Clinical trial NCT02040844
Conditions: Cat Allergy
Sponsor: Circassia Limited
Start date: 2014-02-01; Completion date: 2017-05-01
Enrollment: 430 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate the continued effectiveness and safety of Cat-PAD in cat allergic subjects for up to five years after the start of administration of treatment. The study is an optional follow-up study to a phase III double-blind, placebo controlled, Cat-PAD study; no further investigational product is administered.

Detailed description:

Arms: arm 1: Received Cat-PAD Treatment 1 in Study CP007 \[NCT01620762\].No further treatment received in CP007A arm 2: Received Cat-PAD Treatment 2 in Study CP007 \[NCT01620762\].No further treatment received in CP007A. arm 3: Received Cat-PAD Treatment 3 in Study CP007 \[NCT01620762\]. No further treatment received in CP007A.
Interventions: intervention 1: Received Cat-PAD Treatment 1 in Study CP007 [NCT01620762] intervention 2: Received Cat-PAD Treatment 2 in Study CP007 [NCT01620762] intervention 3: Received Cat-PAD Treatment 3 in Study CP007 [NCT01620762]
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None

Protocol documents:
Prot_000.pdf: 
 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
Circassia Ltd 
Clinical Study Protocol 
Protocol Identifier: CP007A 
 
Version Date 08 Dec 2014  
EudraCT Number: 2013-004669-15 
An Optional Prospective Follow-on Study to Evaluate the 
Continued Efficacy and Safety of Cat-PAD in Cat Allergic 
Subjects up to Five Years after the Administration of Treatment  
PROTOCOL IDENTIFIER: CP007A 
Version 5.0 Final (Incorporating Protocol Amendment 01, 02, 03 and 04 
and replacing Version 4.0 dated 31 July 2014) 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 1 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
STUDY PERSONNEL 
SPONSOR COMPANY 
Circassia Ltd 
The Magdalen Centre 
The Oxford Science Park 
Oxford 
OX4 4GA 
+44 (0) 1865 598078 (‘Phone) 
+44 (0) 7092 987560  (Fax) 
 
 
COORDINATING INVESTIGATOR 
Joerg Kleine-Tebbe, MD 
Spandauer Damm 130 
Berlin 
Germany 
+49 3030307126 (‘Phone) 
kleine-tebbe@allergie-experten.de (Email) 
 
 
STUDY MONITOR 
Roisin McGloughlin 
Quintiles (Irl) Ltd.  
Eastpoint Business Pk 
Dublin 3 
Ireland 
+353 1 8391123 (‘Phone) 
 roisin.mcgloughlin@quintiles.com (Email) 
 
MEDICAL MONITOR 
John Powell 
Circassia Ltd 
+44 (0) 1865 573737 (‘Phone) 
 
 
 
 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 2 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
EMERGENCY NUMBERS 
 
SAE Reporting 
1 888 723 9952 (‘Phone – USA and Canada) 
+44 1628 496 300 (‘Phone - Rest of World) 
1 800 540 1863 (Fax – USA and Canada) 
+44 1865 595 595 (Fax - Rest of World) 
f2m-eastleigh-medical@iconplc.com (Email) 
Circassia Medical Representative 
+44 1865 573737 (‘Phone) 
 
 
 
This study will be conducted in compliance 
with: 
• This protocol  
• ICH E6 GCP guidelines 
• The applicable regulatory 
requirement(s)  
• The principles of the Declaration of 
Helsinki 
 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 3 OF 50 
 




 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
PRINCIPAL INVESTIGATOR’S AGREEMENT 
I agree to conduct this study in accordance with: 
• This protocol 
• ICH E6 GCP guidelines 
• The applicable regulatory requirement(s) 
• The principles of the Declaration of Helsinki 
 
 
 
 
Signature 
 
Date 
dd mmm yyyy 
Name:  
 
 
Principal Investigator 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 5 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
PROTOCOL SYNOPSIS 
Protocol Identifier 
CP007A 
Study Title 
An Optional Prospective Follow-on Study to Evaluate the Continued Efficacy and 
Safety of Cat-PAD in Cat Allergic Subjects up to Five Years after the 
Administration of Treatment  
Protocol Version 
5.0 Final 
Sponsor 
Circassia Ltd 
Phase 
IIIb 
Indication 
Treatment of cat allergen induced rhinoconjunctivitis in subjects with clinically 
relevant symptoms. 
Objectives 
Primary Objective: 
• 
To evaluate the continued efficacy of Cat-PAD, the first in a new class of 
Synthetic Peptide Immuno-Regulatory Epitopes, for a total of up to five years 
after the administration of treatment, based on the reduction of symptoms and 
the use of allergy medication in subjects previously participating in CP007.  
Secondary Objectives: 
• 
To evaluate the continued safety and tolerability of Cat-PAD for up to five 
years after the administration of treatment. 
• 
To evaluate the effect of Cat-PAD on RQLQ for up to five years after the 
administration of treatment. 
• 
To evaluate the effect of Cat-PAD on the onset of asthma for up to five years 
after the administration of treatment. 
• 
To evaluate the effect of Cat-PAD on asthma progression in subjects 
previously enrolled in CP007 with GINA 1 asthma for up to five years after 
the administration of treatment. 
Exploratory Objectives: 
• 
To evaluate the effect of Cat-PAD on changes in asthma control in asthmatic 
subjects for up to five years after the administration of treatment. 
• 
To evaluate the effect of Cat-PAD on changes in sleep quality in adults using 
the PSQI for up to five years after the administration of treatment. 
• 
To evaluate the effect of Cat-PAD on changes in productivity using the 
WPAI:CIQ-AS for up to five years after the administration of treatment. 
• 
To evaluate the effect of Cat-PAD on symptomatology on unplanned 
exposure to a cat in normal daily life in subjects who no longer keep a cat for 
up to five years after the administration of treatment. 
• 
To evaluate the effect of Cat-PAD on health economic outcomes for up to 
five years after the administration of treatment. 
Study Design  
Subjects from participating sites who complete the final Post Administration 
Collection period (PAC3) in CP007 (a randomised, double-blind, superiority, 
multiple dose, placebo-controlled, parallel group, multi-centre, field study) will be 
invited to participate in CP007A.  The CP007A Enrolment Visit may occur at or 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 6 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
after the final Follow-Up Visit (Visit 5) in CP007.  Subjects who wish to participate 
will be issued with a paper diary and digital pen (ePRO) to record the required 
patient reported outcomes data. This comprises annual and monthly evaluations. 
The annual assessment data will be recorded at the same time of year as the Baseline 
Allergy Evaluation visit in CP007. It will include scoring rhinoconjunctivitis 
symptoms and allergy medication use over a 3-week period, as well as single 
assessments of quality of life, sleep quality, asthma status and work/school 
interference. Additionally, on a monthly basis, subjects will record information 
regarding hospital/doctor visits; concomitant medication; illnesses/symptoms; 
asthma progression; and changes in home environment using the ePRO.  
Subjects will have up to four visits each year, two of which may be completed by 
telephone. At each visit, site staff will record any adverse events (AEs) and serious 
adverse events (SAEs), and at the on-site visits subjects will be provided with their 
next diary binder. One of the on-site visits will be scheduled just prior to the 3-week 
symptom and allergy medication use recording period. At this visit, subjects will be 
provided with an Allergy Medication Kit. For all on-site visits, where possible 
subjects will be instructed to complete the closest monthly assessment in the diary 
binder during the visit. Subjects will not be required to undergo any specific 
treatment or lab tests as a participant in this follow-up study.  All physician visits 
and treatments / procedures will be administered per the physician’s direction. 
Subjects will have a final End of Study Visit, which will coincide with the end of 
the final annual Allergy Evaluation Period assessment.  
The duration of data collection for this follow-up study will be up to 4 years for 
each subject. 
Sample Size 
Not Applicable 
Study Population 
Subjects who completed PAC3 in CP007 (a randomised, double-blind, superiority, 
multiple dose, placebo-controlled, parallel group, multi-centre, field study) will be 
invited to participate in this optional, prospective follow-on study. Subjects in 
countries where fewer than 10 subjects were randomised will not be invited to 
participate in this study. 
Inclusion/Exclusion 
Criteria 
Inclusion Criteria  
1. Previously randomised into clinical study CP007 and completed PAC3. 
2. Provide written informed consent or assent, as appropriate. (For subjects less 
than 18 years a Parent/Guardian will also be required to provide written 
informed consent). 
3. Willing and able to comply with the study requirements. 
Exclusion Criteria 
1. Started allergen immunotherapy since completing CP007.  
2. Has been informed of the treatment received in study CP007. 
3. Dependent on the Investigator/site either for employment or education or are 
first degree relatives or partners of the Investigator/study staff. 
4. Subjects institutionalised due to a legal or regulatory order 
Investigational 
Product 
Not applicable - no additional investigational product will be administered 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 7 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
Route of 
Administration 
Not applicable - no additional investigational product will be administered 
Treatment Regimen(s) 
Not applicable - no additional investigational product will be administered 
Efficacy Parameters 
The following efficacy parameters will be measured in the study: 
 Monthly: 
• 
Hospital / Physician office visits 
• 
Number of lost work/ school days 
• 
Current status / change in home environment 
• 
Exposure to cat 
• 
Global assessment of symptoms on exposure to cat during normal life for 
those who no longer keep a cat  
• 
Asthma progression 
• 
Concomitant medications associated with rhinoconjunctivitis or related 
conditions 
Annually: 
• 
Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) 
• 
Pittsburgh Sleep Quality Index (PSQI) (if at least 18 years old at time of 
assessment period) 
• 
6-Question Asthma Control Questionnaire (ACQ) (asthmatic subjects 
only) 
• 
Work Productivity and Activity Impairment Questionnaire plus 
Classroom Impairment Questions: Allergy Specific(WPAI:CIQ-AS) 
• 
Asthma progression 
• 
Change in geographic location 
• 
Total Rhinoconjunctivitis Symptom Score (TRSS) (for a three-week 
period) 
• 
Allergy medication usage (for a three-week period) 
• 
Asthma Symptom Score (for a three-week period) 
• 
Exposure to indoor cat (for a three-week period) 
Safety Parameters 
The safety and tolerability of Cat-PAD will be assessed by measurement/recording 
of: 
• 
AEs 
• 
SAEs 
Pharmacokinetic 
Parameters 
None 
Statistical Analysis 
A detailed Statistical Analysis Plan (SAP) (including dictionaries for coding and 
software used) will be developed and approved by the Sponsor prior to conducting 
any analyses. The nature of the formal statistical testing will be described and 
justified in the SAP, discussing any potential biases and challenges caused by the 
data collected and circumstances of the study.  It is anticipated that the analyses will 
be similar to those performed for the CP007 study and that the statistical tests for 
each endpoint will use a Bonferroni-Holm adjustment for the two treatment 
comparisons (two courses of Cat-PAD versus placebo and one course of Cat-PAD 
versus placebo), thereby keeping the overall type I error rate at 0.05. The tests will 
be two sided. 
The first analysis of the data will be performed on the first year’s data after all 
subjects have completed one year in this study.  Additional analyses of the second, 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 8 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
third and fourth year in the study will be performed after all subjects have completed 
each additional year in the study. At each of the statistical analyses performed after 
one, two, three and four years, there will be no adjustment to the significance level, 
apart from the Bonferroni-Holm correction (due to multiple treatment comparisons) 
stated above. 
Subject data will be pulled from CP007 and will be used as baseline data for 
CP007A. Data will be summarised with respect to demographic and baseline 
characteristics, efficacy variables and safety variables.  Summary statistics will 
include the mean, N, standard deviation, median, minimum and maximum values 
for continuous variables and frequencies and percentages for categorical variables.   
Where appropriate confidence intervals will be used to explore the size and 
direction of any changes in variables or differences between groups. 
For the primary efficacy analysis, the data will be summarised and analysed using 
methods as for study CP007.  The analysis will provide a comparison of the mean 
Combined Score (TRSS/8+Allergy Medication Score [AMS]) for each treatment 
group.  The data will be analysed using covariates including pooled centre, age 
group (as randomised), gender, asthma status and baseline score.  Additional 
informative subgroup descriptive analyses may also be performed. 
Other endpoints will be analysed appropriately to address the secondary objectives 
of the study, including non-parametric methods, where relevant. 
Safety data will be analysed descriptively. 
Study Sites 
Sites previously participating in clinical study CP007 will participate in this study 
with the exception of countries where fewer than 10 subjects were randomised. 
Planned Study Dates 
Start of clinical phase 
End of clinical phase 
 
December 2013 
June 2019 
 
Duration of the Study  
The duration of the study for each subject will be approximately 4 years. 
 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 9 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
TABLE OF CONTENTS 
PROTOCOL SYNOPSIS ........................................................................................................6 
TABLE OF CONTENTS ......................................................................................................10 
1.0 
INTRODUCTION......................................................................................................14 
2.0 
OBJECTIVES ............................................................................................................16 
2.1 
Primary Objective ..........................................................................................16 
2.2 
Secondary Objectives.....................................................................................16 
2.3 
Exploratory Objectives ..................................................................................16 
3.0 
STUDY DESIGN ........................................................................................................18 
3.1 
Overall Study Design .....................................................................................18 
3.2 
Endpoint..........................................................................................................19 
3.2.1 
Primary Endpoint ...............................................................................19 
3.2.2 
Secondary Endpoints .........................................................................19 
3.2.3 
Exploratory Endpoints .......................................................................20 
4.0 
STUDY POPULATION ............................................................................................21 
4.1 
Number of Subjects........................................................................................21 
4.2 
Inclusion Criteria ...........................................................................................21 
4.3 
Exclusion Criteria ..........................................................................................21 
4.4 
Females of Childbearing Potential ...............................................................21 
4.5 
Withdrawal of Subjects from the Study ......................................................21 
4.6 
Criteria for Stopping the Study ....................................................................21 
4.7 
End of the Study .............................................................................................22 
5.0 
STUDY MEDICATION ............................................................................................23 
5.1 
Investigational Product .................................................................................23 
5.2 
Concomitant Medication and Dietary Supplements ...................................23 
5.2.1 
Allergy Medication ............................................................................23 
5.2.2 
Treatment of Suspected Anaphylactic Reactions ..............................23 
5.2.3 
Other Medication ...............................................................................23 
5.3 
Blinding ...........................................................................................................23 
6.0 
STUDY CONDUCT ...................................................................................................25 
6.1 
Schedule of Assessments ................................................................................25 
6.2 
Study Procedures ...........................................................................................27 
6.2.1 
Enrolment ..........................................................................................27 
6.2.2 
Monthly and annual assessments .......................................................27 
6.2.3 
Quarterly / Annual Visits ...................................................................28 
6.2.4 
Study Completion ..............................................................................28 
6.3 
Assessment of Efficacy ...................................................................................28 
6.3.1 
Monthly .............................................................................................29 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 10 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
6.3.2 
Annually (for a three-week period) ...................................................29 
6.4 
Assessment of Safety and Tolerability .........................................................31 
6.4.1 
Adverse Events ..................................................................................31 
6.4.2 
Serious Adverse Events .....................................................................33 
6.4.3 
Reporting of Pregnancy .....................................................................35 
6.4.4 
Safety Evaluations .............................................................................36 
7.0 
STATISTICAL CONSIDERATIONS .....................................................................37 
7.1 
Data Management and Quality Assurance ..................................................37 
7.2 
Sample Size .....................................................................................................37 
7.3 
Analysis Populations ......................................................................................38 
7.3.1 
Intent-to-Treat Population .................................................................38 
7.3.2 
Modified Intent to Treat Population ..................................................38 
7.3.3 
Safety Population ...............................................................................38 
7.4 
Statistical Analysis .........................................................................................38 
7.4.1 
Demographic and Baseline Characteristics .......................................39 
7.4.2 
Efficacy Analysis ...............................................................................39 
7.4.3 
Safety Analysis ..................................................................................41 
8.0 
INVESTIGATOR RESPONSIBILITIES ................................................................43 
8.1 
Investigator Performance ..............................................................................43 
8.2 
Ethical Considerations...................................................................................43 
8.2.1 
Ethics Committee Review and Approval ..........................................43 
8.2.2 
Written Informed Consent .................................................................43 
8.2.3 
Information for Subject’s General Practitioner .................................44 
8.3 
Confidentiality ................................................................................................44 
8.3.1 
Subject Confidentiality ......................................................................44 
8.4 
Study Documentation ....................................................................................44 
8.4.1 
Case Report Forms ............................................................................44 
8.5 
Publication ......................................................................................................45 
8.6 
Non-Protocol Research ..................................................................................45 
9.0 
SPONSOR RESPONSIBILITIES ............................................................................46 
9.1 
General ............................................................................................................46 
9.2 
No Fault Compensation and Indemnity .......................................................46 
9.3 
Monitoring ......................................................................................................46 
9.4 
Confidentiality ................................................................................................46 
9.5 
Finance ............................................................................................................47 
9.6 
Audit ................................................................................................................47 
10.0 
REFERENCES ...........................................................................................................48 
11.0 
APPENDICES ............................................................................................................50 
 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 11 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
LIST OF TABLES 
 
Table 1 Schedule of Assessments – Study Visits ....................................................................25 
Table 2 Schedule of Assessments – Evaluations (to be recorded in the subject 
diary) ..........................................................................................................................26 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 12 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
LIST OF ABBREVIATIONS 
ABPI 
Association of the British Pharmaceutical Industry 
AE 
Adverse Event 
ACQ 
Asthma Control Questionnaire 
AMS 
Allergy Medication Score 
ASS 
Asthma Symptom Score 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
CS 
Combined Score 
EDC 
Electronic Data Capture 
ePRO 
Digital Pen 
Fel d  1  
Cat (Felis domesticus) allergen 1 
FOCBP 
Female of Child-bearing Potential 
GCP 
Good Clinical Practice 
GINA 
Global Initiative for Asthma 
IAF 
Informed Assent Form 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified Intent-to-Treat 
PAC 
Post-Administration Collection 
PAD 
Peptide Antigen Desensitisation 
PSQI 
Pittsburgh Sleep Quality Index 
RQLQ 
Rhinoconjunctivitis Quality-of-Life Questionnaire  
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SMS 
Short Message Service 
TRSS 
Total Rhinoconjunctivitis Symptom Score 
USA 
United States of America 
WAO 
World Allergy Organization 
WHO 
World Health Organization 
WPAI:CIQ-AS 
Work Productivity and Activity Impairment Questionnaire 
plus Classroom Impairment Questions: Allergy Specific 
 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 13 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
1.0 INTRODUCTION 
Allergic rhinitis is a significant global public health concern, particularly in the economically 
developed world, affecting up to 30% of adults (Gupta et al, 2004) and up to 40% of children 
(ISAAC 1998). Allergy to cat dander is one of the most common forms of allergic disease in 
the United States of America (USA) and Europe, affecting 10%-15% of subjects with allergic 
rhinitis and/or asthma. Out of a population of 310 million people in the USA, approximately 
62 million people suffer from allergies, with 26 million of these suffering from cat allergy 
(World Allergy Organization [WAO] 2011). Allergic rhinoconjunctivitis significantly reduces 
quality of life (Laforest et al, 2005). Using the well validated Short Form 36 Health Related 
Quality-of-Life questionnaire, it has been demonstrated that subjects with allergic rhinitis 
report more problems with social activities, difficulties with daily activities as a result of 
emotional problems and poorer mental wellbeing (Leynaert et al, 2000). In addition, it 
interferes with both attendance and performance at school and work (Blaiss 2004; Cockburn et 
al, 1999) and the prevalence of the condition is still rising (Maziak et al, 2003). 
The prevalence of human allergy to pet dander is a growing problem of global public health 
importance, as the morbidity associated with allergic diseases disproportionately affects socio-
economically disadvantaged populations, particularly children (Morris 2010). The animal-
origin allergen Fel d 1 (Felis domesticus allergen 1), is present ubiquitously in the human 
environment, and is widely found in public buildings including schools, the work place, 
automobiles, airplanes and cinemas (Morris 2010). Cats are the dominant source of the allergen 
Fel d 1. Although several molecules in cat extracts are allergenic, the most important one is Fel 
d 1 with approximately 90% of individuals allergic to cats having elevated levels of specific 
immunoglobulin E to the protein. Levels of Fel d 1 are much higher in households with current 
cat residence. In homes where there has never been a resident cat, there is a direct correlation 
of indoor allergen level with the prevalence of cat ownership in the community at large. Fel d 
1 is also detectible in many public places at levels capable of sensitising or exacerbating 
symptoms in susceptible individuals. This is especially relevant and problematic for children 
in schools (Morris 2010).  
Existing treatment for cat-allergy induced allergic rhinoconjunctivitis is essentially 
symptomatic and consists of antihistamines given by mouth, intranasally or as eye drops, 
cromoglycate nasal sprays as well as topical corticosteroids. None of these treatments are 
disease-modifying and, unless taken regularly, offer poor protection. Immunotherapy, on the 
other hand, is directed toward the pathological basis of the disease and this form of treatment 
is used for cat allergy in some countries using whole allergen extract dander. However, there 
are few formal studies of its efficacy despite some reported short-term improvements in 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 14 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
bronchial hyperreactivity and other target organ sensitivities (Taylor et al, 1978; Ohman et al, 
1984; Sundin et al, 1986; Alvarez-Cuesta et al, 1994; Varney et al, 1997).  There are no long-
term follow-up studies evaluating the continued benefit of immunotherapy for cat allergy on 
either allergic rhinoconjunctivitis symptoms or progression to asthma. 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 15 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
2.0 OBJECTIVES 
The proposed study is designed to evaluate the continued efficacy and safety of Cat-PAD in 
cat allergic subjects for up to five years after the start of administration of treatment. This study 
is an optional follow-up study to a phase 3 double-blind placebo-controlled study; no further 
investigational product is being administered.  The study’s principal purpose is to continue to 
monitor subjects who have received investigational product as part of the CP007 study.   
2.1 
Primary Objective 
To evaluate the continued efficacy of Cat-PAD, the first in a new class of Synthetic Peptide 
Immuno-Regulatory Epitopes, for a total of up to five years after the administration of 
treatment, based on the reduction of symptoms and the use of allergy medication in subjects 
previously participating in CP007. 
2.2 
Secondary Objectives 
• To evaluate the continued safety and tolerability of Cat-PAD for up to five years after the 
administration of treatment. 
• To evaluate the effect of Cat-PAD on Rhinoconjunctivitis Quality-of-Life Questionnaire 
(RQLQ) for up to five years after the administration of treatment. 
• To evaluate the effect of Cat-PAD on the onset of asthma for up to five years after the 
administration of treatment. 
• To evaluate the effect of Cat-PAD on asthma progression in subjects previously enrolled 
in CP007 with GINA 1 asthma for up to five years after the administration of treatment. 
2.3 
Exploratory Objectives 
• To evaluate the effect of Cat-PAD on changes in asthma control in asthmatic subjects for 
up to five years after the administration of treatment. 
• To evaluate the effect of Cat-PAD on changes in sleep quality in adults using the Pittsburgh 
Sleep Quality Index (PSQI) for up to five years after the administration of treatment. 
• To evaluate the effect of Cat-PAD on changes in productivity using the Work Productivity 
and Activity Impairment Questionnaire (WPAI:CIQ-AS) for up to five years after the 
administration of treatment. 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 16 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
• To evaluate the effect of Cat-PAD on symptomatology on unplanned exposure to a cat in 
normal daily life in subjects who no longer keep a cat for up to five years after the 
administration of treatment. 
• To evaluate the effect of Cat-PAD on health economic outcomes for up to five years after 
the administration of treatment. 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 17 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
3.0 STUDY DESIGN 
3.1 
Overall Study Design 
An optional prospective, follow-on study to a randomised, double-blind, superiority, multiple 
dose, placebo-controlled, parallel group, multi-centre, field study (CP007).  
Subjects from participating sites who complete the final Post Administration Collection Period 
(PAC3) in CP007 will be invited to participate in CP007A. Where possible the Enrolment Visit 
will occur at the same time as the final Follow-Up Visit as scheduled in CP007.  Subjects who 
consent to take part in this study and who meet all inclusion/exclusion criteria will be issued 
with paper diary binders and a digital pen (ePRO) to record the required patient reported 
outcomes data. This comprises annual and monthly evaluations. The annual assessment data 
will be recorded at the same time of year as the Baseline Allergy Evaluation Period (Visit 2A 
to Visit 2B) established in CP007.  It will include scoring rhinoconjunctivitis symptoms and 
allergy medication use over a 3-week period, as well as single assessments of quality of life, 
sleep quality, asthma status and work/school interference. As with CP007, for this study, 
subjects will receive an Allergy Medication Kit containing approved allergy treatments prior 
to the start of this 3-week period.  The kit will contain the same treatments provided to subjects 
in CP007.   
Additionally, on a monthly basis, subjects will record information in their diary using the 
digital pen regarding hospital/doctor visits; concomitant medication use; illnesses/symptoms; 
asthma progression and changes in home environment. Subjects will be requested to upload 
data from the digital pen monthly via their home computer (internet) directly to a secure 
website or via a mobile ‘phone; if a subject does not have access to a computer, a mobile ‘phone 
will be provided to the subject for the duration of the study and for the sole purpose of 
uploading data and participating in the study.  
Subjects will have up to four visits each year, two of which may be conducted by telephone. 
At each visit, site staff will record any adverse events (AEs) and serious adverse events (SAEs), 
and at the on-site visits subjects will be provided with their next diary binder. One of the on-
site visits will be scheduled just prior to the annual 3-week symptom and allergy medication 
use recording period. At this visit, subjects will be provided with an Allergy Medication Kit. 
For all on-site visits, where possible subjects will be instructed to complete the closest monthly 
assessment in the diary binder during the visit. Subjects will not be required to undergo any 
specific treatment or lab tests at these visits.  
Subjects will have a final End of Study Visit, which will coincide with the end of the final 
annual Allergy Evaluation Period assessment. 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 18 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
The duration of this follow-up study will be up to 4 years for each subject.   
3.2 
Endpoint 
3.2.1 
Primary Endpoint 
• Mean Combined Score (CS) consisting of (TRSS/8 + Allergy Medication Score [AMS]). 
The total rhinoconjunctivitis symptom score (TRSS) is the sum of the eight individual 
symptoms, each of which is scored from 0 to 3 resulting in a range of scores from 0-24. TRSS 
will be divided by the number of symptoms (8) to provide an average score range of 0-3. 
Allergy medications will be provided to subjects to be used according to a pre-specified Allergy 
Medication Plan (See Appendix 1). Subjects will be requested to use antihistamine eye drops 
as first line allergy medication for troublesome ocular symptoms; with oral antihistamines 
and/or intranasal corticosteroids to be added or substituted if subjects have unacceptable nasal 
symptoms or ocular antihistamines do not provide adequate symptom relief. Oral 
corticosteroids may be prescribed at the Investigator’s discretion. The use of allergy 
medications will be scored based on Didier (Didier et al, 2009) as follows: 
• 
AMS = 0; no allergy medication used per day 
• 
AMS = 0.5; at least one dose of antihistamine eye drops used per day 
• 
AMS = 1; at least one dose of oral antihistamine used per day 
• 
AMS = 2; at least one dose of intranasal corticosteroid used per day 
• 
AMS = 3; at least one dose of systemic corticosteroid used per day 
The AMS score is not additive, and therefore the maximum AMS is 3. The TRSS (0-24) and 
the AMS (0-3) will be combined for analysis of the primary endpoint as follows: 
CS = TRSS/8 + AMS 
3.2.2 
Secondary Endpoints 
• Mean TRSS 
• Mean component scores of the TRSS (nasal and ocular) 
• Mean AMS 
• Mean RQLQ Score 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 19 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
• Concomitant medications associated with rhinoconjunctivitis or related conditions 
• AEs 
3.2.3 
Exploratory Endpoints 
• PSQI (if at least 18 years old at time of assessment period) 
• 6-Question Asthma Control Questionnaire (ACQ) (excluding lung function) – for 
asthmatics only 
• WPAI:CIQ-AS 
• Global assessment of symptom severity on unplanned exposure to a cat in normal daily life 
in subjects who no longer keep a cat 
• Health economic outcomes 
• Hospital / Physician office visits 
• Asthma progression 
 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 20 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
4.0 STUDY POPULATION 
Only subjects completing the CP007 study will be allowed to enter this follow-up study.  No 
other subjects will be enrolled in the study. 
4.1 
Number of Subjects 
The population is limited to those in the CP007 study and the maximum number to be enrolled 
in this study will be 1400 subjects. Subjects in countries where fewer than 10 subjects were 
randomised in CP007 will not be invited to participate in this study. 
4.2 
Inclusion Criteria 
1. Previously randomised into the clinical study CP007 and completed PAC3. 
2. Provide written informed consent or assent, as appropriate. (For subjects less than 18 years 
a Parent/Guardian will also be required to provide written informed consent). 
3. Willing and able to comply with the study requirements. 
4.3 
Exclusion Criteria 
1. Started allergen immunotherapy since completing CP007.  
2. Has been informed of the treatment received in study CP007. 
3. Dependent on the Investigator/site either for employment or education or are first degree 
relatives or partners of the Investigator/study staff. 
4. Subjects institutionalised due to a legal or regulatory order. 
4.4 
Females of Childbearing Potential 
Females of Childbearing Potential (FOCBP) may participate in CP007A without taking any 
additional precautions to prevent pregnancy as there is no investigational product 
administration in this study. 
4.5 
Withdrawal of Subjects from the Study 
Subjects will be informed that they have the right to withdraw from the study on their own 
accord at any time, for any reason and without having to state their reason and that this will not 
affect their future management and treatment.  
4.6 
Criteria for Stopping the Study 
Circassia Ltd may terminate the study for safety or administrative reasons. 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 21 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
4.7 
End of the Study 
The end of the study is when the last subject completes the end of study visit (following the 
last four year annual follow-up assessment). 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 22 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
5.0 STUDY MEDICATION 
5.1 
Investigational Product 
No investigational product will be used in this follow-on study.  
Subjects will have received one of the following three study drug regimens in study CP007: 
• Single course of Cat-PAD (4 doses of Cat-PAD 6 nmol, 4 weeks apart, followed by 4 
doses of placebo, 4 weeks apart) 
• Two courses of Cat-PAD (8 doses of Cat-PAD 6 nmol, 4 weeks apart) 
• Placebo (8 doses, 4 weeks apart) 
5.2 
Concomitant Medication and Dietary Supplements 
5.2.1 
Allergy Medication 
In order to ensure consistency with results obtained from CP007, subjects will receive an 
Allergy Medication Kit prior to the start of the Allergy Evaluation Period to be used as needed.  
The Allergy Medication Kit will contain the same standardised therapies as those provided in 
CP007.  Subjects will be asked to use only allergy medications provided in the Allergy 
Medication Kit according to the defined Allergy Medication Plan (Appendix 1) during the 
Allergy Evaluation period. 
5.2.2 
Treatment of Suspected Anaphylactic Reactions 
Not applicable – subjects will not be deliberately exposed to additional allergen during the 
study beyond their normal daily exposure from e.g. living with a cat.   
5.2.3 
Other Medication 
Subjects should record the use of all concomitant medications, both prescribed and over-the-
counter, into the diary.  This includes medications used on both a chronic and an as-needed 
basis. Hormonal contraceptives may be used by FOCBP.  
5.3 
Blinding 
The subject will not know which treatment they received in CP007 and subjects will waive the 
right to be told their treatment in CP007 when they enrol in CP007A.  If subjects wish to know 
the treatment they received in CP007 they will be withdrawn from study CP007A.  New 
sequential subject numbers will be assigned to each subject from CP007 as they are enrolled in 
this study, this reassignment will occur within the electronic data capture (EDC) system to 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 23 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
ensure that all Circassia staff and Quintiles clinical staff directly involved in conduct of the 
study remain blind to the treatment received in CP007. The CP007 screening and 
randomisation numbers will not be presented in the CP007A documentation that is available to 
those who may introduce bias. In order to maintain blinding, once the CP007 study has been 
unblinded, Investigators and site staff will be kept blinded for any CP007 subjects that have 
enrolled into CP007A.   
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 24 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
6.0 STUDY CONDUCT 
6.1 
Schedule of Assessments 
Study assessments will occur as stated in Tables 1 and 2. 
Table 1 Schedule of Assessments – Study Visits 
Visit 
Enrolment Visit 
 
(performed on site at or after 
Visit 5 of CP007) 
Quarterly Visitse  
Annual Visitsg 
End of Study / Early 
Termination Visit 
(performed on site upon 
study completion/subject 
withdrawal/ discontinuation)   
Duration 
1 day 
1 day 
1 day 
1 day 
Informed consent / assenta 
X 
 
 
 
Inclusion / Exclusion Criteriab 
X 
 
 
 
Adverse Eventsc 
 
X 
X 
X 
Subject collects patient diary binder 
X 
X 
X 
 
Subject collects digital pend 
X 
 
 
 
Subject collects Allergy Medication 
Kit 
 
 
X 
 
Subject completion of monthly 
assessment in subject diary 
 
Xf 
Xf 
 
Collection of digital pen (and mobile 
‘phone if applicable) from subject 
 
 
 
X 
a Consent/assent may be taken at the final PAC3 visit in CP007 (Visit 4F) 
b Performed at or after Visit 5 of CP007 
c  Investigator will ask non-leading questions 
d For subjects requiring a mobile ‘phone for the study, a digital pen will be sent directly to the subject along with the mobile ‘phone  
e Three Quarterly Visits performed each year; up to 2 of these may be performed by telephone 
f Where possible, subjects should complete the monthly assessment during all on-site Quarterly and Annual Visits (not required for ‘phone-call visits) 
g Annual Visit performed at site once per year prior to the Allergy Evaluation Period 
 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 25 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
Table 2 Schedule of Assessments – Evaluations (to be recorded in the subject diary) 
Assessments 
Monthly Evaluations 
Annual Evaluation 
Duration 
1 day 
3 weeks 
Subject completion of monthly 
assessments in subject diary 
X 
X 
Daily Diary recording for 3 weeks:  
• TRSS 
• ASS 
• Allergy medication use 
• Exposure to indoor cat 
 
X 
Diagnosis of Asthmaa 
 
X 
Change in geographic locationb 
 
X 
6-Question ACQ (for Asthmatics only)b 
 
X 
RQLQb 
 
X 
PSQI (adults only)b 
 
X 
WPAI:CIQ-ASb 
 
X 
Hospital / Physician office visits 
X 
 
Number of lost work / school days 
X 
 
Current Status / Change in Home 
Environment 
X 
 
Exposure to Cat 
X 
 
Global assessment of symptoms to cat 
exposurec 
X 
 
Asthma Progression 
X 
 
Concomitant medication 
X 
 
Illnesses / Symptoms 
X 
 
a Completed at the start of annual Allergy Evaluation Period 
b Completed at the end of annual Allergy Evaluation Period 
c For subjects who no longer live in a house with an indoor cat  
 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 26 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
6.2 
Study Procedures 
6.2.1 
Enrolment 
Enrolment in to the study may occur at any time after a subject has completed study CP007, 
but ideally will take place at the final follow-up visit for CP007. Consent may also be taken at 
the final PAC3 visit (Visit 4F) in CP007.  
Subjects will be provided with information about this follow-on study, both verbally and in 
writing, and written informed consent/assent will be obtained from the subject.  Subjects will 
be provided with a study information sheet to explain the study objectives, as well as any 
potential risks and benefits.  The subject will be given adequate time to read the information 
sheet and to ask the Investigator any questions.  The Investigator must be satisfied that the 
subject has understood the information provided before written consent/assent is obtained.  If 
there is any doubt as to whether the subject has understood the written and verbal information, 
the subject should not enter the study. 
Subjects agreeing to participate will be asked to sign and date an Informed Consent Form (ICF) 
or an Informed Assent Form (IAF).  For adolescents, informed consent will be obtained from 
the legally-authorised representatives (e.g. parents/guardians) and informed assent will be 
obtained from the subject themselves.  Any adolescent subjects who turn 18 years of age while 
in the follow-up portion of this study will be asked to sign a new informed consent form at the 
next on-site visit, which will include details of an additional questionnaire (PSQI) to be 
completed on an annual basis.  The original signed ICF(s) and IAF(s) will be kept in the 
subject’s medical file and a copy of the signed ICF(s)/IAF(s) will be given to the subject.   
Once eligibility for the study is confirmed, subjects will be provided with their study materials, 
including the subject diary (to include three months of follow-up), digital pen, and if required, 
mobile telephone to support uploading of data.  Site staff will provide training to subjects on 
how to use the digital pen and completion of the subject diary. 
  
6.2.2 
Monthly and annual assessments 
Subjects will complete their subject diary on a monthly basis.  Additionally, on an annual basis, 
subjects will participate in an Allergy Evaluation Period; a 3-week period where subjects will 
complete a number of questionnaires (to occur at the same time each year, coordinated with 
the Baseline Allergy Evaluation period [Visit 2A to Visit 2B] in CP007).   
To support completion of data, email, SMS text messages and/or ‘phone calls will be sent 
and/or made to subjects to remind them to complete both monthly assessments and the Allergy 
Evaluation Period assessments.   
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 27 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
 
6.2.3 
Quarterly / Annual Visits 
Subjects will have up to four visits each year; three Quarterly Visits and one Annual Visit. The 
visits will be conducted at approximately three-monthly intervals. The Annual Visit must take 
place just prior to the Allergy Evaluation Period and must be conducted on-site. At least one 
of the three Quarterly Visits must be conducted on-site; the remaining visits can be conducted 
either on-site or via telephone. There will therefore be a minimum of two on-site visits per year. 
During each visit (Quarterly and Annual), sites will record any AEs/SAEs and subjects will 
collect (or be sent) a new diary binder with the next set of monthly assessments to complete. 
For on-site visits, where possible, subjects will also be instructed to complete the closest 
monthly assessment in the subject diary during the visit. Subjects should complete the 
assessment by themselves without the influence of the site staff. For telephone visits, subjects 
will be reminded to complete their monthly assessment at home.  
During the Annual Visits, subjects will be provided with an Allergy Medication Kit, further 
monthly diary binders and the diary binder pertaining to the Allergy Evaluation Period. In order 
to ensure consistency with results obtained from CP007, the Allergy Medication Kit will 
contain the same therapies as provided to subjects while participating in CP007. The 
medications are to be used on an ‘as needed’ basis in accordance with the Allergy Medication 
Plan (Appendix 1).  
Subjects will not be required to undergo any other specific treatment or lab tests while 
participating in this follow-up study.  All other physician visits and treatments / procedures 
will be administered per the physician’s direction. 
6.2.4 
Study Completion 
Subjects will be asked to return to site for a final End of Study Visit, which will coincide with 
the end of the final annual Allergy Evaluation Period assessment, anticipated to be after four 
years, or upon early discontinuation or subject withdrawal.  During the visit, the date of study 
completion (date of visit) will be recorded, and, in the case of early discontinuation/subject 
withdrawal, the reason for discontinuation/withdrawal will also be recorded. The site will 
collect the digital pen (and mobile ‘phone where applicable) from the subject. Subjects will 
also be asked to complete the Withdrawal/Discontinuation Page in the diary binder (either 
before or during the visit).  
6.3 
Assessment of Efficacy 
Information to be collected for all study subjects will include the following: 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 28 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
6.3.1 
Monthly 
• Hospital / Physician office visits 
• Lost work/ school days 
• Change in home environment 
• Exposure to cat 
• Global assessment of symptoms to cat exposure (only for subjects no longer living with an 
indoor cat) 
• Asthma progression 
• Concomitant medications 
6.3.2 
Annually (for a three-week period) 
• At the start of the 3-week allergy evaluation period: 
o Diagnosis of asthma 
• Daily recording for 3 weeks:  
o TRSS 
o Asthma Symptom Score (ASS) 
o Allergy medication use 
o Exposure to indoor cat 
• At the end of the 3-week allergy evaluation period: 
o Change in geographic location 
o 6-Question ACQ  excluding lung function (for asthmatics only) 
o RQLQ 
o PSQI (if at least 18 years old at time of assessment period) 
o WPAI:CIQ-AS 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 29 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
For each rhinoconjunctivitis symptom, the subject will rate the severity over the last 24 hours 
as follows: 
0 = absent 
1 = mild, barely noticeable 
2 = moderate, annoying/troublesome 
3 = severe, very annoying/ very troublesome 
Symptoms will be captured as follows: 
Nasal Symptoms 
• Runny nose 
• Sneezing 
• Blocked nose 
• Itchy nose 
Ocular Symptoms 
• Itchy eyes 
• Watery eyes 
• Red eyes 
• Sore eyes 
ASS will be captured as follows for all subjects: 
Asthma Symptoms 
• Cough 
• Wheezing 
• Shortness of breath 
In addition, ASS will be captured as follows for subjects with asthma: 
• Limitations of activities  
Over the last 24 hours, how limited have your activities been because of asthma? 
0: Not limited 
1: Very slightly limited 
2: Slightly limited 
3: Moderately limited or worse 
• Nocturnal symptoms or awakenings due to asthma 
Overnight (last night) how has your asthma affected you? 
0: Not at all 
1: Hardly at all 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 30 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
2: A few minutes disturbance 
3: Several times or more 
• Need for short-acting inhaled β2 agonist treatment  
Over the last 24 hours, how many puffs of reliever medication (e.g. albuterol or 
salbutamol) have you used? 
0: None 
1: One 
2: Two 
3: Three or more 
6.4 
Assessment of Safety and Tolerability 
6.4.1 
Adverse Events 
AE reporting begins from signed informed consent and ends when the subject completes the 
study or withdraws.  
 
At each study visit, the Investigator will determine whether any AEs have occurred by asking 
non-leading questions and these will be recorded in the Case Report Form (CRF). Illnesses and 
symptoms information recorded by subjects in the diary binders will be used to aid recollection 
of events. 
 
An AE is any untoward medical occurrence. An AE can therefore be any unfavourable and 
unintended sign, symptom or disease.  
When recording an AE, the following details will be recorded: 
• Event observed (brief description using medical terminology); 
• Start and stop dates; 
• Severity (see below); 
• Relationship to study medication (see below); 
• Action taken (brief description); 
• Outcome (see below); 
• Serious (Yes/No) 
An AE does include: 
• Exacerbation of a pre-existing illness; 
• Increase in frequency or severity of a pre-existing episodic condition; 
• A condition detected after signing informed consent even though it may have been 
present prior to the start of the study. 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 31 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
An AE does not include: 
• Medical or surgical procedures (e.g., surgery, endoscopy, tooth extraction, transfusion); 
the condition that led to the procedure is an AE. 
• Pre-existing disease or conditions documented prior to the signing of informed consent, 
which does not worsen. 
• Disease or disorder being studied or associated signs or symptoms provided these do 
not worsen/appear during follow-up. 
• 
Overdose of concomitant medication without any signs or symptoms. 
• 
Uncomplicated pregnancy. 
 
Adverse events will be recorded as they are reported, whether spontaneously volunteered by a 
subject or in response to questioning about well-being at each study visit. The subject will be 
questioned in a general way and no specific symptoms will be suggested. The questioning about 
AEs will cover the current visit and the period of time between the previous and current visit 
although subjects may report AEs occurring at any other time during the study. Follow up of 
all AEs will continue until the overall clinical outcome is definitive. If any AEs have occurred, 
they will be recorded in the subject’s medical record and transcribed to the CRF. The 
Investigator must detail in the subject records the symptom of the event, the onset of the event, 
the measures taken and the outcome, the date of disappearance or stabilisation. If known, the 
diagnosis should be recorded, in addition to the listing of individual signs and symptoms. The 
Investigator will assess each AE in terms of severity and relationship to study medication as 
indicated in the sections that follow. 
Severity 
Mild 
Noticeable to the subject, but does not interfere with their usual 
activities. Usually does not require additional therapy. 
Moderate  
Interferes with usual activities, possibly requires additional 
therapy. 
Severe  
Incapacitating with inability to perform usual activities. May 
require medical intervention and treatment. 
 
The Investigator will make a judgement regarding whether or not the AE was related to the 
study medication given in study CP007. However, even if the Investigator feels there is no 
relationship to the study medication, the AEs MUST still be recorded in the CRF and the 
rationale for the judgement should be recorded in the medical notes. 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 32 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
Causality 
Related  
Any event that follows a reasonable temporal sequence from 
administration of study medication given in CP007 OR that 
follows a known response pattern to the investigational drug. 
(Any event that does not meet the criteria for unlikely or not 
related should be classified as related). 
Unlikely to be related 
Any event that does not follow a reasonable temporal sequence 
from administration of study medication given in CP007 AND 
does not follow a known response pattern to the suspected drug. 
Not related 
Any event that starts before administration of study medication 
AND/OR for which there is a clear alternative explanation. 
 
Outcome 
For each event, the following outcomes are possible: 
• Recovered; 
• Recovered with sequelae; 
• Ongoing; 
• Death; 
• Unknown (appropriate follow-up to determine the outcome of all AEs will be 
undertaken and therefore “Unknown” should only be used as a last resort). 
Follow-Up of Adverse Events 
If any AEs are present when a subject completes the study or if a subject is withdrawn from 
the study, the subject will be followed up by telephone in 3-7 days. If the AE has still not 
resolved, additional follow-up will be performed as appropriate. Every effort will be made by 
the Investigator to contact the subject until the AE has resolved or stabilised. This should be 
documented in the subject’s medical records. All AEs must be followed until resolution, until 
the condition stabilises, until the subject dies or is lost to follow-up. The Investigator is 
responsible for ensuring that follow-up includes any supplemental investigations that may be 
indicated, including (but not limited to) additional laboratory tests, histopathology or 
consultation with other health care professionals. 
6.4.2 
Serious Adverse Events 
A Serious Adverse Event (SAE) is any untoward medical occurrence that: 
• Results in death; 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 33 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
• Is life-threatening (subject is at immediate risk of death in the judgement of the 
attending physician at the time of the event); 
• Results in persistent or significant disability or incapacity; 
• Requires hospitalisation or prolongation of an existing hospitalisation; 
• Is a congenital abnormality or birth defect; 
• Is a medically significant event. 
Medical and scientific judgement should be exercised in deciding whether expedited reporting 
is appropriate in other situations, such as important medical events that may not be immediately 
life-threatening or result in death or hospitalisation, but may jeopardise the subject or may 
require intervention to prevent one of the other outcomes listed in the definition above. These 
should also be considered to be SAEs. 
6.4.2.1 
Life-Threatening Adverse Event 
The term “life-threatening” in the definition of “serious” refers to an event in which the subject 
was at risk of death at the time of the event; it does not refer to an event which hypothetically 
might have caused death if it were more severe. 
6.4.2.2 
Hospitalisation 
This is defined as the subject being hospitalised overnight. Any pre-planned or anticipated in-
hospital visits at the time of signing informed consent should be documented and will be 
excluded from this category. Hospitalisation for social reasons, e.g. subjects admitted to 
hospital the night before a day surgical procedure due to their distance from the hospital, should 
not be reported as SAEs. 
6.4.2.3 
Unexpected Adverse Event 
An unexpected AE is defined as an AE, the nature or severity of which is not consistent with 
the applicable product information (i.e., the Cat-PAD Investigator’s Brochure). 
6.4.2.4 
Reporting Serious Adverse Events/Expeditable Adverse Events 
Investigators are obliged to notify Circassia’s Pharmacovigilance vendor, ICON, of all SAEs 
as soon as possible and within 24 hours of the Investigator becoming aware of the event. 
SERIOUS ADVERSE EVENTS MUST BE REPORTED  
BY ‘PHONE, FAX OR EMAIL TO ICON IMMEDIATELY 
(NO LATER THAN 24 HOURS OF THE INVESTIGATOR BEING NOTIFIED) 
 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 34 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
Email 
f2m-eastleigh-medical@iconplc.com 
Fax 
USA and Canada: +1 800 540 1863  
Rest of World: +44 1865 595 595 
‘Phone 
USA and Canada: +1 888 723 9952  
Rest of World: +44 1628 496 300 
 
The minimum information required on the SAE report is: 
• Protocol number; 
• Centre number or Investigator name; 
• Subject number; 
• An AE or outcome that can be identified as serious; 
• A suspected investigational product; 
• Investigator’s or Co-Investigator’s assessment of relationship to the investigational 
product; 
• Name and signature of reporter. 
Follow-up information must be actively sought and submitted as soon as it becomes available. 
All serious and unexpected AEs that are reasonably associated with the study medication given 
in study CP007 must also be reported to the reviewing Independent Ethics 
Committee/Institutional Review Board (IEC/IRB) by the Investigator. Circassia Ltd will 
provide details to other Investigators of such AEs for this purpose. Confirmation that these AEs 
have been submitted to the IEC/IRB must be forwarded to Circassia Ltd or designee. 
Reports relating to the subject’s subsequent medical course must be submitted to the Sponsor 
until the event has subsided or, in the case of permanent impairment, until it stabilises and the 
overall clinical outcome has been ascertained. The Investigator will also provide additional 
information, including a copy of the following documents (where applicable): 
• Copies of all test results; 
• Hospital discharge summary (as soon as it is available to the Investigator); 
• Autopsy report (as soon as it is available to the Investigator). 
6.4.3 
Reporting of Pregnancy 
There is no requirement to report pregnancies in this study. However, any outcome of a 
pregnancy that meets the definition of a Serious Adverse Event will need to be reported 
(Section 6.4.2.4). 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 35 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
6.4.4 
Safety Evaluations 
Not applicable, AEs will be the only safety parameters evaluated in this follow-on study. 
 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 36 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
7.0 STATISTICAL CONSIDERATIONS 
7.1 
Data Management and Quality Assurance 
Subjects will complete monthly evaluations in a paper diary using an ePRO pen. Investigators 
will record data onto CRFs at the Quarterly and Annual visits. All data in the study will be 
captured and maintained in a secure, validated EDC system.  All subjects will be assigned a 
new subject ID upon entry in the study.     
The diary and CRF data, once uploaded into the EDC system, will be checked to ensure the 
quality, integrity, accuracy and completeness of the data entered.  
The diary and CRF data will be maintained in a validated study database with an audit trail of 
all changes that are made to the database, including the reason for the data change. Adverse 
events will be coded using a standard dictionary Medical Dictionary for Regulatory Activities 
(MedDRA), while concomitant medications will be categorised using the World Health 
Organization (WHO) drug dictionary. 
Creation and validation of the EDC system and management of the data will be conducted in 
accordance with title 21 of the Code of Federal Regulations (CFR) Part 11 and the Food and 
Drug Administration (FDA) Guidance for Industry on Computerised Systems used in Clinical 
Investigations. Methods used to ensure the quality and integrity of the data will be documented 
in the Data Management Plan, Functional Specifications and Data Transfer Specifications, 
which will be approved by the Sponsor. 
7.2 
Sample Size 
Subjects who were randomised in clinical study CP007 and completed PAC3 will be eligible 
for entry into this study, hence no formal sample size calculation has been performed. 
A sample size of 266 evaluable subjects per arm will have at least 99% power to detect a 25% 
treatment difference in the mean CS during the PAC3 period between each of the Cat-PAD 
treatment groups and placebo. This is based on subjects in the placebo treatment group having 
a CS (0-6) of 2.10 which relates to a 25% Cat-PAD mean CS treatment difference of 0.525, 
with a common within-group standard deviation (SD) of 1.29 (i.e. the same assumptions as for 
CP007). Note: A treatment effect of 20% greater than placebo is considered clinically relevant 
because it exceeds the treatment effect of leukotriene receptor antagonists, antihistamines and 
intranasal corticosteroids (Wilson et al, 2004.) This power calculation is based on a Bonferroni-
Holm adjusted alpha of 0.025 for the primary analysis given there will be two comparisons 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 37 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
(two courses of Cat-PAD versus placebo and one course of Cat-PAD versus placebo) with the 
tests assumed to be two sided.  
It is recognised that some subjects will withdraw from the study before the end of the four year 
period but it will still have at least 80% power to detect a difference between active treatment 
and placebo with 130 subjects per arm.  
7.3 
Analysis Populations 
7.3.1 
Intent-to-Treat Population 
The population for the primary analysis will be the Intent-to-Treat (ITT) population consisting 
of all subjects who are consented into the study. Subjects will be reported by the treatment they 
were randomised to in study CP007. This is the primary population for the study, and all the 
primary and secondary efficacy analyses will be based on the ITT population. Missing data 
will not be replaced meaning that all analyses will be performed on a Full Analysis Set. 
7.3.2 
Modified Intent to Treat Population 
The modified Intent-to-Treat (mITT) population will consist of all subjects who are enrolled 
into the study and continue to live in a house with an indoor cat during the annual Allergy 
Evaluation period. The mITT population will be defined on an annual basis based on the 
subject’s completion of the ePRO question as to whether the subject still lives in a house with 
an indoor cat. The mITT population may therefore change during the course of the study. The 
mITT population will be evaluated for all primary, secondary and exploratory endpoints with 
the exception of the global assessment of symptom severity on unplanned exposure to a cat in 
normal daily life in subjects who no longer keep a cat. 
7.3.3 
Safety Population 
All subjects will be included in the safety population. Safety data will be listed and summarised 
by study medication actually received in CP007. 
7.4 
Statistical Analysis 
Further detail of the statistical analyses and data presentations to be used in reporting the study, 
including dictionaries used for coding and software used, will be provided in the Statistical 
Analysis Plan (SAP), which will be approved by Circassia prior to performing any analysis of 
the data. 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 38 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
The nature of the formal statistical testing will be described and justified in the SAP, discussing 
any potential biases and challenges caused by the data collected and circumstances of the study.  
It is anticipated that the analyses will be similar to those performed for the CP007 study. For 
the primary hypothesis testing versus placebo a Bonferroni-Holm procedure will be used to 
adjust alpha in order to compensate for multiplicity when comparing the two Cat-PAD 
treatment arms versus placebo, thereby keeping the overall type I error rate at 0.05. The 
Bonferroni-Holm procedure will assess each of the two treatment comparisons (two courses of 
Cat-PAD versus placebo and one course of Cat-PAD versus placebo), whereby the smallest p-
value (of the two treatment comparisons) will be tested at the 0.05/2 (i.e. p < 0.025) alpha level. 
If this first comparison is statistically significant then the remaining treatment comparison p-
value will be tested at the 0.05 alpha level. The tests will be two sided.   
If any parametric analyses are found to be inappropriate and/or fail their assumptions then 
supportive analysis will include non-parametric methods, as appropriate. 
All data will be summarised to include the mean, N, SD, median, minimum and maximum 
values for continuous variables and frequencies and percentages for categorical variables. 
The first analysis of the data will be performed on the first year’s data after all subjects have 
completed one year in this study.  Additional analyses of the second, third and fourth year in 
the study will be performed after all subjects have completed each additional year in the study. 
At each of the statistical analyses performed after one, two, three and four years, there will be 
no adjustment to the significance level, apart from the Bonferroni-Holm correction (due to 
multiple treatment comparisons) stated above, because analysis of the later years will only be 
performed if there was a positive outcome in the previous years, and this is, therefore, a 
hierarchical analysis. 
7.4.1 
Demographic and Baseline Characteristics 
Subject data will be pulled from CP007 and will be used as baseline data for CP007A.  Data 
will be summarised with respect to demographic and baseline characteristics by study treatment 
group. 
7.4.2 
Efficacy Analysis 
In such a study it is expected that missing data will play an important role in the interpretation 
of any analysis or description of endpoints.  Statistical methods will be used to explore the 
effects of and the nature of any missing information, including specifically the reasons for non-
entry to or discontinuation from the study.  
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 39 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
7.4.2.1 
Primary Analysis  
The primary efficacy variable for this study is the mean Combined Score (TRSS/8+AMS). 
For the primary efficacy analysis, the data will be summarised and analysed using methods as 
for study CP007.  The analysis will provide a comparison of the mean Combined Score 
(TRSS/8+AMS) for each treatment group.  In addition, 95% Confidence intervals will be used 
to explore the size and direction of any differences between groups. 
The statistical analysis will use covariates as used in CP007, including pooled centre, age group 
(as randomised), gender, asthma status and baseline score.  Additional informative subgroup 
descriptive analyses may also be performed. 
7.4.2.2 
Secondary Analysis 
Secondary endpoints will be statistically analysed appropriately to address the secondary 
objectives of the study, including non-parametric methods, where relevant. 
7.4.2.2.1 
Rhinoconjunctivitis Symptom Scores 
The mean TRSS and the mean component scores of the TRSS (nasal and ocular) during the 
allergy evaluation periods will be analysed and summarised by treatment group.  
7.4.2.2.2 
Allergy Medication Usage 
The mean AMS during the allergy evaluation period will be analysed and summarised by 
treatment group.  
7.4.2.2.3 
Concomitant Medication Use 
An evaluation of the use of any concomitant medications associated with rhinoconjunctivitis 
or related conditions will be performed.  
7.4.2.2.4 
Rhinoconjunctivitis Quality-of-Life Questionnaire 
The mean RQLQ score at the end of the allergy evaluation period will be analysed and 
summarised by treatment group.   
7.4.2.2.5 
Medical Visits 
An evaluation of additional visits to doctors/clinics will be performed. 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 40 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
7.4.2.2.6 
Asthma 
An evaluation of asthma progression and the number of subjects developing asthma during the 
study will be performed in separate analyses. 
7.4.2.3 
Exploratory Analysis 
 Other endpoints will be analysed appropriately to address the exploratory objectives of the 
study, including non-parametric methods, where relevant. 
7.4.2.3.1 
Sleep 
The overall and component scores of the PSQI will be summarised descriptively.  
7.4.2.3.2 
6-Question ACQ 
The data for the 6-Question ACQ will be summarised. 
7.4.2.3.1 
Work Productivity and Activity Impairment Questionnaire 
The overall and component scores of the WPAI:CIQ-AS will be summarised descriptively. 
7.4.2.3.2 
Global Assessment of Symptom Severity 
An evaluation of the global assessment of symptom severity on unplanned exposure to a cat in 
normal daily life in subjects who no longer keep a cat will be performed. 
7.4.2.3.3 
Health Economic Outcomes 
Health economic outcomes will be described and explored. 
7.4.3 
Safety Analysis 
Safety will be evaluated by analysis of the following parameters: 
• 
AEs; 
• 
SAEs 
For safety analysis, frequency distribution will be summarised for categorical variables. No 
formal inferential tests will be performed on safety data. 
The number and percentage of subjects who experience AEs will be presented by treatment 
group. Based on the MedDRA Preferred Term, subjects who experience the same AE on 
multiple occasions will be summarised at the maximum severity and most conservative 
relationship to the study medication. If 2 or more AEs are reported as a single event, the 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 41 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
individual terms will be reported as separate AEs. 
The total number of AEs will be summarised by MedDRA System Organ Class and Preferred 
Term for each treatment group. Descriptive statistics will be presented for differences between 
each treatment group and the placebo group, but no hypothesis testing is planned. 
Any deaths and SAEs and AEs will be summarised by CP007 treatment group. 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 42 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
8.0 INVESTIGATOR RESPONSIBILITIES 
8.1 
Investigator Performance 
The Principal Investigator and each Investigator will ensure that each subject is consented.  
The study will be performed in full accordance with this protocol, the principles of the 
Declaration of Helsinki, ICH E6 Good Clinical Practice (GCP); and applicable local regulatory 
requirement(s). 
8.2 
Ethical Considerations 
8.2.1 
Ethics Committee Review and Approval 
It is the responsibility of the Investigator or designee to submit the protocol, ICF/IAF, and 
subject information sheet, to an IRB/IEC for their review according to local regulation. All the 
required study documents must be approved by the IRB/IEC prior to the consent of the first 
subject. A copy of the IRB/IEC written approvals must be submitted to Circassia Ltd before 
the study may start. Written approval must be obtained from the IRB/IEC for all major changes 
to the protocol, except when necessary to eliminate apparent immediate hazard to the subject. 
In this case, the IRB/IEC should be notified as soon as possible and written approval obtained. 
The study protocol will also be reviewed by the appropriate regulatory authority/authorities. 
The study will not proceed until the appropriate regulatory authority/authorities has/have 
granted a clinical study authorisation. 
8.2.2 
Written Informed Consent 
Prior to enrolment, the study procedures and any known or likely risks will be explained to the 
subjects in lay language by the Investigator or designee. Subjects will also waive their right to 
the unblinding of study medication from CP007, as was previously stipulated in CP007.  Any 
questions will be answered and subjects willing to participate, or their legally authorised 
representative, will provide written informed consent by reading and signing the ICF. 
Adolescent subjects will sign an IAF. Any adolescent subjects who turn 18 years of age while 
in this study will be asked to sign a new informed consent form at their next on-site visit.  All 
subjects will receive a copy of the signed ICF(s), and if appropriate IAF(s), as well as written 
information sheets about the study.  The subjects will be assured that they can withdraw from 
the study at any time and for any reason. Each subject’s ICF/IAF must be signed and dated by 
both the Investigator or designee and the subject.  The original signed ICF(s) and IAF(s) will 
kept in the patient’s medical file and a copy of the signed ICF(s)/IAF(s) will be given to the 
subject. 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 43 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
8.2.3 
Information for Subject’s General Practitioner 
If the subject consents, their general practitioner (and any specialist the subject might be treated 
by) will be notified of the subject’s intended involvement in the study. 
8.3 
Confidentiality 
8.3.1 
Subject Confidentiality 
The Investigator shall reassure subjects that their identity will be kept confidential by third 
parties that conduct audits and inspections of the study centre and its documentation. A unique 
study number assigned to each subject at the start of the study will be used to identify the 
subject in the EDC system, on all study correspondence and in the study database.  
8.4 
Study Documentation 
8.4.1 
Case Report Forms 
Data will be provided from electronically uploaded subject reported diaries and Investigator 
completed CRFs.  Data will be periodically uploaded from the digital pen via secure web access 
from the site’s/subject’s home computer and the internet or via a mobile ‘phone supplied 
specifically and for the sole purpose of uploading study data. Data on CRFs must correspond 
to and be supported by source documentation maintained at the study centre. All CRFs and 
records transmitted to the Sponsor must carry only coded identifiers such that personally 
identifying information is not transmitted. Access to the EDC system is available to authorised 
users via the study’s Internet web site, where an assigned username and password are required 
for access. 
Any changes made to data after collection will be made through the use of Data Clarification 
Forms. Data reported on the CRFs, which are derived from source documents, should be 
consistent with the source documents or the discrepancies should be explained. CRFs will be 
considered complete when all missing and/or incorrect data have been resolved. 
An audit trail of all changes that are made to the database, including the reason for the data 
change, will be created and maintained.  
The database is fully 21CFRpart11 compliant and provides a secure environment for subject 
data.  
The Investigator will keep a copy of the CRFs, the Investigator’s Site File and source 
documents until notified otherwise by Circassia.  
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 44 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
8.5 
Publication 
Circassia intends to publish the results of this study, whether positive or negative, in line with 
the guidance in the Declaration of Helsinki. The Investigators and Circassia will normally 
prepare a manuscript together. To avoid disclosures that may affect the proprietary rights of 
the Sponsor, the Investigator agrees to allow Circassia the opportunity to review all 
manuscripts and abstracts 60 days prior to submission for publication. Circassia reserves the 
right to include the report of this study in any regulatory documentation or submission or in 
any informational materials. 
8.6 
Non-Protocol Research 
No investigational research procedures pertaining to this study other than those outlined in this 
protocol may be undertaken on the subjects without the prior written permission of the subject, 
the Sponsor, the IRB/IEC and, when necessary, the appropriate regulatory authority. 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 45 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
9.0 SPONSOR RESPONSIBILITIES 
9.1 
General 
Circassia agrees to adhere to the most current version of ICH E6 Guidelines on GCP. Circassia 
has a legal responsibility to report fully to regulatory authorities the results of this study. 
9.2 
No Fault Compensation and Indemnity 
Circassia will provide “no-fault” compensation insurance against any injury incurred by a 
subject as a result of participation in the study. Circassia adheres to the ABPI “Clinical Trial 
Compensation Guidelines” (1991). The Investigators in this study will be indemnified as 
detailed in a separate document. 
9.3 
Monitoring 
The study staff may not enter any subjects into the study prior to completion of an initiation 
meeting conducted by a representative of Circassia or designee. 
Monitoring during the study will be undertaken at regular intervals by suitably qualified and 
appropriately trained personnel under contract to Circassia according to standard operating 
procedures.  The monitoring will be conducted via on-site visits or remote monitoring. The 
purpose of the monitoring is to ensure: 
• 
Compliance with the protocol; 
• 
Adherence to regulatory and GCP obligations; 
• 
Ensure filing of all study documents; 
• 
The completeness of the data entered by sites and subjects; 
• 
Accurate and timely reporting of AE(s) and SAEs 
• 
Liaison with the Investigator and study staff to clarify any problems that may arise 
during the study. 
9.4 
 Confidentiality 
Neither Circassia nor its designee(s) will have access to any material on file referring to the 
study subject by their full name. The identity of the subject will be respected and maintained 
as confidential at all times. 
The ePRO provider may hold personal information in a separate database, including name, 
address, email and mobile phone contact details.  Only the ePRO provider will have access to 
this database. This information is required for: 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 46 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
• The potential dispatch of mobile ‘phones for those subjects without internet access 
• The release of email and/or mobile ‘phone reminders and alerts. 
Any collection or use of subject data will be in compliance with Data Protection requirements. 
Note, in Czech Republic, this personal information is not collected by the ePRO provider and 
only the site will hold this information.  
The ePRO provider will ensure the databases are compliant with the clinical industry 
regulations and as such the confidentiality, integrity and accessibility of these systems are fully 
managed and controlled.  Access to the data is provided only to specifically approved and 
authorised individuals for the duration of the study.   
9.5 
Finance 
Financial agreements between Circassia, the Contract Research Organisation and the 
Investigator will be the subject of separate agreements. 
9.6 
Audit 
Circassia may audit or appoint an independent auditor to conduct an audit of this study while 
it is running or after it has been completed. The study may also be inspected by a regulatory 
authority either while it is running or up to several years later. 
 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 47 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
10.0 REFERENCES 
Alvarez-Cuesta E., Cuesta-Herranz J., Puyana-Ruiz J., et al. (1994). Monoclonal antibody-
standardized cat extract immunotherapy: risk-benefit effects from a double-blind placebo 
study. J Allergy Clin Immunol;93:556-566. 
Blaiss M.S. (2004). Allergic rhinitis and impairment issues in schoolchildren: a consensus 
report. Curr Med Res Opin;20:1937-1952. 
Circassia, CP007, Protocol. A double-blind, randomised, placebo-controlled multi-centre field 
study to assess the efficacy and safety of Cat-PAD Peptide Immunotherapy in cat allergic 
stubjects. 
Cockburn I.M., Bailit H.L., Berndt E.R., Finkelstein S.N. (1999). Loss of work productivity 
due to illness and medical treatment. J Occup Environ Med;41:948-953. 
Didier, A., Melac, M., Montaut, A., et al. (2009). Agreement of efficacy assessments for five-
grass pollen sublingual tablet immunotherapy. Allergy;64:166-171. 
Global Initiative for Asthma (GINA) Guidance 2011. http://www.ginasthma.org 
Gupta R., Sheikh A., Strachan D.P., Anderson H.R. (2004). Burden of allergic disease in the 
UK: secondary analyses of national databases. Clin Experimental Allergy;34:520-526. 
ISAAC (1998). The International Study of Asthma and Allergies in Childhood Steering 
Committee. Worldwide variation in prevalence of symptoms of asthma, allergic 
rhinoconjunctivitis, and atopic eczema. Lancet;351:1225-1232. 
Laforest L., Bousquet J., Pietri G., Sazonov K.V., Yin D., Pacheco Y., Van G.E. (2005). 
Quality of life during pollen season in subjects with seasonal allergic rhinitis with or without 
asthma. Int Arch Allergy Immunol;136:281-286. 
Leynaert B., Neukirch C., Liard R., Bousquet J., Neukirch F. (2000). Quality of life in allergic 
rhinitis and asthma. Am J Respir Cit Care Med;162:1391-1396. 
Maziak W., Behrens T., Brasky T.M., Duhme H., Rzehak P., Weiland S.K., Keil U. (2003). 
Are asthma and allergies in children and adolescents increasing? Results from ISAAC phase I 
and phase III surveys in Munster, Germany. Allergy;58:572-579. 
Morris D.O. (2010). Human allergy to environmental pet danders: a public health perspective. 
Vet Dermatol. 21(5):441-449. doi: 10.1111/j.1365-3164.2010.00882.x. Epub 2010 Mar 30. 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 48 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
Ohman J.L., Findlay S.R., Leitermann K.M. (1984). Immunotherapy in cat-induced asthma. 
Double-blind trial with evaluation of in vivo and in vitro responses. J Allergy Clin 
Immunol;74:230-239. 
Sundin B., Lilja G., Graff-Lonnevig V., et al. (1986). Immunotherapy with partially purified 
and standardised animal dander extracts. I. Clinical results from a double-blind study on 
subjects with an animal dander asthma. J Allergy Clin Immunol;77:478-487. 
Taylor W.W., Ohman J.L., Lowell F.C. (1978). Immunotherapy in cat-induced asthma. 
Double-blind trial with evaluation of bronchial responses to cat allergen and histamine.  
J Allergy Clin Immunol;61:283-287. 
Varney V.A., Edwards J., Tabbah K., Brewster H., Mavroleon G., Frew A.J. (1997). Clinical 
efficacy of specific immunotherapy to cat dander: a double-blind placebo-controlled trial. Clin 
Exp Allergy;27:860-867. 
WAO (World Allergy Organization). The global epidemiology of allergy. White Book on 
Allergy, 2011. 
Wilson A.M., O’Byrne P.M., Parameswaran K. (2004). Leukotriene receptor antagonists for 
allergic rhinitis: a systematic review and meta-analysis. Am J Med;116:338-344 
 
 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 49 OF 50 
 


 
DATE 08 DEC 2014 
PROTOCOL IDENTIFIER: CP007A 
 
11.0 APPENDICES 
APPENDIX 1 
Allergy Medication Plan 
The “Allergy Medication Kit” is a package of medications that you may use during the period 
you are scoring your symptoms on the diary to relieve any troublesome allergy symptoms that 
you may experience.  The kit will include the following allergy medications: 
Allergy Medications for Allergy Symptoms (Rhinoconjunctivitis) 
Step 
Allergy Medication 
Dosing Instruction 
1 
Anti-Histamine Eye Drops (Ketotifen) 
1 drop in each affected eye a maximum of 
twice a day 
2 
Anti-Histamine Tablets (Loratadine) 
Maximum of 1 tablet a day 
3 
Steroid Nasal Spray (Fluticasone 
Propionate)  
Maximum of 2 sprays (usually just one) 
in each nostril a day 
4 
Steroid Tablets (Methylprednisolone) 
Not included in the Allergy Medication 
Kit but to be used as prescribed by the 
study doctor  
Allergy Medication Plan 
The Allergy Medication Kit contains three medicines that are commonly used by doctors to 
treat allergy symptoms (rhinoconjunctivitis). You should wait until your allergy symptoms 
become troublesome before using any of the provided medication. The Allergy Medication Kit 
medicines should be used as follows: 
When your allergy symptoms are mainly ocular, such as itchy, watery, red or sore eyes.  
If you mainly have ocular symptoms, wait until these become troublesome and then use the 
eye drops provided in the Allergy Medication Kit.  If you find your ocular symptoms do not 
improve or they are still troublesome half an hour after using an eye drop take one of the anti-
histamine tablets from the Allergy Medication Kit.  
When you have nasal symptoms, such as runny nose, sneezing, blocked or itchy nose or 
when you have both nasal and ocular (eye) symptoms. 
If you mainly have nasal symptoms, or nasal and ocular symptoms, treat them by taking one 
of the anti-histamine tablets from the Allergy Medication Kit.  If you find your nasal symptoms 
do not improve or they are still troublesome two hours after taking the tablet use the steroid 
nasal spray included in the Allergy Medication Kit.  If you find your ocular symptoms do not 
improve or they are still troublesome at two hours after using the tablet use your anti-histamine 
eye drops included in the Allergy Medication Kit. 
VERSION 5.0 FINAL 
CONFIDENTIAL 
PAGE 50 OF 50 
 

SAP_001.pdf: 
 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, 
disclosure or reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 1 of 55 
 
 
STATISTICAL ANALYSIS PLAN 
 
 
PROTOCOL: CP007A 
AN OPTIONAL PROSPECTIVE FOLLOW-ON STUDY TO EVALUATE THE 
CONTINUED EFFICACY AND SAFETY OF CAT-PAD IN CAT ALLERGIC 
SUBJECTS UP TO FIVE YEARS AFTER THE ADMINISTRATION OF TREATMENT 
 
 
 
 
 
AUTHOR: ROLAND KLOPPER 
VERSION NUMBER AND DATE: V2.0, 23FEB2017  
 
 
 
 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 2 of 55 
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE 
Statistical Analysis Plan V2.0 (Dated 23 FEB 2017) for Protocol CP007A. 
 
 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 3 of 55 
MODIFICATION HISTORY 
 
Unique 
Identifier 
for this 
Version 
Date of the 
Document 
Version 
Author 
Significant Changes from  
Previous Authorised Version 
1.0 
18OCT2016 
Roland Klopper 
Not Applicable – First Version 
2.0 
23FEB2017 
Roland Klopper 
Added frequency and percentage of 
subjects included in each population 
to Section 9.  
In Section 13.1.3  specified that all 21 
days of symptom score recording is to 
be populated using each of the 3 
methods of imputation 
Clarified in Section 13.2.1.5 how 
subjects are defined as asthmatic or 
non-asthmatic 
In Section 13.2.2.5 update the 
denominator used for percentage of 
subjects whose symptoms have been 
significantly worse in the past month 
In Section 13.3.2.6 added the total 
number of doctor visits as well as the 
number and percentage of subjects 
with any visit to the doctor 
 
 
 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 4 of 55 
TABLE OF CONTENTS 
LIST OF ABBREVIATIONS 
8 
1.INTRODUCTION 
10 
2.STUDY OBJECTIVES 
10 
2.1. 
Primary Objective 
10 
2.2. 
Secondary Objectives 
10 
2.3. 
Exploratory Objectives 
11 
2.4. 
Safety Objectives 
11 
3.STUDY DESIGN12 
3.1. 
General Description 
12 
3.2. 
Schedule of Events 
14 
4.PLANNED ANALYSES 
14 
4.1. 
Final Analyses 
14 
5.ANALYSIS SETS 
16 
5.1. 
Enrolled population [ENR] 
16 
5.2. 
Full analysis SET [FAS] 
16 
5.3. 
Modified Intent to Treat Population [mITT] 
16 
5.4. 
Safety Population [SAF] 
16 
6.GENERAL CONSIDERATIONS 
17 
6.1. 
Reference Start Date and Study Day 
17 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 5 of 55 
6.2. 
Baseline 
17 
6.3. 
Statistical Tests 
18 
6.4. 
Common Calculations 
18 
6.5. 
Software Version 
18 
7.STATISTICAL CONSIDERATIONS 
19 
7.1. 
Adjustments for Covariates and Factors to be Included in Analyses 
19 
7.2. 
Multicentre Studies 
19 
7.3. 
Missing data 
19 
7.4. 
Multiple Comparisons/Multiplicity 
20 
7.5. 
Examination of Subgroups 
20 
8.OUTPUT PRESENTATIONS 
21 
9.DISPOSITION AND WITHDRAWALS 
22 
10.PROTOCOL DEVIATIONS 
22 
11.DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
22 
12.MEDICATIONS 
23 
12.1. 
Medication use outside annual allergy assessment period 
23 
12.2. 
Medication use during the annual allergy assessment period 
23 
13.EFFICACY OUTCOMES 
24 
13.1. 
Primary Efficacy 
24 
13.1.1. 
Primary Efficacy Variable & Derivation 
24 
13.1.2. 
Primary Analysis of Primary Efficacy Variable(s) 
25 
13.1.3. 
Sensitivity Analysis of Primary Efficacy Variable(s) 
26 
13.1.4. 
Normality and homogeneity of primary efficacy variable 
28 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 6 of 55 
13.2. 
Secondary Efficacy 
28 
13.2.1. 
Secondary Efficacy Variables & Derivations 
28 
13.2.1.1. 
Mean Total Rhinoconjunctivitis Symptom Score (TRSS) 
28 
13.2.1.2. 
Mean Component Scores of Total Rhinoconjunctivitis Symptom Score (TRSS) 
28 
13.2.1.3. 
Rescue Allergy Medication Score (RMS) 
29 
13.2.1.4. 
Mean Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Score 
29 
13.2.1.5. 
Asthma evaluations 
30 
13.2.2. 
Analysis of Secondary Efficacy Variables 
32 
13.2.2.1. 
Mean Total Rhinoconjunctivitis Symptom Score (TRSS) 
32 
13.2.2.2. 
Mean Component Scores of Total Rhinoconjunctivitis Symptom Score (TRSS) 
32 
13.2.2.3. 
Rescue Allergy Medication Score (RMS) 
33 
13.2.2.4. 
Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Score 
33 
13.2.2.5. 
Asthma Evaluations 
34 
13.3. 
Exploratory Efficacy 
35 
13.3.1. 
Exploratory Efficacy Variables & Derivations 
35 
13.3.1.1. 
The Pittsburgh Sleep Quality Index (PSQI) 
35 
13.3.1.2. 
6-Question Asthma Control Questionnaire (ACQ) Score 
36 
13.3.1.3. 
Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment Questions: 
Allergy Specific (WPAI:CIQ-AS) 
36 
13.3.1.4. 
Environmental Changes and Global Assessment of Symptom Severity 
37 
13.3.1.5. 
Monthly Days Off School/Work 
38 
13.3.1.6. 
Hospital/Doctor Office Visits 
38 
13.3.2. 
Analysis of Exploratory Efficacy Variables 
38 
13.3.2.1. 
The Pittsburgh Sleep Quality Index (PSQI) 
38 
13.3.2.2. 
6-Question Asthma Control Questionnaire (ACQ) Score 
38 
13.3.2.3. 
Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment Questions: 
Allergy Specific (WPAI:CIQ-AS) 
38 
13.3.2.4. 
Environmental Changes and Global Assessment of Symptom Severity 
39 
13.3.2.5. 
Monthly Days Off School/Work 
39 
13.3.2.6. 
Hospital/Doctor Office Visits 
39 
14.SAFETY OUTCOMES 
40 
14.1. 
Adverse Events 
40 
14.1.1. 
All AEs 
40 
14.1.1.1. 
Severity 
40 
14.1.1.2. 
Relationship to Study Medication 
41 
14.1.2. 
AEs Leading to Withdrawal from study 
41 
14.1.3. 
Serious Adverse Events 
41 
14.1.4. 
Adverse Events Leading to Death 
41 
15.REFERENCES42 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 7 of 55 
APPENDIX 1.PROGRAMMING CONVENTIONS FOR OUTPUTS 
43 
Quintiles Output Conventions 
43 
Dates 
50 
Spelling Format 
50 
Presentation of Treatment Groups 
50 
Presentation of Visits 
50 
Listings 
50 
APPENDIX 2.COMPLETE QUESTIONNAIRES 
52 
 
 
 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 8 of 55 
LIST OF ABBREVIATIONS 
ACQ 
Asthma control questionnaire  
AE 
Adverse event 
AIC 
Akaike’s information criterion  
ANCOVA 
Analysis of covariance  
ASS 
Mean Asthma Symptom Score 
BOCF 
Baseline Observation Carried Forward  
CGM 
Computer Graphics Metafile 
CI 
Confidence interval 
CMH 
Cochran-Mantel-Haenszel 
CRF 
Case Report Form  
CS 
Combined Score 
ENR 
Enrolled population 
ePRO 
Electronic Patient Reported Outcome 
FAS 
Full Analysis Set 
GINA 
Global Initiative for Asthma 
LOCF 
Last Observation Carried Forward  
LS 
Least squares 
MAR 
Missing at random  
MedDRA 
Medical Dictionary for Regulatory Activities  
mITT 
Modified Intent-to-Treat 
MMRM 
Mixed Model Repeated Measures  
ODS 
Output Delivery System 
PAC3 
Post Administration Collection Period 3 
PSQI 
Pittsburg Sleep Quality Index 
PT 
Preferred Term 
RMS 
Rescue Medication Score  
RQLQ 
Rhinoconjunctivitis Quality of Life Questionnaire 
SAE 
Serious adverse event 
SAF 
Safety 
SAP 
Statistical analysis plan 
SOC 
System Organ Class 
TLF 
Table, Listing, Figure 
TNSS 
Total Nasal Symptom Score 
TOSS 
Total Ocular Symptom Score 
TRSS 
Total Rhinoconjunctivitis Symptom Score 
WHO-DD 
World Health Organization-Drug Dictionary  


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 9 of 55 
WOCF 
Worst Observation Carried Forward 
WPAI:CIQ-
AS 
Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment 
Questions: Allergy Specific  
 
 
 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 10 of 55 
1. INTRODUCTION 
This document describes the rules and conventions to be used in the presentation and analysis of 
efficacy and safety data for Protocol CP007A as set out in the latest version of the output shells. It 
describes the data to be summarised and analysed, including specifics of the statistical analyses to 
be performed.  
This statistical analysis plan (SAP) is based on Protocol version 5 dated 08 December 2014. 
2. STUDY OBJECTIVES 
2.1. PRIMARY OBJECTIVE 
The primary objective is to evaluate the continued efficacy of Cat-PAD, the first in a new class of 
Synthetic Peptide Immuno-Regulatory Epitopes, for a total of up to 5 years after the initial 
administration of treatment in Protocol CP007, based on the reduction of symptoms and the use 
of allergy medication in subjects previously participating in Protocol CP007.  
2.2. SECONDARY OBJECTIVES 
The secondary objectives are: 
 
To evaluate the continued safety and tolerability of Cat-PAD for up to 5 years after the 
administration of treatment.  
 
To evaluate the effect of Cat-PAD on the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) 
for up to 5 years after the administration of treatment.  
 
To evaluate the effect of Cat-PAD on the onset of asthma for up to 5 years after the 
administration of treatment.  
 
To evaluate the effect of Cat-PAD on asthma progression in subjects previously enrolled in 
CP007 with Global Initiative for Asthma (GINA) 1 asthma for up to 5 years after the 
administration of treatment.  
 
 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 11 of 55 
2.3. 
 EXPLORATORY OBJECTIVES 
The exploratory objectives are: 
 
To evaluate the effect of Cat-PAD on changes in asthma control in asthmatic subjects for up to 
5 years after the administration of treatment.  
 
To evaluate the effect of Cat-PAD on changes in sleep quality in adults using the Pittsburg 
Sleep Quality Index (PSQI) for up to 5 years after the administration of treatment.  
 
To evaluate the effect of Cat-PAD on changes in productivity using the Work Productivity and 
Activity Impairment Questionnaire plus Classroom Impairment Questions: Allergy Specific 
(WPAI:CIQ-AS) for up to 5 years after the administration of treatment.  
 
To evaluate the effect of Cat-PAD on symptomatology on unplanned exposure to a cat in 
normal daily life in subjects who no longer keep a cat for up to 5 years after the administration 
of treatment.  
 
To evaluate the effect of Cat-PAD on health economic outcomes for up to 5 years after the 
administration of treatment.  
2.4. SAFETY OBJECTIVES 
The safety and tolerability of Cat-PAD is to be assessed by measurement/recording of adverse 
events (AEs) and serious AEs (SAEs). 
 
 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 12 of 55 
3. STUDY DESIGN 
3.1. GENERAL DESCRIPTION 
This is an optional, prospective, follow-on study to a randomised, double-blind, superiority, 
multiple dose, placebo-controlled, parallel group, multi-centre, field study (CP007). Subjects from 
participating sites who complete the final Post Administration Collection Period (PAC3) in CP007 
are to be invited to participate in CP007A. 
The population is to be limited to those subjects in the CP007 study and hence the maximum 
number to be enrolled in this study is the number of subjects randomised in CP007 which was 
1408 subjects.  
No additional investigational product is to be administered. Subjects will have received one of the 
following three study drug regimens in study CP007:  
 
Single course of Cat-PAD [4 doses of Cat-PAD 6 nmol (one dose administered every 4 weeks), 
followed by 4 doses of Placebo (one dose administered every 4 weeks), 4 x 6 nmol] 
 
Two courses of Cat-PAD [8 doses of Cat-PAD 6 nmol (one dose administered every 4 weeks), 8 
x 6 nmol] 
 
Placebo [8 doses of Placebo (one dose administered every 4 weeks)] 
In CP007, Cat-PAD and/or Placebo doses were administered every 4 weeks (±2 days) for 28 weeks 
(2 x 4 doses per subject). 
Where possible, enrolment for CP007A is to occur at the same time as the final Follow-Up Visit as 
scheduled in CP007. Subjects who consent to take part in this study and who meet all 
inclusion/exclusion criteria are to be issued with paper diary binders and a digital pen (ePRO) or 
mobile phone to record the required subject reported outcomes data.  
Subject reported outcomes are to comprise of monthly and annual evaluations.  
On a monthly basis, subjects are to record information regarding: 
 
Hospital/doctor visits 
 
Lost work/school days 
 
Changes in home environment  
 
Exposure to cat 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 13 of 55 
 
Global assessment of symptoms to cat exposure (only for subject no longer living with an 
indoor cat) 
 
Asthma progression 
 
Concomitant medication 
The annual Allergy Evaluation Period for CO007A is defined as a 3-week (21 day) period, taking 
place at the same time of year as the 3-week Baseline Allergy Evaluation visit in CP007 (Visits 2A 
and 2B) and is to include: 
 
At the start of the 3-week Allergy Evaluation Period 
o 
Diagnosis of asthma 
 
Daily recording for 3 weeks 
o 
Rhinoconjuctivitis symptoms 
o 
Asthma symptoms 
o 
Allergy medication use 
o 
Exposure to indoor cat 
 
At the end of the 3-week Allergy Evaluation Period 
o 
Change in geographic location 
o 
6-Question asthma control questionnaire (ACQ) excluding lung function (for asthmatics 
only) 
o 
RQLQ 
o 
PSQI (if at least 18 years old at the time of assessment) 
o 
WPAI:CIQ-AS 
 
Subjects are to have up to four study visits each year, two of which may be conducted by 
telephone. At each visit, site staff will record any AEs and SAEs, and at the on-site visits subjects 
are to be provided with their next diary binder. 
Subjects will have a final End of Study Visit, which will coincide with the end of the final annual 
Allergy Evaluation Period assessment. 
The duration of this follow-up study is to be up to 4 years for each subject. 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 14 of 55 
3.2. SCHEDULE OF EVENTS 
The schedule of events can be found in Section 6.1 of the Protocol. 
4. PLANNED ANALYSES 
There are four planned unblinded interim analyses.  
The first analysis of the data is to be performed on the first year’s data after all subjects have 
either 
- 
Completed their year 1 annual assessment in CP007A  
- 
Discontinued prior to their year 1 annual assessment 
- 
Progressed beyond their year 1 annual assessment regardless of the completion of the 
assessment 
Additional analyses of the second, third and fourth year in the study are to be performed for each 
relevant year based on the same criteria as above. Analysis of the later years will only be 
performed if there was a positive outcome in the previous years. 
The Quintiles study team, including those responsible for creating the programs to produce the 
outputs for each analysis, will remain blinded. Once the programs have been produced by the 
blinded Quintiles study team, these programs are to be sent to an independent statistician at a 
different geographical location than the blinded team, who will apply the randomisation schedule 
and provide Circassia with a set of unblinded outputs each year. 
Details on independent unblinded team members within Quintiles to perform the analysis and 
members within Circassia authorised to receive unblinded outputs are specified in a separate 
Unblinding Plan document.  
4.1. FINAL ANALYSES  
All final, planned analyses identified in this SAP are to be performed by Quintiles Biostatistics.  
The following events are prerequisites for the production of any of the four interim analyses 
planned.  
 
Sponsor authorisation of the SAP and Table, Listing, Figure (TLF) shells 
 
Quintiles authorisation of final locked database snapshot 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 15 of 55 
For each interim analysis Quintiles Biostatistics will extract all data as entered in the relevant 
year’s diary binder of each subject (there is a separate diary binder for each analysis year). 
After cleaning (no outstanding data queries) of the relevant analysis year’s data by DataMatica 
and authorisation by Quintiles Biostatistics as well as coding of all AEs and concomitant 
medications by Quintiles Coding, the final locked database snapshot for the relevant interim 
analysis (year 1, year 2, year 3 or year 4) is to be provided by DataMatica to Quintiles for the 
purpose of producing the interim analysis. 
AEs entered in the Adverse Event Case Report Form (CRF) are to be cumulative and will not be 
assigned to a specific year for analysis.  
 
Sponsor authorisation of analysis sets  
Prior to each interim analysis Quintiles Biostatistics will programmatically prepare listings of all 
subjects and their status with regards to inclusion or exclusion from each analysis population 
based on the definitions of each analysis population as described in Section 5: Analysis Sets.  
The listings are to be provided to Circassia for authorisation prior to each interim analysis.  
 
 
 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 16 of 55 
5. ANALYSIS SETS 
Agreement and authorisation of subjects included/excluded from each analysis set is to be 
conducted annually prior to each year’s interim analysis. 
5.1. ENROLLED POPULATION [ENR] 
The Enrolled population (ENR) will consist of all subjects who are consented into the study and 
subjects are to be listed and summarised by the treatment they were randomised to in study 
CP007. 
5.2. FULL ANALYSIS SET [FAS] 
The Full Analysis Set (FAS) will consist of all subjects who are consented into the study and have at 
least one day of symptom scores and rescue medication use recorded during the annual Allergy 
Evaluation Period of CP007A. Subjects are to be listed and summarised by the treatment they 
were randomised to in study CP007. The FAS population is to be re-assessed for each analysis year 
to account for subject drop-outs during each year.  
5.3. MODIFIED INTENT TO TREAT POPULATION [MITT] 
The modified Intent-to-Treat (mITT) population will consist of all subjects in the FAS who continue 
to live in a house with an indoor cat during the annual Allergy Evaluation Period. The mITT 
population is to be defined on an annual basis based on the subject’s completion of the ePRO 
question as to whether the subject still lives in a house with an indoor cat. The mITT population 
may therefore change during the course of the study. Subjects are to be listed and summarised by 
the treatment they were randomised to in study CP007. 
5.4. SAFETY POPULATION [SAF] 
All subjects are to be included in the safety population. Safety data is to be listed and summarised 
by study medication actually received in study CP007. 
 
 
 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 17 of 55 
6. GENERAL CONSIDERATIONS 
6.1. REFERENCE START DATE AND STUDY DAY 
Study Day is to be calculated from the reference start date, and is used to show the start/stop day 
of assessments and events.  
Reference start date is defined as the day of written informed consent for CP007A, (Day 1 is the 
day of informed consent), and will appear in every listing where an assessment date or event date 
appears.  
 
If the date of the event is on or after the reference date then:  
Study Day = (date of event – reference date) + 1. 
 
If the date of the event is prior to the reference date then:  
Study Day = (date of event – reference date). 
In the situation where the event date is partial or missing, the date will appear partial or missing in 
the listings, and Study Day, and any corresponding durations will appear missing in the listings. 
6.2. BASELINE 
Subject data is to be obtained from the CP007 database and is used as Baseline data for CP007A.  
Baseline for all efficacy variables listed in Section 13.1: Primary Efficacy, Section 13.2: Secondary 
Efficacy and Section 13.3: Exploratory Efficacy is defined as the 3 week Baseline Allergy Evaluation 
period (Visit 2A to Visit 2B) before randomisation into study CP007.   
For other Baseline characteristics Baseline is defined as follows: 
 
Age as entered on the Enrolment Visit CRF for CP007A 
 
Gender as collected at the CP007 Screening visit 
 
Ethnic group as collected at the CP007 Screening visit 
 
Asthma status as collected at the CP007 Screening visit 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 18 of 55 
6.3. STATISTICAL TESTS 
All tests are two-sided, unless otherwise specified in the description of the analyses. The 
significance level for each analysis is specified in the relevant analysis section of the SAP.  
6.4. COMMON CALCULATIONS 
For quantitative measurements, change from Baseline is calculated as: 
 
 
Test Value at Year xx – Baseline Value 
Percentage change from Baseline is calculated as: 
 
[(Test Value at Year xx – Baseline Value) / Baseline Value] x 100 
Denominator for percentages is either the total number of subjects in the analysis population or 
the number of subjects in the analysis population with data available for the applicable 
assessment and is specified in each analysis section.  
6.5. SOFTWARE VERSION 
All analyses are conducted using SAS® version 9.2 or higher.  
 
 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 19 of 55 
7. STATISTICAL CONSIDERATIONS 
7.1. ADJUSTMENTS FOR COVARIATES AND FACTORS TO BE INCLUDED IN 
ANALYSES 
The following covariates and factors are used in the analyses. For details of their inclusion in the 
models, see the specific analysis section. 
 
Pooled site [Pooled Site 01,...,Pooled Site xx] 
 
Age group [Adolescents/Adults], assigned based on subject’s age as entered on the Enrolment 
Visit CRF for CP007A 
 
Gender [Male/Female], as collected at the CP007 Screening visit 
 
Asthma status [Present/Absent], as collected at the CP007 Screening visit 
 
Baseline score [Represents the Baseline value of the relevant score being analysed], where 
Baseline is defined as in Section 6.2: Baseline.  
7.2. MULTICENTRE STUDIES 
This study is to be conducted by multiple Investigators at multiple centres internationally.   
If a centre has less than five subjects, pooling with other centre(s) is performed based on 
geographical region, and is to be completed and agreed with Circassia prior to unblinding. 
7.3. MISSING DATA 
Missing safety data will not be imputed.  
Missing efficacy data is to be handled as described in Section 13.1.3: Sensitivity Analysis of Primary 
Efficacy Variable.  
 
 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 20 of 55 
7.4. MULTIPLE COMPARISONS/MULTIPLICITY 
For the primary hypothesis testing vs. Placebo a Bonferroni-Holm procedure is to be used to 
adjust alpha in order to compensate for multiplicity when comparing the two Cat-PAD treatment 
arms vs. Placebo, thereby keeping the overall type I error rate at 0.05. More detail on the 
procedure is described in Section 13.1.2: Primary Analysis of Primary Efficacy Variable. 
Multiple analyses are to be performed as specified in Section 4: Planned Analyses. At each of the 
statistical analyses performed after one, two, three and four years, there is no adjustment to the 
significance level, apart from the Bonferroni-Holm correction (due to multiple treatment 
comparisons) stated above, because analysis of the later years will only be performed if there is a 
positive outcome in the previous years, and this is, therefore, a hierarchical analysis. 
7.5. EXAMINATION OF SUBGROUPS 
Subgroup analyses are to be conducted for the primary analysis of primary efficacy variable only. 
It should be noted that the study was not designed to detect treatment differences with high 
statistical power within subgroups. Subgroup analyses are only to be performed if there are at 
least 10 subjects in each category of the subgroup.  
The following subgroups are to be assessed for the primary efficacy variable: 
 
Gender:  
o 
Female 
o 
Male 
 
Age (years): 
o 
≥ 12 to ≤ 17 
o 
≥ 18 to ≤ 49 
o 
≥ 50 to ≤ 65 
o 
> 65 
 
Ethnic group 
o 
Caucasian 
o 
Black 
o 
Asian (Indian) 
o 
Asian (Oriental) 
o 
American Hispanic 
 
Asthma status  


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 21 of 55 
o 
Present  
o 
Absent  
 
All subgroup variables above are from the same source as described in Section 6.2: Baseline.  
8. OUTPUT PRESENTATIONS 
APPENDIX 1: Programming conventions for outputs shows conventions for presentation of data in 
outputs.  
The templates provided within this SAP describe the presentations for this study and therefore the 
format and content of the summary TLFs to be provided by Quintiles Biostatistics. 
 
 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 22 of 55 
9. DISPOSITION AND WITHDRAWALS 
All subjects who provide informed consent are to be accounted for in this study.  
The number and percentage of subjects that signed informed consent to CP007A, failed any 
inclusion/exclusion criteria and were enrolled in the study are to be presented.  
The specific inclusion/exclusion criteria not met is to be listed.  
The frequency and percentage of subjects included in the FAS, mITT and SAF are to be presented.  
Frequency and percentage of premature withdrawals from the study and reason for withdrawals 
will also be presented. Premature withdrawal from the study is defined as subjects who answered 
“No” to “Did the subject complete the study as planned?” on the End of 
Study/Withdrawal/Discontinuation Visit CRF. 
10. PROTOCOL DEVIATIONS 
Protocol deviations are to be tracked on an ongoing basis throughout the conduct of the CP007A 
Study. All subject deviations from the Protocol that are determined to be major are to be reported 
in a by subject listing.  
11. DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
Demographic and other Baseline characteristics are to be presented for the ENR, FAS and mITT 
populations. 
Continuous demographic and Baseline characteristic variables (e.g. Age) are to be summarised by 
treatment arm using descriptive statistics (n, mean, standard deviation (SD), median, minimum 
and maximum). Categorical variables (e.g. Gender) are to be summarised by frequency (n) and 
percentage (%). The denominator for the percentages is the total number of subjects in the 
population treatment arm with data available.  
No statistical testing is to be performed for demographic or other Baseline characteristics. 
The following demographic and other Baseline characteristics are to be reported for this study and 
are from the same source as described in Section 6.2: Baseline: 
 
Age (Years) 
 
Age group (Years), categorised as ≥ 12 to ≤ 17, ≥ 18 to ≤ 49 and ≥ 50 to ≤ 65 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 23 of 55 
 
Age group, categorised as adolescents or adults, where adolescents are defined as subjects 
with age ≥ 12 and < 18 years and adults are defined as subjects ≥ 18 years of age 
 
Gender [Male/Female] 
 
Ethnic group [Caucasian/Black/Asian (Indian)/Asian (Oriental)/American Hispanic] 
 
Asthma status [Absent/Present] 
12. MEDICATIONS 
Medications are to be presented by generic name and are coded using World Health Organization-
Drug Dictionary (WHO-DD) Version 01-Mar-2016. 
 The summaries are to be sorted by descending frequency of the total number of subjects for each 
generic name. 
Medications are to be presented separately for medications taken outside the annual Allergy 
Assessment Period and medications taken during the annual Allergy Assessment Period. 
12.1. MEDICATION USE OUTSIDE ANNUAL ALLERGY ASSESSMENT PERIOD 
Medication use outside of the annual Allergy Assessment Period is to be presented for the SAF 
population. 
Medications outside of the annual Allergy Assessment Period are defined as any medications 
entered on the Medicines page of the monthly diary binder.  
12.2. MEDICATION USE DURING THE ANNUAL ALLERGY ASSESSMENT PERIOD 
Medication use during the annual Allergy Assessment Period is to be presented for the FAS.  
Allergy medications during the annual Allergy Assessment Period are defined as any medications 
entered on the “Allergy Medicines that You Have Taken in the Past 21 Days” page of the annual 
Allergy Assessment Period diary binder.  
 
 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 24 of 55 
13. EFFICACY OUTCOMES  
13.1. PRIMARY EFFICACY 
13.1.1. 
PRIMARY EFFICACY VARIABLE & DERIVATION 
The primary efficacy variable is the daily Combined Score (CS) of the 3-week annual Allergy 
Assessment Period completed after Year 1 to Year 4 in the subject’s annual assessment diary 
binder.  
The daily Total Rhinoconjunctivitis Symptom Score (TRSS) and the daily Rescue Medication Score 
(RMS) are to be combined and a daily CS is to be calculated for each subject as follows: 
 
CS = (TRSS / 8) + RMS  
For the primary analysis, for each subject the mean of the daily non-missing CS during the annual 
Allergy Assessment Period is to be calculated as follows: 
 
Sum(Day 1 CS to Day 21 CS) / Number of non-missing days 
The mean CS is to be calculated over the 21 days of the annual Allergy Assessment Period for each 
subject based on the data available for the non-missing days if a subject does not complete the 
whole annual assessment period. 
The TRSS is the sum of eight individual TRSS symptom scores, namely runny nose, sneezing, 
blocked nose, itchy nose, itchy eyes, watery eyes, red eyes and sore eyes. All symptoms are 
reflective over the previous 24 hours.  
For each symptom, the subject will rate (on a daily basis for the duration of the Allergy 
Assessment Period) the severity as follows: 
0 = absent 
1 = mild, barely noticeable 
2 = moderate, annoying/troublesome 
3 = severe, very annoying/very troublesome 
The TRSS will have a range of 0 to 24. The TRSS on each day is to be calculated as follows: 
TRSS = Runny Nose + Sneezing + Blocked Nose + Itchy Nose + Itchy Eyes + Watery Eyes + 
Red Eyes + Sore Eyes. 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 25 of 55 
Allergy medications are to be provided to subjects to be used according to a pre-specified Allergy 
Medication Plan (Appendix 1 in Protocol). The use of allergy medications are to be scored based 
on Didier (Didier et al, 2009) as follows: 
 
RMS = 0; no allergy medication used per day  
 
RMS = 0.5; at least one dose of antihistamine eye drops used per day  
 
RMS = 1; at least one dose of oral antihistamine used per day  
 
RMS = 2; at least one dose of intranasal corticosteroid used per day  
 
RMS = 3; at least one dose of systemic corticosteroid used per day 
The RMS score is not additive, the maximum value per day is used and therefore the maximum 
RMS per day is 3.  
If any of the eight individual TRSS, namely sneezing, runny nose, blocked nose, itchy nose, itchy 
eyes, watery eyes, red eyes or sore eyes for a given day is missing, the TRSS for that day is to be 
considered missing. If either the TRSS or the RMS is missing for a particular day then the CS will 
also be considered missing. 
13.1.2. 
PRIMARY ANALYSIS OF PRIMARY EFFICACY VARIABLE(S) 
The primary objective of this study is to test the hypothesis that there is a difference between 
either or both Cat-PAD treatment arms and the Placebo arm.  
The primary efficacy analysis is to be performed for the FAS.  
The least squares (LS) mean difference in mean CS between treatment arms, along with 95% two-
sided CIs and p-value are to be estimated by fitting an analysis of covariance (ANCOVA) model, 
adjusting for the stratification factors listed in Section 7.1: Adjustments for Covariates and Factors 
to be Included in Analyses.  
Additionally, the LS mean and 95% CI for the CS at the CP007 study endpoint of PAC3 is to be 
calculated for the CP007A FAS subjects using the same ANCOVA. The LS mean and 95% CI is to be 
presented by treatment arm.  
The Bonferroni-Holm procedure is to be utilised to assess each of the two treatment comparisons 
(two courses of Cat-PAD vs. Placebo and one course of Cat-PAD vs. Placebo), whereby the smallest 
p-value (of the two treatment comparisons) is to be tested at the 0.05/2 (i.e. p < 0.025) alpha 
level. If this first comparison is statistically significant then the remaining treatment comparison p-
value is to be tested at the 0.05 alpha level. The study is to be declared a success if one or more 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 26 of 55 
treatment arms are statistically significantly different from Placebo. 
The differences in LS means for each treatment comparison of active vs. Placebo together with the 
corresponding two-sided 95% CI and the p-values are to be presented. Additionally p-values are to 
be calculated and presented for all model effects. 
The ratio of LS means along with its 95% CI (calculated by using Fieller’s method) is to be 
presented for evaluation of the clinical significance of active treatment vs. Placebo comparisons.  
The primary efficacy variable is also to be analysed for subgroups as specified in Section 7.5: 
Examination of Subgroups, using a simplified ANCOVA including treatment arm as main effect and 
Baseline CS as covariate. Subgroup analyses are not to utilize the Bonferroni-Holm procedure to 
assess each of the two treatment comparisons (two courses of Cat-PAD vs. Placebo and one 
course of Cat-PAD vs. Placebo). Each treatment comparison p-value is to be tested at the 0.05 
alpha level. 
Observed and change from Baseline values are to be summarised by descriptive statistics (n, 
mean, SD, median, minimum and maximum) for each annual Allergy Assessment Period and 
treatment arm.  
A waterfall plot of the percentage change from Baseline in CS for each individual subject is to be 
plotted for each treatment arm. 
The analyses are to be repeated for the mITT population.  
13.1.3. 
SENSITIVITY ANALYSIS OF PRIMARY EFFICACY VARIABLE(S) 
For sensitivity analyses the mean of the daily CS during the annual Allergy Assessment Period is to 
be calculated after imputation of the missing daily CS using the following three methods 
respectively: 
 
If valid data for any given day in the 3-week period is not available for a particular subject for a 
particular day, the previous day’s CS (if complete) is to be carried forward by using Last 
Observation Carried Forward (LOCF) to impute the missing value. If the previous day’s CS is not 
complete, the most recent complete CS is to be used. 
 
For a worst-case sensitivity analysis (WOCF), missing CS data for a particular day is to be 
imputed as the worst (highest) CS in the 3-week assessment period for that subject.  
 
Baseline Observation Carried Forward (BOCF) imputation of missing daily CS using the Baseline 
mean daily CS.  


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 27 of 55 
For each annual assessment period all 21 days of symptom score recording is to be populated using 
each of the 3 methods detailed above, that is, if a subject has less than 21 days of valid symptom 
scores, the CS is to be populated  for the full period of 21 days.  
Using the imputed data (from each imputation method respectively) the LS mean difference in 
mean CS between treatment arms, along with 95% two-sided CIs and p-value are to be estimated 
using the same ANCOVA as for the primary efficacy variable as described in Section 13.1.2: 
Primary Analysis of Primary Efficacy Variable.  
As an additional sensitivity efficacy analysis of the primary efficacy variable the missing at random 
(MAR) assumption will hold for daily CS and the treatment effect is to be estimated using a Mixed 
Model Repeated Measures (MMRM) of the CS at each day of the annual Allergy Assessment 
Period, for the FAS and mITT populations.  
In MAR the probability of an observation being missing depends only on observed measurements. 
This assumption implies that the behaviour of the missing observations can be predicted from the 
observed variables, and therefore a response can be estimated without bias using exclusively the 
observed data without any imputation of the missing days. 
The MMRM will include all stratification factors as specified in Section 7.1: Adjustments for 
Covariates and Factors to be Included in Analyses. 
The following covariance structures will be used to estimate the within-patient errors in preliminary 
analyses:   
- 
Unstructured 
- 
Spatial power 
- 
Heterogeneous Toeplitz 
- 
Heterogeneous compound symmetric 
- 
Simple structures with and without heterogeneous variances by visit 
A different covariance structure is to be used for each treatment group if deemed appropriate.  
This is to be tested by fitting each of the aforementioned covariance structures, with- and without 
a GROUP statement where GROUP = treatment (see SAS code below).  The covariance structure 
converging to the best fit, as determined by Akaike’s information criterion (AIC) (covariance 
structure with the lowest value), is to be selected as the covariance structure for the primary 
analysis. Type III sum-of-squares for the LS means is to be used.   
The following SAS code is to be used: 
PROC MIXED data=<input dataset> IC INFO METHOD = TYPE3;  
CLASS subject treatment pooled_site age_group gender asthma_status;  
MODEL CS = baseline treatment pooled_site age_group gender asthma_status /  


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 28 of 55 
DDFM = kr; 
ESTIMATE ‘Cat-PAD2 vs Placebo’ treatment 1 0 -1 / CL; 
REPEATED day / SUBJECT=subject /*GROUP=treatment*/  
TYPE= <covariance structure option>; 
RUN; 
Appropriate ESTIMATE statements will be added for the comparisons of Cat-PAD1 vs Placebo 
as well as Cat-PAD2 vs Cat-PAD1.  
13.1.4. 
NORMALITY AND HOMOGENEITY OF PRIMARY EFFICACY VARIABLE 
The residuals from the primary efficacy ANCOVA as well as the sensitivity analysis MMRM are to 
be checked for normality and homogeneity of variance. Normality is to be examined by normal 
probability plots, while homogeneity of variance will be assessed by plotting the residuals against 
the predicted values for the model. Any deviation from either assumption may result in further 
analysis using non parametric analysis of the primary efficacy variable or using an appropriate 
alternative transformation (such as logarithmic or power transformation) of the data. 
13.2. SECONDARY EFFICACY 
13.2.1. 
SECONDARY EFFICACY VARIABLES & DERIVATIONS 
13.2.1.1. 
Mean Total Rhinoconjunctivitis Symptom Score (TRSS) 
The daily TRSS is to be derived as described in Section 13.1.1: Primary Efficacy Variable & 
Derivation. 
The mean of the daily TRSS for each annual Allergy Assessment Period is to be calculated over all 
days with complete data.  
13.2.1.2. 
Mean Component Scores of Total Rhinoconjunctivitis Symptom Score (TRSS) 
The TRSS consists of two components: 
 
Total Nasal Symptom Score (TNSS) 
The TNSS is the sum of four individual nasal symptoms: runny nose, sneezing, blocked nose, and 
itchy nose. The TNSS will have a range of 0 to 12. The TNSS is to be calculated on each day as 
follows:  


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 29 of 55 
TNSS = Runny Nose + Sneezing + Blocked Nose + Itchy Nose.  
Mean TNSS is to be calculated for each annual Allergy Assessment Period over all days with 
complete data.  
 
Total Ocular Symptom Score (TOSS) 
The TOSS is the sum of four individual ocular symptoms: itchy eyes, watery eyes, red eyes and 
sore eyes. The TOSS will have a range of 0 to 12. The TOSS is to be calculated on each day as 
follows:  
TOSS = Itchy Eyes + Watery Eyes + Red Eyes + Sore Eyes.  
Mean TOSS is to be calculated for each annual Allergy Assessment Period over all days with 
complete data.  
13.2.1.3. 
Rescue Allergy Medication Score (RMS) 
The daily RMS is to be derived as described in Section 13.1.1: Primary Efficacy Variable & 
Derivation. The mean of the daily RMS for each annual Allergy Assessment Period is to be 
calculated over all days with complete data.  
13.2.1.4. 
Mean Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Score 
The self-administered RQLQ with Standardised Activities for 12 years and older (RQLQ(S) >=12) is 
to be used in this study.  
The RQLQ will be completed as a once off assessment at the end of the annual Allergy Assessment 
Period. 
The RQLQ has 28 questions in seven domains (activities, sleep, non-nose/eye symptoms, practical 
problems, nasal symptoms, eye symptoms, and emotional). Refer to APPENDIX 2: Complete 
Questionnaires, for the complete questionnaire. For each question subjects record how troubled 
they have been during the last week on a 7-point scale. For all domains, except Emotional, the 
scores are (0 = Not troubled to 6 = Extremely troubled). For the Emotional domain the 7-point 
scale is (0 = None of the Time to 6 = All of the Time). The overall RQLQ score is the mean of all 28 
responses and the individual domain scores are the means of the items within those domains. 
The domains are defined as follows: 
 
Activities: Questions 1 to 3 
 
Sleep: Questions 4 to 6 
 
Non-nose/eye symptoms: Questions 7 to 13 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 30 of 55 
 
Practical problems: Questions 14 to 16 
 
Nasal symptoms: Questions 17 to 20 
 
Eye symptoms: Questions 21 to 24 
 
Emotional: Questions 25 to 28 
13.2.1.5. 
Asthma evaluations 
 
Mean Asthma Symptom Score (ASS) 
The ASS has six questions which are answered daily by the subject for each annual Allergy 
Assessment Period.  All subjects are to indicate how they have been in the past 24 hours with 
regards to:  
 
Coughing  
 
Wheezing 
 
Shortness of breath  
In addition, for subjects with asthma only, the ASS is to include the following questions: 
 
Limitation of activities 
 
Nocturnal symptoms or awakenings due to asthma 
 
Need for short-acting inhaled β2agonist treatment 
There is a four point scale (0 to 3) for each question. For cough, wheezing and shortness of breath 
symptoms the subject will rate the severity as follows: 
0 = absent 
1 = mild, barely noticeable 
2 = moderate, annoying/troublesome 
3 = severe, very annoying/ very troublesome 
For limitations of activities the subject will rate the severity as follows: 
0 = not limited 
1 = very slightly limited 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 31 of 55 
2 = slightly limited 
3 = moderately limited or worse 
For nocturnal symptoms or awakenings due to asthma the subject will rate how asthma has 
affected them overnight (last night) as follows: 
0 = not at all 
1 = hardly at all 
2 = a few minutes disturbance 
3 = several times or more 
For use of short-acting inhaled β2 agonist treatments the subjects will record how many puffs of 
reliever medication (e.g. albuterol or salbutamol) they have used as follows: 
0 = none 
1 = one 
2 = two 
3 = three or more 
The questions are equally weighted and the ASS for each day is to be calculated as the mean of 
the six relevant questions (for subjects with asthma) or the mean of the three relevant questions 
(for all other subjects (including subjects with asthma)) separately. For the analysis of all subjects 
(including subjects with asthma) only the symptoms coughing, wheezing and shortness of breath 
are to be used in the calculation of the ASS.  
The mean of the daily ASS for each annual Allergy Assessment Period is to be calculated over all 
days with complete data.  
Subjects are to be classified as having asthma based on the subjects Asthma Progression eDiary 
response to the question, ‘Are you diagnosed with asthma?’. The response to the last monthly 
assessment prior to each year’s annual allergy assessment is to be used to classify subjects as either 
asthmatic (response of ‘Yes’) or non-asthmatic (response of ‘No’).  
 
Asthma onset and progression 
On a monthly basis subjects will enter in their dairy binders the following three questions related 
to asthma onset and progression: 
o 
Are you diagnosed with asthma  
o 
If yes, has your doctor prescribed stronger medicine  
o 
Have your symptoms have been significantly worse in the last month 
Additionally, at the start of each annual Allergy Assessment Period subjects will indicate whether 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 32 of 55 
they have been diagnosed with asthma during the last year.  
13.2.2. 
ANALYSIS OF SECONDARY EFFICACY VARIABLES 
The secondary efficacy analysis is to be performed for the FAS.  
13.2.2.1. 
Mean Total Rhinoconjunctivitis Symptom Score (TRSS) 
 
The LS mean difference in mean TRSS between treatment arms, along with 95% two-sided CIs and 
p-value are to be estimated using the same ANCOVA as for the primary efficacy variable as 
described in Section 13.1.2: Primary Analysis of Primary Efficacy Variable and presented in a 
similar manner, excluding the ratio of LS means and 95% Fieller’s CI.  
Additionally, the LS mean and 95% CI for the TRSS at the CP007 study endpoint of PAC3 is to be 
calculated for the CP007A FAS subjects using the same ANCOVA. The LS mean and 95% CI is to be 
presented by treatment arm.  
The TRSS analysis is not to utilize the Bonferroni-Holm procedure to assess each of the two 
treatment comparisons (two courses of Cat-PAD vs. Placebo and one course of Cat-PAD vs. 
Placebo). Each treatment comparison p-value is to be tested at the 0.05 alpha level. 
Observed and change from Baseline values are to be summarised by descriptive statistics (n, 
mean, SD, median, minimum and maximum) for each annual Allergy Assessment Period and 
treatment arm.  
The analyses are to be repeated for the mITT population.  
13.2.2.2. 
Mean Component Scores of Total Rhinoconjunctivitis Symptom Score (TRSS) 
The LS mean difference in mean TOSS and TNSS between treatment arms, along with 95% two-
sided CIs and p-value are to be estimated using the same ANCOVA as for the primary efficacy 
variable as described in Section 13.1.2: Primary Analysis of Primary Efficacy Variable and 
presented in a similar manner, excluding the ratio of LS means and 95% Fieller’s CI.  
Additionally, the LS mean and 95% CI for the TOSS and TNSS at the CP007 study endpoint of PAC3 
is to be calculated for the CP007A FAS subjects using the same ANCOVA. The LS mean and 95% CI 
is to be presented by treatment arm.  
The TOSS and TNSS analyses are not to utilize the Bonferroni-Holm procedure to assess each of 
the two treatment comparisons (two courses of Cat-PAD vs. Placebo and one course of Cat-PAD 
vs. Placebo). Each treatment comparison p-value is to be tested at the 0.05 alpha level. 
Observed and change from Baseline values are to be summarised by descriptive statistics (n, 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 33 of 55 
mean, SD, median, minimum and maximum) for each annual Allergy Assessment Period and 
treatment arm.  
The analyses are to be repeated for the mITT population.  
13.2.2.3. 
Rescue Allergy Medication Score (RMS) 
The LS mean difference in mean RMS between treatment arms, along with 95% two-sided CIs and 
p-value are to be estimated using the same ANCOVA as for the primary efficacy variable as 
described in Section 13.1.2: Primary Analysis of Primary Efficacy Variable and presented in a 
similar manner, excluding the ratio of LS means and 95% Fieller’s CI.  
Additionally, the LS mean and 95% CI for the RMS at the CP007 study endpoint of PAC3 is to be 
calculated for the CP007A FAS subjects using the same ANCOVA. The LS mean and 95% CI is to be 
presented by treatment arm.  
The RMS analysis is not to utilize the Bonferroni-Holm procedure to assess each of the two 
treatment comparisons (two courses of Cat-PAD vs. Placebo and one course of Cat-PAD vs. 
Placebo). Each treatment comparison p-value is to be tested at the 0.05 alpha level. 
Observed and change from Baseline values are to be summarised by descriptive statistics (n, 
mean, SD, median, minimum and maximum) for each annual Allergy Assessment Period and 
treatment arm.  
The analyses are to be repeated for the mITT population.  
13.2.2.4. 
Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Score 
The LS mean difference in RQLQ total score between treatment arms, along with 95% two-sided 
CIs and p-value are to be estimated using the same ANCOVA as for the primary efficacy variable as 
described in Section 13.1.2: Primary Analysis of Primary Efficacy Variable and presented in a 
similar manner, excluding the ratio of LS means and 95% Fieller’s CI.  
Additionally, the LS mean and 95% CI for the RQLQ at the CP007 study endpoint of PAC3 is to be 
calculated for the CP007A FAS subjects using the same ANCOVA. The LS mean and 95% CI is to be 
presented by treatment arm.  
The RQLQ analysis is not to utilize the Bonferroni-Holm procedure to assess each of the two 
treatment comparisons (two courses of Cat-PAD vs. Placebo and one course of Cat-PAD vs. 
Placebo). Each treatment comparison p-value is to be tested at the 0.05 alpha level. Observed and 
change from Baseline values are to be summarised by descriptive statistics (n, mean, SD, median, 
minimum and maximum) for each annual Allergy Assessment Period  and treatment arm, for the 
total score as well as each domain.  
The analyses are to be repeated for the mITT population.  


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 34 of 55 
13.2.2.5. 
Asthma Evaluations 
 
Mean Asthma Symptom Score (ASS) 
Mean ASS is to be summarised separately for: 
- 
Subjects with asthma  
- 
All subjects (including subjects with asthma)  
Observed and change from Baseline values are to be summarised by descriptive statistics (n, 
mean, SD, median, minimum and maximum) for each annual Allergy Assessment Period and 
treatment arm.  
 
Asthma Onset and Progression 
The number and percentage of subjects that answer “Yes” or “No” to each asthma progression 
question are to be presented for each monthly assessment and treatment arm. 
The denominator for the percentage of subjects diagnosed with asthma as recorded at each 
month’s asthma assessment is the total number of subjects in the population treatment arm with 
data available. 
The denominator for the percentage of subjects whose doctor has prescribed stronger medicine 
and whose symptoms have been significantly worse in the past month is the total number of 
subjects in the population treatment arm that are diagnosed with asthma at each relevant 
month’s asthma assessment.  
The number and percentage of subjects that have been diagnosed with asthma in the past year 
are to be presented for each annual assessment and treatment arm.  
The percentage of subjects diagnosed with asthma in the past year are to be compared between 
the two active treatments and Placebo by using a logistic regression model with pooled site, 
treatment as main effect and age group (adolescents, adults), gender, asthma status (present, 
absent) and Baseline CS as covariates. Odds ratios with 95% CI and p-values are to be presented 
for the individual treatment comparisons vs. Placebo.  
The analysis is to be repeated for the mITT population.  


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 35 of 55 
13.3. EXPLORATORY EFFICACY  
13.3.1. 
EXPLORATORY EFFICACY VARIABLES & DERIVATIONS 
13.3.1.1. 
The Pittsburgh Sleep Quality Index (PSQI) 
The PSQI assesses sleep quality during the past month and is to be completed as a once off 
assessment by subjects at the end of each annual Allergy Assessment Period. It consists of 19 self-
rated questions and five completed by a bed-partner/roommate. Refer to APPENDIX 2: Complete 
Questionnaires, for the complete questionnaire. For the self-rated questions there are four 
questions about bed and sleep times and 15 questions (each scored in one of four categories) that 
elicit the quality of sleep.  
The range of values for questions five through 10 are all 0 to 3. 
Questions one through nine are not allowed to be missing except as noted below.  If these 
questions are missing then any scores calculated using missing questions are also missing.  Thus it 
is important to make sure that all questions one through nine have been answered.   
In the event that a range is given for an answer (for example, ‘30 to 60’ is written as the answer to 
Q2, minutes to fall asleep), split the difference and enter 45. 
The total PSQI and component scores (duration of sleep, sleep disturbance, sleep latency, day 
dysfunction due to sleepiness, sleep efficiency, overall sleep quality and need medications to 
sleep) are calculated from the questionnaire and the scoring instructions below:  
Table 1 : Scoring Instructions 
Domain 
Question (Q) Result or Algorithm  
Analysis 
Value 
Duration of Sleep 
Q4 > 7 
0 
  
6 < Q4 <= 7  
1 
 
5 <= Q4 <= 6 
2 
 
Q4 < 5  
3  
Sleep Disturbance 
Q5b + Q5c + Q5d + Q5e + Q5f + Q5g + Q5h + Q5i + Q5j = 0 
NOTE: If Q5j-Other reason(s), is null or Q5j is null, set the value of Q5j 
to 0  
0 
 
Q5b + Q5c + Q5d + Q5e + Q5f + Q5g + Q5h + Q5i + Q5j  >= 1 and <= 9 
1 
 
Q5b + Q5c + Q5d + Q5e + Q5f + Q5g + Q5h + Q5i + Q5j >=10 and <= 18 
2 
 
Q5b + Q5c + Q5d + Q5e + Q5f + Q5g + Q5h + Q5i + Q5j >= 19 and <= 27 
3 
Sleep Latency 
Step 1: 
 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 36 of 55 
 
If 0 <= Q2 <= 15 then set Q2 = 0  
 
 
If 15 < Q2 <= 30 then set Q2 = 1  
 
 
If 30 < Q2 <= 60 then set Q2 = 2 
 
 
If Q2 > 60 then set Q2 = 3 
 
 
Step 2: 
 
 
Q5a + Q2 = 0 
0 
 
1 <= Q5a + Q2 <= 2  
1 
 
3 <= Q5a + Q2 <= 4  
2 
 
5 <= Q5a + Q2 <= 6  
3 
Day Dysfunction 
Due to Sleepiness  
Q8 + Q9 = 0 
0 
  
1 <= Q8 + Q9 <= 2 
1 
 
3 <= Q8 + Q9 <= 4 
2 
 
5 <= Q8 + Q9 <= 6 
3 
 
13.3.1.2. 
6-Question Asthma Control Questionnaire (ACQ) Score 
Asthmatic subjects are to complete the 6-Question ACQ at the end of each annual Allergy 
Assessment Period as a one off assessment. Refer to APPENDIX 2: Complete Questionnaires, for 
the complete questionnaire. 
The six ACQ questions are answered by the subject, stating how they have been in the past week 
with regards to five symptoms and the average daily use (the number of puffs/inhalations) of 
short-acting bronchodilator in the past week.  
There is a 7 point scale (0 to 6) for each question where 0 represents optimum control and six 
represents the poorest control. The questions are equally weighted and the ACQ score is the 
mean of the six questions and therefore between 0 (totally controlled) and six (severely 
uncontrolled). 
13.3.1.3. 
Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment 
Questions: Allergy Specific (WPAI:CIQ-AS) 
The WPAI:CIQ-AS is to be completed at the end of each annual Allergy Assessment Period  and 
consists of nine questions. Refer to APPENDIX 2: Complete Questionnaires, for the complete 
questionnaire. 
The WPAI:CIQ-AS consists of seven domains calculated as follows: 
 
Percent work time missed due to allergy; Q3/Q2 x 100 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 37 of 55 
 
Percent impairment while working due to allergy; Q4/10 x 100 
 
Percent overall work impairment due to allergy; ((Q3/Q2)+[(1-(Q3/Q2))x(Q4/10)])x 100 
 
Percent class time missed due to allergy; Q7/Q6 x 100 
 
Percent impairment in the classroom due to allergy; Q8/10 x 100 
 
Percent overall classroom impairment due to allergy; ((Q7/Q6)+[(1-(Q7/Q6))x(Q8/10)]) x 100 
 
Percent activity impairment due to allergy; Q9/10 x 100 
The outcomes are expressed as impairment percentages, with higher numbers indicating greater 
impairment and less productivity. If any questions within a domain are missing, the domain value 
will also be missing.  
13.3.1.4. 
Environmental Changes and Global Assessment of Symptom Severity 
On a monthly basis subjects will provide information on changes to their home environment via 
six questions in the diary binder: 
 
Any changes to number of cats in your home? 
 
Have you been to a house in the last month where there is a cat? 
 
Significant change to the number of hours spent in a house with a cat? 
 
Have the cats in your home been spending more time outside? 
 
Any significant changes in your exposure to cat(s)? 
 
Any significant changes to your home furnishings? 
The global assessment of symptoms is only applicable to subjects that no longer keep a cat. On a 
monthly basis, if these subjects had some unplanned exposure to a cat in normal daily life, the 
subject will rate his/her symptoms in the following categories:  
 
Absent 
 
Mild, Barely noticeable 
 
Moderate, Annoying/troublesome 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 38 of 55 
 
Severe, Very annoying/Very troublesome 
13.3.1.5. 
Monthly Days Off School/Work 
On a monthly basis subjects will enter in their dairy binders the total number of days that either 
school or work was missed due to allergic Rhinoconjunctivitis symptoms during the past month. 
13.3.1.6. 
Hospital/Doctor Office Visits 
On a monthly basis subjects will enter in their dairy binders the dates of doctor/hospital visits as 
well as the date of entry and discharge from the hospital, if applicable, during the past month.  
The length of stay in hospital per hospital visit is to be calculated as follows: 
 
Length of Stay (weeks) = [(Date of discharge – Date of entry + 1)] / 7. 
13.3.2. 
ANALYSIS OF EXPLORATORY EFFICACY VARIABLES 
The exploratory efficacy analysis is to be performed for the FAS.  
13.3.2.1. 
The Pittsburgh Sleep Quality Index (PSQI) 
Observed and change from Baseline values for the overall and component scores of the PSQI are 
to be summarised by descriptive statistics (n, mean, SD, median, minimum and maximum) for 
each annual Allergy Assessment Period and treatment arm.  
13.3.2.2. 
6-Question Asthma Control Questionnaire (ACQ) Score 
Observed and change from Baseline values for the ACQ score are to be summarised by descriptive 
statistics (n, mean, SD, median, minimum and maximum) for each annual Allergy Assessment 
Period and treatment arm for subjects with a history of asthma as assessed at the Screening visit 
of the CP007 study.  
13.3.2.3. 
Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment 
Questions: Allergy Specific (WPAI:CIQ-AS) 
Observed values for the seven WPAI:CIQ-AS component scores are to be summarised by 
descriptive statistics (n, mean, SD, median, minimum and maximum) for each annual Allergy 
Assessment Period  and treatment arm.  
The number and percentage of subjects that are either currently working (question 1) or currently 
students (question 5) are to be presented.  The denominator for the percentages is the total 
number of subjects in the population treatment arm with data available.  


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 39 of 55 
13.3.2.4. 
Environmental Changes and Global Assessment of Symptom Severity 
The number and percentage of subjects that answer “Yes” or “No” to each home environment 
question and fall within each of the symptom severity categories are to be presented for each 
monthly assessment and treatment arm. 
The percentages for global assessment of symptom severity categories are to be calculated 
relative to the number of subjects in the relevant population that answered “Yes” to “Have you 
been to a house in the last month where there is a cat?” at each month. 
A p-value for the difference in global assessment of symptom severity between treatment arms is 
to be calculated using the Cochran-Mantel-Haenszel (CMH) row mean score difference for all 
subjects that no longer keep a cat and presented for each treatment arm vs. Placebo.  
13.3.2.5. 
Monthly Days Off School/Work 
The number of days that either school or work was missed due to allergic Rhinoconjunctivitis 
symptoms is to be summarised by descriptive statistics (n, mean, SD, median, minimum and 
maximum) for each month and treatment arm. 
13.3.2.6. 
Hospital/Doctor Office Visits 
The total number of hospitalisations as well as the number and percentage of subjects 
hospitalised are to be presented for each monthly assessment and treatment arm.  
The length of stay of visits is to be summarised by descriptive statistics (n, mean, SD, median, 
minimum and maximum) for each monthly assessment and treatment arm. 
Similarly, the total number of doctor visits as well as the number and percentage of subjects with 
any visit to the doctor are to be presented for each monthly assessment and treatment arm.  
 
 
 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 40 of 55 
14. SAFETY OUTCOMES 
All outputs for AEs are to be based on the Safety population.  
There are to be no statistical comparisons between the treatment arms for safety data, unless 
otherwise specified with the relevant section.  
14.1. ADVERSE EVENTS 
AEs are to be coded using the Medical Dictionary for Regulatory Activities (MedDRA) Version 19.0. 
AE reporting begins from signed informed consent and ends when the subject completes the 
study or withdraws.  
An AE is any untoward medical occurrence. An AE can therefore be any unfavourable and 
unintended sign, symptom or disease.  
An overall summary of number of subjects (n), percentage of subjects (%) and total number of 
mentions (m) within each of the following categories is to be presented: 
 
Any AE 
 
Any AE by maximum severity 
 
Any AE by strongest relationship 
 
Any AE leading to premature withdrawal from the study 
 
Any serious AE 
 
Any AE leading to death 
Listings will include all AEs. 
14.1.1. 
ALL AES  
Incidences of AEs are to be presented by System Organ Class (SOC) and Preferred Term (PT) and 
also broken down further by maximum severity and strongest relationship to study medication. 
14.1.1.1. 
Severity 
Severity is classed as mild/moderate/severe (increasing severity). AEs with a missing severity are 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 41 of 55 
to be classified as severe. If a subject reports an AE more than once within that SOC/PT, the AE 
with the worst-case severity is to be used in the corresponding severity summaries. 
14.1.1.2. 
Relationship to Study Medication 
Relationship, as indicated by the Investigator, is classed as not related/ unlikely to be related/ 
related (increasing severity of relationship). AEs with a missing relationship to study medication 
are to be regarded as related to study medication. If a subject reports the same AE more than 
once within that SOC/PT, the AE with the strongest relationship to study medication is to be used 
in the corresponding relationship summaries.  
14.1.2. 
AES LEADING TO WITHDRAWAL FROM STUDY 
AEs leading to withdrawal from the study are to be identified on the Adverse Events CRF as events 
with an action taken of “Subject withdrawn because of this event”. 
For AEs leading to withdrawal from study, summaries of incidence rates (frequencies and 
percentages) by SOC and PT are to be presented. 
14.1.3. 
SERIOUS ADVERSE EVENTS 
SAEs are those events recorded as “Serious” on the Adverse Events CRF. A summary of SAEs by 
SOC and PT is to be presented. 
14.1.4. 
ADVERSE EVENTS LEADING TO DEATH 
AEs leading to Death are those events with a recorded outcome of ”Death” on the Adverse Events 
CRF. A summary of AEs leading to death by SOC and PT is to be presented. 
 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 42 of 55 
15. REFERENCES  
CP007A Protocol Version 5 (Incorporating Protocol Amendment 01, 02, 03 and 04) dated 08 Dec 2014.  
CP007 Statistical Analysis Plan Final Version dated 08 June 2016.  
Dobson, A. J. (2002). An introduction to generalized linear models, 2nd ed. Chapman & Hall/CRC. 
EMA. (n.d.). Guideline on Missing Data in Confirmatory Clinical Trials. Retrieved December 15, 2011, from European 
Medicines Agency: 
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/09/WC500096793.pdf. 
Little, R., & Yau, L. (1996). Intent-to-Treat Analysis for Longitudinal Studies with Drop-Outs. Biometrics , vol 52, 
1324-1333. 
Hogan, J., & Laird, N. (1997). Mixture models for the joint distribution of repeated measures and event times. 
Statistics in Medicine , 239-258. 
 
 
 
 
 
 
 
 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 43 of 55 
APPENDIX 1. PROGRAMMING CONVENTIONS FOR OUTPUTS 
QUINTILES OUTPUT CONVENTIONS 
OUTPUT FILE NAMING CONVENTIONS 
File names should only consist of uppercase letters, lowercase letters, digits (0 to 9) and 
underscores. A period should only be used to indicate a separator between the file name and the 
extension. No spaces, other special characters or punctuation marks are permitted. 
As far as possible, output files should be in RTF format, although .DOC files are also permitted. 
The program, program log and output file name should reflect the type and number of the 
statistical output. If this is not possible, then the output name should be at least as descriptive as 
possible. A prefix can be used to distinguish between a Table, Listing and Figure document (‘T’ for 
table, ‘L’ for listing and ‘F’ for figure). If there is only 1 digit in the number of the table, listing or 
figure in the place where 2 digits are possible, a leading zero should be added in the file name to 
make sorting consistent with the sequence (eg T14_3_01_1.RTF) 
PAPER SIZE, ORIENTATION AND MARGINS 
The size of paper will be Letter for the United States, otherwise A4. 
The page orientation should be landscape. 
Margins should provide at least 1 inch (2.54 centimeters) of white space all around the page, 
regardless of the paper size. 
The number of columns per page (linesize) should be 145 for A4. 
The number of rows per page (pagesize) should be 49 for A4. 
FONTS 
The font type ‘Courier New’ should be used as a default for tables and listings, with a font size of 
8. The font color should be black. No bolding, underlining italics or subscripting should be 
permitted. Try to avoid using super-scripts, unless absolutely necessary. Single spacing should be 
used for all text. 
Figures should have a default font of “Times Roman”. 
This can be achieved by using the following options in SAS: 
goptions 
gunit = pct 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 44 of 55 
cback = white 
colors = (black) 
hby = 2.4 
ftext = "TimesRoman" 
htext = 2.5 
device = cgmof97l 
gaccess = gsasfile; 
filename gsasfile "….cgm"; 
HEADER INFORMATION 
Headers should be defined as follows: 
 
The header should be placed at the top of the page (same place on each page) regardless of 
the size or orientation of the table or listing 
 
The customer name and protocol number should appear in row 1 and 2, left-aligned 
 
The page identification in the format Page X of Y (where Y is the total number of pages for the 
output) should appear in row 2, right aligned 
 
The output identification number should appear in row 3, centered 
 
The output title should start in row 4, centered 
 
The output population should appear in row 5, centered. The population should be spelled out 
in full, e.g. Intention-to-Treat in preference to ITT. 
 
Row 6 should be a continuous row of underscores (‘_’) (the number of underscores should 
equal the linesize) 
 
Row 7 should be a blank line 
 
Mixed case should be used for titles 
 
The output titles should be designed so that they are arranged consistently through all 
outputs. For example, content (eg Vital Signs) followed by metric (eg Change from Baseline) 
e.g. Vital Signs – Change from Baseline. 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 45 of 55 
 
Titles should not contain quotation marks or footnote references 
 
The column headings should be underlined with a row of underscores (‘_’) 
 
Column headings spanning more than one column should be underlined and have underscores 
on either side of the title and should be centered 
 
Column headings containing numbers should be centered 
 
Column headings should be in sentence case 
 
In general, the population count should appear in the column header in the form “(N=XXX)” 
 
“Statistic” should be the column header over n, Mean, SE, n (%) etc. 
 
As a rule, all columns should have column headings. 
TABLE AND LISTING OUTPUT CONVENTIONS 
General: 
 
The first row in the body of the table or listing should be blank 
 
The left hand column should start in column 1. No indenting or centering of the output should 
occur. 
 
Rounding should be done with the SAS function ROUND. 
 
Numbers in tables should be rounded, not truncated. 
 
Alphanumeric output should be left aligned. 
 
Numbers should be decimal point aligned. 
 
Whole numbers should be right aligned. 
 
Text values should be left aligned. 
 
The first letter of a text entry should be capitalized 
 
Listings of AEs, concomitant medications, medical histories etc. should be sorted in 
chronological order, with earliest AE, medication or history coming first. 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 46 of 55 
 
The study drug should appear first in tables with treatment as columns 
 
In general, only present totals (across treatment arms) at Baseline/randomization, and do not 
present them post randomization, unless the customer specifically requests it. 
 
If possible, include 100% frequencies in the table shell, so that it is clear what the denominator 
is for percentage calculations. 
 
All listing outputs should be sorted (preferably by Pooled Site, Treatment, and Subject 
Number). 
 
Do not use superscripts and subscripts 
 
Exponentiation is to be expressed using a double asterisk, i.e., mm3 is to be written as mm**3. 
 
All variables that are output in the CRF (which have data present) should appear in the listings, 
along with all derived data appearing in the corresponding tables 
 
The width of the entire output should match the linesize 
Univariate Statistics: 
 
Statistics should be presented in the same order across tables (i.e., n, Mean, SD, Median, 
Minimum, Maximum) 
 
Table statistics should line up under the N part of the (N=XXX) in the table header. All decimal 
points should line up. If the minimum and maximum are output on one line as Minimum, 
Maximum then the comma should line up with the decimal point. 
 
If the original data has N decimal places, then the summary statistics should have the following 
decimal places: 
o 
Minimum and maximum: N 
o 
Mean, median and CV%: N + 1 
o 
SD: N + 2 
Frequencies and percentages (n and %): 
 
Percent values should be reported inside parentheses, with one space between the count and 
the left parenthesis of the percentage. Parentheses should be justified to accept a maximum of 
100.0 as a value and padded with blank space if the percent is less than 100.0. An example is 
given below: 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 47 of 55 
 
o 
77 (100.0%) 
o 
50 (  64.9%) 
o 
   0 (   0.0%) 
Missing category for categorical data is only to be presented if there is missing data for a specific 
category and percentage will not be calculated for missing category counts. An example is given 
below: 
Gender 
 
 
 
 Male 
n (%) 
 
xxx (xxx.x) 
 Female 
n (%) 
 
xxx (xxx.x) 
 Total 
n (%) 
 
xxx (100.0) 
 Missing 
n 
 
xxx 
 
Percentages are to be reported to one decimal place, except percents <100.0% but >99.9% is 
to be presented as ‘>99.9%’ (e.g., 99.99% is presented as >99.9%); and percents < 0.1% is to be 
presented as ‘<0.1%’ (e.g., 0.08% is presented as <0.1%). Rounding is applied after the <0.1% 
and >99.9% rule. 
o 
Eg ( <0.1%) 
o 
( 6.8%) 
o 
(>99.9%) 
Percentages may be reported to 0 decimal places as appropriate (for example, where the 
denominator is relatively small). 
 
Where counts are zero, percentages of 0.0% should appear in the output. 
Confidence Intervals (CIs): 
 
As a rule CIs are output to one place more than the raw data, and standard deviations and 
standard errors to two places more than the raw data 
 
CIs should be justified so that parentheses displayed on consecutive lines of a table “line up”. 
 
Boundary values of confidence CIs should be separated by a comma. 
 
Boundary values should be padded as necessary to accept negative values and to allow 
alignment of the decimal place. 
 
An example is given below: 
o 
(-0.12, -0.10) 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 48 of 55 
o 
( 9.54, 12.91) 
P-values: 
 
P-values should be reported to three decimal places, except values <1.000 but >0.999 are to be 
presented as ‘>0.999’ (e.g., 0.9998 is presented as >0.999); and values <0.001 are to be 
presented as ‘<0.001’ (e.g., 0.0009 is presented as <0.001). Rounding is applied after the 
<0.001 and >0.999 rule 
Ratios: 
 
Ratios should be reported to one more decimal place than the original data. 
Spacing: 
 
There must be a minimum of 1 blank space between columns (preferably 2) 
Denominators: 
 
If a different count other than the population count is used for a denominator (within the 
table) to calculate percentages, there should be a row in the table that identifies that number 
“n”. 
 
Alternatively, a footnote should be included in each table with percentages to indicate the 
denominator for percentages. 
Missing values 
 
A “0” should be used to indicate a zero frequency. 
 
A blank is to be used to indicate missing data in an end-of-text table or subject listing. 
FIGURE OUTPUT CONVENTIONS 
 
Figures should be provided in RTF files using the SAS Output Delivery System (ODS), as 
Computer Graphics Metafile (CGM) formatted graphical output generated by SAS. 
 
The CGM file itself should contain the title or footer. 
 
The image should be clear and of high quality when viewed in the Word document, and when 
printed. 
 
In general, boxes around the figures should be used. 
FOOTNOTE INFORMATION 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 49 of 55 
Footers should be defined as follows: 
 
A continuous line of underscores (‘_’) will follow the body of the table or listing prior to any 
footnotes at the bottom of the page 
 
Table footnotes should be defined using compute statements in the proc report, and should 
appear directly after the body of the table 
 
The program path and name and version number (if applicable) should appear as footnote 1 at 
the bottom of the page 
 
The date/time stamp should appear as footnote 2 at the bottom of the page 
 
Footnotes should be left-aligned. 
 
Footnotes should be in sentence case. 
 
Only “typewriter” symbols are permitted – eg “*”, “$”, “#”, “@”, “&” and “+”. 
 
The choice of footnote symbols should be consistent. E.g. if you have the footnote “# indicates 
last observation carried forward” for one table, the same symbol and footnote should indicate 
LOCF for all tables. 
Ordering of footnotes should be as follows: 
1.) Source data listing reference, if necessary 
2.) Abbreviations and definitions 
3.) Formulae 
4.) P-value significance footnote 
5.) Symbols 
6.) Specific notes 
 
Common notes from table to table should appear in the same order. 
 
The symbols should appear in the same order as what they are defined in the table or listing, 
from left to right. 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 50 of 55 
DATES  
Depending on data available, dates will take the form DDMMYYYY. 
SPELLING FORMAT 
English UK. 
PRESENTATION OF TREATMENT GROUPS 
For outputs, treatment groups are to be represented as follows and in this order: 
Treatment Group 
For Tables, Graphs and 
Listings 
Placebo [8 doses of Placebo (one dose administered every 4 weeks)] 
Placebo 
Single course of Cat-PAD [4 doses of Cat-PAD 6 nmol (one dose 
administered every 4 weeks), followed by 4 doses of Placebo (one dose 
administered every 4 weeks) ] 
Cat-PAD 4x6 nmol 
Two courses of Cat-PAD [8 doses of Cat-PAD 6 nmol (one dose 
administered every 4 weeks)] 
Cat-PAD 8x6 nmol 
 
 
PRESENTATION OF VISITS 
For outputs, visits are to be represented as follows: 
Annual Assessment 
Year xx, where xx = 01 to 04 
Monthly Assessment 
Month xx, where xx = 01 to 12 
LISTINGS 
All listings are to be ordered by the following (unless otherwise indicated in the template): 
 
Pooled Site 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 51 of 55 
 
Randomised treatment group (or treatment received if it’s a safety output), first by 
control/placebo and then by dose group (Cat-PAD 4x6 nmol, Cat-PAD 8x6 nmol).  
 
Subject ID 
 
Date (where applicable) 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 52 of 55 
APPENDIX 2. COMPLETE QUESTIONNAIRES  
Rhinoconjunctivitis Quality of Life Questionnaire (S) Self-administered ≥ 12 
01. REGULAR ACTIVITIES AT HOME AND AT WORK/ SCHOOL (tasks that you have to do regularly at 
work/school and around your home) 
02. SOCIAL ACTIVITIES (e.g., activities with your family and friends, playing with children and pets, 
sex, hobbies) 
03. OUTDOORS ACTIVITIES (e.g., gardening, mowing the lawn, sitting outdoors, sports, going for a 
walk) 
04. Difficulty getting to sleep 
05. Wake up during night 
06. Lack of a good night’s sleep 
07. Fatigue 
08. Thirst 
09. Reduced productivity 
10. Tiredness 
11. Poor concentration 
12. Headache 
13. Worn out 
14. Inconvenience of having to carry tissues or handkerchief 
15. Need to rub nose/eyes 
16. Need to blow nose repeatedly 
17. Stuffy/blocked 
18. Runny 
19. Sneezing 
20. Post nasal drip 
21. Itchy eyes 
22. Watery eyes 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 53 of 55 
23. Sore eyes 
24. Swollen eyes 
25. Frustrated 
26. Impatient or restless 
27. Irritable 
28. Embarrassed by your symptoms 
Asthma Control Questionnaire 
01. On average, during the past week, how often were you woken by your asthma during the 
night?  
02. On average, during the past week, how bad were your asthma symptoms when you woke up 
in the morning? 
03. In general, during the past week, how limited were you in your activities because of your 
asthma? 
04. In general, during the past week, how much shortness of breath did you experience because of 
your asthma? 
05. In general, during the past week, how much of the time did you wheeze? 
06. On average, during the past week, how many puffs/inhalations of short-acting bronchodilator 
(eg. Ventolin/Bricanyl) have you used each day?  
Pittsburgh Sleep Quality Index 
01. During the past month, what time have you usually gone to bed at night?  
02. During the past month, how long (in minutes) has it usually taken you to fall asleep each 
night?  
03. During the past month, what time have you usually gotten up in the morning? 
04. During the past month, how many hours of actual sleep did you get at night? (This may be 
different than the number of hours you spent in bed.)  
05. During the past month, how often have you had trouble sleeping because you… 
a) Cannot get to sleep within 30 minutes  
b) Wake up in the middle of the night or early morning  
c) Have to get up to use the bathroom  
d) Cannot breathe comfortably  


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 54 of 55 
e) Cough or snore loudly  
f) Feel too cold  
g) Feel too hot  
h) Had bad dreams  
i) Have pain  
j) Other reason(s), please describe How often during the past month have you had trouble 
sleeping because of this?  
06. During the past month, how would you rate your sleep quality overall? 
07. During the past month, how often have you taken medicine to help you sleep (prescribed or 
“over the counter”)?  
08. During the past month, how often have you had trouble staying awake while driving, eating 
meals, or engaging in social activity?  
09. During the past month, how much of a problem has it been for you to keep up enough 
enthusiasm to get things done?  
10. Do you have a bed partner or room mate?  
If you have a room mate or bed partner, ask him/her how often in the past month you have had… 
a) Loud snoring 
b) Long pauses between breaths while asleep 
c) Legs twitching or jerking while you sleep  
d) Episodes of disorientation or confusion during sleep  
e) Other restlessness while you sleep; please describe 
Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment Questions: 
Allergy Specific 
01. Are you currently employed (working for pay)? (If NO, check “NO” and skip to question 5.) 
02. In general, how many hours per week do you usually work?  
03. During the past seven days, how many hours did you miss from work because of problems 
associated with your allergies? Include hours you missed because you were sick, times you went in 
late, left early, etc. because you were experiencing problems with your allergies. (Do not include 
time you missed to participate in this study.)  
04. During the past seven days, how much did allergies affect your productivity while you were 


 
 
Document: 
CP007A SAP.docx 
Author: 
Roland Klopper 
Version Number: 
V 2.0 
 
 
Version Date: 
23 Feb 2017 
Template No:  CS_TP_BS016 – Revision 3 
Reference:  CS_WI_BS005 
Effective Date: 01May2012 
 
Copyright © 2012 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited.  
 
STATISTICAL ANALYSIS PLAN: CP007A 
Page 55 of 55 
working? Think about days you were limited in the amount or kind of work you could do, days you 
accomplished less than you would like, or days you could not do your work as carefully as usual. If 
allergies affected your work only a little, choose a low number. Choose a high number if allergies 
affected your work a great deal. 
05. Do you currently attend classes in an academic setting (middle school, high school, college, 
graduate school, additional course work, etc.)? (If NO, check “NO” and skip to question 9.) 
06. In general, how many hours per week do you usually attend classes?  
07. During the past seven days, how many hours did you miss from class or school because of 
problems associated with your allergies? (Do not include time you missed to participate in this 
study.) 
08. During the past seven days, how much did allergies affect your productivity while in school or 
attending classes in an academic setting? Think about days your attention span was limited, you 
had trouble with comprehension or days in which you could not take tests as effectively as usual. 
If allergies affected your productivity at school or in class only a little, choose a low number. 
Choose a high number if allergies affected your productivity a great deal. (Cross a number.) 
09. During the past seven days, how much did your allergies affect your ability to do your regular 
daily activities, other than work at a job or attend classes? By regular activities, we mean the usual 
activities you do, such as work around the house, shopping, childcare, exercising, studying, etc. 
Think about times you were limited in the amount or kind of activities you could do and times you 
accomplished less than you would like. If allergies affected your activities only a little, choose a 
low number. Choose a high number if allergies affected your activities a great deal. (Cross a 
number.)