
6.4 
Study Duration 
The total duration of the study for an individual patient will be between 14 and 20 months, 
including a 1- to 6-month screening phase (including a run-in period of 5 weeks), a treatment phase 
of 12 months and a post-treatment follow-up phase of 2 weeks. 
In total, 10 visits will be conducted: 2 screening visits, 1 randomization visit, 6 regular follow-up 
visits (Months 1, 3, 6, 9, 11 and 12) and 1 post-treatment visit (Month 12.5). 
Evaluation periods 
The evaluation periods will be defined as follows: 
- 
Baseline evaluation period: last 4 weeks of the 5-week run-in period  
- 
Interim evaluation periods: 2 weeks every 3 months after randomization (i.e., Month 3, Month 
6 and Month 9) 
- 
Primary evaluation period: 4 weeks prior to the end of the treatment period 
7. SELECTION AND WITHDRAWAL OF PATIENTS 
Before any study procedures are initiated for any patient in this study, approval of the Institutional 
Review Board (IRB) or Ethics Committee will have to be obtained, and written informed consent, 
including signing of the informed consent/assent form, must be documented. 
7.1 
Inclusion Criteria 
The patient must fulfill the following inclusion criteria to be eligible for the study 
1. Have house dust mite (HDM)-associated allergic rhinitis (AR) (with or without asthma) for 
at least 1 year based on the presence of:  

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• Symptoms for 4 or more consecutive weeks in the previous year and for at least 
4 days per week during those weeks. 
• Symptoms requiring regular intake of symptomatic treatment(s). 
• Symptoms evaluated as “troublesome” by the patients or impairing their daily 
activities, leisure or sport, school or work or involving sleep disturbance. 
2. Have given signed informed consent to participate, after having been informed of the nature 
and aims of the study, in accordance with local regulation and requirements. 
3. Male or female outpatients 12 to 65 years of age.  
4. Sensitized to D. pteronyssinus (D. pte) and/or D. farinae (D. far) defined as skin prick test 
wheal diameter at least 5 mm greater than the negative control and HDM-specific serum 
IgE ≥3.5 kU/L. 
5. Willing to and capable of completing the e-diary, study questionnaires and scales. 
7.2 
Exclusion Criteria  
If a patient meets any of the following criteria, s/he cannot participate in this study: 
1. A history of rhinitis, rhino-conjunctivitis or asthma to allergens other than HDM, likely to 
result in rhinitis symptoms during the baseline and primary evaluation periods. 
Specifically, when the following are present: 
• documented sensitization (positive Skin Prick Test [wheal diameter at least 5 mm 
greater than the negative control] or allergen specific serum IgE >3.5kU/L) and 
history of clinically relevant symptoms to allergen(s) other than HDM 
• anticipated exposure to such allergen(s) during the baseline and primary evaluation 
periods 
For example, the following patients are to be excluded:  
- 
patients sensitized to cat or dog allergens and regularly exposed to these animals 
- 
patients sensitized to perennial allergens, such as aspergillus, cladosporium, alternaria, 
cockroach 
- 
patients sensitized to seasonal allergens such as parietaria, ragweed or mugwort, if these 
allergens are endemic in the region during the baseline and primary evaluation periods. 
2. Any diagnosed nasal (other than HDM allergic rhinitis) or oral disease that could interfere 
with the efficacy or safety assessments, such as nasal polyposis, recurrent chronic rhino-
sinusitis (at least 2 isolated episodes per year in the 2 previous years, each episode lasting 
more than 8 weeks) or a history of chronic oral inflammation or current active oral 
inflammation from any etiology (e.g., oral lichen planus, oral ulceration or oral mycosis) 
and/or oral wounds. 
3. Recent nasal surgery (i.e., within the previous 6 months). 

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4. Partly controlled or uncontrolled asthma defined in the Global Initiative for Asthma 2014 
guidelines (GINA 2014) as the presence of daytime asthma symptoms more than 
twice/week or nocturnal symptoms/awakening or need for reliever/rescue treatment more 
than twice/week or FEV1 <80% of predicted or personal best value.  
5. Asthma therapies consistent with GINA treatment Step 3, Step 4 and Step 5 i.e., the 
preferred controller medication consists of inhaled corticosteroid (ICS) combined with 
long-acting beta (β)-2 agonist (LABA) according to GINA classification 2014 (refer to 
Appendix II for the full details of other controller options). 
Eligible asthmatic patients will be those with asthma, controlled by treatment(s) consistent 
with GINA 2014 treatment Steps 1 or 2 [i.e., reliever treatment with as needed short acting 
β2-agonist with or without controller treatment consisting of low dose inhaled 
corticosteroid (i.e., 400 g of budesonide/day or equivalent dose of other corticosteroid) 
or leukotriene receptor antagonist or low dose theophylline].  
6. Experienced a life-threatening asthma attack or an asthma exacerbation that resulted in 
Intensive Care Unit (ICU) hospitalization. 
7. Requiring continuous treatment with systemic corticosteroids for any indication. 
8. Requiring continuous treatment with β-blockers or with Monoamine Oxidase Inhibitors 
(MAOIs). 
9. Received an immunosuppressive treatment within 3 months prior to screening. 
10. Received allergen immunotherapy (AIT) by any route: 
- 
for house dust mites: AIT for more than 1 month within the 5 years before screening  
- 
for other allergen(s): ongoing or recently stopped (within 6 months) AIT. 
11. Any history of anaphylaxis after previous allergen immunotherapy, exposure to allergen(s) 
or of unknown cause.  
12. A history of hypersensitivity to STG320 or its excipients or contraindication to the use of 
rescue medications (i.e., antihistamines and corticosteroids). 
13. Female with positive urine pregnancy test or lactating or expecting to conceive within the 
duration of the study. 
14. Sexually active female of child-bearing potential without medically accepted contraceptive 
method: hormonal birth control (orally, injectable or by implant, for at least 2 months before 
enrollment), intrauterine device, male condom or diaphragm used with spermicide, 
monogamous relationship with a vasectomised partner. Women are considered not to have 
childbearing potential prior to menarche or at least 2 years after menopause or if they have 
had a bilateral tubal ligation or a total hysterectomy or bilateral oophorectomy or 
ovariectomy.  
15. Unable or unwilling to comply with the study protocol requirements, including those who 
anticipate significant changes in their daily environment in relation to HDM exposure or 

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who are likely to travel for extended periods of time during the main efficacy assessment 
period.  
16. Patients with past or current disease(s) which, as judged by the Investigator, may affect the 
patient’s participation in or the outcome of this study. These diseases include, but are not 
limited to, cardiovascular disease, malignancy, active tuberculosis, hepatic disease, renal 
disease, hematologic disease, neurologic or psychiatric disease, severe autoimmune 
disorder, immunodeficiency or immunologic disease and endocrine disease. 
17. Patients with a history of eosinophilic esophagitis or with current severe or persistent 
gastroesophageal symptoms including dysphagia or chest pain. 
18. Contraindications to allergen specific immunotherapy. 
19. Patients with history of drug or alcohol abuse. 
20. Participation in any clinical study within 30 days prior to the selection visit. 
21. Possible dependency of the patient on sponsor or investigators/subinvestigators or study 
personnel. 
 
Patients who fulfill all of the above inclusion criteria and none of the exclusion criteria will be 
eligible for the 5-week placebo run-in period. During this period, patients will take placebo tablets 
(single-blind) and will score their HDM-associated allergic rhinoconjunctivitis symptoms and 
record rescue medication usage on a daily basis. The last 4 weeks will be used as the baseline 
evaluation period. 
7.3 
Inclusion Criterion at the end of the run-in/baseline evaluation period 
Only patients who fulfill the following criterion will be eligible for randomization: 
• Patients with an average TCS 5 (on a scale of 0 to 15) over the baseline evaluation period. 
7.4 
Patient Withdrawal 
In case of patient withdrawal or early discontinuation, the Investigator should make every effort to 
complete the final evaluation as stipulated in the Section 9 “Study Procedures”. 
Any information, evaluations and observations, together with a narrative description of the 
reason(s) for which the patient discontinued the study, must be recorded in the patient source 
documents and in the appropriate pages in the e-CRF. The investigator should determine a primary 
reason for discontinuation and document it in the e-CRF.  
In order to avoid missing data, patients who discontinue treatment before the first interim 
evaluation period (i.e., Visit 5, after 3 months of treatment) will be asked to score their 
rhinoconjunctivitis symptoms and rescue medication use on the e-diary during the first interim 
evaluation period, off study treatment. 

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7.4.1 
Withdrawal Criteria 
A patient may be withdrawn from the clinical study for any of the following reasons: 
Ineligibility, 
Withdrawal of consent by the patient for any reason, at any time, 
Withdrawal by the Investigator for safety reasons, 
Withdrawal by the Investigator for lack of compliance with the protocol, 
Withdrawal by the Investigator for pregnancy during the study, 
Lost to follow-up. The Investigator should document all efforts made to contact the patient. In 
case of failure to collect any information on the patient, he/she will be considered as lost to 
follow-up, 
Any other reason (to be specified). 
If the reason for withdrawal is an adverse event (AE), the investigator will follow the patient 
through resolution of the AE or until the end of the study and provide STALLERGENES with a 
final report of the AE or a report explaining why no final report will be available. 
7.4.2 
Patient Replacement Policy 
Randomized patients who withdraw during this study will not be replaced. 
8. TREATMENT OF PATIENT (INVESTIGATIONAL PRODUCTS AND 
CONCOMITANT MEDICATIONS) 
8.1 
Study Investigational Products 
8.1.1 
Description of Investigational Products 
To enable the double-blind design, STG320 tablets of HDM allergen extracts (Dermatophagoides 
pteronyssinus and Dermatophagoides farinae) at the doses of 100 IR and 300 IR, and matching 
placebo tablets, Placebo 100 (P100) and Placebo 300 (P300), will be administered in this study. 
• Run-in phase 
Each patient eligible for the run-in period of the screening phase will be administered one tablet of 
Placebo 300 (P300) sublingually per day, for a period of 5 weeks. 
• Study treatment phase 
Each randomized patient will receive either STG320 sublingual tablets or matching placebo. 

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The different total daily doses for active treatment will be obtained as follows: 
Daily doses 
Active tablets 
Initiation period 
100 IR on  
Day 1 
1 tablet of 100 IR of STG320 from the initiation 
blisters 
200 IR on  
Day 2 
2 tablets of 100 IR of STG320 from the initiation 
blisters, taken simultaneously 
Maintenance period: 300 IR 
from Day 3 until the end of 
treatment 
1 tablet of 300 IR of STG320 from the maintenance 
blisters 
 
The different total daily placebo intakes will be obtained as follows: 
Daily doses 
Placebo tablets 
Initiation period  
Placebo  on 
Day 1 
1 tablet of P100 from the initiation blisters 
Placebo  on 
Day 2 
2 tablets of P100 from the initiation blisters, taken 
simultaneously  
Maintenance period: Placebo  
from Day 3 until the end of 
treatment 
1 tablet of P300 from the maintenance blisters 
8.1.2 
Packaging  
IPs will be packaged, labeled and dispatched under the responsibility of subcontracted packaging 
company on behalf of STALLERGENES.  
• Run-in phase 
The run-in phase treatment unit for each patient will consist of 2 boxes of one blister pack card; 
each blister pack card will contain 20 tablets of P300. 
• Study treatment phase 
o The initiation phase treatment unit for each patient will consist of one box containing 
3 blister pack cards; each blister pack card will contain one tablet of STG320 HDM 
allergen extracts at the dose of 100 IR or matching placebo (P100). 
o The maintenance phase treatment units for each patient will consist of four boxes 
containing 5 blister pack cards each. Each blister pack card will contain 20 tablets of 
STG320 HDM allergen extracts at the dose of 300 IR or matching placebo (P300). 

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8.1.3 
Labeling 
The IP will be labeled in compliance with the applicable US regulations, Canadian regulations, 
European Directive 2003/94/EC, Good Manufacturing Practice guidelines (Volume 4 Annex 13) 
and local regulations. Details of labeling and dispensing procedures will be in accordance with the 
standard operating procedures of subcontracted packaging company. 
The labels will be adapted to local regulatory requirements, to the size of the investigational product 
package and translated as appropriate.  
The IP labels consist of two parts: the first is a tear-off sticker which must be attached to the patient 
source document/medical record at the time of dispensation and the second remains fixed to the IP 
package. 
8.1.4 
Storage Requirements 
Investigational products should be stored in a secured, limited access area. They do not require any 
special storage conditions.  
The Investigator or the Pharmacist is responsible for the appropriate storage of IP at the 
investigative site. 
The Investigator will instruct the patients/parents/legally acceptable representative to store the IP 
in a secure place out of the reach of children. 
8.1.5 
Investigational Product Dispensation 
At Visit 2, eligible patients will be given 2 run-in period treatment kits consisting of 1 blister pack 
card (20 tablets of placebo each) for the 5-week run-in period (run-in period treatment kit numbers 
will be allocated through IVRS/IWRS). 
At randomization (Visit 3), allocation of patients to treatment groups will proceed through the use 
of IVRS or IWRS. The site will be requested to enter the protocol number, the Investigator site 
number and the patient-specific screening number. The caller will be provided with treatment kit 
number(s). Each patient will receive one initiation phase treatment unit (i.e., one box containing 
3 blister pack cards; each blister pack card will contain one tablet of STG320 HDM allergen 
extracts at the dose of 100 IR or matching placebo) and one maintenance phase treatment unit (i.e., 
one box containing 5 blister pack cards. Each blister pack card will contain 20 tablets of STG320 
HDM allergen extracts at the dose of 300 IR or matching placebo). 
At Visits 5-7, each patient will receive one maintenance phase treatment unit (i.e., one box 
containing 5 blister pack cards. Each blister pack card will contain 20 tablets of STG320 HDM 
allergen extracts at the dose of 300 IR or matching placebo). 
The call/connection to IVRS/IWRS will be repeated prior to each dispensation of IP in order to 
obtain a treatment kit number. 
Patients will be treated for approximately 12 months. The first dose (Visit 3) is to be taken in the 
presence of the Investigator and the patient observed for the next 30 minutes. 

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Subsequent doses are to be taken at home, daily, at approximately the same time in the morning. 
Tablets are to be taken in an empty mouth and the patient instructed to leave the tablets under the 
tongue until complete disintegration before swallowing. The patient is not to eat or drink before 
the tablet is completely disintegrated. On Day 2, the two tablets which comprise the treatment dose 
are to be taken simultaneously. 
In the event IP is discontinued for more than 7 days, it is to be restarted under medical supervision 
at the dosage of last intake. 
8.1.6 
Monitoring of Patient Compliance 
At each visit after drug is dispensed, the patients must return all unused investigational product as 
well as any empty boxes and blisters.  
Drug reconciliation must be done in the patient’s presence in order to obtain required explanations 
regarding any discrepancies in compliance with the dosing regimen. 
The number of tablets returned and the date they were returned must be recorded in the e-CRF and 
the IP Accountability Form. Explanations of non-compliance must also be recorded in the e-CRF. 
Compliance with study medication is defined as investigational product consumption by the patient 
greater than or equal to 80% of that prescribed. In case of persistent non compliance, the patient’s 
withdrawal from the study should be considered. 
8.1.7 
Investigational Products (IP) Accountability 
The Investigator or the Pharmacist will receive blinded numbered treatments. 
A Drug Accountability Form will be supplied to the site and is to be kept up-to-date. On this form, 
the following information will be recorded: the treatment kit number allocated to the patient, the 
initials of the person who dispenses the IP to the patient, the dates of dispensation and return, and 
the number of returned tablets. The site monitor will check the supplies of the IP and will review 
the accountability records during monitoring visits and at the completion of the study. 
In case of interruption of investigational product intake (permanent or temporary) the stop date has 
to be documented in the e-CRF. For temporary interruptions, the resume date must also be 
recorded. 
Partially used treatment boxes or blister cards must never be used for another patient. 
After completion of the study, all used (including empty containers) and unused IP boxes must be 
reconciled and returned to the subcontracted packaging company. 
8.2 
Concomitant Treatments and Rescue Medications  
8.2.1 
Concomitant Treatments 
An accurate record of all medications other than the IP must be kept in the clinic chart/patient’s 
medical record (source documentation) and in the e-CRF. This record should include the generic 
name of the drug, the dose, the date(s) of administration, and the indication for use. 

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Patients will be instructed to record all intake of concomitant medications in the “Adverse Event 
and Concomitant Medication Card.” 
The use of concomitant medication will be reviewed during the Data Review Meeting (DRM) prior 
to database lock and unblinding to assess protocol deviation and their potential impact on study 
results. 
8.2.2 
Rescue Medications 
Patients will be supplied with antihistamines, intranasal corticosteroids, and oral corticosteroids as 
rescue medications. Beginning at Visit 2 and thereafter, as necessary through Visit 8, 
antihistamines and intranasal corticosteroids will be provided to patients for managing allergic 
rhinitis symptoms. No other rescue medications should be taken by the patients without 
authorization of the Investigator. 
If AR symptoms are not sufficiently alleviated despite these treatments, the Investigator will 
evaluate with the patient if systemic corticosteroid is indicated and will prescribe this treatment. 
Management of allergic rhinoconjunctivitis rescue medications will follow a stepwise regimen: 
Step 1: Antihistamine 
Patients will be instructed to initiate treatment of AR symptoms with oral antihistamine (e.g., 
cetirizine 10 mg, 1 tablet daily in the morning). 
In cases where ocular allergic symptoms are present (i.e., itchy/red eyes and/or watery eyes) 
and the oral antihistamine is not sufficient to control the ocular symptoms, topical antihistamine 
by the ocular route can be added (e.g., olopatadine 0.1% eye drops).  
Note: Use of topical nasal antihistamines and decongestants (e.g., azelastine, phenyephrine, 
oxymetazoline) is not permitted during the study. 
Step 2: Intranasal corticosteroid 
If the allergic rhinitis symptoms are not sufficiently alleviated by treatment with oral 
antihistamine (step 1), patients are to be instructed to initiate treatment with intranasal 
corticosteroid (e.g., budesonide aqueous nasal spray, 64 g/nostril daily in the morning, total 
of 128 g/day), with or without oral antihistamine.  
In cases where ocular allergic symptoms are present, topical antihistamine by the ocular route 
may be continued. While a decrease in nasal symptoms may occur as soon as 12 hours after 
starting treatment, it may take several days to reach the maximum effect. Therefore, it is 
recommended that treatment with intranasal corticosteroid be maintained for a minimum of 
4 consecutive days and intermittent use of intranasal corticosteroid should be discouraged. 
Step 3: Oral corticosteroid 
If the allergic rhinitis symptoms are not sufficiently alleviated by intranasal corticosteroid (step 
2), the patient should consult the Investigator and treatment with oral corticosteroid should be 
considered: prednisolone at a dose adapted to the patients’ weight and to their symptom 
severity. Previously used intranasal corticosteroid with or without oral antihistamine will be 

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continued concomitantly with the step 3 treatment. The treatment with oral corticosteroid 
should be gradually reduced and stopped after 5 to 10 days and treatment with step 2 therapy 
(intranasal corticosteroid) continued.  
In cases where ocular allergic symptoms are present, topical antihistamine by the ocular route 
may be continued. 
 
The patient’s supply of rescue medication will be checked at each visit and replenished, as needed. 
Apart from the management of AEs, no anti-allergy medication other than the rescue medication 
is to be taken by a patient unless it has been agreed with the investigator and with 
STALLERGENES, as this will constitute a protocol deviation. Any antihistamine or corticosteroid 
treatments, even those provided as rescue medication, taken for a reason other than as treatment 
for allergic rhinitis symptoms due to HDM, is to be reported in the e-CRF as concomitant 
medication. 
8.2.3 
Epinephrine Auto-Injector  
8.2.3.1 Special Warnings and Precautions 
Treatment with allergen immunotherapy can cause life-threatening allergic reactions such as 
anaphylaxis and severe laryngopharyngeal edema that require treatment with epinephrine.  
Study participation may not be suitable for patients with certain medical conditions that may reduce 
the ability to survive a serious allergic reaction or increase the risk of adverse reactions after 
epinephrine administration. Examples of these medical conditions include but are not limited to: 
markedly compromised lung function (either chronic or acute), unstable angina, recent myocardial 
infarction, significant arrhythmia, and uncontrolled hypertension. In addition, study participation 
may not be suitable for patients who are taking medications that can potentiate or inhibit the effect 
of epinephrine. These medications include beta-adrenergic blockers, alpha-adrenergic blockers, 
ergot alkaloids, tricyclic antidepressants, levothyroxine sodium, monoamine oxidase inhibitors, 
cardiac glycosides, and diuretics. 
Adequate resuscitation equipment and facilities for managing severe allergic reactions must be 
available at each study site.  
Patients will be provided with a study site-specific contact phone number and be instructed to call 
at any time for questions about any adverse reactions they may experience.  
8.2.3.2 Safety and Emergency Procedures  
At Visit 3, patients will be instructed to recognize the signs and symptoms of a severe allergic 
reaction. They will be trained on the proper use of emergency self-injection of epinephrine. Patients 
will receive an epinephrine auto-injector to be used in case of a severe allergic reaction. Patients 
will be instructed to seek immediate medical care upon its use. They are to discontinue study 
therapy and contact the study site as soon as possible for further evaluation. The epinephrine auto-
injector will be replaced as necessary.  

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8.2.4 
Prohibited Concomitant Treatments (Medications and Therapies)  
8.2.4.1 Prohibited Treatments During the Screening Phase  
Before SPT and spirometry are performed certain medications must be stopped and wash-out 
periods observed. Patients entering the run-in period (Visit 2) will be provided with oral 
antihistamine and intranasal corticosteroid as rescue medication to treat symptoms of allergic 
rhinitis. If a patient was using different treatments than the study rescue medications before 
entering the run-in period, s/he will have to switch to the rescue medications provided for the study 
and respect the wash-out periods described below. During the run-in period, the stepwise regimen 
for use of rescue medication will apply (Section 8.2.2 “Rescue Medications”). 
The prohibited medications and the corresponding wash-out periods are described below: 
Prohibited medication before SPT and before entering the Run-in 
period 
Wash-out period 
At least: 
Short-acting antihistamines (e.g., acrivastine, diphenhydramine, 
chlorpheniramine, doxepine) 
3 days before SPT or  
start of run-in period 
Long-acting antihistamines (e.g., cetirizine, fexofenadine, loratadine, 
desloratadine, azelastine, ebastine),  
7 days before SPT or  
start of run-in period 
Astemizole 
10 days before SPT or  
start of run-in period 
Hydroxyzine, ketotifen, tricyclic antidepressants and Monoamine 
oxidase inhibitors 
14 days before SPT or  
start of run-in period 
Moderate-high dose topical steroids on the forearm 
14 days before SPT  
Oral or systemic corticosteroids 
30 days before SPT or  
start of run-in period 
Long Acting Systemic corticosteroids 
90 days before or  
start of run-in period 
Anti-IgE (Omalizumab) 
60 days before SPT or  
start of run-in period 
Immunosuppressive drugs 
90 days before SPT or  
start of run-in period 
Prohibited medication for Spirometry 
Wash-out period 
At least: 
Short-acting beta 2-agonists (SABA) or anticholinergic agent 
(ipratropium bromide)  
6 hours prior to spirometry testing 
 

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8.2.4.2 Prohibited Concomitant AR Treatments During Run-in and Treatment Phase 
Except for the rescue medications provided as part of the study or for asthma controller treatments 
initiated before patient selection, continuation or initiation of any other anti-allergic medications 
are not permitted after randomization. 
The following are prohibited:  
From Visit 2 (baseline) to Visit 9 (End of Treatment Phase): 
- 
Oral antihistamines, including ketotifen (except those provided as rescue medications) and 
intranasal antihistamine 
- 
Oral, systemic and intranasal corticosteroids (except those provided as rescue medications) 
- 
Cromone: cromoglycate and nedocromil 
- 
Anti-leukotrienes (if not used before patient selection as asthma controller treatment) 
- 
Theophylline or inhaled corticosteroid (if not used before patient selection as asthma controller 
treatment) and Long acting Beta 2 agonist (refer to asthma patients exclusion criteria) 
- 
Long-acting anticholinergic agents (e.g., tiotropium bromide) 
- 
Anti-IgE 
- 
Decongestants (oral, nasal, or ophthalmic) 
- 
Any topical nasal or ocular treatments except those provided as rescue medications 
- 
Beta-blocker therapy whatever the route 
- 
Tricyclic antidepressants and mono amine oxidase inhibitors (MAOIs) 
If one of these treatments becomes required during the course of the study, the investigator is to 
liaise with the Sponsor to determine if the patient may remain in the study. 
8.2.5 
Maintenance Asthma Therapy (When Used) 
Asthmatic patients eligible to participate in the study will be those with asthma controlled by 
treatment(s) consistent with GINA 2014 treatment Steps 1 or 2 (Appendix II). 
The following asthma treatments are permitted during the study: reliever treatment with as needed 
short acting β2-agonist with or without controller treatment consisting of low dose inhaled 
corticosteroid (i.e., <400 g of budesonide/day or equivalent dose of other corticosteroid) or 
leukotriene receptor antagonist or low dose theophylline. 
 
If a patient requires adaptation of their asthma treatment, s/he should return to the investigator for 
medical assessment. 

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9. STUDY PROCEDURES 
9.1 
Patient Identifier 
All patients who have signed an Informed Consent Form (ICF) or Assent Form together with their 
parent(s)/legal representative in the case of adolescents, whether they are randomized in this study 
or not, will receive a screening number allocated in ascending order of screening. 
9.2 
Description of Procedures 
9.2.1 
Informed Consent Form 
At Visit 1, an Informed Consent Form (ICF) has to be dated and signed by the patient (and 
parent(s)/legal representative in the case of adolescents) before any study procedure may be 
performed.  
If the patient is <16 years old, an assent form will be used instead of the informed consent form in 
addition to the ICF dated and signed by the parents. If the patient is aged between 16 and <18 years 
old, s/he may sign an ICF on her/his own, or sign an assent form in addition to the ICF signed by 
the parent(s)/legal representative, depending on the local regulations. 
The Investigator who informs the patient (and parent(s)/legal representative) and obtains their 
written consent/assent has to also date and sign the ICF/Assent form. A copy of the ICF /Assent 
form will be given to the patient (and parent(s)/legal representative) and the original is to be 
retained by the Investigator. 
9.2.2 
Inclusion and Exclusion Criteria 
Inclusion and exclusion criteria should be checked at Visit 1 and Visit 2 (run-in) and confirmed 
before randomization at Visit 3. To be randomized in the study, a patient must meet all the inclusion 
criteria and none of the exclusion criteria. 
At the Investigator’s discretion a Nasal Provocation Test for HDM may be performed to confirm 
the diagnosis of HDM-associated AR. The study site’s standard practice should be followed. 
9.2.3 
Medical and Allergy History 
Medical history including complete allergy history will be collected at Visit 1. 
9.2.4 
Demographic Data, Height and Weight 
Information on gender, date of birth, ethnic origin, height and weight will be collected at Visit 1. 
9.2.5 
Prior and Concomitant Medication 
At Visit 1, AR and asthma medications taken within the six previous months will be recorded. 
During the study, any intake of medication will be reported by the Investigator in the medical 
source data and in the e-CRF. Information regarding drug name (generic name), total daily dose, 
route, start and end date or whether ongoing, and indication for use will be recorded. 

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9.2.6 
Physical Examination and Vital Signs 
At Visits 1 and 9, a physical examination will be conducted including vital signs (systolic and 
diastolic blood pressure, and pulse rate), and examination of the skin, eyes, ears, nose, throat, 
cardiovascular, respiratory, gastrointestinal, musculoskeletal and nervous systems. 
At Visits 2 through 8, and at Visit 10, a directed physical examination will be performed if judged 
necessary by the investigator based on symptoms and physical signs. 
9.2.7 
Skin Prick Test  
At Visit 1, Skin Prick Testing [Heinzerling et al.,2005; Heinzerling et al.,2009] will be performed 
using the following battery of aeroallergens: Dermatophagoides pteronyssinus, Dermatophagoides 
farinae, cat, dog, cockroach, Aspergillus, Cladosporium, Parietaria, and Alternaria and other 
geographically relevant, potentially confounding aeroallergens such as cypress, birch, grass, 
ragweed… as well as positive (histamine dihydrochloride) and negative (saline diluent) controls. 
SPT allergens used in this study will be provided by the Sponsor using locally approved extracts. 
Testing is to be performed according to the USPI/Summary of Product Characteristics. 
For the HDM allergens, Dermatophagoides pteronyssinus and Dermatophagoides farinae, a test 
will be considered positive when, 20 minutes after testing, the largest wheal diameter is at least 
5 mm greater than that of the negative control. For the other allergens, a wheal diameter at least 
5 mm greater than the negative control will be considered positive. 
The tests will be considered valid when the positive control induces a wheal diameter of at least 
3 mm and negative control induces a wheal diameter less than 2 mm. In the event of non valid 
controls or borderline results, the SPT should be repeated.  
The outline of wheals (and, if present, pseudopods and satellites) will be traced with a sharp black 
felt pen. The real limits of the wheal are confirmed by palpation. Hypoallergenic transparent 
adhesive tape will be applied on the tracings and will be then transferred on the source document 
sheet. 
Wash-out periods for specific categories of medications are provided in Section 8.2.4.1 “Prohibited 
Treatments During the Screening Phase.” 
9.2.8 
Spirometry 
At Visit 1, lung function testing will be performed according to American Thoracic 
Society/European Respiratory Society (ATS/ERS) Task Force: Standardization of Lung Function 
Testing [Miller et al.,2005] (see Appendix I). The Forced Vital Capacity/Forced Expiratory Volume 
in one second (FEV1) maneuver will be performed three times and the best of the values will be 
retained. To be eligible for enrollment, the FEV1 must be at least 80% of the predicted value. Ethnic 
corrective factors may be used in accordance with the recommendations of the equipment 
manufacturer. 
At Visit 3 and Visit 9, lung function testing will be repeated only for asthmatic patients. 

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9.2.9 
Classification of Asthma Status 
At Visit 1, the asthma status (Yes or No) of all patients will be assessed. 
If present, asthma will be classified according to the GINA Guidelines (Global Initiative for 
Asthma – GINA 2014 – ref. Appendix II and Appendix III).  
Eligible asthmatic patients will be those with asthma, controlled by treatment(s) consistent with 
GINA 2014 treatment Steps 1 or 2 [i.e., reliever treatment with as needed short acting β2-agonist 
with or without controller treatment consisting of low dose inhaled corticosteroid (400 g of 
budesonide/day or equivalent dose of other corticosteroid) or leukotriene receptor antagonist or 
low dose theophylline]. 
9.2.10 
Blood sampling 
At Visits 1 and 9, blood samples (approximately 20 mL) will be drawn at for: 
• Safety laboratory tests: 
Hematology (i.e., hemoglobin, hematocrit, red blood cells (RBC), platelets, white blood cells 
(WBC), differential count (neutrophils, basophils, eosinophils, monocytes, lymphocytes) 
Biochemistry (i.e., sodium, potassium, chloride, creatinine, glucose, bilirubin (direct, indirect, 
total), ASAT (SGOT), ALAT (SGPT), Gamma Glutamyl Transferase (GGT) 
• Immunological markers (IgE and IgG4 specific for D. pte and D. far allergens) 
Blood safety laboratory tests and measurement of immunological markers will be performed by a 
subcontracted Central Laboratory. Study sites will be provided with a separate laboratory manual 
and with laboratory kit material. The laboratory manual contains the sampling, handling and 
shipment procedures. 
• Serum and RNA banking 
A serum and RNA bank will be set up. Out of the total 20 mL of drawn blood, approximately 8 mL 
will be used for serum and RNA banking. 
Data obtained from the serum and RNA banks will not be part of the clinical database. These banks 
will serve for complementary and exploratory immunological analyses. 
Analyses will be carried out and/or coordinated by STALLERGENES.  
Wherever permitted by local regulations, the study sites will be provided with laboratory kit 
material and sampling, handling, and shipment procedures will be specified in the laboratory 
manual. The samples will be stored for a period of up to 10 years after completion of the Clinical 
Study Report. The results will be provided in a separate report.  
9.2.11 
Dust sampling 
In order to document exposure to HDM, dust will be collected by the patient at their residence. At 
Visit 3, a sampling kit for dust collection as well as detailed sampling, handling and shipment 

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instructions will be provided to the patients (Appendix IV). Patients will be asked to vacuum 
mattresses and bedding until the filter from the collector is at least ¼ full. 
The HDM allergen load will be measured centrally by a subcontracted laboratory.  
9.2.12 
Pregnancy Test  
At Visits 1 and 3, a urinary pregnancy test will be performed on all females of childbearing 
potential.  
Females are considered not to have childbearing potential prior to menarche, at least 2 years after 
menopause, or if they have had a total hysterectomy, bilateral oophorectomy or ovariectomy. 
Urine pregnancy tests will be provided by STALLERGENES. 
9.2.13 
IVRS/IWRS 
Allocation of patients to treatment groups will proceed through the use of an Interactive Voice 
Response System (IVRS) or Interactive Web Response System (IWRS). The site will be requested 
by the IVRS/IWRS to enter the protocol number, the Investigator site number and the screening 
number. The caller will be provided with treatment kit number(s). 
The call/connection to IVRS/IWRS will be repeated prior to each dispensation of IP. 
9.2.14 
Dispensation and Use of the Electronic Diary (e-diary) 
At Visit 2, each patient will be provided with an electronic diary (e-diary) and will be instructed 
by site staff as to how and when to score their allergic rhinoconjunctivitis symptoms (i.e., itchy 
nose, sneezing, runny nose, blocked nose, itchy/red eyes and watery eyes) and record their use of 
rescue medication. Site staff should emphasize to the patient the importance of the accurate and 
regular completion of the e-diary. Patients will be asked to bring the device to each visit. 
Symptom scoring and recording of rescue medication use are to be performed daily during the 
5-week run-in period, the two weeks prior to Visits 5, 6, and 7 (interim evaluation periods at 
Months 3, 6, and 9) and during the 4 weeks between Visits 8 and 9 (primary evaluation period, 
Month 12). 
 
The assessment will address symptom intensity over the previous 24 hours and is to be performed 
at the same time every morning after awakening, using the following 4-point scale: 
0 = no symptom  
1 = mild symptom; symptom clearly present, but minimal awareness; easily tolerated  
2 = moderate symptom; definite awareness of symptom that is bothersome but tolerable 
3 = severe symptom; symptom that is hard to tolerate; causes interference with activities of daily 
living and/or sleeping 

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- Patients will be supplied with antihistamines, intranasal corticosteroids, and oral corticosteroids 
as rescue medications. Beginning at Visit 2 and thereafter, as necessary through Visit 8, 
antihistamines and intranasal corticosteroids will be provided to patients for managing allergic 
rhinitis symptoms. If AR symptoms are not sufficiently alleviated despite these treatments, the 
Investigator will evaluate with the patient if systemic corticosteroid is indicated and will 
prescribe this treatment. For a description of the stepwise treatment regimen Section 8.2.2 
“Rescue Medications.” Patients are to record their rescue medication use over the previous 
24 hours. 
- A Visual Analogue Scale (VAS), comprising 101 pixels (0-100), ranging from “absence of 
symptoms” (score = 0) to “very severe symptoms” (score = 100), will be completed by the 
patient weekly basis (at the end of each week) during the run-in period, the interim evaluation 
periods and the primary evaluation period. 
- The data from the e-diary device will be automatically transmitted to the study database. Patient 
compliance with data recording is to be monitored by the site staff via a dedicated web portal. 
In addition, an alert will be sent to the study center in case of patient’s non completion or non 
transmitted data.  
- At Visit 9, the site staff will collect the e-diary device and deactivate it. 
9.2.15 
Standardized Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ(S)≥12)  
The RQLQ was developed to evaluate the impact of rhinoconjunctivitis symptoms on quality of 
life [Juniper et al.,1999]. It is designed to evaluate the change in a patient's quality of life over 
some period of time. The RQLQ(S)≥12 was developed subsequently to enable the evaluation of 
adolescents 12-17 years of age in addition to adults. It consists of 28 questions, divided into seven 
domains as follows: Activities (3 questions), Sleep (3 questions), Non-nose/eye symptoms (7 
questions), Practical problems (3 questions), Nasal symptoms (4 questions), Eye symptoms (4 
questions) and Emotional (4 questions). Patients are asked to recall their experiences during the 
previous week and to give their responses on a 7-point Likert scale (lower being better). 
In this study, the self-administered questionnaire is to be completed by the patient at the study site 
at Visit 3 (before first dosing) and Visit 9. 
9.2.16 
Global Rating of Change Questionnaire 
The global evaluation of the efficacy of study therapy relative to the allergic symptoms during the 
baseline evaluation period is to be assessed by the patient at Visit 9.  
The following 15-point Likert scale will be used [Juniper et al.,1994]: 
Symptom improvement: 
1 = Almost the same, hardly any better at all 
2 = a little better 
3 = somewhat better 

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4 = moderately better 
5 = a good deal better 
6 = a great deal better 
7 = a very great deal better 
 
0 = No change 
 
Symptom worsening 
1 = Almost the same, hardly any worse at all 
2 = a little worse 
3 = somewhat worse 
4 = moderately worse 
5 = a good deal worse 
6 = a great deal worse 
7 = a very great deal worse 
9.2.17 
Work Productivity and Activity Impairment Questionnaire plus Classroom 
Impairment Questions: Allergy Specific (WPAI + CIQ: AS) 
The Work Productivity and Activity Impairment (WPAI) Questionnaire plus Classroom 
Impairment Questions (CIQ), Allergy Specific (AS) is a patient-reported quantitative assessment 
of the amount of absenteeism (work time missed), presenteeism (impairment at work / reduced on-
the-job effectiveness), work productivity loss (overall work impairment / absenteeism plus 
presenteeism) and regular daily activity impairment attributable to allergy (moderate-to-severe 
allergy symptoms).  
It is a 9-item self-administered questionnaire assessing the patient’s productivity and allergy-
induced activity impairment during the past seven days.  
This questionnaire will be completed by the patient at the study site at Visit 3 (before first dosing) 
and at Visit 9. 
9.2.18 
EQ-5D-5L Generic Health-Related Quality of Life 
The EQ-5D describes the patients’ health state using 5 dimensions, namely: 1. Mobility, 2. Self-
care, 3. Usual activities, 4. Pain/Discomfort and 5. Anxiety/Depression. Each dimension is 
evaluated on a 5-point scale: no problems / slight problems / moderate problems / severe problems 
/ extreme problems. The responses are then transformed into a single index by applying a formula 
that attaches weights to each of the response levels in each dimension. The patients also assess their 
overall health on a VAS ranging from 0 (“the worst health you can imagine”) to 100 (“the best 

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health you can imagine”) [Herdman et al.,2011]. This questionnaire will be completed by the 
patient at the study site at Visit 3 (before first dosing) and Visit 9.  
9.2.19 
HDM Avoidance Measures Questionnaire 
At Visit 9, patients will be asked to indicate any and all HDM avoidance measures/interventions 
implemented at their home since they entered the study (e.g., encasing mattresses, pillows and/or 
quilts in mite impermeable covers, replacement of mattress, pillows and/or quilts, regular washing 
of bedding in hot temperature (55-60°C) water, replacement of carpets, removing carpeting in favor 
of hard flooring, use of acaricides and/or tannic acid).  
9.2.20 
Adverse Events/Concomitant Medication Card  
Patients will be given an Adverse Events/Concomitant Medication card (AE/Conc. Med. card) to 
report any changes in their medical condition and use of any concomitant medication throughout 
the study. 
The AE/Conc. Med. card will be issued at Visit 1 and will have to be brought back to the study site 
at Visit 2, collected by the Investigator and discussed with the patient. A new AE/Conc. Med. card 
will be issued at each subsequent visit, and discussed and collected the visit thereafter. 
Any adverse reactions/events and/or concomitant medication use should be reported in the patient’s 
medical chart and, in the e-CRF. 
9.3 
Visit by Visit Description 
9.3.1 
Visit 1 (Selection Visit)  
• 
Before any study procedures are performed, the Investigator/co-Investigator must obtain the 
signed informed consent form from the patient/legal guardian, as applicable, according to local 
laws and requirements. Signed assent should be obtained from adolescents in addition to the 
informed consent form signed by the parent/legal guardian. 
• 
The site staff will access IVRS/IWRS to obtain a screening number. 
• 
The Investigator/co-Investigator will check the patient’s eligibility (inclusion/exclusion 
criteria). 
• 
The Investigator/co-Investigator will record the patient’s medical history and prior and 
concomitant medication use over the previous 6 months.  
• 
Patient date of birth, ethnic origin, gender, height and weight will be collected. 
• 
Vital signs will be measured (after 5 min rest) and a physical examination will be performed. 
• 
Spirometry will be performed. 
• 
Asthma status (Yes/No) will be assessed. If present, asthma will be further categorized 
according to GINA 2014 treatment Step and level of control. 

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• 
Skin Prick Test (SPT) will be performed after verification that no medication that could 
interfere with the results has been taken during the prohibited period (Section 8.2.4 “Prohibited 
Concomitant Treatments (Medications and Therapies)”. The following allergens should be 
tested: D pteronyssinus, D. farinae and a battery including cat, dog, cockroach, Aspergillus, 
Cladosporium, Parietaria and Alternaria, and other geographically relevant potentially 
confounding allergens such as cypress, birch, grass, ragweed… as well as positive (histamine 
dihydrochloride) and negative (saline diluent) controls. 
Note: At the Investigator’s discretion a Nasal Provocation Test for HDM may be performed to 
confirm the diagnosis of HDM-associated AR. The study site’s standard practice should be 
followed. 
• 
In patients with positive SPT to D. pte and/or D. far, a blood draw will be performed for: 
– Laboratory tests (hematology and biochemistry). 
– Immunological markers. 
– Serum and RNA banking wherever permitted by local regulations. 
• 
A urine pregnancy test will be performed for all female patients of childbearing potential. 
• 
Patient will be provided with a paper-card allowing him/her to record any adverse event(s) 
occurred and medication(s) taken (other than those of the study protocol) between this visit 
and the next visit. The patient is to be instructed to bring this card back to the site at the next 
visit. 
• 
The Investigator will instruct the patient not to change his/her daily environment in relation to 
HDM exposure during the conduct of the study. 
• 
An appointment will be made for Visit 2 for all eligible patients. 
9.3.2 
Visit 2 (Run-in period Visit) 
• 
Patients meeting all the selection criteria will enter a single-blind placebo run-in period of 
5 weeks (including the baseline evaluation period). This 5-week period is to be selected based 
on the patient’s history of HDM-related rhinitis symptoms and the investigator’s knowledge 
of the peak season for HDM in the area. The Investigator/co-Investigator must check the 
patient eligibility (inclusion/exclusion criteria), in particular the HDM-specific IgE levels.  
• The Investigator/co-Investigator should check the “AE/Concomitant Medication” paper card 
provided to the patient at the previous visit. Adverse events and concomitant medication will 
be recorded. A physical examination will be performed depending on medical findings, if any. 
• A new “AE/Concomitant Medication” paper card will be provided to the patient, to be brought 
back at the next visit. 
• 
The Investigator/co-Investigator is to call the IVRS or connect to IWRS in order to obtain the 
run-in phase treatment kit numbers. 

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• 
The Investigator/co-Investigator will dispense the placebo sublingual tablets and instruct the 
patient to take one tablet sublingually every day at approximately the same time (in an empty 
mouth) for a period of 5 weeks. The patient must be instructed to leave the tablets under the 
tongue until complete disintegration before swallowing. Patient is not to eat or drink before 
the tablet is completely disintegrated. The first dose should be taken under the supervision of 
the Investigator/co-Investigator and the patient monitored for 30 minutes. The patient should 
be instructed to return blisters and box (whether empty/used or unused) to the study site at the 
next visit. 
• 
The Investigator/co-Investigator will dispense the rescue medication (RM) and instruct the 
patient that RM is to be used to treat at least moderate allergic rhinitis symptoms (i.e., one or 
more symptoms that are at a minimum bothersome but tolerable). Patients will be instructed 
regarding the stepwise regimen to be followed (Section 8.2.2 “Rescue Medications”). 
• 
The e-diary will be activated by the study site staff and this device will be provided to the 
patient. A detailed training will be provided to the patient to ensure the full understanding of 
how the device is to be used. The patient will be instructed to score his/her rhinoconjunctivitis 
symptoms and rescue medication use daily, in the morning, and the VAS weekly, for a period 
of 5 weeks (Section 9.2.14 “Dispensation and Use of the Electronic Diary (e-diary)”). 
• 
An appointment for Visit 3 will be made for all eligible patients. 
9.3.3 
Visit 3 (Randomization Visit) 
• 
This visit is to be performed within the 7 days following the 5-week run-in period. 
• 
The Investigator/co-Investigator must confirm the patient eligibility (inclusion/exclusion 
criteria), in particular that the Baseline Average TCS was >5/15 during the last 4 weeks of the 
run-in period. Spirometry will be repeated only for asthmatic patients. 
• The Investigator/co-Investigator should check the “AE/Concomitant Medication” paper card 
provided to the patient at the previous visit. Adverse events and concomitant medication will 
be recorded. A physical examination will be performed depending on medical findings, if any. 
• A new “AE/Concomitant Medication” paper card will be provided to the patient, to be brought 
back at the next visit. 
• 
The site staff checks that the box and blisters of the placebo tablets are returned by the patient. 
The “Drug Accountability Form” should be kept up-to-date by the study site staff.  
• 
The Investigator/co-Investigator should check the completion of the e-diary via the web portal. 
• 
Urine pregnancy test for all female patients of childbearing potential will be performed. 
• 
Patient self-administered questionnaires should be completed at the site prior to the first 
investigational product (IP) administration: Standardized Rhinoconjunctivitis Quality of Life 
Questionnaire (RQLQ(S)≥12), Work Productivity and Activity Impairment (WPAI) 
Questionnaire plus Classroom Impairment Questions (CIQ), Allergy Specific (AS), EQ-5D. 

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• 
The Investigator/co-Investigator is to call the IVRS or connect to IWRS in order to obtain two 
treatment kit numbers (one for escalation phase and one for maintenance phase): patients will 
be randomized and assigned to one of the two treatment groups. 
• 
The IP will be dispensed to the patient and the IP kit numbers will be entered in the e-CRF. 
The tear-off labels will be affixed to the patient’s medical records. Patient will be instructed to 
bring back the IP boxes and blisters (whether empty/used or unused) to the site at the next 
visit. 
• 
The first dose of IP is to be taken at the site under the supervision of the Investigator and the 
patient monitored for at least 30 minutes. The patient must be instructed to keep the tablet 
under the tongue until complete disintegration before swallowing. The patient is not to eat or 
drink before the tablet is completely disintegrated. 
• 
All used and unused rescue medication (RM) previously dispensed should be checked and the 
“Drug Accountability Form” should be kept up-to-date. Resupply of RM may be provided, as 
necessary. 
• 
Patient will be provided with an epinephrine auto-injector and instructed and trained in its use 
(Section 8.2.3 “Epinephrine Auto-Injector”). 
• 
Patient will be provided with a kit for dust sampling at their residence and be instructed 
regarding the sampling, handling and shipment procedures. 
• 
An appointment will be made for Visit 4, 1 month after Visit 3. 
• 
In order to prevent missing data, patients who discontinued the treatment before the first 
interim evaluation period (i.e., before 3 months of treatment) will be asked to continue the 
study (without study treatment) until Visit 5 (i.e., until the end of the first interim evaluation 
period). Patients will be asked to score their rhinoconjunctivitis symptoms and rescue 
medication use on the e-diary during the first interim evaluation period.  
9.3.4 
Visit 4 (Month 1 Visit) 
• 
This visit is to be performed 30 days +/- 4 days after Visit 3. 
• The Investigator/co-Investigator should check the “AE/Concomitant Medication” paper card 
provided to the patient at the previous visit. Adverse events and concomitant medication will 
be recorded. A physical examination will be performed depending on medical findings, if any. 
• A new “AE/Concomitant Medication” paper card will be provided to the patient, to be brought 
back at the next visit. 
• 
IP boxes and blisters dispensed at the previous visit should be checked and given back to the 
patient. The “Drug Accountability Form” should be kept up-to-date by the study site staff. 
Patient will be reminded to bring back the IP boxes and blisters (whether empty/used or 
unused) to the site at the next visit. 

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• All used and unused rescue medication (RM) previously dispensed should be checked and the 
“Drug Accountability Form” should be kept up-to-date. Resupply of RM may be undertaken, 
as necessary. 
• 
Patient will be instructed that the scoring of rhinoconjunctivitis symptoms and recording of 
RM consumption and completion of the VAS is to be started 2 weeks before the next visit 
(Visit 5). Patients will be informed that during this 2-week evaluation period, VAS should be 
completed on a weekly basis, and scoring of rhinoconjunctivitis symptoms and RM 
consumption should be recorded on a daily basis (Section 9.2.14 “Dispensation and Use of the 
Electronic Diary (e-diary)”). 
• 
An appointment will be made for Visit 5. 
9.3.5 
Visit 5 (Month 3 Visit) 
• This visit is to be performed 90 days +/- 7 days after Visit 3. In preparation for Visit 5, the site 
staff should check (approximately 1 week after the start of the recording period) the web portal 
to confirm that the patient started to properly complete the e-diary. If it is not the case, the staff 
should call the patient and remind him/her of the necessity to record their data in the e-diary. 
The Investigator/co-Investigator will monitor the quality of the data recorded by the patient in 
the e-diary, and correct or retrain the patient as needed. 
• The Investigator/co-Investigator should check the “AE/Concomitant Medication” paper card 
provided to the patient at the previous visit.  Adverse events and concomitant medication will 
be recorded. A physical examination will be performed depending on medical findings, if any. 
• A new “AE/Concomitant Medication” paper card will be provided to the patient, to be brought 
back at the next visit. 
• 
IP boxes and blisters dispensed at the previous visit should be checked and collected. The 
“Drug Accountability Form” should be kept up-to-date by the study site staff.  
• The Investigator/co-Investigator is to call the IVRS or connect to IWRS in order to obtain one 
treatment kit number (maintenance phase). 
• The IP will be dispensed to the patient and the IP kit number will be entered in the e-CRF. The 
tear-off label will be affixed in the patient’s medical records. Patient will be reminded to bring 
back the IP box and blisters (whether empty/used or unused) to the site at the next visit. 
• All used and unused rescue medication (RM) previously dispensed should be checked and the 
“Drug Accountability Form” should be kept up-to-date. Resupply of RM may be undertaken, 
as necessary. 
• 
Patient will be instructed that the scoring of rhinoconjunctivitis symptoms and recording of 
RM consumption and completion of the VAS is to be started 2 weeks before the next visit 
(Visit 6). Patients will be informed that during this 2-week evaluation period, VAS should be 
completed on a weekly basis, and scoring of rhinoconjunctivitis symptoms and RM 

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consumption should be recorded on a daily basis (Section 9.2.14 “Dispensation and Use of the 
Electronic Diary (e-diary)”). 
• An appointment will be made for Visit 6. 
9.3.6 
Visit 6 (Month 6 Visit) 
• This visit is to be performed 180 days +/- 7 days after Visit 3. 
• In preparation for Visit 6, the site staff should check the web portal (approximately 1 week after 
the start of the recording period) to confirm that the patient started to properly complete the e-
diary. If it is not the case, the staff should call the patient and remind him/her of the necessity 
to record their data in the e-diary. The Investigator/co-Investigator should check the 
“AE/Concomitant Medication” paper card provided to the patient at the previous visit. Adverse 
events and concomitant medication will be recorded. A physical examination will be performed 
depending on medical findings, if any. 
• A new “AE/Concomitant Medication” paper card will be provided to the patient, to be brought 
back at the next visit. 
• IP box and blisters dispensed at the previous visit should be checked and collected. The “Drug 
Accountability Form” should be kept up-to-date by the study site staff. 
• The Investigator/co-Investigator is to call the IVRS or connect to IWRS in order to obtain one 
treatment kit number (maintenance phase). 
• 
The IP will be dispensed to the patient and the IP kit number will be entered in the e-CRF. The 
tear-off label will be affixed to the patient’s medical records. Patient will be reminded to bring 
back the IP box and blisters (whether empty/used or unused) to the site at the next visit. 
• All used and unused rescue medication (RM) previously dispensed should be checked and the 
“Drug Accountability Form” should be kept up-to-date. Resupply of RM may be undertaken, 
as necessary. 
• The Investigator/co-Investigator will monitor the quality of the data recorded by the patient in 
the e-diary, and correct or retrain the patient as needed. 
• 
Patient will be instructed that the scoring of rhinoconjunctivitis symptoms and recording of 
RM consumption and completion of the VAS is to be started 2 weeks before the next visit 
(Visit 7). Patients will be informed that during this 2-week evaluation period, VAS should be 
completed on a weekly basis, and scoring of rhinoconjunctivitis symptoms and RM 
consumption should be recorded on a daily basis (Section 9.2.14 “Dispensation and Use of the 
Electronic Diary (e-diary)”). 
• An appointment will be made for Visit 7. 
9.3.7 
Visit 7 (Month 9 Visit) 
• This visit is to be performed 270 days +/- 7 days after Visit 3. 

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• In preparation for Visit 7, the site staff should check the web portal (approximately 1 week after 
the start of the recording period) to confirm that the patient started to properly complete the e-
diary. If it is not the case, the staff should call the patient and remind him/her of the necessity 
to record their data in the e-diary. The Investigator/co-Investigator will monitor the quality of 
the data recorded by the patient in the e-diary, and correct or retrain the patient as needed. 
• The Investigator/co-Investigator should check the “AE/Concomitant Medication” paper card 
provided to the patient at the previous visit. Adverse events and concomitant medication will 
be recorded. A physical examination will be performed depending on medical findings, if any. 
• A new “AE/Concomitant Medication” paper card will be provided to the patient, to be brought 
back at the next visit. 
• IP box and blisters dispensed at the previous visit should be checked and collected. The “Drug 
Accountability Form” should be kept up-to-date by the study site staff.  
• The Investigator/co-Investigator is to call the IVRS or connect to IWRS in order to obtain one 
treatment kit number (maintenance phase). 
• 
The IP will be dispensed to the patient and the IP kit number will be entered in the e-CRF. The 
tear-off label will be affixed to the patient’s medical records. Patient will be reminded to bring 
back the IP box and blisters (whether empty/used or unused) to the site at the next visit. 
• All used and unused rescue medication (RM) previously dispensed should be checked and the 
“Drug Accountability Form” should be kept up-to-date. Resupply of RM may be undertaken, 
as necessary. 
• 
Patient will be instructed that the scoring of rhinoconjunctivitis symptoms and recording of 
RM consumption and completion of the VAS is to be started 4 weeks after the next visit (Visit 
8). Patients will be informed that during this 4-week evaluation period, VAS should be 
completed on a weekly basis, and scoring of rhinoconjunctivitis symptoms and RM 
consumption should be recorded on a daily basis (Section 9.2.14 “Dispensation and Use of the 
Electronic Diary (e-diary)”). 
• An appointment will be made for Visit 8. 
9.3.8 
Visit 8 (Month 11 Visit) 
• This visit is to be performed 323 to 330 days after Visit 3. For patients who enter the study in 
late winter or spring (from February to June), Visit 8 should be anticipated to avoid as much as 
possible unfavorable conditions for mite exposure and prevent confounding symptoms to 
seasonal allergens; however, it should not be performed earlier than 270 days after Visit 3. 
• During Visit 8, the Investigator/co-Investigator will instruct the patient to score his/her allergic 
symptoms and record RM use daily and complete the VAS weekly for the next 4 weeks (i.e., 
until Visit 9). This 4-week period will represent the primary evaluation period and should be 
performed close to the 4 weeks as the baseline evaluation period. The good functioning of the 
e-diary will be verified. Verification of e-diary recording by the patient will be checked 

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approximately 1 week after the start of the period. If needed, the patient may be contacted by 
the study team to discuss the detected issues. 
• The Investigator/co-Investigator should check the “AE/Concomitant Medication” paper card 
provided to the patient at the previous visit. Adverse events and concomitant medication will 
be recorded. A physical examination will be performed depending on medical findings, if any. 
• A new “AE/Concomitant Medication” paper card will be provided to the patient, to be brought 
back at the next visit. 
• 
IP box and blisters dispensed at the previous visit should be checked and given back to the 
patient. The “Drug Accountability Form” should be kept up-to-date by the study site staff. 
Patient will be instructed to bring the IP box and blisters (whether empty/used or unused) back 
to the site at the next visit. 
• All used and unused rescue medication (RM) previously dispensed should be checked and the 
“Drug Accountability Form” should be kept up-to-date. Resupply of RM may be undertaken, 
as necessary. 
• An appointment will be made for Visit 9. 
• Approximately one week after Visit 8, the site staff should check the web portal to confirm that 
the patient started to properly complete the e-diary. If it is not the case, the staff should call the 
patient and remind him/her of the necessity to record their data in the e-diary. The 
Investigator/co-Investigator will monitor the quality of the data recorded by the patient in the 
e-diary, and correct or retrain the patient as needed. 
9.3.9 
Visit 9 (Month 12, End of Treatment Visit) 
• 
This visit is to be performed 360 to 367 days after Visit 3. For patients who enter the study in 
late winter or spring (from February to June), Visit 9 should be anticipated to avoid as much 
as possible unfavorable conditions for mite exposure and prevent confounding symptoms to 
seasonal allergens; however, it should not be performed earlier than 300 days after Visit 3. 
• 
The Investigator/co-Investigator will monitor the quality of the data recorded by the patient in 
the e-diary, and will deactivate the device. 
• Patient will be asked to complete the questionnaire relative to the HDM avoidance measures 
implemented (if any) at their residence since Visit 1. The Investigator should question the 
patient and record any change in the patient’s environment in relation to HDM exposure during 
the study in the e-CRF. 
• A complete physical examination will be performed and vital signs measured (after 5 min rest) 
(Section 9.2.6 “Physical Examination and Vital Signs”). 
• 
Spirometry will be performed in asthmatic patients only.  
• 
Blood collection will be done for: 
– Laboratory tests (hematology and biochemistry) 

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– Immunological markers 
– Serum and RNA banking wherever permitted by local regulations 
• The Investigator/co-Investigator should check the “AE/Concomitant Medication” paper card 
provided to the patient at the previous visit.  Adverse events and concomitant medication will 
be recorded.  
• 
Patient self-administered questionnaires are to be completed at the site: Standardized 
Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ(S)≥12), Work Productivity and 
Activity Impairment (WPAI) Questionnaire plus Classroom Impairment Questions (CIQ), 
Allergy Specific (AS), and EQ-5D-5L.  
• 
Patient should complete the Global Rating of Change Questionnaire at the site.  
• 
IP boxes and blisters (whether empty/used or unused) should be collected and checked, and 
the “Drug Accountability Form” kept up-to-date by the study site staff. 
• 
All used and unused RM previously dispensed should be collected and the “Drug 
Accountability Form” kept up-to-date by the study site staff. 
• 
Unused epineprine auto-injector should be returned to the study site. 
• 
An appointment will be made for Visit 10. 
9.3.10 
Visit 10 (Post-Treatment Follow-Up Visit) 
• 
This visit is to be performed 14 days ± 7 days after Visit 9. 
• Adverse events and concomitant medication will be recorded. A physical examination will be 
performed depending on medical findings, if any. 
9.3.11 
Early Termination Visit 
In case of Early Termination Visit, all assessments described for Visit 9 are to be done. 
In order to avoid missing data, patients who discontinued treatment before the first interim 
evaluation period (i.e., Visit 5, after 3 months of treatment) will be asked to score their 
rhinoconjunctivitis symptoms and rescue medication use on the e-diary during the first interim 
evaluation period, off study treatment. 
9.4 
Other Supplies  
9.4.1 
Rescue Medication (Section 8.2.2 “Rescue Medications”) 
Patients will be supplied with rescue medication by the sites. 
9.4.2 
Skin Prick Test Kits (Section 9.2.7 “Skin Prick Test”) 
STALLERGENES will supply the investigational sites with a SPT kit. 
The SPT kit will contain: 

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- Vials of allergen solutions of each of the allergen listed in Appendix V, 
- Positive control (Histamine dihydrochloride 10 mg/mL) and negative control (saline diluent), 
- Pricking device, 
- Hypoallergenic transparent tape (Blenderm), 
- Black fine-tip rolling pen. 
The allergen solutions and controls are to be stored in the refrigerator at 2°C-8°C. 
9.4.3 
Blood Sampling Kits (Section 9.2.10 “Blood sampling”) 
Wherever permitted by local regulations, the sites will be provided with a separate laboratory 
manual and laboratory kit material. The laboratory manual will contain the sampling, handling and 
shipment procedures. 
9.4.4 
Dust Sampling Kits (Section 9.2.11 “Dust Sampling”) 
Patients will be supplied by STALLERGENES with a dust collector kit, the packaging /shipment 
material and procedure for sampling the dust at their residence. 
9.4.5 
Pregnancy Tests (Section 9.2.12 “Pregnancy Test”) 
The investigational sites will be supplied with urine pregnancy tests by STALLERGENES. 
10. ASSESSMENT OF EFFICACY 
10.1 Primary Efficacy Variable  
The primary efficacy variable will be the average Total Combined Score (TCS). The average TCS 
is calculated for each patient as the average of the non-missing daily TCSs. 
The daily TCS (scale 0-15) is the sum of the patient’s daily Rhinitis Total Symptom Score (RTSS, 
scale 0-12) and daily Rescue Medication Score (RMS, scale 0-3).  
The RTSS is defined as the sum of the four rhinitis symptom scores (i.e., itchy nose, sneezing, 
runny nose, and blocked nose) evaluated daily by the patient. The patient assessment will address 
symptom intensity over the previous 24 hours and will be performed at the same time every 
morning, using a 4-point scale (0 = no symptoms; 1 = mild symptoms (symptom clearly present, 
but minimal awareness; easily tolerated), 2 = moderate symptoms (definite awareness of symptom 
that is bothersome but tolerable), 3 = severe symptoms (symptom that is hard to tolerate; causes 
interference with activities of daily living and/or sleeping).  
If any of the four individual rhinitis symptoms for a given day is missing, then the RTSS for that 
day will be considered missing. 
The RMS is based on the assumptions that an intranasal corticosteroid is more effective than an 
antihistamine and an oral corticosteroid is more effective than an intranasal corticosteroid, leading 

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to a derived ordinal scale: 0=absent, 1=oral associated or not with topical (ocular drops) non-
sedative H1 antihistamine (H1A), 2= intranasal corticosteroids (INS) with or without oral or topical 
(ocular drops) H1A, 3=oral corticosteroids with or without INS or oral or topical (ocular drops) 
H1A. 
If rescue medication data for a given day are missing, then the RMS for that day will be considered 
missing. 
The average TCS will be calculated for each patient and each evaluation period as the average of 
the non-missing daily TCSs during the corresponding period. 
10.2 Secondary Efficacy Variables 
The following variables will be calculated for each evaluation period (baseline, interim, primary): 
10.2.1 
Rhinitis Total Symptom Score (RTSS)  
The daily RTSS ranges from 0 to 12. The average RTSS is calculated for each patient as the average 
of the non-missing daily RTSSs during the evaluation periods.  
10.2.2 
Rescue Medication Score (RMS) 
The Rescue Medication Score (RMS) ranges from 0 to 3. The average RMS is calculated for each 
patient as the average of the non-missing daily RMSs during the evaluation periods. 
10.2.3 
Adjusted Symptom Score (ASS)  
The Adjusted Symptom Score (ASS) ranges from 0 to 12. This score is derived from the daily 
RTSSs, after adjustment for the patient's rescue medication use. It is patient specific, and will take 
into account that patients are permitted to make use of any of the three categories of rescue 
medication [Grouin et al.,2011]. 
The ASS is derived as follows: 
- 
ASS and RTSS are equal the first valid day: ASS1 = RTSS1. 
- 
If a patient did not take rescue medication at day d and the day before (d-1) then: 
ASSd = RTSSd. 
- 
If a patient took rescue medication at day d, the ASSd will equal the higher value between 
the RTSS at day d and the ASS of the previous day. 
ASSd = max (RTSSd, ASSd-1) 
ASSd+1 = max (RTSSd+1, ASSd) 
Missing data management:  
- 
If the RTSSd is missing, the ASSd is missing  
- 
If the information on rescue medication intake is missing, then: ASSd = RTSSd  
- 
If a patient takes rescue medication at day (d) and RTSSd-1 is missing then: ASSd = RTSSd  

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The patient estimates the intensity of his/her rhinitis symptoms retrospectively over the previous 
24 hours. When he/she takes a rescue medication like antihistamine or nasal corticosteroids, this 
rescue medication may impact the symptom score assessment on the day of intake and also on the 
following day. For oral corticosteroids, impact on symptoms probably lasts more than 24 hours and 
an adjustment for more than 2 consecutive days could be considered. However, by doing so, the 
adjustment may be overestimated. 
The average ASS is calculated for each patient as the average of the non-missing daily ASSs during 
the evaluation periods. 
10.2.4 
Combined Symptom and MedicationScore (CSMS)  
The CSMS is a score combining the patient’s daily RTSS and RMS, assuming equivalent 
importance of symptoms and medication scores [Pfaar et al.,2014]. Since the RMS ranges from 0 
to 3 and the RTSS ranges from 0 to 12, the CSMS will be calculated by adding the RMS to the 
RTSS/4, in order to obtain comparable scales. Thus 
CSMS = RTSS/4 + RMS resulting in a daily CSMS ranging from 0 to 6. 
10.2.5 
Total Ocular Symptom Score (TOSS) 
The Total Ocular Symptom Score (TOSS) ranges from 0 to 6. TOSS is calculated as the sum of 
individual scores for itchy/red eyes and watery eyes (each on a scale 0-3). The average TOSS is 
calculated for each patient as the average of the non-missing daily TOSSs during the evaluation 
periods.  
10.2.6 
Rhinoconjunctivitis Total Symptom Score (RCTSS)  
The daily RCTSS ranges from 0 to 18. RCTSS is calculated as the sum of the four rhinitis scores 
and the two ocular scores (each on a scale 0-3). The average RCTSS is calculated for each patient 
as the average of the non-missing daily RCTSSs during the evaluation periods.  
10.2.7 
Six Individual Rhinoconjunctivitis Symptom Scores (RSSs) 
The severity of the six rhinoconjunctivitis symptoms (itchy nose, sneezing, runny nose, blocked 
nose, itchy/red eyes and watery eyes during the previous 24 hours will be scored using a 4-point 
scale (0: Absence, 1: Mild, 2: Moderate, 3: Severe). The average of each of the six individual RSSs 
is calculated for each patient as the average of the non-missing daily RSSs during the evaluation 
periods. 
10.2.8 
Rhinoconjunctivitis Rescue Medication Usage 
The rhinoconjunctivitis rescue medication usage (yes/no), overall and by type of treatment, will be 
recorded on the e-diary during all the evaluation periods.  

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10.2.9 
Visual Analogue Scale (VAS) 
At the end of each week of the evaluation periods, patients will assess the intensity of their allergic 
rhinitis symptoms using a Visual Analog Scale (VAS), ranging from “absence of symptoms” (score 
= 0) to “very severe symptoms” (score = 100) [Jamison et al.,2002; Bousquet et al.,2009]. 
The average VAS is calculated for each patient as the average of the non-missing weekly VAS 
scores during the evaluation period. 
10.2.10 Proportion of Symptom-Controlled Days (PSCD)  
The PSCD is defined for each patient during the evaluation periods as the proportion of days (%) 
in the evaluation period where RTSS ≤2 and no rescue medication is used (RMS=0), i.e., PSCD2-0. 
This variable will be calculated for the baseline, interim and primary evaluation periods.  
10.2.11 Proportion of Not-Controlled Days (PNCD)  
The PNCD is defined for each patient during the evaluation periods as the proportion of days (%) 
with: 
- At least one individual rhinitis symptom score = 2 and RMS>0, or 
- At least two individual rhinitis symptom scores = 2 whatever the RMS, or 
- At least one individual rhinitis symptom score = 3 whatever the RMS 
This variable will be calculated for the baseline, interim and primary evaluation periods. 
10.2.12 Controlled patients (CP)  
Controlled patients are defined as follows: 
CP752-0: Patients with at least 75% of the days with RTSS ≤2 and no rescue medication used 
(controlled for at least three quarters of the days in the evaluation periods). 
This variable will be calculated for the baseline, interim and primary evaluation periods. 
10.2.13 Standardized Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ(S)≥12) scores 
The RQLQ(S)≥12 consists of 28 questions, divided into 7 domains (activities (3 items), sleep (3), 
non-nose/eye symptoms (7), practical problems (3), nasal symptoms (4), eye symptoms (4) and 
emotions (4)), each question being evaluated on a 7-point Likert scale, from 0 to 6 (lower being 
better). All items are weighted equally. The score for each domain is the mean of the items in that 
domain (provided that all items of the domain are completed), while the overall RQLQ(S)≥12 score 
is the mean of all items (provided that the 28 items are completed). The RQLQ(S)≥12 will be used 
for both adult and adolescent patients. 
This quality of life variable will be calculated at Visit 3 (before treatment) and Visit 9 (end of 
treatment period). 

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10.2.14 EQ-5D-5L Generic Health-Related Quality of Life Questionnaire 
The EQ-5D-5L describes the patients’ health state using 5 questions assessing 5 dimensions, 
namely: 
1. Mobility, 
2. Self-care, 
3. Usual 
activities, 
4. Pain/Discomfort 
and 
5. Anxiety/Depression. Each question is evaluated on a 5-point scale. The patients also self-rate 
their overall health on a VAS ranging from 0 (“the worst health you can imagine”) to 100 (“the 
best health you can imagine”). 
This quality of life variable will be calculated at Visit 3 (before treatment) and Visit 9 (end of 
treatment period). 
10.2.15 Global Rating of Change Score (GRCS) 
The GRCS measured on the Global Rating of Change questionnaire, is a global assessment of the 
treatment efficacy compared to the baseline evaluation period on a 15-point Likert scale.  
This variable will be assessed at Visit 9 (end of treatment period). 
10.3 Other Variables 
10.3.1 
Work Productivity and Activity Impairment Questionnaire plus Classroom 
Impairment Questions: Allergy Specific (WPAI + CIQ: AS) 
The questionnaire is divided in 3 parts: work performance (4 questions), school performance 
(4 questions) and impact of allergic rhino-conjunctivitis on the daily activities (one question). 
Seven scores, expressed as percentages, will be calculated from the questions at baseline (Visit 3) 
and at the end of the treatment (Visit 9). 
10.3.2 
Immunological Markers (IgE and IgG4) 
D. pte and D. far specific serum IgE and IgG4 will be assayed at Visit 1 (before treatment) and 
Visit 9 (after 12 months of treatment). 
10.4 Exploratory Variables 
10.4.1 
Candidate Biomarkers 
The candidate biomarkers to be assayed will be listed in a separate document. 
10.5 Baseline Characteristics 
The baseline characteristics are: gender, date of birth, ethnic origin, height, weight, start date of 
HDM-associated AR, asthma status, FEV1 measurements, and Skin Prick Tests results. 
The following baseline variables will be derived/calculated:  
- 
Age, age class, Body Mass Index (BMI) 
- 
Duration of allergic rhinitis 

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- 
Sensitization status (mono- versus poly-sensitivity): derived from the skin prick test results 
at Visit 1. Patients will be categorized as mono-sensitized if they are positive to HDM (D. 
pte and/or D. far) allergens only or poly-sensitized if they are positive to HDM and at least 
one other allergen  
- 
Average rhinoconjunctivitis symptom and rescue medication scores recorded during the 
baseline period. Recordings performed before the 4-week baseline period will be 
considered as training in the use of the e-diary and will be excluded from the analysis 
- 
Rhinoconjunctivitis rescue medication use 
- 
RQLQ(S)≥12 overall score and scores by domain 
- 
Overall assessment of rhinoconjunctivitis symptoms by a VAS 
- 
EQ-5D-5L five questions and VAS score  
- 
Work Productivity and Activity Impairment questionnaire scores plus Classroom questions 
- 
Baseline HDM exposure level assessed by the content of mite group 1 allergen per gram of 
dust in the sample collected at the patients’ residence. This variable will be categorized as: 
• HDM exposure level ≥2 μg of mite group 1 allergen per gram of dust 
• HDM exposure level <2 μg of mite group 1 allergen per gram of dust 
The baseline values will correspond to the last evaluation before the first IP intake in the treatment 
period.  
10.6 Methods and Timing for Assessing, Recording, and Analyzing the Efficacy Variables 
A one-year treatment period is considered adequate for assessing the efficacy of allergen 
immunotherapy [Burks et al.,2013].Therefore, the primary efficacy variable, the average TCS, will 
be assessed at the end of the 12 months of treatment. 
For specific immunotherapy, onset of efficacy is not expected in the first weeks of treatment. 
Therefore, in this study, the first interim evaluation period for efficacy is at Month 3.  
The methods and timing for assessing and recording the efficacy variables are found in Section 9 
“Study Procedures”. 
The analysis methods are found in Section 12 “Statistics”. 
11. ASSESSMENT OF SAFETY 
11.1 Specifications of Safety Variables 
The safety variables are adverse events (AEs) and data from the physical examination assessments, 
vital signs, and safety laboratory tests. 
11.2 Methods and Timing for Assessing, Recording, and Analyzing the Safety Variables 

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The methods and timing for assessing and recording the safety variables are described in 
Section 3.6 “Flow Chart” and Section 9.3 “Visit by Visit Description”. 
 
The analysis methods are described in Section 11.3 “Adverse Events”. 
11.3 Adverse Events 
The Investigator is responsible for recording all AEs experienced by the patient from the time the 
Informed Consent Form is signed until the patient is discharged from the study.  
At each visit, the patient will be given the opportunity to report AEs.  
A general prompt will also be given: 
“Did you notice anything unusual about your health since your last visit?” 
In addition, the Investigator should review all patient self-assessment tools for information 
regarding AEs. 
11.3.1 
Definitions 
11.3.1.1 Adverse Event 
An Adverse Event (AE) is defined as any untoward medical occurrence in a patient or clinical 
investigation subject administered an investigational product (IP) and which does not necessarily 
have a causal relationship with this treatment. An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom or disease temporally 
associated with the use of an IP, whether or not considered related to the IP. 
Signs or symptoms of the condition/disease for which the IP is being studied should be recorded 
as AEs only if their nature changes considerably or their frequency or intensity increases in a 
clinically significant manner as compared to the clinical profile known to the Investigator from the 
patient’s history or the baseline period. 
In cases of surgical or diagnostic procedures, the condition/illness leading to such a procedure is 
considered as an AE rather than the procedure itself. 
The following guidelines and definitions should be used by the Investigator for the description of 
an AE when reporting information. 
Nature of the Adverse Event 
It should be preferably an overall diagnosis or syndrome, rather than individual symptoms or signs. 
The Investigator must report AEs using standard medical terminology. The same terms must be 
used in the source documentation and in the e-CRF. Any discrepancies between the patient’s own 
words on his/her own record (i.e., “AE/Concomitant Medication” card) and the corresponding 
medical terminology should be clarified in the source documentation. 

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Assessment of Severity of the Adverse Event 
Investigators must assess the severity of AE according to the following qualitative scale. The 
severity grade does not reflect the clinical seriousness of the event only the degree or extent of the 
affliction or occurrence (e.g., severe nausea, mild seizure), and does not reflect the relationship to 
Investigational Product (IP). 
- 
Mild: The patient is aware of the event or symptom, but the event or symptom is easily tolerated 
and not interfering with his/her daily activity. 
- 
Moderate: The patient experiences sufficient discomfort to interfere with or reduce his/her 
daily activity. 
- 
Severe: Significant impairment for the patient who is unable to carry out his/her daily activity. 
An AE reflecting a change in severity grade should be reported on two separate lines with 
respective severity grade. The Investigator’s original description of the AE must be the same for 
the first and repeated AE, so that they are coded with the same dictionary term. The outcome date 
of the first AE should be the same as the start date of the repeated AE, and the outcome of the first 
AE should be ticked for data management purpose, as resolved. 
Example: 
Adverse Event 
Severity 
Start Date 
End Date 
Outcome 
Headache 
Mild 
01-MAR-2012 
03-MAR-2012 
Resolved 
Headache 
Moderate 
03-MAR-2012 
Ongoing 
Not Resolved 
In the case of local side effects, the grade “severe” should be considered only when these local side 
effects lead to the permanent discontinuation of the IP [Passalacqua et al.,2013]. 
Occurrence 
- 
Intermittent: An AE which occurs repeatedly with the same intensity with an interval of less 
than 24 hours between occurrences. There are intervals within the specified time period when 
the AE is not present. 
- 
Continuous: The AE is present with the same intensity for the entire time period specified. 
There is no time at which the event abates or is not present during the time period specified. 
Action taken with the Investigational Product following AE occurrence: 
- 
Not applicable: For AEs occurring before the IP is administered or occurring after the 
administration of the IP was stopped. 
- 
Dose not changed: IP dosing remained the same in spite of an AE being present. 
- 
Drug interrupted: IP usage is temporarily discontinued because of the AE, either because the 
patient chooses to interrupt the IP or the physician feels it is in the patient’s best interest to 
temporarily discontinue the IP. 

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- 
Drug withdrawn: IP usage is permanently discontinued because of the AE, either because the 
patient chooses to discontinue the IP or the physician feels it is in the patient’s best interest to 
discontinue the IP. 
Other action taken following AE occurrence: 
Any other action taken in response to an AE is to be selected as: 
- 
None: No other action was taken for the AE. 
- 
Medication: The patient took a medication (either prescription or non-prescription) 
specifically for the AE. 
- 
Emergency visit 
- 
Therapeutic or diagnostic procedure: The patient used other therapeutic measures (for 
example, ice, heating pad, brace or cast) or the patient underwent a diagnostic procedure (for 
example, additional lab test or X-ray) for the AE. 
Outcome at the time of last observation 
- 
Resolved: The AE is no longer present at any severity grade - symptoms have completely 
abated or returned to baseline value in case of worsening of a pre-existing condition. 
- 
Resolved with sequelae: The patient recovered from the event but retained pathological 
conditions resulting from the AE. 
- 
Not resolved: The AE has not resolved, and is still present either with the same severity grade 
(or has not returned to the baseline value in case of worsening of a pre-existing condition) or is 
improving. 
- 
Fatal: The AE directly caused or contributed to the patient’s death. In this case a Serious 
Adverse Event (SAE) form must be completed. 
- 
Unknown: There is no information available on the outcome of the AE. 
Assessment of Relationship to the Investigational Product 
Investigators must systematically assess the causal relationship of AEs to the IP using the following 
definitions. Decisive factors for the assessment include, but may not be limited to, temporal 
relationship between the AE and IP, known adverse reactions, medical history, concomitant 
medication, course of the underlying disease, alternative etiology, etc. 
The relationship between the administration of IP and the occurrence of the AE is described as 
belonging to one of the two following categories: 
- 
Not suspected: The event is not suspected to be reasonably related to the IP and could not 
medically (pharmacologically/clinically) be attributed to the IP. A reasonable alternative 
explanation must be available. 
- 
Suspected: The event is suspected to be reasonably related to the IP and could medically 
(pharmacologically/clinically) be attributed to the IP. 

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11.3.1.2 Serious Adverse Event 
A Serious Adverse Event (SAE) is defined as any untoward medical occurrence or effect that at 
any dose: 
- 
Results in death, 
- 
Is life-threatening*, 
- 
Requires hospitalization or prolongation of existing inpatients hospitalization**, 
- 
Results in persistent or significant disability or incapacity, 
- 
Is a congenital anomaly or birth defect, 
- 
Is otherwise considered as medically significant***. 
* Life-threatening refers to an event in which the patient was at immediate risk of death at time of 
event; it does not refer to an event which hypothetically might have caused death if it was more 
severe. 
** The following hospitalizations may not be considered serious: 
- 
Hospitalization planned before entry into the clinical study, 
- 
Hospitalization for elective treatment of a pre-existing condition, 
- 
Consultation in an emergency ward, on outpatient basis and which do not result in overnight 
hospitalization (unless fulfilling one of the above criteria). 
*** Medically significant events that may not result in death, be life-threatening, or require 
hospitalization may be considered as SAEs when, based upon appropriate medical judgment, they 
may jeopardize the patient or may require medical or surgical intervention to prevent one of the 
other outcomes listed above (e.g., an event such as bronchospasm that requires intensive treatment 
but does not result in hospitalization). 
Any suspected transmission of an infectious agent via the IP is also considered a SAE. 
11.3.1.3 Pre-defined Adverse Event of Special Interest 
An Adverse Event of Special Interest (AESI) is a noteworthy event that requires careful 
monitoring. It could be serious or non-serious.  
Special attention should be paid to any symptoms evoking one the 4 following clinical pictures 
fulfilling the definition of an AESI: 
- 
Severe anaphylactic reactions, 
- 
Severe laryngopharyngeal disorders, 
- 
Autoimmune disorders, 
- 
Eosinophilic esophagitis. 
AESIs will be identified and reviewed during the Data Review Meeting (DRM). 

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11.3.2 
Reporting 
11.3.2.1 Reporting of AE 
All AEs will be actively sought for at each visit. Complete, accurate and consistent data on all AEs, 
whether spontaneously reported by the patient, discovered by Investigator questioning, or detected 
through physical examination, laboratory test or other means, will be reported on an ongoing basis 
in the e-CRF in the "Adverse events" section and followed as appropriate. 
If an AE is still present at the time the e-CRF is being locked, a follow-up report shall be provided 
later on. If no follow-up report is provided, the Investigator shall provide a justification. 
If a patient is withdrawn from treatment due to safety reasons, the patient should be followed until 
the event resolves or the patient’s condition has stabilized. 
For each AE, the Investigator should specify its nature, start date, time to onset between last IP 
intake and AE occurrence , duration (if less than 24 hours), stop date, occurrence, action(s) taken 
with IP, other(s) action(s) taken and outcome. The Investigator should evaluate the event in terms 
of severity, relationship to IP, and seriousness.  
Specific guidance can be found in the e-CRF completion guidelines provided by the Sponsor or 
designee. 
All AEs occurring during the study (from signature of the Informed Consent Form/Assent Form to 
last visit) must be reported, even if no IP was taken. 
 
Medical conditions present at the initial study visit and that do not worsen in severity or frequency 
during the study are defined as Baseline Medical Conditions, and are NOT to be considered as 
AEs. 
11.3.2.2 Reporting of SAE and Serious AESI  
All SAEs including serious AESIs, as defined above, whether or not considered as related to IP, 
must be transmitted according to the following process: 
SAEs including serious AESIs must be reported by the Investigator immediately (i.e., within a 
maximum of 24 hours of occurrence or Investigator’s awareness) by fax or email (relevant contact 
name, fax number and email address can be found in the Investigator Site File). 
The Investigator must duly complete the SAE form even if the data are incomplete or if it is obvious 
that more data will be needed to draw any conclusions. Reporting procedures and timelines are the 
same for any follow-up information. 
Additional information (e.g., lab data, hospital report) should be provided to the Sponsor or 
designee in a timely manner to ensure accurate follow-up of each case. SAEs and serious AESIs 
must be followed up until resolution or until stabilization. If needed, the Sponsor or designee may 
contact the Investigator to obtain further relevant information regarding a SAE or a serious AESI. 
All SAEs and serious AESIs occurring during the study (from signature of the Informed Consent 
Form/Assent Form to last visit) must be reported even if no IP was taken. 

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After the end of the study, it is the Investigator’s obligation to report to the Sponsor any SAE of 
which he becomes aware and that he considers as possibly related to the IP, if the SAE occurs up 
to 30 days after the last IP administration. 
SAE occurring after the study 
SAEs occurring after the study completion and considered related to the IP have to be reported 
directly to the Sponsor immediately (i.e., within a maximum of 24 hours of occurrence or 
Investigator’s awareness). 
Sponsor fax number: +33 1 55 59 26 62 or email: pharmacovigilance@stallergenes.com and copy 
to STALLERGENES Clinical Project Manager. 
Safety reporting to Health Authorities, Ethics Committees and Investigators 
The Sponsor is responsible for complying with the applicable requirements related to adverse 
experiences by reporting to the appropriate Health Authorities, Ethics Committees and 
Investigators. 
The Investigator must comply with any applicable site-specific requirements related to the 
reporting of SAEs involving patients to the Ethics Committees that approved the study. 
11.4 Unblinding 
Under normal circumstances, the treatment blind must be maintained. 
In the case of medical emergency in which knowledge of the treatment allocation is considered by 
the Investigator as critical in managing the patient’s condition, the Investigator will utilize 
IVRS/IWRS and use the unblinding functions. In case of technical issues with the IVRS/IWRS 
system, the Investigator will contact either the responsible person from the Pharmacovigilance 
department or primary CRO designee to unblind the patient. 
If the blind is broken, the date, the reason for breaking the blind, and person doing so is to be 
recorded on the source document, and in the appropriate e-CRF page, and STALLERGENES or 
its representative must be notified immediately. Once the randomization code has been broken, the 
particular patient’s data will no longer be considered eligible for the “Per Protocol” set efficacy 
analysis.  
However, when the unblinding was only performed by the Pharmacovigilance department for an 
adverse event declaration to the regulatory authorities, and not shared with the investigators or 
study staff, then the patient’s data will still be considered as blinded. The patient’s data will be 
valid for the “Per Protocol” set efficacy analyses if the patient is otherwise valid. 
11.5 Overdose 
During the study, any daily intake superior to the dose specified in the protocol will be recorded as 
a misuse. When the data are unblinded, any daily intake of at least 400 IR will be considered as an 
overdose. 
Symptoms associated with a misuse must be recorded as AEs. 

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Misuse should be documented in the e-CRF. 
11.6 Pregnancy 
A newly diagnosed pregnancy itself will not be considered as an AE unless it is suspected that the 
IP interacted with a contraceptive method or had some association with the occurrence of 
pregnancy. 
A congenital anomaly, spontaneous or therapeutic abortion, stillborn, neonatal death or birth defect 
as a pregnancy outcome is a SAE. 
Before study enrolment, female patients of childbearing potential must be advised of the 
importance of avoiding a pregnancy during their study participation. Pregnancy should be avoided 
for the duration of the study so as to ensure that any possible risk to the embryo, fetus and baby be 
minimized. All females of childbearing potential must be willing to undergo a urine pregnancy test 
before any IP is administered. 
For all pregnancies confirmed after the first IP administration, the Investigator must complete a 
pregnancy notification form which must be transmitted according to the same process as described 
for SAE reporting. The Sponsor must be notified without delay. Patient must be withdrawn from 
the study. Investigators must actively follow-up, document and report on the outcome of all 
pregnancies, including prenatal and neonatal outcome, even after the patients are withdrawn from 
the study. Infants will be followed for a minimum of 6 months. Protocol-required procedures for 
clinical study discontinuation and follow-up must be performed unless contra-indicated by the 
pregnancy. Other appropriate pregnancy follow-up procedures should be considered if indicated. 
11.7 Management of Adverse Events and Patient Discontinuation from Study  
11.7.1 
Adverse Event Necessitating Temporary Discontinuation of the IP 
In case of oral surgery, including dental extraction or any intervention affecting oral mucosa, IP 
administration should be stopped until complete healing.  
Whenever IP has to be discontinued temporarily, IP may be restarted at the dosage of last intake. 
Should the interruption period be longer than 7 days, it is recommended to restart the treatment 
under medical supervision, at the dosage of last intake. 
11.7.2 
Patient Discontinuation from Study  
It is ultimately the Investigator’s decision as to whether or not to withdraw a patient from the study 
in case of an AE. 
In the occurrence of one of the following events, patients will be systematically discontinued from 
the study and the IP should be stopped: 
- 
an anaphylactic reaction  
- 
or a severe laryngopharyngeal reaction 

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- 
or 
eosinophilic 
esophagitis(*) 
confirmed 
by 
characteristic 
findings 
on 
esophagogastroduodenoscopy (EGD) and histologic analysis of EGD biopsies.  
(*)Patients with symptoms suggestive of esophagitis will be assessed in accordance with Appendix 
VI “Management of Suspected Esophagitis”. 
11.7.3 
Management of Adverse Events 
Management of AEs is at the discretion of the Investigator. 
11.8 Independent Data Safety Monitoring Board Review 
An independent DSMB will be responsible for assuring that study patients are not exposed to 
unnecessary or unreasonable risks and that the study is being conducted according to high scientific 
and ethical standards. Specifically, the DSMB will: 
• assess the performance of the study with respect to patient recruitment, retention and 
follow-up, protocol adherence, and data quality and completeness, in order to ensure the 
likelihood of successful and timely study completion, 
• 
blindly assess the overall safety and re-assess the risk/benefit of the study on a regular 
basis. 
12. STATISTICS 
The statistical methods are summarized below and will be developed and finalized prospectively 
in the Statistical Analysis Plan (SAP) before unblinding. All analyses will be carried out using 
SAS® Version 9.4. 
Unless otherwise specified, all variables will be summarized descriptively by treatment group (and 
overall for initial characteristics only) as follows: 
• continuous variables will be summarized descriptively using summary statistics (number 
of subjects, number of missing values, mean, Standard Deviation [SD], 95% two-sided 
Confidence Interval [CI] of the mean, minimum, lower quartile, median, upper quartile, 
and maximum). 
• categorical variables will be presented using absolute and relative frequencies and 95% CIs 
for each class of the studied parameter, where appropriate. 
For all analyses, the probability of a type I error will be set at 5% and the confidence level at 95% 
for CI. All inferential tests will be two-sided tests.  
 
In order to control the overall type I error and to draw robust conclusions with regard to the key 
secondary endpoints, a step-down sequential closed testing procedure will be applied on six 
secondary endpoints if the primary endpoint is statistically significant. The key secondary 
endpoints will be tested in the following order:  

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• 1. Rhinitis Total Symptom Score (RTSS) during the primary evaluation period 
• 2. Overall score of Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) at the end of 
the treatment period 
• 3. Rhinoconjunctivitis Total Symptom Score (RCTSS) during the primary evaluation period 
• 4. Blocked nose symptom score during the primary evaluation period 
• 5. Proportion of Symptom-Controlled Days (PSCD, proportion of days with RTSS≤2 and 
no rescue medication use) during the primary evaluation period 
• 6. Rescue Medication Score (RMS) during the primary evaluation period 
12.1 Determination of Sample Size 
The primary endpoint is the average TCS defined, for each patient, as the average of the non-
missing daily TCSs over the last four weeks prior to the end of the treatment period. 
As recommended by the US Food and Drug Administration (FDA), the clinical relevance of the 
efficacy results on the primary endpoint is pre-defined as follows [Nelson et al.,2017]: 
• The relative difference of the TCS versus placebo should be ‐15%, and  
• The upper bound of the 95% CI of the TCS relative difference versus placebo should be 
‐10% 
In the European study VO57.07 [Bergmann et al., 2014] conducted in 509 patients, the analysis of 
the average TCS showed a placebo mean of 3.65 and a relative mean difference of ‐17% between 
groups with a 95% CI of [‐30% ; ‐3%]. The CV was of 67% in the placebo group and 77% in the 
active group. 
Based on this 95% CI (i.e., [‐30% ; ‐3%]), an expected  relative difference versus placebo of ‐20% 
was considered as a possible and reasonable value for the true relative difference between both 
groups. Besides, a CV of 75% was assumed to account for a possible higher variability of the data in 
this international study (i.e., North America, Europe, Israel and Russia). 
Thus, assuming a two-sided nominal level of significance of 5%, a relative difference versus 
placebo of ‐20%, a placebo mean of 3.65, and a CV of 75%, simulations were performed based on 
5,000 samples and showed that 739 evaluable patients per treatment group were sufficient to 
achieve a power of around 80% so as to fulfill both requirements (estimated relative difference 
versus placebo ≤‐15% and upper bound of the 95% CI ≤‐10%). 
Of note, with the same assumptions and 739 evaluable patients per treatment group, the power of 
detecting a significant difference between both groups is greater than 99%.  
Assuming a drop-out rate of 15% during the study, a total of 1,740 randomized patients 
(870 patients per group) will be required to ensure that 1,478 patients are included in the primary 
efficacy analysis. The screen failure rate is estimated at 50%, leading to a planned total number of 
screened patients of 3,480. 

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12.2 Definition of Clinical Relevance of the Efficacy Results 
As recommended by the US Food and Drug Administration (FDA), the clinical relevance of the 
efficacy results on the primary endpoint is pre-defined as follows [Nelson et al.,2017]: 
• The relative difference of the TCS versus placebo should be ‐15%, and  
• The upper bound of the 95% CI of the TCS relative difference versus placebo should be 
‐10% 
See Section 12.5.2 “Primary Efficacy Analysis” for the definition of the relative difference and its 
95% CI. 
Based on historical data obtained with STG320 in study VO57.07 [Bergmann et al.,2014], it is 
expected that the baseline average Total Combined Score (TCS) will be close to 7. Thus, a 
clinically meaningful effect of 15% in a given patient with an initial TCS of 7 would correspond 
to an improvement of about 1 point (15% of 7 is 1.08). More specifically, this threshold may be 
illustrated using e.g., the two following clinical cases:  
• With an initial TCS of 7 and a constant RM intake, the patient will benefit from a symptom 
improvement of 1 point corresponding to a change of one severity class in one symptom 
e.g., from “severe” to “moderate”  
• With an initial TCS of 7 and a stable symptom severity, the patient will experience a 
decrease of one step in RM intake e.g., s/he will stop the intranasal corticosteroids (from 
step 2: intranasal corticosteroids with or without antihistamine to step 1: antihistamine) or 
s/he will not take rescue medication anymore (from step 1: antihistamine to no rescue 
medication) 
This clinical benefit is expected to last all year round as HDM allergic rhinitis induces perennial 
symptoms. 
12.3 Determination of Study Population for Analysis 
Safety Set: 
The Safety Set will include all randomized patients who received at least one dose of the IP. 
All safety analyses will use the Safety Set. 
Full Analysis Set (FAS): 
In order to be as close as possible to the Intent-To-Treat (ITT) principle, the Full Analysis Set will 
include all randomized patients who received at least one dose of the IP and have at least one 
primary efficacy evaluation during a treatment period, (i.e., at least one day with a valid TCS during 
one of the evaluation periods). 
The FAS will be the primary analysis set for all efficacy analyses (primary, secondary, exploratory 
and other analyses). 

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Per Protocol Set (PPS): 
The Per Protocol Set will include all patients in the FAS who complied with the study protocol 
without any major protocol deviations and had at least 14 days with a valid TCS during the primary 
evaluation period. 
The primary efficacy analysis will be replicated in the PPS. 
The definition of protocol deviations (minor or major) will be specified in the SAP. The 
classification of the protocol deviations as minor or major will be performed during the Data 
Review Meeting (DRM) before unblinding of the data.  
12.4 Handling of Missing and Incomplete Data 
Missing data will be handled according to the guideline on missing data in confirmatory trials 
(Guideline on Missing Data in Confirmatory Clinical Trials EMA/CPMP/EWP/1776/99 Rev.1, 
2010). 
If any of the individual rhinoconjunctivitis symptom scores or rescue medication data for a given 
day are missing, the TCS, RTSS, ASS, TOSS, RMS including the missing score(s) for that day will 
be considered missing. Average scores will be calculated using the non-missing days in the 
respective evaluation period. 
The proportion of valid TCS days during the primary period will be summarized by treatment group 
in the FAS in order to evaluate the extent of missing TCS data. 
In order to prevent missing data, patients who discontinued the treatment before the first interim 
evaluation period (i.e., before 3 months of treatment) will be asked to continue the study (without 
study treatment) until Visit 5 (i.e., until the end of the first interim evaluation period). Patients will 
be asked to score their rhinoconjunctivitis symptoms and rescue medication use on the e-diary 
during the first interim evaluation period.  
In addition, different sensitivity analyses will be investigated and developed prospectively in the 
SAP, to assess the robustness of the primary analysis with regard to missing data. These include 
but are not limited to the following: 
• Pattern-Mixture Models (PMMs) with reference-based imputation methods using each interim 
evaluation period and the primary period as repeated measures. These multivariate models 
implement Missing Not At Random assumptions using multiple imputations 
• Mixed Model with Repeated Measures (MMRM) with each interim evaluation period and the 
primary period as repeated measures. This multivariate model applies a missing at random 
assumption and is a direct likelihood method in which information from the observed data is 
used via the within-patient correlation structure to provide information about the unobserved 
data  
• Last Observation Carried Forward (LOCF) as a single imputation method that imputes the last 
measured outcome value for patients who either drop out or for whom the final outcome 
measurement is missing 

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12.5 Efficacy analyses 
12.5.1 
Evaluation Periods 
Rhinoconjunctivitis symptoms and rescue medication use will be recorded daily on the e-diary at 
the following periods: 
- 
baseline period (placebo run-in): last 4 weeks of the 5-week run-in period 
- 
interim evaluation periods: 2 weeks every 3 months after randomization (i.e., Month 3, Month 6 
and Month 9), 
- 
primary period: 4 weeks prior to the end of the treatment period. 
12.5.2 
Primary Efficacy Analysis 
The primary variable, the average TCS, will be summarized descriptively. The square root of the 
average TCS will be analyzed in the FAS during the primary evaluation period using an Analysis 
of Covariance (ANCOVA) with treatment group as main effect and pooled center, the square root 
of the baseline average TCS, age class (adolescent, adult), gender, asthma status (presence/absence) 
and sensitization status (mono-/poly-sensitized) as covariates. 
Patients in the FAS having no efficacy evaluation during the primary period (i.e., no valid 
assessment) will not be part of the primary analysis. They will be included in the sensitivity 
analyses to assess the robustness of the primary analysis with regard to missing data. 
Due to the high number of centers, a pooling of the centers will be considered to ensure a sufficient 
number of patients in each treatment group at each level of the covariate “pooled center”. The 
pooling will be performed during the DRM before unblinding of the data and according to the 
geographic area. 
The LS means of square root-transformed average TCS will be assessed in each treatment group. 
The back-transformed LS means will be calculated in each treatment group. The point estimate, 
i.e., the LS mean difference, will be calculated from the back-transformed LS means. 
The corresponding relative LS mean difference (%) will be derived as follows: 
Relative LS mean difference (%) = [(active LS mean - placebo LS mean) / placebo LS mean] * 
100 
Both the 95% CI for the LS mean difference and the 95% CI for the relative LS mean difference 
(%), will be calculated using bootstrap method. 
 
Supportive analyses 
• The primary efficacy analysis will be repeated in the PPS. 
• The average TCS will be analyzed in the FAS during the primary evaluation period using 
a Wilcoxon rank-sum test (non-parametric method). 

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Sensitivity analyses 
Sensitivity analyses will include PMMs, a MMRM for the four evaluation periods and primary 
analysis of the average TCS during the primary evaluation period using LOCF method. 
Sensitivity analyses are described in Section 12.4 “Handling of Missing and Incomplete Data”. 
Summary statistics 
The average TCS during each evaluation period will be summarized descriptively and graphically 
by treatment group in the FAS.  
The average TCS during the primary evaluation period will be summarized descriptively per 
treatment group by each level of each covariate. The average TCS during the primary evaluation 
period will also be described: 
- in the PPS without imputation of missing data 
- in the FAS with imputation of missing data using LOCF method 
12.5.3 
Secondary Efficacy Analyses 
Secondary efficacy analyses will be conducted in the FAS. 
If the primary endpoint is statistically significant, the six key secondary endpoints will be tested 
in the following order: 
• 
1. Rhinitis Total Symptom Score (RTSS) during the primary evaluation period 
• 
2. Overall score of Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) at the end of 
the treatment period 
• 
3. Rhinoconjunctivitis Total Symptom Score (RCTSS) during the primary evaluation period 
• 
4. Blocked nose symptom score during the primary evaluation period 
• 
5. Proportion of Symptom-Controlled Days (PSCD, proportion of days with RTSS≤2 and 
no rescue medication use) during the primary evaluation period 
• 
6. Rescue Medication Score (RMS) during the primary evaluation period 
The analysis of the non-ranked secondary endpoints will be considered supportive and will 
contribute to document the consistency of the study results. 
 
The average of RTSS, RMS, ASS, CSMS, TOSS, RCTSS and each of the six average individual 
RSSs (calculated as the average of the non-missing daily scores) during the primary evaluation 
period will be analyzed similarly to the average TCS using the corresponding baseline scores 
(except PPS analysis and sensitivity analyses). They will be summarized descriptively during each 
evaluation period. 

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The proportions of days with rescue medication intake will be summarized descriptively, overall 
and for each rescue medication category, and analyzed using a Wilcoxon rank-sum test at each 
evaluation period. 
The PSCD2-0 and PNCD will be summarized descriptively and analyzed using a Wilcoxon rank-
sum test at each evaluation period. 
The CP752-0 will be summarized descriptively and analyzed using a χ2 test at each evaluation 
period. 
The average VAS score (calculated as the average of the non-missing weekly scores), the overall 
RQLQ(S)≥12 score and RQLQ(S)≥12 scores by domain will be analyzed similarly to the primary 
efficacy variable using the corresponding baseline scores (except PPS analysis and sensitivity 
analyses). 
The EQ-5D-5L health profile (5 questions) and EQ-5D-5L VAS score will be summarized 
descriptively. 
The GRCS will be analyzed by means of a Cochran Mantel-Haenszel test (row mean score statistic) 
using pooled centers as a stratification variable. The proportions of improved patients will be 
compared between groups using a ² test or Fisher exact test. 
12.6 Other Analyses 
The WPAI + CIQ: AS scores will be summarized descriptively. Percentage of impairment for each 
score will be calculated and described. 
Immunological markers (D. pte and D. far specific serum IgE and IgG4) before and after treatment 
as well as the fold-changes (i.e., the ratio after treatment to before treatment) will be summarized 
descriptively using number of subjects, number of missing values, geometric mean, 95% 
confidence interval of the geometric mean, minimum, lower quartile, median, upper quartile, and 
maximum.  
12.7 Exploratory Analyses 
Exploratory variables will be summarized descriptively. 
Efficacy analyses will be performed by subgroup of HDM exposure level. 
 
Correlation between candidate serum and RNA biomarkers and clinical response will be 
investigated. 
12.8 Safety Analyses 
The safety analyses will be performed in the Safety Set. 
Safety data will be summarized in the Safety Set by treatment group using descriptive statistics: 
continuous variables by summary statistics and categorical variables by absolute and relative 
frequencies. 

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Adverse events 
Adverse events (AEs) will be coded using the latest version of the Medical Dictionary for 
Regulatory Activities (MedDRA). 
A Non-Treatment Emergent AE (Non-TEAE) is any AE with a start date on or after Visit 1 and 
before the first administration of IP in the placebo run-in period, or with a start date at least 31 days 
after the last administration of IP in the treatment period. 
A Placebo run-in Emergent AE is any AE with a start date on or after the first administration of IP 
in the placebo run-in period and before the first IP administration in the treatment period. 
A Treatment-Emergent AE (TEAE) is any AE with a start date on or after the day the first 
administration of IP in the treatment period was administered and up to 30 days after the date of 
the last administration of IP in the treatment period, inclusive. If the start date is missing, the AE 
will be considered as a TEAE. If the end date is missing, the AE will be considered ongoing. The 
rules of imputation for incomplete dates for AEs will be detailed in the Statistical Analysis Plan. 
AEs of Special Interest (AESIs) are defined in Section 11.3.1.3 “Pre-defined Adverse Event of 
Special Interest”. 
An overall summary of all AEs, including the number of events and the number and percentage of 
subjects with AEs will be provided. Tables by MedDRA System Organ Class (SOC) and Preferred 
Term (PT) will be provided for Non-TEAEs, TEAEs and for Placebo run-in Emergent AEs. 
Additional tables will summarize TEAEs by severity grade and relationship to the IP. Separate 
tables will also be provided for AESIs, serious TEAEs and TEAEs leading to death, treatment 
withdrawal or withdrawal from the study. 
Detailed subject listings of all AEs will be provided including the onset day and the duration of 
event (days).  
Laboratory values 
Laboratory values will be summarized descriptively over Visit 1 and Visit 9 (or Early Termination 
Visit, ETV), and for the changes from Visit 1 to Visit 9 or ETV. The individual values will be listed 
with flags for values below and above the laboratory reference ranges. 
Pregnancy test 
Pregnancy test results will be listed individually. 
Physical examination, weight and vital signs 
Abnormalities in physical examination will be reported either as AEs or as medical history. Weight 
and vital signs (systolic and diastolic blood pressure, and pulse rate) will be presented using 
summary statistics at the screening visit and for vital signs, at the end of treatment visit with 
changes from baseline to the end of treatment visit (Visit 9). 

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FEV1 
FEV1 (L and % of predicted value) will be summarized descriptively at Visit 1 for all subjects and 
at Visit 3 and Visit 9 for asthmatic patients. 
12.9 Baseline Evaluation 
Descriptive analysis of baseline characteristics will be presented by treatment group and overall. 
Demographic characteristics (age, gender, height, weight, Body Mass Index [BMI]) will be 
summarized for the Safety Set, the FAS and the PPS. 
Baseline characteristics related to the condition (e.g., duration of allergic rhinitis) will be described 
by treatment group and overall, in the Safety Set, the FAS and the PPS. 
Previous and concomitant medical conditions will be presented in the Safety Set as the number of 
mentions (m), number of subjects (n), and percentage (%) of subjects by MedDRA SOC and PT. 
Skin prick tests results and patient’s residence dust content in mite group 1 allergen will be 
summarized descriptively in the FAS and the PPS. 
12.10 Prior and Concomitant Medication Usage Evaluation 
Descriptive analysis of prior medication usage will be performed by treatment group and overall. 
Concomitant medication usage will be described by treatment group. 
Prior and concomitant medications will be presented for the Safety Set as the number of mentions 
(m), number of subjects (n) and percentage of subjects (%) by Anatomical Therapeutic Class 
(ATC) class Levels 1 and 3. 
12.11 Subject Disposition 
The number of screened subjects will be presented overall with the reasons for screen failure. 
Randomized, treated, completed and discontinued subjects, and subjects allocated to each analysis 
set will be tabulated and presented in each treatment group. 
The subjects who discontinued the treatment and those who did not complete the study will be 
described, along with a summary of reasons for IP discontinuation and early withdrawal 
respectively. The subjects who were excluded from an analysis set will be presented with the 
reasons for exclusion. 
Protocol deviations will be listed per subject, describing the nature of the deviation and specifying 
whether it was a major or a minor deviation. The definition of major and minor will be specified 
in the SAP and refined during the DRM before unblinding of the data. 
The number of subjects at each study visit will be provided. 

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12.12 Compliance with the Investigational Product in the Treatment Period 
Summary statistics for the treatment duration (number of days between the first and the last IP 
intakes in the treatment period, both inclusive) and the IP compliance (%) will be presented by 
treatment group for the Safety Set, FAS and PPS. 
Overall treatment compliance (%) will be calculated as follows: 
(‘Number of tablets dispensed’ – ‘Number of tablets returned’) x 100 
‘Number of tablets the subjects should have taken’ 
The proportion of compliant subjects (overall compliance 80%) will be presented in frequency 
tables in the Safety Set, FAS and PPS. 
12.13 Criteria for Unblinding the Results 
The DRM will take place: 
• after all the data have been verified/coded/entered into the database 
• before unblinding of the data 
The meeting will be held to decide how to allocate the subjects with protocol deviations or 
incomplete data (for example missing values, withdrawals, drop outs, non-compliance) to the 
various analysis sets. The appropriateness of the pooling of sites will be discussed. After the DRM 
and documentation of all decisions concerning how data issues will be handled, the database will 
be locked. After database lock and approval of the final SAP, the treatment codes will be requested 
from the statistician in charge of the randomization. 
13. ETHICS 
13.1 Approval 
The study will not start in a center before the written approval of the corresponding Independent 
Review Board (IRB) or Independent Ethics Committee (IEC) has been obtained, the local 
regulatory requirements have been complied with, and the signature of the clinical study protocol 
of each contractual party involved have been obtained. 
The final protocol and subsequent protocol amendments must be submitted to and approved by: 
a) Concerned IRB / IEC 
b) Relevant Regulatory Authorities, according to local regulations.  
Upon receipt, a copy of the IRB’s / IEC’s written approval (including clear identification of the 
submitted document(s)) and a list of members attending the meeting) should be forwarded by the 
Investigator to STALLERGENES. The study is not allowed to start until the protocol and related 
documents (e.g., informed consent, advertisements) have received written approval from the 
IRB/IEC and Regulatory Authorities, and all other GCP prerequisites are fulfilled. 

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The final protocol and any subsequent amendments will be signed by the Principal Investigator of 
the center, the Coordinating Investigator of the study and the STALLERGENES team members 
listed on the signature page. 
If new important information related to the study or the product become available during the course 
of the study, it should be communicated without delay to the patients, the Investigators and the 
IRBs / IECs, and Regulatory Authorities whenever required. 
13.2 Patient Informed Consent / Assent 
Adequate information will be provided to adult and adolescent patients and parent(s)/legal 
representatives in both oral and written form and consent/assent will be obtained in writing prior 
to the patients’ participation in the study.  
If the patient is <16 years old, an assent form will used instead of the informed consent form. The 
content and process of obtaining informed consent/assent will be in accordance with applicable 
regulatory requirements.  
An informed consent form or a patient information sheet will be provided to the patients, the 
parent(s)/legal representatives and an assent form will be provided to the adolescent patients. Each 
of the two final forms must be approved by the IRB / IEC and must contain all ICH-GCP (Section 
4.8.10 of ICH-E6 [R1]) elements in a language readily understandable by the patients, the 
adolescents or/and their parent(s)/legal representatives. 
If the informed consent/assent form is amended during the study, the Investigator must comply 
with all applicable regulatory and IRB / IEC requirements and use of the amended forms with the 
on-going and the new patients. 
13.2.1 
Information  
The Investigator, or a person designated by the Investigator, should fully inform the patients and 
their parent(s)/legal representative, of all relevant aspects of the study. Patients will be informed of 
the nature, the aim, the procedures, the constraints, the possible risks and expected benefits of the 
study in a clear and easily understandable language. The patient’s participation has to be clearly 
presented as voluntary and the patient has to understand that s/he will be able to stop, at any time, 
her/his participation without any consequences for her/his future medical management or 
treatments. The patient and parent(s)/legal representative must be informed that the anonymity of 
her/his identity will be guaranteed, especially during the analysis of the patient’s personal data. 
They will be encouraged to ask any questions they may have about the study and they should 
receive relevant answers. They will receive complete written information on the study in the 
“Patient Information Sheet”. 
The Investigator will take into consideration that the parent(s)/legal representative, since they bear 
the responsibility of the adolescent, might need more detailed and explicit information and hence 
more time, to consider the expected benefits and potential risks of the study. 

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13.2.2 
Informed Consent / Assent 
All the participating patients will have to document their consent to participate in the study by 
signing and dating an informed consent form. Adolescents from the age of 16 years old are 
considered of appropriate intellectual maturity and capable of giving their assent to participate in 
the study and they should personally sign and date the specifically designed assent form. Younger 
patients will receive the information regarding the study, adapted to the patient’s age, and their 
consent will be sought by the investigators. Adolescent parents/ legal representative will have to 
sign the informed consent form. 
If the signature of a witness is required, the witness should sign and date the consent form, next to 
the patient’s own signature. By signing the consent form, the witness testifies that the relevant 
information regarding the study was accurately explained to and apparently understood by the 
patient and that the informed consent was freely given by the patient. 
All the forms will also be dated and signed by the Investigator or the designated person who 
obtained the informed consent/assent according to local regulations. Informed consent procedure 
will be documented in the patient’s medical source data and in the e-CRF. 
The patient or/and parent(s)/legal representative will receive a copy of the corresponding form(s) 
and the original(s) will be filed in the Investigator’s Trial File. 
The patient may withdraw his/her consent to his/her study participation at any time, without any 
justification. 
A patient is considered as enrolled in the study when he/she or/and his/her parent(s)/legal 
representative have signed the informed consent/assent form. An e-CRF must not be started, nor 
may any study specific procedure be performed before having obtained his/her or/and 
parent(s)/legal representative written consent/assent. The Investigator will keep a patient screening 
log to document identification of patients who were screened for the study. 
If any new information that could influence the patient and/or parent(s)/legal representative 
decision to remain in the study becomes available, it will be communicated without delay to the 
patient or/and parent(s)/legal representative. 
13.3 Patient Confidentiality 
Patient’s identification and data confidentiality is to be strictly ensured at any times. 
Personnel from the Sponsor (or its representative), from Regulatory Authorities and members of 
IRB/IEC may inspect patient’s medical records and e-CRFs for verification of accuracy of data and 
have to comply with strict medical secrecy and are forbidden disclosing the patient's identity or 
any other patient’s personal information. 
13.4 Informing the General Practitioner  
When legally required or if considered as necessary by the Investigator, and if the patient agrees, 
the Investigator will inform the patient’s regular physician of his/her participation in the study, by 
sending him/her a “letter to the GP” prepared by the Sponsor or the Investigator. 

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14. STUDY MANAGEMENT AND ADMINISTRATION 
14.1 Monitoring  
STALLERGENES may subcontract with a Contract Research Organization (CRO) to perform all 
monitoring responsibilities for this clinical study. The CRO’s monitors will work in accordance 
with the defined monitoring SOPs and have the same rights and responsibilities as monitors from 
STALLERGENES. Monitors will establish and maintain regular contacts between the investigator 
and STALLERGENES. 
The monitor will advise the Investigator regarding the practical conduct of the study and assist 
him/her in working according to the protocol, Good Clinical Practice (GCP), and the regulatory 
requirements. 
The Investigator will allow the Sponsor or its representatives to periodically monitor all e-CRFs 
and the corresponding source documents, at mutually convenient times during the study and after 
it has been completed. The monitor will have direct access to these records. The monitoring visits 
provide the Sponsor or its representatives with the opportunity to evaluate the progress of the study, 
to verify the accuracy and completeness of e-CRFs, to ensure that all protocol requirements, 
applicable local authority regulations and Investigator's obligations are being fulfilled, and to 
resolve any inconsistencies in the study records. 
14.2 Direct Access to Source Data/Documents 
The Investigator(s) and/or Institution(s) will permit study-related monitoring, audits by or on behalf 
of STALLERGENES, IRB/IEC and regulatory inspector(s), and authorized direct access to source 
data/documents. 
Source documents are original records in which raw patient data are recorded. These may be: 
hospital / clinic / General Practitioner (GP) records, charts, diaries, X-rays, SPT and laboratory 
results, spirometry, ECG and other printouts, pharmacy records, care records, completed 
psychometric scales, diary cards, Quality of Life questionnaires, etc. 
Directly entered data in the e-diaries / e-CRF will be considered as source data. 
All source documents must be accurate, clear, unambiguous, and readily auditable. They should be 
generated by using a permanent means of recording (e.g., ink, typing, printing, optical disc). 
Hospital/Clinic/Medical files that are computer generated and stored on digital support media 
should be printable. The Investigator will sign and date the printouts when kept as data source. The 
Investigator will authorize the monitor to compare the content of the printouts and the data stored 
in the computer to ensure data consistency. 
The minimum requirements for medical source data include the identity of the patient (and any 
study related identifiers, treatment kit numbers, CRF numbers if used), the patient's participation 
in the study and identification of the study (e.g., Study Code), the date of obtaining signed informed 
consent/assent, the dates of the visits, the patient's medical history, the experimental and 
concomitant treatments, AEs and SAEs and any important relevant information. The source 

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documents should also provide evidence that inclusion/exclusion criteria were evaluated and met. 
Information recorded in the e-CRF must be fully consistent with entries in the source documents. 
14.3 Audit and Inspection 
The Investigator will permit study-related audits by auditors mandated by STALLERGENES, and 
inspections by domestic or foreign regulatory authorities, after reasonable notice. The main 
purposes of an audit or inspection are to confirm that the rights and well-being of the patients 
enrolled have been protected, and that all data relevant for the evaluation of the IP have been 
processed and reported in compliance with the planned arrangements, GCP and applicable 
regulatory requirements. The Investigator will provide direct access to all study documents, source 
records and source data. If a regulatory inspection is announced, the Investigator will immediately 
inform STALLERGENES. 
14.4 Electronic Case Report Forms (e-CRFs) 
Electronic case report forms (e-CRFs) will be used for the study and the study site staff will be 
trained on how to use the e-CRFs and capture the data required by the protocol. The e-CRF is 
essentially a data electronic entry media and should not routinely constitute the original (or source) 
medical record.  
The Sponsor cannot interpret a blank answer as “NONE” or “N/A”, therefore, all fields must be 
completed.  
Data reported in the e-CRF should be consistent with the source documents or the discrepancies 
should be explained in these source documents. 
The Investigator must complete an e-CRF for each patient who signed an ICF.  
It is the responsibility of the Investigator to ensure that the e-CRFs are kept up-to-date so that they 
always contain the latest observations on the patients enrolled. All supportive documentation 
submitted to the Sponsor in addition to the e-CRF, such as laboratory results or hospitalization 
records, must be clearly identified with the study or protocol number, and study patient number. 
Any personal information, including the study patient’s name, must be removed or rendered 
illegible to preserve patient confidentiality. The Investigator’s signature of the e-CRF will attest its 
accuracy and completeness. Study data will be transferred and stored in a clinical database 
maintained by the CRO. Data recorded by patients in e-Diaries will also be stored in the same 
clinical database. 
14.5 Adherence to Protocol 
The Investigator/Institution should conduct the study in compliance with the protocol approved by 
the Sponsor, the IRB/IEC and, if required, by the regulatory authority(ies) The 
Investigator/Institution and the Sponsor should sign the protocol to confirm this agreement. 
The Investigator should not deviate from the protocol. In medical emergencies, the Investigator 
will use his/her medical judgment and may withdraw the study patient from the study to prevent 
immediate hazard. Notification to the Sponsor, its representatives and, if required, the IRB/Ethics 

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committee will be made regarding the type of emergency and the course of action taken. Significant 
and/or systematic changes in or deviations from the protocol will ONLY be made as an amendment 
to the protocol and must be approved in writing by the Sponsor and the IRB/IEC prior to being 
implemented. Unless the Sponsor has agreed to any such deviations or changes in writing, they 
cannot be implemented and the Sponsor will not assume any resulting responsibility or liability. 
Any significant protocol deviation will be documented and explained by the Investigator or the 
designated personnel. 
14.6 Termination of the Study  
Upon completion of the study, the monitor will conduct the following activities in conjunction with 
the Investigator, as appropriate: 
- 
transfer of all study data to STALLERGENES or its representative, 
- 
data clarification and/or resolution, 
- 
accountability, reconciliation and arrangements for used and unused study drugs, 
- 
accountability, reconciliation and arrangements for used and unused other supplies, 
- 
review of site study records for completeness, 
- 
discussion/reminder on archiving responsibilities, 
- 
discussion/reminder on investigator’s responsibility in case of study audit or inspection.  
14.7 Stopping Rules for the study 
STALLERGENES reserves the right to temporarily suspend or prematurely discontinue this study 
at any time for reasons including, but not limited to, safety (including Data Safety Monitoring 
Board recommendation) or ethical issues, severe non-compliance, recurrent non-compliance, or 
unsatisfactory enrolment with respect to quality or quantity. 
If the study is prematurely terminated or suspended, STALLERGENES will promptly inform the 
Investigators/institutions, and the regulatory authority (ies) of the termination or suspension and 
the reason(s) for the termination or suspension. The information will be shared with the study sites 
via a formal letter from the Sponsor that will also contain the procedure to manage the practical 
aspects regarding study patients. 
The IRBs/IEC will be promptly informed and provided with the reason(s) for the termination or 
suspension, as specified by the applicable regulatory requirement(s). In addition, arrangements will 
be made for the management of all unused IP in accordance with procedures for the study. 
14.8 Investigator Site File  
The content of the study Investigator Site File is structured in a manner that eases the filing, 
retrieval, and/or auditing of study-related documents. All documents will be filed according to 
Standard File Categories that identify specific aspects of the study. 

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14.9 Data Handling and Record Keeping 
Data processing will be subcontracted by the sponsor to the designated CRO. 
e-CRF data will be entered in an electronic database using a clinical data management system 
(CDMS). Computerized edit-checks will be developed in addition to manual review to detect any 
discrepancies and to ensure consistency of the data. An electronic audit trail system will be used to 
track all data changes in the database subsequent to the first data entry. The SAS system will be 
used for the statistical analysis of the data. Regular back-ups of the electronic data will be carried 
out. 
The data of patients who signed an informed consent/assent and underwent any study specific 
procedures(s) before entering the treatment phase, will be entered in the e-CRF. In case of screen 
failure before visit 2, only data on demography, adverse events and reason for screen failure will 
be entered into the e-CRF and clinical database and should therefore be monitored and retrieved 
from the site.  
To ensure data quality all efforts will be made to capture data as soon as they are available. Study 
sites and patients will be alerted in case data are not submitted in a timely manner. 
Sponsor will take advantage of using electronic devices (e-diary, e-CRF) to have a centralized 
monitoring approach to enhance quality of study data as advocated by National Guidances. 
Appropriate actions (e.g., feedback towards study staff in case of repeated inconsistencies) will be 
undertaken if any missing data, inconsistent data, outlier data and potential protocol deviations are 
identified during routine remote data review. 
14.10 Clinical Study Report 
The Sponsor will prepare a clinical study report (CSR) according to the relevant ICH guidelines. 
The report will include a thorough description of the study, its conduct, efficacy and safety data, 
statistical analyses and a discussion of the results  
The Principal Investigator will receive and review the CSR. He/she must give his/her comments 
within 30 days of receiving the CSR.  
In addition, he/she will sign the CSR for approval within 15 days of receipt of the revised version 
or a satisfactory reply to these comments. 
The CSR and the study data may not be used or communicated by the investigators without prior 
written approval from the Sponsor. 
14.11 Patient Insurance 
The Sponsor will contract liability insurance for the total duration of the study, covering the patients 
with respect to the potential risks related to the study, carried out according to the protocol. In case 
of injury or disability related to the participation in the study, the patient is to inform the 
investigator without delay. 

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14.12 Publication and Presentation Policy  
In signing the final protocol, the Investigator agrees to keep all information and results related to 
the study and the IP confidential. The confidentiality obligation also applies to all personnel 
involved at the investigational study center.  
No unpublished data given to the Investigator may be transmitted to a third party without written 
approval of the Sponsor. 
Publication and communication policy are addressed in the clinical study agreement. 
14.13 Archiving and Data Retention 
At the end of the study, the Investigator will maintain adequate study records, including e- 
electronic copies of e-CRF, medical records, laboratory reports, informed consent/assent 
documents, drug disposition records, safety reports, information regarding patients who 
discontinued, and other relevant data. 
All records are to be retained by the Investigator/Institution until at least 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the investigational product. However these 
documents are to be retained for a longer period if required by the national applicable regulatory 
requirement(s) or by an agreement with the sponsor (ICH-GCP Guideline-section 4.9.5). 
The Investigator will contact the Sponsor for authorization prior to the destruction of any study 
records or in the event of accidental loss or destruction of any study records. The Investigator will 
also notify the Sponsor should he/she relocate or move the study related files to a location other 
than that specified to the Sponsor. 
14.14 Allocation of Responsibilities 
The Investigator is responsible for the conduct of the study in compliance with the protocol but can 
delegate any tasks to his/her research team. He/she remains responsible for selecting his/her staff 
and for coordinating, training and informing them about the protocol, study procedures and any 
possible amendments. 
The Investigator should maintain a list of appropriately qualified persons to whom each significant 
study-related duty is delegated using an "authorized signatures" document including name, 
function, signature, initials, start and end dates of participation in the study conduct and type of 
delegated tasks. 
This list is to be kept current during the entire course of the study. 
14.15 Curriculum Vitae  
The Investigator should provide his/her updated Curriculum Vitae (English version), dated and 
signed, together with a list of his/her collaborators responsible for the practical conduct of the 

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study. These designated collaborators should also provide a recent English version of their 
Curriculum Vitae, dated and signed. 
14.16 FDA Form 1572 (Statement of Investigator – Mandatory for US) 
No Investigator may participate in an investigation (which will be part of an IND) until he/she 
provides the Sponsor with a completed signed Statement of Investigator (FDA Form 1572). This 
form is a contractual agreement between the Investigator and the FDA, whereby the Investigator 
agrees to comply with the study protocol and with all other requirements regarding the obligations 
of clinical investigators and all other pertinent requirements in 21 CFR 312. This form must be 
updated in the event of a change of facilities or study personnel. 
14.17 Financial Disclosure 
A financial disclosure statement must be obtained from each clinical site for the Investigator and 
sub-investigator(s) participating in the study. This will be collected before patient enrollment. The 
Investigator must inform the Sponsor if information related to financial disclosure changes during 
the course of the study and for one year after completion of the study. 

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16. APPENDICES  
APPENDIX I: Procedures for lung function testing according to ATS/ERS Task Force: 
Standardization of Lung Function Testing .............................................. 106 
APPENDIX II: 
Asthma treatment steps in adults and adolescents 12 years of age and 
older according to the 2014 Global Initiative for Asthma Guidelines .... 108 
APPENDIX III: 
Estimated Equipotent Daily Doses of Inhaled Corticosteroids for Adults 
and Adolescents according to the 2014 Global Initiative for Asthma 
Guidelines ................................................................................................ 109 
APPENDIX IV: 
Dust Collection Patient Leaflet................................................................ 110 
APPENDIX V: 
Skin Prick Test Procedure ....................................................................... 112 
APPENDIX VI: 
Management of Suspected Esophagitis ................................................... 123 
 
 
 

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STALLERGENES 
Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 106 of 123 
 
APPENDIX I: Procedures for lung function testing according to ATS/ERS 
Task Force: Standardization of Lung Function Testing 
 
REFERENCE 
 
Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al. Standardisation of spirometry. European 
Respiratory Journal. 2005;26(2):319-338 

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Protocol version 7.0 – 05 October 2017 – Page 108 of 123 
 
APPENDIX II: Asthma treatment steps in adults and adolescents 12 years of 
age and older according to the 2014 Global Initiative for 
Asthma Guidelines 
 
 
Step 1 
Step 2 
Step 3 
Step 4 
Step 5 
Reliever 
As needed short-acting 
2-agonist 
As needed short-acting 2-agonist or 
low dose of ICS/formoterol 
Preferred 
controller 
choice 
 
Low dose ICS 
Low dose ICS + 
long-acting 2-
agonist 
Medium or high 
dose ICS + 
long-acting 2-
agonist 
Anti-IgE treatment 
Other 
controller 
options 
Consider 
low dose 
ICS 
Leukotriene 
receptor 
antagonist 
Medium or high 
dose ICS 
High dose ICS + 
leukotriene 
receptor 
antagonist 
Add low dose oral 
corticosteroid  
Low dose 
theophylline 
Low dose ICS + 
leukotriene 
receptor antagonist 
High dose ICS + 
theophylline 
 
Low dose ICS + 
theophylline 
 
ICS = Inhaled corticosteroids 
 
 

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STALLERGENES 
Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 109 of 123 
 
APPENDIX III: Estimated Equipotent Daily Doses of Inhaled Corticosteroids 
for Adults and Adolescents according to the 2014 Global 
Initiative for Asthma Guidelines 
 
Drug 
Low doses 
(mcg) 
Medium doses 
(mcg) 
High doses 
(mcg) 
Beclomethasone dipropionate (CFC) 
200 – 500 
>500 – 1000 
>1000 
Beclomethasone dipropionate (HFA) 
100 – 200 
>200 – 400 
>400 
Budesonide (DPI) 
200 – 400 
>400 – 800 
>800 
Ciclesonide (HFA) 
80 – 160 
>160 – 320 
>320 
Fluticasone propionate (DPI) 
100 – 250 
>250 – 500 
>500 
Fluticasone propionate (HFA) 
100 – 250 
>250 – 500 
>500 
Mometasone fuorate 
110 – 220 
>220 – 440 
>440 
Triamcinolone acetonide 
400 – 1000 
>1000 – 2000 
>2000 
 
 

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STALLERGENES 
Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 110 of 123 
 
APPENDIX IV: Dust Collection Patient Leaflet 
 

CONFIDENTIAL 
STALLERGENES 
Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 111 of 123 
 
 
 
 
 Procedure for Collection of a Dust Sample using the DUSTREAM® 
You have just attended Study SL75.14(*) Visit 3, and your study doctor (or designee) has provided you 
with a dust collection kit to perform the dust sampling at your residence.  It is important that you 
proceed to the dust sampling as indicated below within the next few days following this visit. 
(*)  Sponsor: Stallergenes S.A. 
1. Insert the plastic filter into the DUSTREAM® collector and attach the collector to the vacuum 
cleaner tube. 
2. If the collector alone does not fit the vacuum cleaner tube, attach the adaptor piece to the 
collector in the configuration that fits the vacuum tube firmly. 
 
 
 
 
3. Remove the bed sheets and pillowcases. Turn on the vacuum cleaner and vacuum the 
bedding (i.e., mattress, pillow(s), blanket). Remove the filter from the collector by pressing 
on the closed, bottom end of the filter. If the filter is ¼ full then sufficient sample has been 
collected. If not, allow the vacuum to cool down and then repeat vacuuming until the filter is 
¼ full. 
 
4. Remove the filter containing the sufficient dust sample from the collector and place it in the 
small Ziploc bag provided in the Patient Pack. 
 
 
 
 
 
 
 
5. Fill in the date collection label on the large Ziploc bag and place the small Ziploc bag 
containing the dust sample into the large bag. 
 
6. Place the large Ziploc bag in the provided courier wrapper and book a pick-up through the 
courier agent as indicated by your study doctor (or designee) to allow the sample to be 
picked up within 24 hours after that the dust has been vacuumed.  
 
Please be prepared to give the following information: your contact details, including your 
name and telephone number. You will also need to provide details of the exact location, 
including building number or department name, from where the sample is to be collected. 
DUSTREAM®   
collector + filter 
DUSTREAM® collector + adaptor 
DUSTREAM® collector + adaptor 
DUSTREAM® filter 

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STALLERGENES 
Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 112 of 123 
 
APPENDIX V: Skin Prick Test Procedure 
 
STALLERGENES SKIN PRICK TEST PROCEDURE 
Skin Prick Tests (SPTs) will be performed at screening (Visit 1) for D pteronyssinus, D. farinae 
and a battery including cat, dog, cockroach, Aspergillus, Cladosporium, Parietaria and Alternaria, 
and other geographically relevant potentially confounding allergens such as cypress, birch, grass, 
ragweed… as well as positive (histamine dihydrochloride) and negative (saline diluent) controls. 
Preparation for the Skin Prick Tests 
- 
Check that the SPT vials are arranged in the rack in the SAME ORDER as on the Case Report 
Form (CRF) page. 
- 
Preparation of the skin: clean an area of healthy skin at the interior site of the forearm, with a 
cotton swab impregnated with alcohol and allow to dry. 
- 
Identify the SITES on the two forearms with a pen, respecting the same distance as displayed 
on the test sheet of the CRF, which facilitates recording of the test responses onto the results 
sheet. 
- 
For a good reading of skin reactions, it is advised to space the tests with a minimum 3 cm. 
Skin Prick Tests procedure 
- 
The allergen vials will be ordered in the box in the same order than the SPTs. 
- 
Apply one drop of each test solution on the appropriate marked locations respecting the same 
order as on the test sheet.  
- 
Stallerpoint® is a single-use needle. Each needle is used only once in order to eliminate false 
positive tests caused by previously tested solution. Prick the skin vertically, performing a slight 
twisting movement through each extract drop with a Stallerpoint® (a polymethacrylate needle 
of 1.1 mm length) held by its superior third part which has an enlarged diameter. It is necessary 
each time to exert a regular and moderate pressure (a pressure can be considered as moderate 
when it produces a skin depression between 2 and 5 mm from the bottom of the Stallerpoint®). 
Usually, a good execution of the test results in a print of the Stallerpoint® circumference. 
- 
For valid interpretation of the SPTs, it is essential to perform the positive controls (histamine 
dihydrochloride) and negative control (saline diluent). 
- 
Sponge up the drops after 2 min for each prick without transferring a drop on another location, 
and by changing cotton for each prick test site. 
- 
Record the time of the SPTs precisely on the results sheet: hours, minutes. 

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STALLERGENES 
Study # SL75.14 
Protocol version 7.0 – 05 October 2017 – Page 113 of 123 
 
Collecting the wheals’ outlines 
- 
SPTs are read after 20 minutes. Record the time of the reading on the results sheet: hours, 
minutes. 
- 
Carefully clean the skin with alcohol to eliminate any trace of saline diluent, which could 
interfere with pen tracings. 
- 
Use a very fine black pen to trace the outline of wheals and any pseudopodes or satellites. The 
real limits of the wheal are determined by palpation. 
- 
Hypoallergenic transparent adhesive tape (Blenderm) is applied on the tracings to obtain 
imprints and is then transferred on the results sheet. 

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Protocol version 7.0 – 05 October 2017 – Page 114 of 123 
 
GREER SKIN PRICK TEST SUGGESTED DOSAGE SCHEDULE AND INSTRUCTIONS 
 
 
 

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8.5 
 
 

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APPENDIX VI: Management of Suspected Esophagitis 
 
 
Management of Suspected Esophagitis  
SL75.14 
 
This procedure is designed to guide investigators in managing patients with symptoms suggestive 
of esophagitis during conduct of this study.  
1. Occurrence of symptoms consistent with esophagitis 
Throughout the study, patients will be asked to complete a daily diary card to record information 
on adverse events and concomitant medication use. Diary cards are to be reviewed at each visit 
after the initiation of study therapy. A patient reporting onset of one or more symptoms suggestive 
of esophagitis (e.g., severe or persistent dysphagia or chest pain) will be instructed to discontinue 
the study therapy and referred to a Gastroenterologist for evaluation. 
2. Evaluation by a Gastroenterologist 
- 
At the initial consultation, if the assessment of the Gastroenterologist is that further 
evaluation for EoE is warranted, an esophagogastroduodenoscopy (EGD) with biopsy will 
be performed. If the diagnosis of EoE is confirmed [Liacouras et al., 2011; Miehlke, 2014], 
the patient will be withdrawn from the study and medical treatment provided. See protocol 
Section 7.4 “Patient Withdrawal” and Section 9.3.11 “Early Termination Visit”. 
- 
If an alternate diagnosis is made, the cause of the symptoms will be treated as appropriate. 
Study therapy may be resumed at the discretion of the investigator. 
All medical information, including the consultation report of the Gastroenterologist, results of the 
EGD, and tissue pathology reports are to be retrieved and communicated to the Sponsor for 
documentation and review by the Data Safety Monitoring Board.  
 
 
REFERENCES 
 
Liacouras CA, Furuta GT, Hirano I, Atkins D, Attwood SE, Bonis PA, et al. Eosinophilic esophagitis: updated 
consensus recommendations for children and adults. J Allergy Clin Immunol. 2011;128(1):3-20 e26; quiz 21-22. 
 
Miehlke S. Clinical Features of Eosinophilic Esophagitis. Digestive Diseases. 2014;32(1-2):61-67.