A Phase IIb, Randomized, Double-blind, Placebo-controlled, Parallel Group, Multicenter Dose Ranging Study of a Subcutaneous Anti-OX40L Monoclonal Antibody (KY1005) in Moderate-to-Severe Atopic Dermatitis
Phase: PHASE2
Conditions: Eczema, Atopic Dermatitis
Sponsor: Kymab Limited

 
 
Property of the Sanofi Group - strictly confidential                                                   PAGE 1 OF 147 
 
AMENDED CLINICAL TRIAL PROTOCOL 08   
Protocol title: 
A 
Phase 
IIb, 
Randomised, 
Double-blind, 
Placebo-controlled, Parallel Group, Multicentre Dose 
Ranging Study of a Subcutaneous Anti-OX40L 
Monoclonal Antibody (KY1005) in Moderate-to-Severe 
Atopic Dermatitis 
Protocol number: 
KY1005-CT05/DRI17366 
Amendment number: 
08 
Compound number 
(INN/Trademark): 
KY1005/SAR445229 
(Amlitelimab/Not applicable) 
Brief title: 
Study Testing Response Effect of KY1005 Against 
Moderate-to-Severe Atopic Dermatitis  
The STREAM-AD Study  
Study Phase: 
2b 
Sponsor name: 
Kymab Ltd, a Sanofi Company 
Legal registered 
address: 
The Bennet Building (B930) 
Babraham Research Campus 
Cambridge, CB22 3AT 
United Kingdom 
Tel: +44(0)1223 833301 
Monitoring team’s 
representative name 
and contact 
information: 
 
Regulatory agency 
identifier number(s): 
 
IND: 
153717 
EudraCT: 
2021-000725-28 
NCT: 
NCT05131477 
WHO: 
U1111-1271-1438 
EUDAMED: 
Not applicable 
Other 
Not applicable 
Date: 1-Mar-2022 
 
Total number of pages: 
147 
 
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PROTOCOL AMENDMENT SUMMARY OF CHANGES  
DOCUMENT HISTORY  
Document 
Country/countries impacted 
by amendment 
Date, version 
Amended Clinical Trial Protocol 08 
All 
1 March 2022, version 1 
(electronic 5.0) 
Amended Clinical Trial Protocol 07 
Germany only 
10 February 2022, 
version 1 (electronic 4.0) 
Amended Clinical Trial Protocol 06 
Hungary only 
03 February 2022, 
version 1 (electronic 3.0) 
Amended Clinical Trial Protocol 05 
All 
18 January 2022, version 1 
(electronic 2.0) 
Amended Clinical Trial Protocol 04 
All 
14 December 2021, 
version 1 (electronic 1.0) 
Clinical Study Protocol Version 3.0 
Japan only 
03 November 2021 
Clinical Study Protocol Version 2.0 
All 
14 September 2021 
Clinical Study Protocol Version 1.1 
All 
08 July 2021 
Clinical Study Protocol Version 1.0 
(original) 
All 
16 June 2021 
Note: The name and numbering of the protocol is based on a new numbering system followed by the Sponsor.  
Amended Clinical Trial Protocol 08 (1 March 2022) 
This amended clinical trial protocol 08 is considered substantial based on the criteria set forth 
in Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union. 
OVERALL RATIONALE FOR THE AMENDMENT 
The reasons for this amendment to Protocol KY1005-CT05 are to fulfil requirements from the 
German authorities Paul-Ehrlich-Institut and Ethics Committee of the State of Berlin 
(Ethik-Kommission des Landes Berlin) with global impact, requirements from Czech Health 
Authorities (STÁTNÍ ÚSTAV PRO KONTROLU LÉČIV), requirements from Hungarian 
Emberi Erőforrások Minisztériuma, (Ministry of Human Capacities). Also the inclusion of an 
interim analysis, modification in the biopsy requirements, and overall clarifications. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Protocol amendment summary of changes table 
Section # and Name 
Description of Change 
Brief Rationale 
Protocol Synopsis, 
Section 3.1, 
Section 6.6.2 
 
 
 
 
 
 
 
Protocol Synopsis, 
Section 4.2 
Adding clarification in inclusion 
criterion 10 that the signed informed 
consent form must actually be present at 
the time of inclusion. 
To clarify that the signed informed 
consent form should be present when 
patient is included into this study. 
Protocol Synopsis, 
Section 4.2 
Inclusion criterion 11 “For patients at 
sites selected for skin biopsy collection: 
(until up to approximately one third 
[30%] of patients have enrolled to the 
skin biopsy sub-study), able and willing 
to provide skin biopsies at required 
timepoints.” has been changed to “For 
patients who decide to join the biopsy 
sub-study at sites selected for skin biopsy 
collection, be able and willing to provide 
skin biopsies at 
 
To keep consistency with the 
optional skin biopsy sub-study. 
Protocol Synopsis, 
Section 4.3 
Adding clarifications on excluded 
systemic therapy for AD and targeted 
biologic and small molecule treatments 
in exclusion criterion 1. 
To further clarify criterion on 
excluded systemic therapy for AD 
and targeted biologic and small 
molecule treatments. 
Protocol Synopsis, 
Section 4.3 
Exclusion criterion 4 “completion of 
required administrations of COVID-19 
vaccine within 14 days prior to Baseline 
or within 7 days immediately prior to or 
following IMP administration” has been 
changed to “completion of required 
administrations of COVID-19 vaccine 
within 14 days prior to Baseline or 
within 14 days immediately prior to or 
following IMP administration.” 
To clarify that patients who complete 
COVID-19 vaccine within 14 days 
immediately prior to or following 
IMP administration should be 
excluded. 
Protocol Synopsis, 
Section 4.3, 
Section 17.15.5 
Exclusion criterion 6 “Basal and 
squamous cell skin cancer in the last 
3 years prior to Baseline. Any other 
malignancies in the last 5 years prior to 
Baseline (excluding in situ cervical 
carcinoma that has been excised and 
cured)” has been changed to “Any 
malignancies or history of malignancies 
prior to Baseline (except for 
non-melanoma skin cancer that has been 
excised and cured for more than 3 years 
prior to Baseline; in situ cervical 
carcinoma that has been excised and 
cured).”  
To clarify the requirement on 
malignancies of enrolled patients. 
 
To fulfil requirement from the Czech 
Health Authorities (STÁTNÍ 
ÚSTAV PRO KONTROLU 
LÉČIV). 
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Section # and Name 
Description of Change 
Brief Rationale 
 
Country-specific clarification has been 
added regarding the exclusion criterion 6 
“Any malignancies or history of 
malignancies prior to Baseline (except 
for non-melanoma skin cancer that has 
been excised and cured for more than 
3 years prior to Baseline; in situ cervical 
carcinoma that has been excised and 
cured). Where a patient meets the above 
criteria but is still under the care of an 
oncologist, the investigator should 
confirm with oncologist that enrolment 
into this Phase 2b study is suitable.” 
 
Protocol Synopsis, 
Section 4.3 
Exclusion criterion 10 “Elective surgery 
planned to be scheduled for any time in 
the period up to 12 weeks following the 
last dose of IMP” has been changed to 
“Elective surgery planned to be 
scheduled for any time in the period from 
Screening up to 12 weeks following the 
last dose of IMP that in the investigator’s 
opinion would impact the conduct of the 
trial”. 
To clarify requirements on planned 
elective surgery of enrolled patients. 
Protocol Synopsis, 
Section 4.3 
Exclusion criterion 11 “Anticipated 
initiation of prohibited medications up to 
12 weeks following the last dose of IMP” 
has been changed to “Anticipated 
initiation of prohibited medications from 
Screening up to 12 weeks following the 
last dose of IMP. 
To clarify that those patients have 
anticipated initiation of prohibited 
medications from Screening up to 
12 weeks following the last dose of 
IMP should be excluded. 
Protocol Synopsis, 
Section 4.3 
Adding clarification regarding history of 
or known or suspected hypersensitivity 
to KY1005/placebo and other mAbs in 
exclusion criterion 18. 
To clarify that patients with history 
of or known or suspected 
hypersensitivity to KY1005/placebo 
and other mAbs should be excluded. 
Protocol Synopsis, 
Section 4.3 
Changing “prisoner” in exclusion 
criterion 19 to “persons who have been 
placed in an institution on the basis of an 
official or court order” for clarification. 
To clarify the definition of patients 
under coercion. 
Protocol Synopsis, 
Section 3.3, 
Section 10.4.8 
Wording regarding interim analysis has 
been added. 
To obtain early information for 
planning the phase 3 program, the 
interim analysis is added to support 
the timely analysis of data from 
patients who have completed the 
Day 113 (Week 16) assessments. No 
study conduct will be modified based 
on interim analysis results. 
Protocol Synopsis, 
Section 10.4.2 
Information on how the type I error rate 
will be controlled has been added. 
To elaborate specific approach used 
to control the overall type I error rate 
for multiple comparisons requested 
by German Ethics Committee of the 
State of Berlin (Ethik-Kommission 
des Landes Berlin). 
Section 1.1 
Adding information that KY1005 also 
refers to SAR445229 or amlitelimab. 
To elaborate terminology of 
KY1005, especially the International 
Nonproprietary Name (INN) of 
amlitelimab. 
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Section # and Name 
Description of Change 
Brief Rationale 
Section 3.5 
Adding specific reasons which may be 
used by the sponsor to make a decision 
to terminate the study: approval or the 
favorable opinion is revoked; in the 
event of a negative change in the 
benefit/risk ratio when the necessary 
adjustment to the maximum sum insured 
is not possible. 
To elaborate specific reasons which 
may be used by the sponsor to 
terminate the study requested by 
German Ethics Committee of the 
State of Berlin (Ethik-Kommission 
des Landes Berlin). 
Section 3.7 
Specific description regarding IDMC 
access to unblinded data has been added: 
IDMC members can have access to 
unblinded data sooner than the 
mentioned timepoint if that is necessary 
to perform data monitoring activities, 
and for safety purposes. 
To elaborate that IDMC members 
can access to unblinded data sooner 
than timepoint (Day 169 [Week 24]) 
if for data monitoring activities and 
safety purposes. 
Section 4.5 
Adding specific requirements on 
breastfeed of female patients: female 
patients must not breastfeed until 
5 months after Day 337 (Week 48) or the 
early termination visit (if prior to 
Day 337). 
To clarify the requirements on 
breastfeed of female patients. 
Section 5.2.6, 
Section 8.1.3 
The definition of overdose has been 
updated. 
To align the overdose definition 
within the program. 
Section 5.2.7 
 
 
 
 
 
 
Section 5.3.3 
A consideration of the impact of 
KY1005 on other vaccines besides 
COVID-19 vaccination in AD patients 
has been added: The impact of KY1005 
on overall vaccination response, new and 
recall response, for both COVID19 and 
other vaccines, has not been tested to 
date in AD patients. 
“The vaccine should not be administered 
within 7 days immediately prior to, or 
following, IMP administration.”  has 
been changed to “The vaccine should not 
be administered within 14 days 
immediately prior to, or following, IMP 
administration.” 
To clarify the impact of amlitelimab 
on overall vaccinations in AD 
patients and to clarify that when the 
study is ongoing the COVID 19 
vaccine should not be administered 
within 14 days immediately prior to 
or following, IMP administration. 
 
Section 5.3.4 
“No rescue is permitted in the first 
14 days following randomisation. Any 
administration of topical or systemic 
therapies during this period will result in 
permanent discontinuation from the 
study.” has been changed to “No AD 
rescue therapy is permitted in the first 
14 days following randomisation. Any 
AD rescue therapy administration either 
topical or systemic during this period 
will result in permanent discontinuation 
from the IMP. Bland emollients are not 
considered rescue therapy for AD, and 
To clarify rescue therapy for AD, 
especially to claim that bland 
emollients are not considered rescue 
therapy. 
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Section # and Name 
Description of Change 
Brief Rationale 
should be maintained during this period 
as per protocol.” 
Section 6.1 (Table 6-1), 
Section 6.6.2 
 
 
 
Section 6.2.3.1 
Clarification regarding how to interpret 
and handle QuantiFERON®-TB Gold 
blood test results has been added. 
To clarify QuantiFERON®-TB Gold 
blood test results interpretation. 
Section 6.7 (Table 6-6) 
Blood volume per safety sample and 
total blood volume has been adjusted. 
To adjust safety blood volume. 
Section 7 
The sample storing time has been 
changed to 25 years. 
To keep consistency with Sanofi 
requirements on sample retention 
time.  
Section 17.15.3 
Adding clarification that patients in 
Hungary will need to have received the 
COVID-19 vaccines and booster(s) 
approved in Hungary in accordance with 
the official recommendations. 
To fulfil requirements from 
Hungarian Emberi Erőforrások 
Minisztériuma, (Ministry of Human 
Capacities). 
Throughout the 
document 
Other minor editorial changes (eg, 
grammatical, stylistic, and minor 
typographical corrections). 
To increase the clarity or consistency 
of the protocol. 
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STUDY PERSONNEL  
Sponsor: 
Kymab Ltd, a Sanofi Company, 
The Bennet Building (B930) 
Babraham Research Campus 
Cambridge, CB22 3AT 
United Kingdom 
Tel: +44 (0) 1223 833301 
 
 
Sponsor 
Authorised 
Protocol 
Approver: 
Kymab Ltd, a Sanofi Company 
 
 
Global Project Head: 
 
 
 
Clinical Research Director: 
 
Medical Monitor: 
 
 
Emergency Numbers 
Emergency Contact: 
This study will be conducted in compliance with: 
• This protocol.  
• International Conference on Harmonisation (ICH) E6(R2) Good Clinical Practice (GCP) 
guidelines. 
• The applicable regulatory requirement(s).  
• The general principles of the Declaration of Helsinki. 
 
 
 
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COMPLIANCE STATEMENT  
The study will be conducted in compliance with the protocol, informed consent regulations, 
the general principles of the Declaration of Helsinki and the International Conference on 
Harmonisation (ICH) E6(R2) guidelines related to Good Clinical Practice (GCP). In addition, 
the study will adhere to all applicable local regulatory requirements. 
The electronic data capture (EDC) systems and other applicable electronic systems used in the 
conduct of the study will comply with ICH E6(R2), Section 5.5.3 guidance on use of electronic 
trial data handling and/or remote electronic trial data systems, the Food and Drug 
Administration (FDA), 21 CFR Part 11, Electronic Records, Electronic Signatures, and FDA, 
Guidance for Industry: Computerized Systems Used in Clinical Trials. 
All analyses will be performed in laboratories qualified in accordance with the procedures of 
the Sponsor or Sponsor’s contracted Clinical Research Organisation (CRO).   
All episodes of non-compliance will be documented and addressed.  Significant 
non-compliance (with potential to impact on safety or the integrity of data) will be notified to 
the Sponsor promptly.  Non-compliance with the protocol, SOPs, ICH GCP, and/or applicable 
regulatory requirement(s) will lead to prompt action by the Sponsor to secure compliance.  If 
serious and/or persistent non-compliance is identified on the part of an Investigator/institution, 
Sponsor will terminate the Investigator's/institution’s participation in the trial in accordance 
with ICH GCP. 
The Sponsor will ensure oversight of any trial-related duties and functions carried out on its 
behalf, by contracted vendors, and where applicable ensure the Sponsor’s contracted CRO(s) 
have appropriate systems and processes to provide oversight of duties subcontracted to another 
party by them.  
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PROTOCOL SYNOPSIS  
Protocol identifier: 
KY1005-CT05 (DRI17366) 
Study title: 
A Phase IIb, Randomised, Double-blind, Placebo-controlled, Parallel Group, 
Multicentre Dose Ranging Study of a Subcutaneous Anti-OX40L Monoclonal 
Antibody (KY1005) in Moderate to Severe Atopic Dermatitis 
Brief title: Study Testing Response Effect of KY1005 Against Moderate to 
Severe Atopic Dermatitis (STREAM-AD) 
Protocol version: 
8.0 
Sponsor: 
Kymab Ltd, a Sanofi Company 
Development Phase: 
2b 
Study type: 
Interventional  
Indication: 
Atopic dermatitis (AD) 
Study sites: 
Sites will be selected globally to participate in this study. 
Study rationale and 
purpose: 
The aim of this study is to characterise the efficacy (including dose/exposure 
response) and safety of KY1005 across a range of doses/exposures for a 
maximum duration of 52 weeks in adult patients with moderate-to-severe AD 
who have had an inadequate response to topical therapies or where topical 
therapies are not advised.  In addition, the durability of response and 
pharmacokinetics (PK) following withdrawal from the Investigational 
Medicinal Product (IMP) from Day 169 (Week 24) will be characterised.   
KY1005 is a human anti-OX40 ligand (OX40L) immunoglobulin G (IgG) 4 
monoclonal antibody (mAb) that, via blockade of the OX40/OX40L pathway, 
is expected to suppress T helper (Th) cell Th2-driven inflammation, as well as 
potentially modulating Th1, Th17 and Th22 responses.  Atopic dermatitis is a 
chronic/relapsing inflammatory skin disease, characterised by intense pruritus 
and recurrent eczematous lesions, driven by epidermal barrier dysfunction and 
cluster of differentiation (CD) 4+ driven inflammation which is dominated by 
Th2 cytokines. 
Primary objective: 
To characterise the efficacy (including dose/exposure-response) across a range 
of KY1005 exposures compared to Placebo on the signs of AD using the Eczema 
Area and Severity Index (EASI) in those patients with a documented history, 
within 6 months prior to Baseline, of either inadequate response to topical 
treatments or inadvisability of topical treatments.  Dose response of 4 different 
dose regimens of KY1005 in patients with AD versus Placebo will be evaluated.  
The primary efficacy endpoint will be the percentage change in EASI from 
Baseline to Day 113 (Week 16).   
Secondary objectives: 
The key secondary efficacy objectives will be to characterise the efficacy 
(including dose/exposure-response) across a range of KY1005 exposures 
compared to Placebo on additional physician assessments of AD 
activity/severity: EASI at Day 169 (Week 24), EASI-75, Investigator Global 
Assessment [IGA], and Numerical Rating Scale [NRS] for pruritus. 
Other secondary objectives include: 
To characterise: 
• 
Safety and tolerability of KY1005. 
• 
The PK profile of KY1005 across a range of KY1005 doses/exposures. 
• 
The response across a range of KY1005 exposures on additional 
physician assessments of AD activity/severity EASI, EASI 50, 
EASI 75, EASI 90, EASI 100, IGA, SCORing of Atopic Dermatitis 
(SCORAD) Index and affected body surface area (BSA). 
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• 
The response across a range of KY1005 exposures on patient reported 
AD activity/severity (Patient Oriented [PO] Eczema Measure [POEM], 
Dermatology Quality of Life Index [DLQI], Atopic Dermatitis Control 
Tool [ADCT], Hospital Anxiety and Depression Scale [HADS], NRS 
for pruritus). 
• 
The pharmacodynamic (PD) response to KY1005 including but not 
limited to:  
o 
The immunogenicity of KY1005, including the anti-KY1005 
antibody response. 
• 
The maintenance of clinical response in patients randomised to 
withdrawal of IMP who achieve ≥ EASI 75 or who attain IGA 0/1 
response following 24 weeks of treatment. 
Exploratory objectives: 
• 
  
o 
 
• 
 
 
  
• 
 
 
  
• 
 
• 
 
Study design: 
This is a Phase IIb, randomised, double-blind, placebo-controlled, parallel 
group, multicentre dose ranging study to characterise the efficacy and safety of 
subcutaneous 
(SC) 
administered 
KY1005 
in 
adult 
patients 
with 
moderate-to-severe AD who have a documented history, within 6 months prior 
to Baseline, of either inadequate response to topical treatments or inadvisability 
of topical treatments.  The study will include a Screening period of up to 
28 days.   
During the Screening period,
 
 
 
 
 
  Patients who continue to meet the eligibility 
criteria at Baseline will be randomised 1:1:1:1:1 to receive a SC dose of 
KY1005, or matching Placebo.   
At Baseline those patients not receiving a KY1005 loading dose will receive 
both KY1005 and Placebo to maintain the study blind. 
Four different SC KY1005 dosing regimens will be tested versus Placebo.  From 
Baseline up to Day 169 (Week 24), IMP will be administered at the following 
doses and intervals; 500 mg loading dose (given as 
 SC administration) 
followed 28 days later and thereafter with 250 mg every 4 weeks (Q4W) or the 
following regimens from Baseline: 250 mg Q4W, or 125 mg Q4W or 62.5 mg 
Q4W or Placebo Q4W.   
In accordance with the study blind at Baseline, a 
 Placebo SC dose will be 
administered along with the 
 KY1005 SC administration.  All patients will 
therefore receive 
 SC doses at Baseline.  
As part of the study design, patients initially enrolled at Baseline into the 
Placebo, 62.5 mg, 125 mg and 250 mg KY1005 treatment arms who do not 
achieve ≥ EASI 75 or IGA 0/1 at Day 169 (Week 24) will have the opportunity 
to receive KY1005 from Day 169 (Week 24) by enrolling in a long-term 
extension (LTE) study (LTS17367, LTE). The LTE is a separate study to 
KY1005-CT05 (DRI17366) and will therefore have a separate protocol and 
undergo submission for regulatory approval separately to the parent study. This 
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LTE enables all enrolled patients to have an opportunity to receive treatment at 
doses expected to elicit a meaningful clinical response (based on observations 
from the Phase 2a KY1005-CT02 study).  Patients who achieve ≥ EASI 75 or 
who attain IGA 0/1 at Day 169 (Week 24) will be randomised 3:1 to either enter 
a maintenance withdrawal phase or continue on their pre-Week 24 dose/interval.  
The purpose being to characterise the durability of response in conjunction with 
PK following treatment discontinuation in those withdrawn from therapy and to 
assess the clinical response and long-term safety in those continuing to receive 
Q4W treatment at their pre-Week 24 dose. Those patients who are 
re-randomised at Day 169 (Week 24) and who subsequently lose clinical 
response, defined during that study period as the first instance of < EASI 50 and 
where rescue therapy is no longer permitted as per Section 5.3.4 on or after the 
Day 197 (Week 28) study visit, will be offered the opportunity to receive 
retreatment with KY1005 in the LTE study. Results from this randomised 
withdrawal maintenance phase will inform the subsequent later stage 
development of KY1005 in the treatment of AD.  
At Day 365 (Week 52), patients who complete the second study period without 
loss of clinical response will have an additional 112 days’ safety follow-up to 
Day 477 (Week 68) and will then be discharged from the study. The last dose 
will be administered no later than Day 337 (Week 48). If during safety follow-up 
or after the end of study this cohort of patients experience worsening of their 
AD, and in the investigator’s opinion re-treatment with KY1005 is considered 
appropriate, they may be considered for enrolment in the LTE (subject to 
meeting inclusion/exclusion criteria). 
 
 
 
 
 
 
 
  
 
 
  
Number of subjects: 
A total of 350 patients (approximately 70 patients per treatment arm) will be 
randomised. 
Study population: 
Adult patients with moderate-to-severe AD who have a documented history, 
within 6 months prior to Baseline, of either inadequate response to topical 
treatments or inadvisability of topical treatments (eg, not well tolerated). 
Key inclusion criteria: 
Patients must fulfil all the following inclusion criteria for entry into the study: 
1. Adults (18 to <75 years of age) with AD, as defined by the American 
Academy of Dermatology Consensus Criteria, for 1 year or longer at 
Baseline (Day 1; prior to first administration of IMP). For United Kingdom, 
see Section 17.15.2 (Appendix 15). 
2. EASI of 12 or higher at the Screening Visit and 16 or higher at Baseline. 
3. IGA of 3 or 4 at Baseline. 
4. AD involvement of 10% or more of BSA at Baseline. 
5. Baseline worst/maximum pruritus NRS of ≥4.  The Baseline weekly average 
of daily worst/maximum pruritus NRS will be calculated from the 
7 consecutive days immediately preceding the Baseline visit. A minimum of 
4 daily scores out of the 7 will be required.  
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6. Documented history, within 6 months prior to Baseline, of either inadequate 
response to topical treatments or inadvisability of topical treatments: 
a) Acceptable documentation includes contemporaneous chart notes that 
record TCS (topical corticosteroids) and topical medication prescription 
and treatment outcome, or Investigator documentation based on 
communication with the patient’s treating physician.  
b) Failure to achieve and maintain remission or low disease activity (eg, 
IGA 0, clear skin to 2, mild disease) despite treatment with TCS of 
medium to high potency (± topical calcineurin inhibitor as appropriate), 
applied daily for at least 28 days or for the maximum duration 
recommended by the product prescribing information (eg, 14 days for 
super-potent TCS), whichever was shorter. 
NOTE: Patients who failed systemic therapies intended to treat AD 
within 6 months preceding screening, such as cyclosporine, 
methotrexate, azathioprine, and mycophenolate will be also considered 
as surrogate for having inadequate response to topical therapy. Washout 
of prior systemic medications must be completed as per the protocol 
requirements.  
c) Important side effects or safety risks defined as those that outweigh the 
potential 
treatment 
benefits 
including 
(but 
not 
limited 
to) 
hypersensitivity 
reactions, 
significant 
skin 
atrophy, 
treatment 
intolerance and adverse systemic effects, as assessed by the investigator 
or treating physician. 
7. Must have applied a stable dose of topical bland emollient (simple 
moisturiser, no additives [eg, urea]) at least twice daily for a minimum 
of 7 consecutive days before Baseline. 
8. Able to complete patient questionnaires, including collection of NRS 
(pruritus) on each of the 7 days prior to Baseline.  For patients who do 
not have at least 4 daily scores reported during the 7 days immediately 
preceding the planned randomisation date, randomisation should be 
postponed until this requirement is met, but without exceeding the 
28-day maximum duration for screening. 
9. Able and willing to comply with requested study visits/telephone visits 
and procedures. 
10. Able and willing to provide written informed consent. This document 
must also actually be presented at the time of inclusion. 
11. For patients who decide to join the biopsy sub-study at sites selected 
for skin biopsy collection, be able and willing to provide skin biopsies 
at 
 
Key exclusion criteria: 
Patients fulfilling any of the following criteria will be excluded from the study: 
1. Treatment with any of the following prior to first IMP administration 
(Baseline): 
o Systemic corticosteroids, and systemic calcineurin inhibitors (tacrolimus 
and cyclosporin) 
 
o Leukotriene inhibitors 
 
o Systemic therapy for AD, including but not limited to methotrexate, 
cyclosporine, azathioprine, phosphodiesterase type 4 (PDE4)-inhibitors, 
IFN-γ and mycophenolate mofetil
 (except for the drugs 
mentioned on other criteria with specific washout periods); 
o Targeted biologic and small molecule treatments 
 
 
 
o Previous treatment with systemic janus kinase (JAK) inhibitors
 
 
o Topical corticosteroids, tacrolimus or pimecrolimus, or topical PDE4 
 
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o Prescription or non-prescription moisturisers with additives (eg, urea, 
filaggrin) 
 
o Phototherapy or allergen immunotherapy 
 
o Regular use (>2 visits/week) of a tanning booth/parlour 
;  
o Any prior use of anti OX40 or anti OX40L mAb, including KY1005. 
o Investigational therapy for the treatment of AD or other conditions within 
5 half-lives or the limit of PD effects or 12 weeks where the t1/2 is 
unknown. 
2. Known history of, or suspected, significant current immunosuppression, 
including history of invasive opportunistic or helminth infections despite 
infection resolution or otherwise recurrent infections of abnormal frequency 
or prolonged duration. 
3. Weight <40 kg or >150 kg at Baseline. 
 
 
4. Treatment with a live (attenuated) immunisation within 12 weeks prior to 
Baseline; completion of required administrations of COVID-19 vaccine 
within 14 days prior to Baseline or within 14 days immediately prior to or 
following IMP administration. 
 
 
5. Men and women (of reproductive potential) unwilling to use birth control 
and women who are pregnant or breastfeeding. 
6. Any malignancies or history of malignancies prior to Baseline (except for 
non-melanoma skin cancer that has been excised and cured for more than 
3 years prior to Baseline; in situ cervical carcinoma that has been excised 
and cured). 
 
 
7. Positive for human immunodeficiency virus, hepatitis B surface antigen, 
hepatitis B core antibody or hepatitis C antibody at the Screening Visit.
 
 
8. History (within last 2 years prior to Baseline) of prescription drug or 
substance abuse, including alcohol, considered significant by the 
Investigator. 
9. Current or any past history of tuberculosis or non-tuberculous mycobacterial 
infections (including a positive QuantiFERON®-Tuberculosis Gold blood 
test at the Screening Visit). 
10. Elective surgery planned to be scheduled for any time in the period from 
Screening up to 12 weeks following the last dose of IMP that in the 
investigator’s opinion would impact the conduct of the trial. 
11. Anticipated initiation of prohibited medications from Screening up to 
12 weeks following the last dose of IMP. 
12. Severe concomitant illness that would in the Investigator’s opinion inhibit 
the patient’s participation in the study, including for example, but not limited 
to, hypertension, renal disease, neurological conditions, heart failure and 
pulmonary disease. 
13. Skin comorbidity that would adversely affect the ability to undertake AD 
assessments. 
14. Any medical or psychiatric condition which, in the opinion of the 
investigator may present an unreasonable risk to the study patient as a result 
of his/her participation in this clinical study, may make patient’s 
participation unreliable, or may interfere with study assessments. 
15. Any active or chronic infection requiring systemic treatment within 2 weeks 
prior to Baseline (1 week in the event of superficial skin infections). 
16. Laboratory values at the Screening Visit:  
• 
 
 
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• 
 
 
 
 
• In the Investigator’s opinion, any additional clinically significant laboratory 
results from the clinical chemistry, haematology or urinalysis tests at the 
Screening visit. 
17. In the Investigator’s opinion, any significant abnormality on 12-lead 
electrocardiogram (ECG) at the Screening Visit. 
18. History of or known or suspected hypersensitivity to KY1005 or the 
matching placebo formulation, or excipients used in the presentation of 
KY1005 or placebo, or in preparation for administration. History of or 
known or suspected severe hypersensitivity reactions to other mAbs and/or 
their excipients.  
19. Patients for whom coercion by either the Investigator or the Sponsor (eg, 
employee, student or persons who have been placed in an institution on the 
basis of an official or court order) cannot be discounted. (No patients will be 
included who are related to, or in a relationship with, or employed by the 
Investigator, the Sponsor or any organisations contracted on behalf of the 
Sponsor in the design, setting up or running of the study).  
20. Concurrent participation in any other clinical study, including 
noninterventional studies. 
Investigational medicinal 
products: 
At Baseline, those patients not receiving a KY1005 loading dose will receive 
both KY1005 and placebo to maintain the study blind. Thereafter, patients will 
receive either SC KY1005 or matching Placebo.  
Route of administration: 
Subcutaneous administration to the abdomen (or outer thigh if skin involvement 
entirely precludes the abdominal region. However, the anatomical region of 
administration must remain consistent throughout study participation and 
documented in the electronic case report form). 
Treatment regime(s): 
All patients will receive IMP every 4 weeks from Day 1 to Day 337 (Week 48).  
Randomisation will occur on Day 1, and re-randomisation on Day 169 
(Week 24) for patients who achieve ≥ EASI 75 or who attain IGA 0/1.  IMP will 
be administered in a 
 volume to the abdomen by SC injection. 
From Baseline (Day 1) to Day 169 (Week 24) 
Patients will receive either: 
a) 500 mg loading at Baseline 
 
 followed 28 days later with 250 mg KY1005 Q4W as 
a single 
 administration to Day 169 (Week 24).  
b) 250 mg KY1005 Q4W. 
c) 125 mg KY1005 Q4W.  
d) 62.5 mg KY1005 Q4W.  
e) 0.0 mg Placebo Q4W.   
To maintain the blind for all those groups that do not have a 500 mg loading 
dose, a 
 Placebo administration will be given at Baseline along with the 
 administration of the allocated KY1005 dose or Placebo.  
From Day 169 (Week 24) to Day 365 (Week 52): Patients who achieve 
≥ EASI 75 or attain IGA 0/1 at Day 169 (Week 24) only 
• Patients who achieve ≥ EASI 75 or attain IGA 0/1 at Day 169 (Week 24) 
will be randomised 3:1 to withdrawal or to remain on their pre-Week 24 
dose/interval.  Those randomised to withdrawal will receive Placebo Q4W. 
Main efficacy/PD 
assessments:  
The following efficacy/PD assessments will be performed in this study: 
• EASI, IGA, SCORAD Index, affected BSA, POEM, DLQI, ADCT, HADS, 
NRS for pruritus. 
• Anti-KY1005 anti-drug antibodies (ADAs).  
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Safety assessments: 
The safety and tolerability of KY1005 will be assessed by the 
measurement/recording of: 
• Adverse events and serious adverse events. 
• Adverse events of special interest (AESI). 
• Vital signs. 
• Laboratory safety tests (haematology, clinical chemistry, and urinalysis). 
• 12-lead ECGs. 
• Physical examination, including injection site reactions. 
• Concomitant medications. 
Pharmacokinetic and 
anti-drug antibody 
variables: 
Serum PK and ADA samples on 
, plus additional 
assessment of PK and ADA from 
 (plus safety 
follow-up where it occurs beyond study 
).  Pharmacokinetic and ADA 
samples will be collected from all patients including those receiving Placebo. 
Primary endpoints 
• Percentage change in EASI from Baseline to Day 113 (Week 16). 
Secondary endpoints: 
Safety endpoints: 
• Incidence of treatment emergent adverse events including AESIs.  
Pharmacokinetic endpoints:  
• Serum KY1005 concentration assessed throughout the study for each patient 
(receiving KY1005).  
Key secondary efficacy endpoints: 
• Percentage change from Baseline in EASI at Day 169 (Week 24).  
• Percentage of patients with at least a 75% reduction from Baseline in EASI 
(EASI 75) at Days 113 (Week 16) and 169 (Week 24). 
• Percentage of patients with a response of IGA 0 or 1 and a reduction from 
Baseline of ≥2 points at Days 113 (Week 16) and 169 (Week 24). 
• Proportion of patients with improvement (reduction) of weekly average of 
pruritus NRS ≥4 with a Baseline pruritis NRS of ≥4 from Baseline to 
Days 113 (Week 16) and 169 (Week 24). 
Other secondary efficacy endpoints: 
• Absolute change from Baseline in EASI at Days 15 (Week 2), 29 (Week 4), 
57 (Week 8), 85 (Week 12), 113 (Week 16), 141 (Week 20) and 
169 (Week 24). 
• Percentage change from Baseline in EASI at Days 15 (Week 2), 
29 (Week 4), 57 (Week 8), 85 (Week 12) and 141 (Week 20). 
• Percentage of patients with at least a 50% reduction from Baseline in EASI 
(EASI 50) at Days 15 (Week 2), 29 (Week 4), 57 (Week 8), 85 (Week 12), 
113 (Week 16), 141 (Week 20) and 169 (Week 24). 
• Percentage of patients with at least a 75% reduction from Baseline in EASI 
(EASI 75) at Days 15 (Week 2), 29 (Week 4), 57 (Week 8), 85 (Week 12) 
and 141 (Week 20). 
• Percentage of patients with at least a 90% reduction from Baseline in EASI 
(EASI 90) at Days 15 (Week 2), 29 (Week 4), 57 (Week 8), 85 (Week 12), 
113 (Week 16), 141 (Week 20) and 169 (Week 24). 
• Percentage of patients with a 100% reduction from Baseline in EASI 
(EASI 100) at Days 15 (Week 2), 29 (Week 4), 57 (Week 8), 85 (Week 12), 
113 (Week 16), 141 (Week 20) and 169 (Week 24). 
• Change in IGA from Baseline to Day 113 (Week 16) and over time. 
• Percentage of patients with a response of IGA 0 or 1 and a reduction from 
Baseline of ≥2 points at Days 15 (Week 2), 29 (Week 4), 57 (Week 8), 
85 (Week 12) and 141 (Week 20). 
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• Absolute and percentage change in SCORAD Index from Baseline to 
Day 169 (Week 24) and over time. 
• Absolute and Percentage change in affected BSA from Baseline to Day 169 
(Week 24) and over time. 
• Absolute and Percentage change in POEM from Baseline to Day 169 
(Week 24) and over time. 
• Absolute and Percentage change in DLQI from Baseline to Day 169 
(Week 24) and over time. 
• Absolute and Percentage change in ADCT from Baseline to Day 169 
(Week 24) and over time. 
• Absolute and Percentage change in HADS from Baseline to Day 169 
(Week 24) and over time. 
• Absolute and Percentage change in weekly average of pruritus NRS from 
Baseline to Day 169 (Week 24) and over time.  
• Proportion of patients with improvement (reduction) of weekly average of 
pruritus NRS ≥3 with a Baseline pruritis NRS of ≥3 from Baseline to 
Days 113 (Week 16) and 169 (Week 24). 
PD endpoints:  
• Anti-KY1005 antibody titre and number of patients with positive response.  
Main exploratory 
endpoints: 
• 
 
• 
 
 
• 
 
• 
 
• 
 
Statistical analysis: 
Sample Size: 
A sample size of 350 patients (70 patients / treatment arm) in the target 
population, (adults with moderate-to-severe AD who have a documented 
history, within 6 months prior to Baseline, of either inadequate response to 
topical treatments or inadvisability of topical treatments), randomised 1:1:1:1:1 
to 4 KY1005 groups or Placebo group is estimated to provide at least 84% power 
to detect a pairwise difference in means between each KY1005 and Placebo with 
respect to the percentage change in EASI from Baseline to Day 113 (Week 16), 
based on a 2-sided 2-sample equal-variance t-test.  
 
  
 
 
 
Analysis Sets: 
Efficacy Analysis Set: 
The full analysis set (FAS) includes all randomised patients.  Efficacy analysis 
will be based on treatment allocated at randomisation and stratified by disease 
severity (moderate/severe) and region.  
Methods: 
Statistical analysis of all endpoints will be defined in detail in the Statistical 
Analysis Plan. 
For continuous variables, descriptive statistics will include: the number of 
patients, mean, median, standard deviation, minimum, and maximum. 
For categorical or ordinal data, frequencies and percentages will be displayed 
for each category.  
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Efficacy Analyses:  
An overall test for the treatment effect of KY1005 will be conducted.  For each 
treatment regimen and all efficacy variables, the analysis will be comparisons 
of each of the KY1005 treatment groups with the Placebo group. For the primary 
endpoint, the overall type I error rate will be controlled using a hierarchical 
testing procedure across the four dose regimens against placebo. For each 
secondary endpoint analyzed, the same multiplicity adjustment approach will be 
applied as for the primary endpoint. No multiplicity adjustment will be made 
across the endpoints.  
For the continuous endpoints: An analysis of covariance (ANCOVA) model will 
be used.  This model includes treatment, randomisation strata (region, disease 
severity) as fixed effects, and baseline value as a covariate.  
 
 
 
A mixed-effect model with repeated measures will be used as a sensitivity 
analysis for primary and continuous key secondary endpoints.  This model 
includes the factors (fixed effects) for treatment, randomisation strata (region, 
disease severity), visit, treatment-by-visit interaction, and relevant baseline 
value.   
For the categorical endpoints: Cochran-Mantel-Haenszel test stratified by 
randomisation strata (region, disease severity) will be used at each analysis 
timepoint. 
 
 
 
 
   
 
 
Data will be presented graphically, where applicable, and with summary 
statistics by visit and by treatment regimen.   
Safety Analyses:  
Adverse events will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA, latest version) and will be summarised in incidence tables 
by System Organ Class and Preferred Term, and by treatment regimen.  Adverse 
events will be further summarised by maximum severity and relationship to 
study medication.  Concomitant medications will be coded using the World 
Health Organization Drug Dictionary and will be summarised in incidence 
tables by Drug Class and Preferred name, and by treatment regimen. 
Other routine safety assessments such as vital signs, 12-lead ECG and safety 
laboratory tests will be summarised by treatment regimen using statistics for 
continuous or categorical data, as appropriate. 
Pharmacokinetic Analyses:  
For each KY1005 treatment regimen, PK endpoints for each patient will be 
determined once final dose regimens confirmed.  Charts to demonstrate both the 
individual concentration-time profiles and the mean (with standard errors, 
untransformed and with logarithmic transformation of concentrations) profiles 
will be generated by KY1005 regimen.  Summary statistics by treatment group 
will be provided. 
Pharmacodynamic Analyses:  
Data will be presented graphically, where applicable, and with summary 
statistics by visit and by treatment regimen.   
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Interim analysis: 
An interim analysis will be planned when approximately
 participants in each 
arm complete the Day 113 (Week 16) assessments. The interim analysis will 
evaluate the percentage change in EASI from baseline to Day 113 (Week 16) 
and proportions of participants with EASI 75 at Day 113 (Week 16), as well as 
the other available data as needed. 
Planned study dates: 
Start of clinical phase: 
End of treatment phase: 
 
November 2021 
March 2024 
Duration of the study: 
The duration of the study will be up to 28 days for screening and then up to 
approximately Day 477 (last dose no later than Day 337 plus 140 days safety 
follow-up) for all patients unless enrolled into the LTE protocol at either 
Day 169 depending on responder status or no later than Day 365 due to loss of 
clinical response.  
Key words: 
KY1005, Monoclonal Antibody, Atopic Dermatitis, Atopic Eczema, OX40L, 
Phase IIb. 
 
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TABLE OF CONTENTS 
AMENDED CLINICAL TRIAL PROTOCOL 08 .................................................................... 1 
PROTOCOL AMENDMENT SUMMARY OF CHANGES .................................................... 2 
STUDY PERSONNEL .............................................................................................................. 7 
COMPLIANCE STATEMENT ................................................................................................. 8 
PROTOCOL SYNOPSIS .......................................................................................................... 9 
TABLE OF CONTENTS ......................................................................................................... 19 
LIST OF TABLES ................................................................................................................... 23 
LIST OF FIGURES ................................................................................................................. 24 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS .......................................... 25 
1 
BACKGROUND INFORMATION ................................................................................. 29 
1.1 
Introduction ...................................................................................................... 29 
1.2 
Introduction to Atopic Dermatitis and its Biology/Mechanism of Action ....... 29 
1.3 
Overview of Disease and Current Trends in Treatment ................................... 29 
1.4 
Investigational Medicinal Product(s) ............................................................... 30 
1.4.1 
Overview of KY1005 ...................................................................... 30 
1.5 
Rationale ........................................................................................................... 36 
1.5.1 
Study Rationale and Purpose ........................................................... 36 
1.5.2 
Rationale for Dose Selection ........................................................... 37 
1.5.3 
Study Design Rationale ................................................................... 40 
1.5.4 
Study Setting .................................................................................... 41 
1.6 
Summary of Known and Potential Risks and Benefits .................................... 42 
1.6.1 
Benefit/Risk of KY1005 Regarding Potential Infections with 
Severe 
Acute 
Respiratory 
Syndrome 
Coronavirus 
2 
(SARS-Cov-2) ................................................................................. 43 
1.7 
Route of Administration, Dosage, Dosage Regimen and Treatment Period(s) 43 
2 
OBJECTIVES AND ENDPOINTS .................................................................................. 44 
2.1 
Study Objectives .............................................................................................. 44 
2.1.1 
Primary Objective and Endpoint ..................................................... 44 
2.1.2 
Secondary Objectives and Endpoints .............................................. 44 
2.1.3 
Exploratory Objectives and Endpoints ............................................ 46 
3 
STUDY DESIGN ............................................................................................................. 46 
3.1 
Overall Study Design and Plan ........................................................................ 46 
3.2 
Study Duration ................................................................................................. 48 
3.2.1 
Study flow ........................................................................................ 48 
3.3 
Timing of Interim Analysis and Design Adaptations....................................... 51 
3.4 
Definition of End of Study ............................................................................... 51 
3.5 
Early Study Termination .................................................................................. 51 
3.6 
Randomisation .................................................................................................. 52 
3.7 
Blinding ............................................................................................................ 53 
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3.8 
Independent Data Monitoring Committee........................................................ 54 
4 
STUDY POPULATION ................................................................................................... 54 
4.1 
Number of Patients ........................................................................................... 54 
4.2 
Inclusion Criteria .............................................................................................. 54 
4.3 
Exclusion Criteria ............................................................................................. 55 
4.4 
Reproductive Status .......................................................................................... 57 
4.5 
Contraceptive Precautions ................................................................................ 58 
4.6 
Screen Failures ................................................................................................. 59 
4.7 
Strategies for Recruitment and Retention ........................................................ 59 
5 
TREATMENT OF PATIENTS ........................................................................................ 60 
5.1 
Presentation of Investigational Medicinal Product(s) ...................................... 60 
5.1.1 
KY1005 ............................................................................................ 60 
5.1.2 
Matching Placebo ............................................................................ 60 
5.1.3 
Non-investigational Medicinal Products/Auxiliary Medicinal 
Products/ Ancillary Treatments ....................................................... 60 
5.2 
Study Treatment Administration ...................................................................... 60 
5.2.1 
Treatment Regimen ......................................................................... 60 
5.2.2 
Administration of IMP ..................................................................... 62 
5.2.3 
Precautions for Administration ........................................................ 62 
5.2.4 
Monitoring During Administration .................................................. 62 
5.2.5 
Treatment Duration .......................................................................... 62 
5.2.6 
Guidance for Overdose .................................................................... 63 
5.2.7 
Dose Modification ........................................................................... 63 
5.3 
Concomitant Medication and Dietary Supplements ......................................... 63 
5.3.1 
Permitted Concomitant Therapy ...................................................... 63 
5.3.2 
Prohibited Concomitant Therapy (and Procedures)......................... 63 
5.3.3 
COVID-19 Vaccination and Other Vaccines .................................. 64 
5.3.4 
Rescue Therapy ............................................................................... 65 
5.3.5 
Background Therapy ....................................................................... 65 
5.4 
Lifestyle Restrictions ........................................................................................ 66 
5.5 
Patient Numbering and Treatment Assignment ............................................... 66 
5.6 
Supply, Packaging, Labelling and Storage ....................................................... 66 
5.7 
Procedures for Monitoring Patient Compliance ............................................... 67 
5.8 
Study Drug Accountability Records ................................................................ 67 
5.9 
Study Drug Destruction .................................................................................... 68 
6 
STUDY PROCEDURES .................................................................................................. 69 
6.1 
Study Schedule of Assessments ....................................................................... 69 
6.2 
Screening Procedures ....................................................................................... 81 
6.2.1 
Written Informed Consent ............................................................... 81 
6.2.2 
Demographic Information ............................................................... 81 
6.2.3 
Medical History ............................................................................... 82 
6.2.4 
Concomitant Medications ................................................................ 82 
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6.3 
Efficacy Assessments ....................................................................................... 82 
6.3.1 
Eczema Area Severity Index............................................................ 83 
6.3.2 
Investigator Global Assessment ...................................................... 83 
6.3.3 
SCORing of Atopic Dermatitis Index .............................................. 83 
6.3.4 
Body Surface Area Involvement of Atopic Dermatitis ................... 84 
6.3.5 
Patient Oriented Eczema Measure ................................................... 84 
6.3.6 
Dermatology Life Quality Index ..................................................... 84 
6.3.7 
Atopic Dermatitis Control Tool ....................................................... 84 
6.3.8 
Hospital Anxiety and Depression Scale .......................................... 84 
6.3.9 
Numerical Rating Scale for Pruritus ................................................ 85 
6.4 
Safety and Tolerability Assessments ................................................................ 85 
6.4.1 
Physical Examination ...................................................................... 85 
6.4.2 
Body Weight and Height ................................................................. 85 
6.4.3 
Adverse Events ................................................................................ 85 
6.4.4 
Standard Laboratory Safety Tests .................................................... 86 
6.4.5 
Virology ........................................................................................... 87 
6.4.6 
Drugs of Abuse Testing ................................................................... 87 
6.4.7 
Vital Signs ....................................................................................... 87 
6.4.8 
12-lead ECG .................................................................................... 87 
6.4.9 
Local Skin Reactions ....................................................................... 88 
6.5 
Pharmacokinetic and Anti-drug Antibodies Assessments ............................... 88 
6.5.1 
Pharmacokinetic Procedures ............................................................ 88 
6.5.2 
Anti-drug Antibody Procedures ....................................................... 89 
6.6 
Assessment of Pharmacodynamics Markers .................................................... 89 
 .................................................................. 89 
 .. 90 
 ............................................... 90 
 .................................................................. 90 
 ...................................... 91 
6.7 
Total Blood Volume ......................................................................................... 91 
7 
USE OF BIOLOGICAL SAMPLES AND DATA FOR FUTURE RESEARCH ........... 92 
8 
SAFETY MONITORING AND REPORTING ............................................................... 93 
8.1 
Definition of an Adverse Event ........................................................................ 93 
8.1.1 
Adverse Events Categorisation, Recording, and Follow-up ............ 93 
8.1.2 
Serious Adverse Event Assessment and Reporting to Sponsor ....... 95 
8.1.3 
Adverse Events of Special Interest .................................................. 96 
8.1.4 
Deaths .............................................................................................. 96 
8.1.5 
Disease-related events and/or disease-related outcomes not 
qualifying as AEs or SAEs .............................................................. 97 
8.1.6 
Regulatory reporting requirements for SAEs .................................. 97 
8.1.7 
Reporting to Regulatory Authorities, IECs/IRBs and other 
Investigators ..................................................................................... 97 
8.2 
Emergency Procedures ..................................................................................... 98 
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8.2.1 
Emergency Treatment Code-break .................................................. 98 
8.3 
Pregnancy ......................................................................................................... 98 
8.3.1 
Maternal Exposure ........................................................................... 98 
8.3.2 
Paternal Exposure ............................................................................ 99 
9 
WITHDRAWAL OF PATIENTS FROM TREATMENT AND/OR THE STUDY ....... 99 
9.1 
Discontinuation of the Patient from Investigational Medicinal Product .......... 99 
9.1.1 
Reasons for Permanent Discontinuation of Investigational 
Medicinal Product ............................................................................ 99 
9.1.2 
Reasons for Temporary Discontinuation of Investigational 
Medicinal Product .......................................................................... 100 
9.1.3 
Follow-up of Patients Off Treatment ............................................. 101 
9.1.4 
Discontinuation of the Patient from Study .................................... 102 
9.2 
End of Treatment and End of Study Procedures ............................................ 102 
9.3 
Study Discontinuation .................................................................................... 102 
9.4 
Patient Replacement Policy ............................................................................ 103 
10 STATISTICAL CONSIDERATIONS ........................................................................... 103 
10.1 
Sample Size Determination ............................................................................ 103 
10.2 
Estimands and Intercurrent Event .................................................................. 103 
10.3 
Analysis Sets .................................................................................................. 105 
10.3.1 
Full Analysis Set ............................................................................ 105 
10.3.2 
Safety Set ....................................................................................... 105 
10.3.3 
Pharmacokinetic Set ...................................................................... 105 
10.3.4 
Anti-drug Antibody Set ................................................................. 105 
10.4 
Statistical Analyses ........................................................................................ 105 
10.4.1 
Demographic and Baseline Characteristics ................................... 105 
10.4.2 
Efficacy Analysis ........................................................................... 106 
10.4.3 
Pharmacokinetic Analysis ............................................................. 111 
10.4.4 
Pharmacodynamic Analysis ........................................................... 111 
10.4.5 
Handling of Withdrawals and Missing Data ................................. 111 
10.4.6 
Protocol Deviations ....................................................................... 111 
10.4.7 
Other analysis ................................................................................ 111 
10.4.8 
Interim analysis .............................................................................. 112 
11 QUALITY CONTROL AND QUALITY ASSURANCE.............................................. 112 
11.1 
Monitoring ...................................................................................................... 112 
11.1.1 
Audits and Inspections ................................................................... 113 
11.2 
Data Quality Assurance .................................................................................. 113 
12 REGULATORY AND ETHICAL CONSIDERATIONS .............................................. 113 
12.1 
Regulatory Approval ...................................................................................... 114 
12.2 
Patient Confidentiality and Data Protection ................................................... 114 
12.3 
Protocol Amendments .................................................................................... 116 
12.4 
Principal Investigator Responsibilities ........................................................... 116 
13 DATA HANDLING AND RECORD KEEPING .......................................................... 117 
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13.1 
Data Capture ................................................................................................... 117 
13.2 
Data Management .......................................................................................... 117 
13.3 
Record Archiving and Retention .................................................................... 118 
14 FINANCING AND INSURANCE ................................................................................. 118 
15 PUBLICATION POLICY .............................................................................................. 118 
16 REFERENCES ............................................................................................................... 120 
17 APPENDICES ................................................................................................................ 123 
17.1 
Appendix 1 - Protocol Amendments .............................................................. 123 
 
 .............................................. 123 
17.1.2 
Amended Clinical Trial Protocol 04 (14 December 2021) ............ 124 
17.1.3 
Amended Clinical Trial Protocol 05 (18 January 2022) ................ 125 
17.1.4 
Amended Clinical Trial Protocol 06 (03 February 2022) .............. 127 
17.1.5 
Amended Clinical Trial Protocol 07 (10 February 2022) .............. 127 
17.2 
Appendix 2 - Eczema Area and Severity Index ............................................. 129 
17.3 
Appendix 3 - Investigator Global Assessment Scale ..................................... 132 
17.4 
Appendix 4 - SCORing of Atopic Dermatitis Index (SCORAD Index) ........ 133 
17.5 
Appendix 5 - Patient Oriented Eczema Measure ........................................... 134 
17.6 
Appendix 6 - Dermatology Quality of Life Index .......................................... 136 
17.7 
Appendix 7 - Atopic Dermatitis Control Tool ............................................... 137 
17.8 
Appendix 8 - Hospital Anxiety and Depression Scale ................................... 138 
17.9 
Appendix 9 - Pruritus Numeric Rating Scale ................................................. 139 
17.10 
Appendix 10 - Contraceptive and Barrier Guidance ...................................... 140 
17.11 
Appendix 11 - Reporting of Serious Adverse Events .................................... 141 
17.12 
Appendix 12 - Liver safety: suggested actions and follow-up assessments .. 142 
 .................................................................................. 143 
17.14 
Appendix 14 - Contingency Measures for a Regional or National Emergency 
That is Declared by a Governmental Agency ................................................ 144 
17.15 
Appendix 15 - Country-specific Requirements .............................................. 146 
 ........................................................... 146 
 ......................................... 146 
 ...................................................... 146 
 ..................................................... 147 
 .......................................... 147 
 
LIST OF TABLES  
Table 1-1: 
Efficacy Data for the Primary and Key Secondary Endpoints from Baseline 
to Day 113(Week 16) ............................................................................... 34 
Table 1-2 
Efficacy Data for in Those Subjects Defined as a Responder at Day 113 
(Week 16) (IGA 0/1) from Baseline to Day 169 (Week 24) and 
Day 253(Week 36) ................................................................................... 35 
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Table 1-3 
DosingSchedule ........................................................................................ 43 
Table 5-1 
TreatmentRegimes ................................................................................... 61 
Table 6-1: 
Schedule of Assessments Screening to Day 113(Week 16) ..................... 70 
Table 6-2: 
Schedule of Assessments - Day 120 (Week 17) to Day 169 (Week 24) .. 74 
Table 6-3: 
Schedule of Assessments - Day 176 (Week 25) to Day 365(Week 52) ... 77 
Table 6-4: 
Schedule of Assessments - SafetyFollow-up ........................................... 80 
Table 6-5: 
Standard Laboratory SafetyTests ............................................................. 86 
 .......................................................................................... 92 
 ......................................................................... 104 
 
 .................................................................................... 104 
 ................................. 107 
 
LIST OF FIGURES  
Figure 3-1: 
Overall StudyDesign ................................................................................ 49 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS  
Abbreviation 
Definition 
AD 
Atopic dermatitis 
ADA 
Anti-drug antibody 
ADCT 
Atopic Dermatitis Control Test 
AE 
Adverse event 
AESI 
Adverse event of special interest 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of covariance 
AST 
Aspartate aminotransferase 
AUC 
Area under the serum concentration curve 
BMI 
Body mass index 
BSA 
Body surface area 
cEv 
Intercurrent event 
C1q 
Complement component 1q 
CCL 
Chemokine [C-C motif] ligand 
CD 
Cluster of differentiation  
Cmax 
Maximum observed serum/plasma drug or metabolite concentration 
Cmin 
Trough concentrations 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CMC 
Chemistry and Manufacturing Controls 
CONSORT 
Consolidated Standards of Reporting Trials 
COVID-19 
Coronavirus Disease 2019  
CPK 
Creatine phosphokinase 
CRO 
Contract Research Organisation 
CSR 
Clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
DC 
Dendritic cells 
DLQI 
Dermatology Quality of Life Index 
DMP 
Data management plan 
DNA 
Deoxyribonucleic acid 
DTH 
Delayed type hypersensitivity 
EASI 
Eczema Area and Severity Index 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form  
EDC 
Electronic data capture 
ELISA 
Enzyme-linked immunosorbent assay 
EOS 
End of study  
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Abbreviation 
Definition 
EP 
Endpoint 
ePRO 
Electronic patient-reported outcome 
eTMF 
Electronic Trial Master File 
FAS 
Full analysis set 
FBC 
Full blood count 
FDA 
Food and Drug Administration 
FIH 
First-in-human 
Foxp3 
Forkhead box P3 
FSH 
Follicle-stimulating hormone 
GATA3 
GATA Binding Protein 3 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
GGT 
Gamma-glutamyl transferase 
GLP 
Good Laboratory Practice 
GMP 
Good Manufacturing Practice 
HADS 
Hospital Anxiety and Depression Scale 
Hb 
Haemoglobin 
HbsAg 
Hepatitis B surface antigen 
HBcAb 
Hepatitis B core antibody 
HCT 
Haematocrit 
HD 
High dose 
HIV 
Human immunodeficiency virus 
IB 
Investigator Brochure 
IC90 
90% inhibitory concentration 
IcEv 
Intercurrent event 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation  
IDMC 
Independent Data Monitoring Committee 
IEC 
Independent Ethics Committee 
IF 
Immunofluorescence 
IFN 
Interferon 
Ig 
Immunoglobulin 
IGA 
Investigator Global Assessment 
IHC 
Immunohistochemistry 
IL 
Interleukin 
IMP 
Investigational medicinal product 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
IRT 
Interactive response technology 
ISF 
Investigator Site File 
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Abbreviation 
Definition 
IV 
Intravenous(ly) 
JAK 
Janus kinase 
JAKi 
Janus kinase inhibitor 
K16 
Keratin 16 
KLH 
Keyhole limpet haemocyanin 
LD 
Low dose 
LDH 
Lactate dehydrogenase 
LoE 
Lack of efficacy 
LS 
Least squares 
LTE 
Long-term extension 
mAb 
Monoclonal antibody 
MCH 
Mean cell haemoglobin 
MCHC 
Mean cell haemoglobin concentration 
MCV 
Mean cell volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
Mixed-effect model with repeated measures 
NA 
Not applicable 
NOAEL 
No observed adverse effect level 
NRS 
Numerical Rating Scale 
OX40L 
OX40 ligand 
PBO 
Placebo 
PD 
Pharmacodynamic(s) 
PDE4 
Phosphodiesterase type 4 
PEI 
Paul-Ehrlich-Institut  
PI 
Principal Investigator  
PIS 
Patient information sheet 
PK 
Pharmacokinetic 
PO 
Patient Oriented 
POEM 
Patient Oriented Eczema Measure 
PRO 
Patient reported outcome 
PT 
Preferred term 
Q4W 
Every 4 weeks 
QoL 
Quality of life 
RBCC 
Red blood cell count 
RNA 
Ribonucleic acid 
SAE(s) 
Serious adverse event(s) 
SAF 
Safety analysis set 
SAP 
Statistical analysis plan 
SAS 
Statistical Analysis System 
SC 
Subcutaneous(ly)  
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Abbreviation 
Definition 
SCORAD 
SCORing of Atopic Dermatitis 
SEM 
Standard error of the mean 
SD 
Standard deviation 
SDV 
Source data verification 
SDTM 
Study Data Tabulation Model 
SOC 
System organ class 
SOP 
Standard operating procedure 
SUSAR(s) 
Suspected unexpected serious adverse reaction(s) 
t1/2 
Half-life 
TARC 
Thymus- and activation-regulation chemokine 
TB 
Tuberculosis 
TCS 
Topical corticosteroids 
TDAR 
T-dependent antibody response 
TEAE(s) 
Treatment emergent adverse event(s) 
Th 
T helper 
tmax 
Time to maximum observed concentration 
TReg 
Regulatory T cell(s) 
TSLP 
Thymic stromal lymphopoietin 
UK 
United Kingdom 
ULN 
Upper limit of normal 
USA 
United States of America 
UV 
Ultraviolet 
VAS 
Visual analogue scale 
WBCC 
White blood cell count 
WOCBP 
Women of childbearing potential 
WHO 
World Health Organisation 
 
Definition of Terms 
Investigator 
The Principal Investigator, person responsible for the conduct of the 
study at each site or their appropriately qualified delegate 
Baseline 
Last observation before first administration of IMP (Day 1) 
 
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1 
BACKGROUND INFORMATION  
1.1 
Introduction  
Atopic dermatitis (AD), also known as atopic eczema, is a common, chronic inflammatory skin 
disorder, which has a significant impact on the health and quality of life (QoL) of individuals 
with the disease especially social functioning and psychological well-being.  Treatment of AD 
in general depends on the extent and severity/activity of the disease, and when topical therapies 
are insufficient to treat signs and symptoms, systemic therapy or phototherapy are added.  
Although several systemic treatments are available, many patients do not derive optimal benefit 
due to either incomplete treatment responses or to adverse reactions.  KY1005 (also refers to 
SAR445229 or amlitelimab), a human anti-OX40 ligand (OX40L) monoclonal antibody 
(mAb), has therefore been developed to address the significant unmet medical need for 
treatment options in this patient population.   
1.2 
Introduction to Atopic Dermatitis and its Biology/Mechanism of 
Action  
Atopic dermatitis is a chronic/relapsing inflammatory skin disease, characterised by intense 
pruritus and recurrent eczematous lesions, driven by epidermal barrier dysfunction and cluster 
of differentiation (CD) 4+ driven cutaneous inflammation [Weidinger Nat Rev 2018, Langan 
The Lancet 2020].  Lesional skin shows an altered expression of genes related to keratinocyte 
activity and differentiation as well as T cell infiltration and activity, of genes encoding T helper 
(Th) cell Th2 associated (interleukin [IL]-4, IL-10, IL-13) and Th22-associated (IL-22) 
proteins.  In more chronic disease stages, Th1-mediated and Th17-mediated responses appear 
to be upregulated as well.   
1.3 
Overview of Disease and Current Trends in Treatment  
Atopic dermatitis is the most common inflammatory skin disorder in the developed world.  
Data from the World Health Organisation (WHO) Global Burden of Diseases initiative indicate 
that at least 230 million individuals worldwide have AD (lifetime prevalence >15%), with AD 
being the leading cause of the non-fatal disease burden conferred by skin conditions on a global 
level [Weidinger Nat Rev 2018].  At the patient level, AD has a diverse and marked negative 
impact on QoL and places a tremendous financial burden on society and patients [Drucker 
J Invest Dermatol 2017].  Atopic dermatitis can manifest at any point in life, but the incidence 
peaks in infancy with an estimated 80% of cases showing an onset before 6 years of age [Kay 
J Am Acad Dermatol 1994; Perkin Pediatr Allergy Immunol 2004].  After initiation, the course 
may be continuous for long periods, but may also show a relapsing remitting nature 
[Garmhausen Allergy 2013].  Conventional clinical teaching is that AD clears in more than 
50% of affected children, but recent data indicate that the proportion of patients with persistent 
or adult-onset disease or with relapses after longer asymptomatic intervals is much higher, and 
that AD is a lifelong disease with a highly variable phenotypic expression [Abuabara Allergy 
2018; Silverberg J Allergy Clin Immunol 2013].  
Atopic dermatitis management aims to improve symptoms and establish long-term disease 
control using a multi-stepped approach.  The main principles are continuous epidermal barrier 
repair with emollients and anti-inflammatory therapy with topical corticosteroids or calcineurin 
inhibitors.  When topical therapies are insufficient to treat signs and symptoms, systemic 
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therapy or phototherapy are indicated.  The duration of use of many systemic 
immunomodulatory agents are limited due to (cumulative) toxicity.  Newer biologic agents 
such as dupilumab which target the IL-4 receptor (IL-4R) have been shown to significantly 
improve both clinical and patient reported outcomes, but the long-term durability of response 
and the ability to be disease modifying will only become apparent with broader and long-term 
use.  There remains a significant unmet need in AD with a real need to develop disease 
modifying therapies that can address the underlying immunopathogenic process and improve 
the outcomes for patients with this common but often disabling skin disease [Weidinger Nat 
Rev 2018]. 
1.4 
Investigational Medicinal Product(s)  
The Investigational Medicinal Products (IMPs) are KY1005 and matching Placebo. 
1.4.1 Overview of KY1005  
KY1005 (also known as KY1005-2D10) is a biotechnology derived human anti-OX40L mAb 
(subclass G4) generated by a Chinese Hamster Ovary (CHO) cell line that binds OX40L to 
block the interaction with its receptor, OX40 (CD134). The Fc regions were modified to the 
immunoglobulin (Ig) G4PE variant to reduce Fc receptor binding and stabilise the antibody 
hinge region. The resulting molecule is therefore expected to have null effector function 
(known not to deplete target cells) and would not undergo fragment antigen-binding arm 
exchange as has been reported for natural IgG4. 
Blockade of the OX40/OX40L co-stimulation pathway represents a scientifically plausible 
approach to modulating the persistent inflammation caused by autoreactive memory T-cell 
populations and may provide a means of inducing immune tolerance to autoantigens (eg, in 
autoimmune disease) or alloantigens (eg, following transplants). 
OX40L is inducibly expressed on professional antigen-presenting cells, such as B-cells, 
dendritic cells (DCs) and macrophages upon activation [Webb Clin Rev Allergy Immunol 
2016].  Other cells such as endothelial cells, smooth muscle cells, mast cells and natural killer 
cells can also be induced to express OX40L [Croft Annu Rev Immuno 2010].  OX40L interacts 
‘monogamously’ with OX40, which is expressed on activated T-cells [Brunner J Allergy Clin 
Immuno 2017], CD4 and CD8 T-cells), inducing differentiation towards Th2, Th1, Th17 and 
Th22.  The OX40/OX40L axis has also been shown to enhance the proliferation and activation 
of memory T cells and abrogate forkhead box P3 (Foxp3) positive regulatory T cells (Treg) 
function [Kitamura Int J Cancer 2009]. OX40-OX40L interaction is also necessary for the 
differentiation of activated B-cells into highly Ig-producing cells. 
The interaction between OX40 and OX40L occurs during the T-cell-DC interaction, between 
hours and days after antigen recognition. After disengaging from DCs, the OX40-expressing 
T-cell may then interact with other OX40L-expressing cells, which in turn provide essential 
signals for the generation of memory T-cells with a drive to Th2 polarisation and the 
prolongation of the inflammatory responses.  OX40 signals render T-cells resistant to Treg 
cell-mediated suppression and furthermore, OX40 signalling in Treg cells directly inhibits their 
suppressive function. 
In AD, OX40L has been observed to be upregulated on DCs by several different factors 
including exogenous allergens, thymic stromal lymphopoietin (TSLP) and other cytokines 
from Langerhans cells and keratinocytes.  It is these activated DCs that appear to require 
OX40/OX40L interaction to drive the observed Th2 activation [Ilves J Eur Acad Dermatol 
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Venereol 2013].  OX40 blockade has been shown to reduce the Th2 response in AD, and 
suppression of Th1 and Th17/Th22 inflammatory biomarkers has also been observed 
supporting the notion that the OX40/OX40L pathway has a central role in both acute and 
chronic phases of AD [Guttman-Yassky J Invest Dermatol 2018].  
KY1005 has been administered to healthy volunteers and to patients with moderate-to-severe 
AD.  The findings from both studies are summarised below in Section 1.4.1.2 and more detailed 
information can be found in the KY1005 Investigator’s Brochure (IB).   
Further to the data generated with KY1005an anti-OX40 IgG1 mAb, GBR 830/ISB830, has 
been tested in patients with moderate-to-severe AD in a Phase 2a study (NCT02683928) 
[Guttman-Yassky J Invest Dermatol 2018; Gutman-Yassky J Allergy Clin Immunol 2019].  
Data from this study also support inhibition of the OX40/OX40L pathway as a target for the 
treatment of AD.  Clinical improvement elicited by GBR 830 was associated with statistically 
significant reductions from Baseline (p <0.01) in AD biomarkers, including Th2 chemokines 
(chemokine [C-C motif] ligand [CCL] 17 and 11, TSLP receptor), Th1/interferon (IFN) 
markers (IFN-γ, chemokine [C-X-C motif] ligand [CXCL] 10) and Th17/Th22-associated 
products (IL-23p19, S100A9/S100A12), indicating an effect on both the acute and chronic 
stages of AD.   
These data support the hypothesis that blocking the OX40/OX40L pathway may not only 
deliver symptomatic relief but also have potential to be disease modifying.  There was no 
immediate evidence of treatment limiting adverse events (AEs), although it should be noted 
that only small numbers of patients were treated. 
1.4.1.1 Non-clinical Data  
In Vitro Characterisation 
KY1005 has high affinity for human OX40L and blocks its interaction with OX40 in 
biochemical assays in vitro.  OX40L evoked cytokine release was inhibited in a concentration 
dependent manner by KY1005 in primary human T-cell preparations and in an allogeneic 
mixed lymphocyte reaction stimulated by native human OX40L expressed on primary DCs.  
Demonstration of poor or no binding to human Fc receptors indicates that KY1005 is unlikely 
to cause Fc receptor-mediated OX40L-superclustering and consequent activation of target 
downstream pathway(s).  
In Vivo Characterisation 
Treatment of cynomolgus monkeys with KY1005 resulted in inhibition of the T-dependent 
antibody response (TDAR).  KY1005 reduced the IgG antibody response to primary and 
secondary keyhole limpet haemocyanin (KLH) challenge to a similar extent at all dose levels 
tested (5 to 100 mg/kg). 
Pharmacokinetics and Non-clinical Safety 
 
   
   
 
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1.4.1.2 Clinical Data  
KY1005 has been administered to healthy volunteers (Studies KY1005-CT01 and 
KY1005-CT04) and to patients with moderate-to-severe AD (Study KY1005-CT02).  These 
studies are summarised below; further information can be found in the KY1005 IB.  
Study KY1005-CT01 
Study KY1005-CT01 was the First-in-Human (FIH) study of KY1005 that explored the safety 
and tolerability of single and repeat doses of KY1005 in healthy volunteers.   
This study was conducted at a single investigative site, in line with a typical FIH dose escalation 
design.  The study was composed of 8 ascending dose cohorts.  All cohorts comprised 8 healthy 
volunteers allocated at random to either active (6 subjects) or matching Placebo (2 subjects). 
 
  
Study KY1005-CT02 
The recently completed Phase 2a (KY1005-CT02), randomised, double-blind, placebo 
controlled, parallel group, multicentre study was designed to explore the efficacy and safety of 
monotherapy KY1005 in adult patients with moderate-to-severe AD who have a documented 
history, within 6 months prior to Baseline, of either inadequate response to topical treatments 
or inadvisability of topical treatments.  
During the screening period, treatments for AD including topical corticosteroids were washed 
out for at least 14 days prior to Baseline (except bland moisturisers).  Patients were randomised 
in a 1:1:1 ratio to receive either an IV lower dose (200 mg loading/100 mg maintenance) or 
higher dose (500 mg loading/250 mg maintenance) of KY1005, or matching Placebo.  Patients 
received KY1005 or Placebo every 4 weeks (Q4W) from Baseline to Day 85 (Week 12) when 
the last dose was received.  
The primary analysis occurred once all patients had completed Day 113 (Week 16) (or 
earlier/withdrawal).  All patients were expected to be followed to Day 253 (Week 36) for 
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safety.  The co-primary endpoints were percentage change in the EASI score from Baseline to 
Day 113 (Week 16) and the incidence of treatment-emergent adverse events (TEAEs). 
To explore the durability of effect for up to Day 253 (Week 36) from Baseline, patients who 
responded (IGA 0/1) at the Day 113 (Week 16) assessment were invited to continue with 
assessments up to the time that they relapse or commence drugs that have a significant impact 
on AD.   
All patients were followed from Day 113 (Week 16) to Day 253 (Week 36) as part of safety 
follow-up. 
Efficacy Outcomes  
Meaningful efficacy differences in the key endpoints (EASI and SCORAD) between those 
receiving KY1005 and Placebo from Day 15 (Week 2) and maintained to the primary endpoint 
(Day 113 [Week 16]).  Supporting efficacy, an improvement in pruritis was also observed.  No 
meaningful difference between the KY1005 treatment arms was noted (Table 1-1). 
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Table 1-1: 
Efficacy Data for the Primary and Key Secondary Endpoints from Baseline 
to Day 113(Week 16) 
 
 
KY1005 LD (n=27) 
KY1005 HD (n=27) 
Placebo (n=24) 
Primary Endpoint: 
% change in EASI  
MMRM (FAS) 
Least Square Means 
[95% CI]  
-80.12  
[-95.55, -64.68] 
-69.97 
[-85.04, -54.90] 
-49.37  
[-66.02, -32.72] 
P = 
0.009 
0.072 
 
Key Secondary Endpoints: 
% change in SCORAD 
MMRM (FAS) 
Least Square Means 
[95% CI] 
-60.30  
[-72.57, -48.04] 
-58.96  
[-71.04, -46.87] 
-36.79 [-49.94, -23.65] 
P =  
0.011 
0.016 
 
IGA 0/1 with ≥2 point 
improvement 
CMH (FAS) 
N (%)  
[95% CI] 
12 (44.4%)  
[25.70, 63.19] 
10 (37.0%)  
[18.82, 55.25] 
2 (8.3%)  
[0.00, 19.39] 
P = 
<0.001 
<0.001 
 
EASI 75 
Descriptive statistics 
(FAS) 
N (%)   
[95% CI] 
16 (59.3%) 
[40.73, 77.79] 
14 (51.9%) 
[33.01, 70.70] 
6 (25.0%) 
[7.68, 42.32] 
EASI 90 
Descriptive statistics 
(FAS) 
N (%)   
[95% CI] 
9 (33.3%) 
[15.55, 51.11] 
8 (29.6%) 
[12.41, 46.85] 
3 (12.5%) 
[0.00, 25.73] 
 
 
KY1005 LD (n=19) 
KY1005 HD (n=24) 
Placebo (n=21) 
NRS improvement of 
≥4-point improvement 
based on patients with a 
baseline NRS of at 
least 4 
Descriptive statistics 
N (%)   
[95% CI] 
11 (57.9%) 
[35.69, 80.10] 
15 (62.5%) 
[43.13, 81.87] 
8 (38.1%) 
[17.33, 58.87] 
CI=confidence interval; EASI=Eczema Area and Severity Index: FAS=full analysis set: MMRM=Mixed-effect model with 
repeated measures; NRS=numerical rating scale; SCORAD=SCORing of Atopic Dermatitis. 
In those patients achieving a IGA of 0/1 at Day 113 (Week 16), additional efficacy assessments 
through the safety follow-up demonstrated a maintenance of response in the majority of 
patients of up to 5.5 months (End of Study [EOS]) following the last dose of KY1005 (see 
Table 1-2).
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Table 1-2 
Efficacy Data for in Those Subjects Defined as a Responder at Day 113 
(Week 16) (IGA 0/1) from Baseline to Day 169 (Week 24) and Day 253(Week 36) 
 
 
KY1005 LD (n=12) 
KY1005 HD (n=10) 
Placebo (n=2) 
Primary Endpoint: 
% change in EASI  
Least Square Means  
[95% CI] 
Descriptive statistics (FAS) 
Day 169 
(Week 24) 
-94.34 
[-98.81, -89.87] 
-95.71 
[-101.78, -89.64] 
-85.15 
[-210.31, 40.01] 
Day 253 
(Week 36) 
-83.85 
[-97.44, -70.27] 
-94.10 
[-101.77, -86.43] 
-87.65 
[-134.03, -41.27] 
Key Secondary Endpoints: 
% change in SCORAD   
Least Square Means  
[95% CI] 
Descriptive statistics (FAS) 
Day 169 
(Week 24) 
-79.43 
[-90.10, -68.75] 
-87.72 
[-96.31, -79.13] 
-58.05 
[-298.83, 182.73] 
Day 253 
(Week 36) 
-68.29  
[-88.58, -48.00] 
-83.00  
[-96.68, -69.32] 
-57.75  
[-166.39, 50.89] 
IGA 0/1 with ≥2-point 
improvement 
N (%)  
[95% CI] 
Descriptive statistics (FAS) 
Day 169 
(Week 24) 
10 (83.3%) 
[62.25, 100.00] 
9 (90.0%) 
[71.41, 100.00] 
1 (50.0%) 
[0.00, 100.00] 
Day 253 
(Week 36) 
8 (66.7%) 
[39.99, 93.34] 
7 (70.0%)  
[41.60, 98.40] 
1 (50.0%) 
[0.00, 100.00] 
EASI 75  
N (%)  
[95% CI] 
Descriptive statistics (FAS) 
Day 169 
(Week 24) 
12 (100.0%) 
[100.00, 100.00] 
9 (90.0%) 
[71.41, 100.00] 
2 (100.0%) 
[100.00, 100.00] 
Day 253 
(Week 36) 
8 (66.7%) 
[39.99, 93.34] 
7 (70.0%)  
[41.6, 98.4] 
2 (100%) 
[100.00, 100.00] 
EASI 90  
N (%)  
[95% CI] 
Descriptive statistics (FAS) 
Day 169 
(Week 24) 
11 (91.7%) 
[76.03, 100.00] 
9 (90.0%) 
[71.41, 100.00] 
1 (50.0%) 
[0.00, 100.00] 
Day 253 
(Week 36) 
6 (50.0%) 
[21.71, 78.29] 
7 (70.0%) 
[41.60, 98.40] 
1 (50.0%) 
[0.00, 100.00] 
 
 
KY1005 LD (n=11) 
KY1005 HD (n=10) 
Placebo (n=1) 
NRS improvement of 
≥4-point improvement 
based on patients with a 
Baseline NRS of at least 4  
N (%)  
[95% CI] 
Descriptive statistics 
Day 169 
(Week 24) 
8 (72.7%) 
[46.41, 99.05] 
6 (60.0%) 
[29.64, 90.36] 
0 (0.0%)  
[0.00, 0.00] 
Day 253 
(Week 36) 
9 (81.8%)  
[59.03, 100.00] 
5 (50.0%)  
[19.01, 80.99] 
0 (0.0%)  
[0.00, 0.00] 
Source: Tables 14.2.2-1 E, 14.2.2-3 E, 14.2.2-4 E, 14.2.2-6 E, 14.2.2-7 E, 14.2.2-23 E 
LD: low dose KY1005 arm (200 mg/100 mg)  
HD: high dose KY1005 arm (500 mg/250 mg)  
CI=confidence interval; EASI=Eczema Area and Severity Index: FAS=full analysis set: NRS=numerical rating scale. 
 
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Safety Outcomes  
 
 
 
 
 
 
  
 
 
 
 
  
 
  
 
 
Study KY1005-CT04 
KY1005-CT04 (NCT04449939) was a Phase 1, open label study to assessing the PK of 
KY1005 after single dose administration by the SC and IV routes in male healthy volunteers.  
The purpose of this study was to assess the PK of KY1005 after SC administration and to 
compare the safety and tolerability of KY1005 when given via SC injection and IV infusion, 
to support SC administration.  Intravenous KY1005 was included as a reference treatment.  
Twenty-four healthy volunteers were enrolled as 3 treatment groups of 8 healthy male subjects. 
The primary endpoint was the characterisation of the PK of SC and IV administered KY1005 
after a single dose.  Key secondary endpoints included safety and tolerability.  
 
 
 
   
1.5 
Rationale  
1.5.1 Study Rationale and Purpose  
The aim of this current study is to further characterise the efficacy (including 
dose/exposure-response) and safety of KY1005 across a range of doses/exposures for a 
maximum duration of 52 weeks in adult patients with moderate-to-severe AD who have had 
an inadequate response to topical therapies or where topical therapies are not advised.  This 
24-week Placebo-controlled dose ranging period will be followed, in those patients who 
achieve an ≥ EASI 75 and/or IGA 0/1, with a randomised withdrawal period to Day 365 
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(Week 52) to characterise the durability of response ahead of the anticipated Phase III 
programme.   
KY1005 is a subclass G4 mAb that targets human OX40L to block interaction with its receptor 
OX40 and is predicted to suppress the inflammatory responses associated with AD.  The ability 
of KY1005 to improve the signs and symptoms of this disease has been reported in an initial 
Phase 2a study (Study KY1005-CT02) in this patient population.  Based on observations from 
the completed healthy volunteer studies (KY1005-CT01 and KY1005-CT04), and the 
KY1005-CT02 study in AD, KY1005 has, to date, been shown to be well tolerated.  
Whilst KY1005 has previously been evaluated as an IV formulation the current study will 
evaluate SC KY1005.  A SC formulation would potentially provide more flexible options for 
patients, enabling treatment in a patient’s home as well as in the clinic.  In a toxicology study 
in cynomolgus monkeys using the same SC formulation intended for administration to humans, 
no KY1005-specific risks associated with any local toxicity at the injection sites were 
identified.  In the healthy volunteer SC KY1005-CT04 safety and tolerability study no 
treatment limiting AEs were noted and the safety and tolerability profile was unremarkable.  
Based on these data, in combination with the available information for the IV formulation, the 
SC KY1005 is anticipated to be well tolerated.  
1.5.2 Rationale for Dose Selection  
A total of 4 dosing groups plus Placebo will be tested in this study.  The chosen doses and 
dosing regimens will allow for thorough assessment of the dose and exposure response 
relationship.  This type of approach has been adopted in previous Phase 2b studies in AD 
[Thaçi D et al, 2016, Guttman-Yassky E 2020].  Given the challenges of needle burden on 
compliance in AD the ability to provide less frequent dosing has been an influencing factor on 
the choice of doses and intervals proposed. 
 
  
 
 
  The 250 mg SC Q4W with a 500 mg loading dose, 
250 mg SC Q4W, 125 mg SC Q4W and 62.5 mg SC Q4W KY1005 doses will be administered 
to patients to assess the dose/exposure response across an appropriate exposure range. 
 
 
 
 
 
 
 
 
 
  
 
 
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Initial treatment period: Dose and interval justification to Day 169 (Week 24) 
The dose and dosing regimen that is expected to be able to maintain similar exposures to those 
observed in CT02 trial, as well as concentrations in tissues above the targeted range 
, during the 24-week double-blind period is a dose of 250 mg administered 
Q4W. A broad range of doses will be tested in this dose response study to cover the dose range 
which will capture the dose response and inform the benefit/risk assessment across these dose 
levels. 
The dose and dosing regimen for the period from Baseline to Day 169 (Week 24) for dosing 
Group 1 is 250 mg administered Q4W, 28 days following a loading dose of 500 mg at Baseline 
(
).  Using this approach, this dose and dose regimen is 
expected to achieve an earlier steady-state, and a Cmax, from the first dosing, close to that 
observed in the CT02 trial.   
The dose and dosing regimen for the period from Baseline to Day 169 (Week 24) for dosing 
Group 2 is 250 mg SC administered Q4W 
 with a second injection of 
 placebo dose at Baseline (Day 1) to protect the blind.  Using this approach this dose and 
dosing regimen is expected to maintain concentrations in blood (Cmin) 
 
 
 
The dose and dosing regimen for the period from Baseline to Day 169 (Week 24) for dosing 
Group 3 is 125 mg administered Q4W 
 with a second injection of 
 
Placebo dose at Baseline (Day 1) to protect the blind.  This is expected to provide exposures 
slightly lower than the ones observed in CT02 at the low dose.  This dose and dosing regimen 
is expected to maintain concentrations in blood 
  
The dose and dosing regimen for the period from Baseline to Day 169 (Week 24) for the last 
KY1005 dosing Group 4 is 62.5 mg administered Q4W 
 with a second 
injection of 
 placebo dose at Baseline (Day 1) to protect the blind.  The objective of this 
dose and dosing regimen is to characterize a dose response that was not evaluated during the 
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Phase 2a where only 2 dose levels were tested. The addition of this dose level will allow for 
expanded characterization of the dose response. 
 
 
 
 
 
 
 
 
The 24-week Placebo-control period has been selected as based on the Phase 2a study the 
maximum clinical response was not observed at the Day 113 (Week 16) primary endpoint after 
12 weeks of treatment ie, a plateau in clinical response was not achieved.  It is expected with 
further treatment improved benefits will be observed.  The use of a 24-week Placebo controlled 
period has been employed in the AD study setting before [Silverberg et al. 2019].  The primary 
endpoint of percentage change in EASI will be at Day 113 (Week 16).  This timepoint is typical 
for Phase 2b studies in AD.  Topical rescue therapy will be permitted from Day 15 (Week 2) 
of the study for intolerable symptoms of AD (Section 5.3.4). Recipients of topical therapies 
will be handled as outlined in Section 5.3. 
Safety considerations 
The highest dose-regimen chosen for the Phase 2b study (a loading dose of 500 mg SC followed 
by Q4W administration of 250 mg SC) is the same as the highest dose administered via the IV 
route in the Ph 2a study (KY1005-CT02).  
 
 Even higher doses were administered to healthy volunteers in the FIH study 
(KY1005-CT01), where the top (loading) dose was 12 mg/kg, which in an 85 kg individual 
would equate to a single flat dose of 1,020 mg. In this study, one AE of note occurred at the 
top dose of systemic allergic reaction. However, this dose level was far higher than that being 
tested in patients in the Phase 2b study. No otherwise clinically significant AEs, SAEs or deaths 
occurred at any dose level in KY1005-CT01.  
The total patient exposure (years) for KY1005-CT02 is 15.4 patient years for KY1005 low 
dose, and 16.5 patient years for KY1005 high dose. However, no safety or tolerability concerns 
have been identified across the clinical development programme to date, and the overall 
adverse event profile of KY1005 is unremarkable.  
 
 
 
 
 
 
 
 
Post Week 24 period: Randomised withdrawal design to inform Phase III extended dosing 
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As part of this study, the intention is to build on the sustained clinical response observed in the 
Phase 2a study with an assessment of the durability of response during a 28-week withdrawal 
period in those patients who achieve ≥ EASI 75 or who attain IGA 0/1 at Day 169 (Week 24). 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
   
Loss of clinical response  
Loss of clinical response is defined as the first instance of <EASI 50 during the second study 
period and where rescue therapy is no longer permitted as per Section 5.3.4.   
If loss of clinical response occurs on or after the Day 197 (Week 28) visit, Investigators will 
be able to choose to either discontinue the patient from KY1005-CT05 (DRI17366) or to 
progress to the LTE study (LTS17367, LTE).  
 
 
 
 
 
 
 
 
 
 
1.5.3 Study Design Rationale  
This Phase IIb study is a randomised, double-blind, placebo-controlled study of 365 days 
duration (plus screening and safety follow-up) that will be conducted to assess the efficacy and 
safety of monotherapy SC KY1005 in approximately 350 adult patients with 
moderate-to-severe AD.  Sites will be selected globally to participate in this study.  A parallel 
group design will be employed due to the testing of up to 4 different dose regimens versus 
Placebo.  This is considered appropriate for a study of this type (EMEA/CHMP/SWP/28367/07 
[Rev. 1] and ICH E4).   
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The study design, including the washout period and the use of Placebo, is in keeping with other 
trials in moderate-to-severe AD.  The study is designed to assess monotherapy KY1005 in 
patients with limited treatment options. All patients therefore must have either had an 
inadequate response to topical therapies or be individuals for whom such topical treatment is 
inadvisable.  It is recognised, based on prior studies in AD with a similar design [Thaçi The 
Lancet 2016], that the dropout rate can be relatively high (~20%) and this has been factored 
into the anticipated numbers of patients that will be recruited. 
Although the study represents the initial clinical evaluation of SC KY1005, the enrolment of 
up to 350 patients in a Phase IIb study is considered to be acceptable due to the available 
clinical data for IV KY1005 in which no KY1005-specific risks have been identified.  
Furthermore, the non-clinical and clinical data for SC KY1005 have identified no 
KY1005-specific risks or local toxicity at the injection sites at clinically relevant doses. 
The primary objective of this study will be to compare the dose response of 4 different dose 
regimens of KY1005 in patients with AD versus Placebo to Day 113 (Week 16).  As part of 
the study design, patients initially enrolled at Baseline into the Placebo, 62.5 mg,125 mg and 
250 mg KY1005 treatment arms who do not achieve ≥ EASI 75 or IGA 0/1 at Day 169 
(Week 24) will have the opportunity to be to receive KY1005 from Day 169 (Week 24) by 
enrolling in an LTE study.  This will enable all enrolled patients to have an opportunity to 
receive treatment at doses expected to elicit a meaningful clinical response (based on what was 
observed in the Phase 2a KY1005-CT02 study).   
Patients who achieve ≥ EASI 75 or who attain IGA 0/1 at Day 169 (Week 24) be randomised 
3:1 to either enter a maintenance withdrawal phase or continue their pre-Week 24 dose/interval.  
The purpose being to characterise the durability of response in conjunction with PK following 
treatment discontinuation in those withdrawn from therapy and to assess the clinical response 
in those continuing to receive Q4W treatment at their pre-Week 24 dose.  Those patients who 
are randomised to the second study period who subsequently lose clinical response will be 
offered the opportunity to receive retreatment with KY1005 in the LTE study.  Results from 
this randomised withdrawal maintenance phase will inform the subsequent later stage 
development of KY1005 in the treatment of AD.  
The maximum length of the study is 365 days plus safety follow-up. Those patients who 
achieve ≥ EASI 75 or who attain IGA 0/1 at Day 169 (Week 24) and complete the second study 
period without loss of clinical response at Day 365 (Week 52) will have an additional 112-day 
safety follow-up after Day 365 (Week 52) (total of 140 days safety follow-up from receipt of 
last dose of IMP on Day 337 [Week 48]). If during safety follow-up or after the end of study 
this cohort of patients experience worsening of their AD, and in the investigator’s opinion 
re-treatment with KY1005 is considered appropriate, they may be considered for enrolment in 
the LTE (subject to meeting inclusion/exclusion criteria). 
1.5.4 Study Setting  
The Sponsor plans to conduct the study at selected global sites. 
All study procedures will be conducted by trained Investigators and medical staff with 
appropriate levels of training, including Good Clinical Practice (GCP) and experience of 
clinical trials.  Investigators must understand specific characteristics of the IMP and of its target 
and mode of action.  This information can be found within this protocol and within the IB. 
Unless Appendix 14 (Section 17.14) is activated, IMP administration must take place in 
appropriate clinical facilities, under controlled conditions with the possibility of close 
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supervision of study patients during and after dosing, as required by the protocol.  Units must 
have immediate access to equipment and appropriately qualified staff for resuscitating and 
stabilising individuals in an acute emergency (such as cardiac emergencies, anaphylaxis, 
cytokine release syndrome, convulsions, hypotension), and ready availability of intensive care 
unit and other hospital facilities.  
1.6 
Summary of Known and Potential Risks and Benefits  
Clinical and non-clinical studies confirm that KY1005 exerts the intended pharmacological 
effect in relevant immune systems, and can provide meaningful clinical improvement in the 
signs and symptoms of AD.  The benefits of KY1005 in moderate-to-severe AD have been 
demonstrated in the KY1005-CT02 Phase 2a study where both KY1005 treatment groups 
provided clinically meaningful improvements in the signs and symptoms of disease. 
KY1005-specific risks, including none associated with SC administration, have not been 
identified to date from the non-clinical or clinical programme.  Potential risks include 
malignancy and impaired response to infection (discussed 
 
 
 tested 
to date.  One patient in the prior healthy volunteer study (KY1005-CT01) experienced a 
reaction of the mouth and throat during systemic administration on first exposure to KY1005.  
No similar events were noted in the KY1005-CT02 Phase 2a study in AD patients nor the 
KY1005-CT04 SC healthy volunteer study.  Systemic or localised allergic reactions that 
require immediate treatment are therefore defined as an adverse event of special interest (AESI; 
see Section 8.1.3) so that specific information can be collected prospectively.   
 
 
 
  
 
  
  
 
  
 
 
 
 
 
   
Overall, to date blockade of OX40/OX40L in humans is precedented without acute severe 
adverse consequences.  These findings suggest that OX40L-mediated clearance is not relevant 
at pharmacological doses and that such binding, in disease states in which OX40L is 
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upregulated, does not lead to common adverse reactions.  Mitigation of the theoretical risks is 
possible through selection of appropriate study populations and monitoring in clinical trials.  
The overall benefit risk is therefore in favour of continued development of KY1005 in immune 
mediated disease such as AD. 
Further details can be found in the IB. 
1.6.1 Benefit/Risk of KY1005 Regarding Potential Infections with Severe Acute 
Respiratory Syndrome Coronavirus 2 (SARS-Cov-2)  
There is no change in the overall benefit/risk of treating patients with KY1005 regarding the 
Coronavirus Disease 2019 (COVID-19) pandemic.  In case of the implementation of 
restrictions due to COVID-19, the advice provided in Section 17.14 (Appendix 14) should be 
followed. 
1.7 
Route of Administration, Dosage, Dosage Regimen and Treatment 
Period(s)  
KY1005 will be administered by SC injection.  Each dose will be administered as described in 
the Pharmacy manual (Section 5.2).  Following completion of the SC injection, patients will 
be monitored for at least 60 minutes.   
Patients will receive treatment with KY1005 or matching Placebo every 28 days throughout 
the study. Those patients randomised to withdrawal post-Week 24 will be administered Placebo 
every Q4W when KY1005 is not received.  This is to maintain the blinding of the study.  
The dosing schedule is presented in Table 1-3. 
Table 1-3 
DosingSchedule 
 
Baseline** 
Day 29 (Week 4) 
to Day 169 
(Week 24)** 
Randomised Withdrawal Period 
From Day 169 (Week 24) to Day 365 
(Week 52) 
Treatment regime 
Dose IMP (SC) 
Dose IMP (SC) 
Dose IMP (SC) 
Group 1 
500 mg 
 
  
 250mg 
Q4W  
Withdrawal: Placebo 
 0 mg 
Q4W 
Pre-Week 24: 
 250 mg Q4W 
Group 2 
 and  
 PBO 
(0 mg)* 
 250 mg 
Q4W  
Withdrawal: Placebo 
 0 mg 
Q4W 
Pre-Week 24: 
 250 mg Q4W 
Group 3 
 125 mg and  
 PBO 
(0 mg)* 
 125 mg 
Q4W  
Withdrawal: Placebo 
 0 mg 
Q4W 
Pre-Week 24: 
 125 mg Q4W 
Group 4 
 62.5 mg 
and  
 PBO 
(0 mg)* 
 62.5 mg 
Q4W  
Withdrawal: Placebo 
 0 mg 
Q4W 
Pre-Week 24: 
 62.5 mg Q4W 
Placebo 
 PBO 
(0 mg)* 
 0 mg 
Q4W  
Withdrawal: Placebo 
 0 mg 
Q4W 
Pre-Week 24: 
 0 mg Q4W 
IMP=investigational medicinal product; PBO=placebo; Q4W= every 4 weeks; SC=subcutaneous. 
* Placebo will be administered as a second 
 SC injection at Baseline to maintain the blind. 
 
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2 
OBJECTIVES AND ENDPOINTS  
2.1 
Study Objectives  
2.1.1 Primary Objective and Endpoint  
Objective  
Endpoint 
To characterise the efficacy (including 
dose/exposure-response) across a range of 
KY1005 exposures compared to Placebo on 
the signs of AD using the Eczema Area and 
Severity Index (EASI) in those patients who 
have who have a documented history, within 
6 months prior to Baseline, of either 
inadequate response to topical treatments or 
inadvisability of topical treatments. 
• Percentage change in EASI from Baseline to Day 113 
(Week 16). 
2.1.2 Secondary Objectives and Endpoints  
Objectives  
Endpoints  
Safety and tolerability of KY1005. 
• Incidence of treatment-emergent adverse events. 
The pharmacokinetic profile across a range of 
KY1005 doses/exposures. 
• Serum KY1005 concentration assessed throughout the 
study. 
The response across a range of KY1005 
exposures on additional physician 
assessment-s of atopic dermatitis (AD) 
activity/severity (EASI 50, EASI 75, 
EASI 90, EASI 100, Investigator Global 
Assessment [IGA], SCORing of Atopic 
Dermatitis [SCORAD] Index and affected 
body surface area [BSA]). 
Key secondary endpoints: 
• Percentage change from Baseline in EASI at Day 169 
(Week 24). 
• Percentage of patients with at least a 75% reduction from 
Baseline in EASI (EASI 75) at Days 113 (Week 16) and 
169 (Week 24). 
• Percentage of patients with a response of IGA 0 or 1 and a 
reduction from Baseline of ≥2 points at Days 113 
(Week 16) and 169 (Week 24). 
• Proportion of patients with improvement (reduction) of 
weekly average of pruritus NRS ≥4 with a Baseline pruritis 
NRS of ≥4 from Baseline to Days 113 (Week 16) and 
169 (Week 24). 
Other secondary endpoints: 
• Absolute change from Baseline in EASI at Days 15 
(Week 2), 29 (Week 4), 57 (Week 8), 85 (Week 12), 
113 (Week 16), 141 (Week 20) and 169 (Week 24). 
• Percentage change from Baseline in EASI at Days 15 
(Week 2), 29 (Week 4), 57 (Week 8), 85 (Week 12) and 
141 (Week 20). 
• Percentage of patients with at least a 50% reduction from 
Baseline in EASI (EASI 50) at Days 15 (Week 2), 
29 (Week 4), 57 (Week 8), 85 (Week 12), 113 (Week 16), 
141 (Week 20) and 169 (Week 24). 
• Percentage of patients with at least a 75% reduction from 
Baseline in EASI (EASI 75) at Days 15 (Week 2), 
29 (Week 4), 57 (Week 8), 85 (Week 12), and 
141 (Week 20). 
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Objectives  
Endpoints  
• Percentage of patients with at least a 90% reduction from 
Baseline in EASI (EASI 90) at Days 15 (Week 2), 
29 (Week 4), 57 (Week 8), 85 (Week 12), 113 (Week 16), 
141 (Week 20) and 169 (Week 24). 
• Percentage of patients with at least a 100% reduction from 
Baseline in EASI (EASI 100) at Days 15 (Week 2), 
29 (Week 4), 57 (Week 8), 85 (Week 12), 113 (Week 16), 
141 (Week 20) and 169 (Week 24). 
• Change in IGA from Baseline to Day 169 (Week 24) and 
over time. 
• Percentage of patients with a response of IGA 0 or 1 and a 
reduction from Baseline of ≥2 points at Days 15 (Week 4), 
29 (Week 4), 57 (Week 8), 85 (Week 12), and 
141 (Week 20). 
• Absolute and Percentage in SCORAD Index from Baseline 
to Day 169 (Week 24) and over time. 
• Absolute and Percentage change in affected BSA from 
Baseline to Day 169 (Week 24) and over time. 
The response across a range of KY1005 
dose/exposures on patient reported AD 
activity/severity (Atopic dermatitis Control 
Tool [ADCT], Patient Oriented [PO] Eczema 
Measure [POEM], Dermatology Quality of 
Life Index [DLQI], Hospital Anxiety and 
Depression Scale [HADS], and Numerical 
Rating Scale [NRS] for pruritus). 
• Absolute and Percentage change in POEM from Baseline 
to Day 169 (Week 24) and over time. 
• Absolute and Percentage change in DLQI from Baseline to 
Day 169 (Week 24) and over time. 
• Absolute and Percentage change in ADCT from Baseline 
to Day 169 (Week 24) and over time. 
• Absolute and Percentage change in HADS from Baseline 
to Day 169 (Week 24) and over time. 
• Absolute and Percentage change in weekly average of 
pruritus NRS from Baseline to Day 169 (Week 24) and 
over time.  
• Proportion of patients with improvement (reduction) of 
weekly average of pruritus NRS ≥3 with a Baseline pruritis 
NRS of ≥3 from Baseline to Days 113 (Week 16) and 
169 (Week 24). 
The pharmacodynamic response to KY1005 
including but not limited to:  
The immunogenicity of KY1005, including 
the anti-KY1005 antibody response. 
• The 
immunogenicity 
of 
KY1005, 
including 
the 
anti-KY1005 antibody response. 
The explore the continued clinical response in 
those patients who achieve ≥ EASI 75 or who 
attain IGA 0/1 at Day 169 (Week 24)  
• Continued assessment of the efficacy endpoints from 
Day 169 (Week 24) and over time. 
• Time to loss of EASI 75 in participants randomised to 
withdrawal post-Week 24. 
• Time to loss of IGA 0/1 in participants randomised to 
withdrawal post-Week 24. 
• Time to loss of EASI 50 in participants randomised to 
withdrawal post-Week 24. 
• Continued 
assessment 
of 
patient 
reported 
AD 
activity/severity endpoints from Day 169 (Week 24) and 
over time. 
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2.1.3 Exploratory Objectives and Endpoints  
Objectives  
Endpoints  
3 
STUDY DESIGN  
3.1 
Overall Study Design and Plan  
This is a Phase IIb, randomised, double-blind, placebo-controlled, parallel group, multicentre 
dose ranging study to characterise the efficacy and safety of SC administered KY1005 in adult 
patients with moderate-to-severe AD who have a documented history, within 6 months prior 
to Baseline, of an inadequate response to, or inadvisability of, topical treatments.  
 
 
 
   
Up to 350 patients (approximately 70 patients per treatment arm) will be enrolled.  Patients 
who continue to meet the eligibility criteria at Baseline will be randomised to 1 of 5 treatment 
groups (4 different KY1005 regimens or Placebo) in an equal (1:1:1:1:1) ratio.  
From Baseline up to Day 169 (Week 24) IMP will be administered at the following dose and 
intervals: 
• 500 mg loading at baseline (
) followed 4 weeks later with 
250 mg Q4W as 
; 
Or  
• 250 mg 
 at Baseline followed 4 weeks 
later with 250 mg Q4W 
; 
Or  
• 125 mg (
 at Baseline followed 4 weeks 
later with 125 mg Q4W as 
; 
Or  
• 62.5 mg (
 at Baseline followed 4 weeks 
later with 62.5 mg Q4W as 
; 
Or  
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• Placebo given as 
 at Baseline followed 4 weeks later with 
 
Placebo (0 mg).  
At Baseline, those patients not receiving a KY1005 loading dose will receive both KY1005 
and Placebo to maintain the study blind. 
The Day 113 (Week 16) primary analysis will occur once all patients have reached the Day 169 
(Week 24) visit (or earlier in the event of termination).   
To enable Placebo patients and those patients randomised to the KY1005 62.5 mg Q4W, 
125 mg and 250mg Q4W treatment arms to receive KY1005 at a dose expected to elicit a 
meaningful clinical response (based on prior clinical evidence), patients who do not achieve 
≥ EASI 75 or IGA 0/1 at Day 169 (Week 24) will be invited to enrol in the LTE study where 
they will receive KY1005.  
In those patients who achieve ≥ EASI 75 or who attain IGA 0/1 at Day 169 (Week 24), a 
randomisation will occur pre-dose at Day 169 (Week 24) and patients will enter the second 
study period.  This will occur irrespective of whichever dose group the patient was randomised 
to at Baseline including Placebo. Patients will be randomised in a 3:1 manner to be withdrawn 
from therapy or to continue their pre-Week 24 dose/interval. To maintain the blind, those 
patients randomised to the Withdrawal arm will receive Placebo Q4W.  Those patients who are 
re-randomised at Day 169 (Week 24) who lose their clinical response will be offered the 
opportunity to be retreated with KY1005 in the LTE study.  Loss of clinical response is defined 
as the first instance of <EASI 50 during the second study period and where rescue therapy is 
no longer permitted as per Section 5.3.4.  If loss of clinical response from Day 197 (Week 28) 
occurs, Investigators will be able to choose to discontinue the patient from KY1005-CT05 
(DRI17366) or to progress to the LTE study.  
 
 
 
 
 
 
 
  Where patients prematurely withdraw from 
the KY1005-CT05 (DRI17366) study and enter the LTE study, an early termination visit must 
be completed as per the Schedule of Assessments before enrolment in the LTE study. 
At Day 365 (Week 52), patients who have completed the post-Week 24 period and have not 
experienced loss of clinical response will have an additional 112 days’ safety follow-up up to 
Day 477 (Week 68) and then be discharged from the study.  The last dose will be given no later 
than Day 337 (Week 48) and as such safety follow-up will be 140 days following last dose of 
IMP. If during safety follow-up or after the end of study this cohort of patient’s experience 
worsening of their AD, and in the investigator’s opinion re-treatment with KY1005 is 
considered appropriate, they may be considered for enrolment in the LTE (subject to meeting 
inclusion/exclusion criteria). 
  
 
 
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The overall study design is presented in Figure 3-1. 
3.2 
Study Duration  
The duration of the study will be up to 28 days for screening and then up to approximately 
Day 477 (Week 68) (to Day 365 [Week 52] plus 112 days safety follow-up, 
 
 for all 
patients unless enrolled into the LTE study at Day 169 (Week 24) or due to loss of clinical 
response at or after Day 197 (Week 28).  The last dose will be given no later than Day 337 
(Week 48).    
3.2.1 Study flow  
The overall study design is presented in Figure 3-1. 
 
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Figure 3-1: 
Overall StudyDesign 
 
AD=atopic dermatitis; IMP=investigational medicinal product; EP=endpoint; EASI=eczema area and severity index; IGA= investigator global assessment; LTE=long-term extension; Q4W=every 
4 weeks; NA=not applicable. 
a 
On Day 169 (Week 24), patients are re-randomised prior to IMP administration on the basis of their Day 169 (Week 24) response. 
b 
Patients initially enrolled at Baseline into the Placebo, 62.5 mg, 125 mg and 250 mg KY1005 treatment arms who do not achieve ≥ EASI 75 or IGA0/1 at Day 169 (Week 24) will have the 
opportunity to receive KY1005 Q4W from Day 169 (Week 24) by enrolling in a long-term extension (LTE) study (LTS17367 LTE).  Participation in the LTE is subject to meeting the 
inclusion/exclusion criteria. Any patient who in the Investigator’s opinion should not be enrolled into the LTE, or where the patient declines further participation will have an additional 
112 days safety follow-up from Day 141 (Week 20) and then be discharged from the study. 
c 
Patients who achieve ≥ EASI 75 or who attain IGA0/1 at Day 169 (Week 24), irrespective of their Baseline group will be randomised 3:1 to either enter a maintenance withdrawal phase or 
continue on their pre-Week 24 dose/interval.  
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d 
If loss of response from Day 197 (Week 28) occurs between visits and retreatment with KY1005 is considered appropriate, patients will be permitted to move to the LTE (subject to meeting 
the inclusion/exclusion criteria for the LTE). Loss of clinical response is defined as < EASI 50 during the second study period and where rescue therapy is no longer permitted as per 
Section 5.3.4. Patients who in the Investigator’s opinion should not be enrolled into the LTE, or where the patient declines further participation, will enter safety follow-up. 
e    Patients who are responders at Day 169 (Week 24) and complete the second study period to Day 365 (Week 52) without loss of clinical response will enter safety follow-up. If during safety 
follow-up or after end of study the patients experience worsening of their AD, and in the investigator’s opinion re-treatment with KY1005 is considered appropriate, they may be considered 
for enrolment in the LTE (subject to meeting inclusion/exclusion criteria).  
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3.3 
Timing of Interim Analysis and Design Adaptations  
An interim analysis will be planned when approximately 
 participants in each arm complete 
the Day 113 (Week 16) assessments. The purpose of the interim analysis would be to obtain 
early information for planning the phase 3 program. No study conduct will be modified based 
on interim analysis results. 
The interim analysis will evaluate the percentage change in EASI from baseline to Day 113 
(Week 16) and proportions of participants with EASI 75 at Day 113 (Week 16), as well as the 
other available data as needed. Details will be documented in the statistical analysis plan (SAP). 
3.4 
Definition of End of Study  
The EOS is defined as the last patient undergoing the last visit of the study.  This will either 
be: 
• Day 169 (Week 24) (or earlier termination) for those patients who do not achieve 
≥ EASI 75 or IGA 0/1 at Day 169 (Week 24), and are subsequently enrolled in the LTE;  
Or 
• Day 281 (Week 40) (or earlier termination) for those patients who do not achieve 
≥ EASI 75 or IGA 0/1 at Day 169 (Week 24), and are not enrolled in the LTE and have 
additional safety follow-up to a total of 140 days after the last dose of IMP;  
Or 
• Day 365 (Week 52) (or earlier termination) for those patients who achieve ≥ EASI 75 
or who attain IGA 0/1 at Day 169 (Week 24) and continue on either their pre-Week 24 
dose/interval or enter the withdrawal arm, experience loss of clinical response at or after 
Day 197 (Week 28) and are enrolled in the LTE. Those patients not enrolled in the LTE 
will have additional safety follow-up to a total of 140 days after the last dose of IMP; 
Or 
• Day 477 (Week 68) (or earlier termination) for those patients who reach Day 365 
(Week 52), are still considered to be responding to study treatment, and are not enrolled 
in the LTE and have additional safety follow-up to a total of 140 days after the last dose 
of IMP. 
3.5 
Early Study Termination  
The study can be terminated at any time for any reason by the Sponsor (including approval or 
the favourable opinion is revoked, in the event of a negative change in the benefit/risk ratio 
when the necessary adjustment to the maximum sum insured is not possible; failure to enrol; 
futility; safety decision etc).  If the trial is suspended or terminated early, the Investigator will 
promptly inform the trial patients and should assure appropriate therapy and follow-up. 
No further IMP will be given to a patient if any study permanent discontinuation rules are met 
(see Section 9.1), including recommendation of the Independent Data Monitoring Committee 
(IDMC; Section 3.8).  If a patient withdraws from the study treatment early but consent is 
retained, study assessments may be continued until a) Day 169 (Week 24) for patients who 
withdraw from study treatment during the first study period and therefore are not eligible for 
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LTE, or b) until Day 365 (Week 52) or the end of the safety follow-up period in patients who 
withdraw from study treatment after Day 169 (Week 24). 
Unless patients continue in the LTE at Day 169 (Week 24) or due to loss of clinical response 
at or after Day 197 (Week 28), a safety follow-up for 140 days after the last dose of IMP will 
be required. 
In addition, the Investigator may withhold further IMP from a patient if they report 
moderate-or-severe (regardless of seriousness) adverse reactions which are attributed to the 
IMP.  There will be no obligation to unblind treatment allocation in making this decision. 
The Sponsor may discontinue the entire study at any time based on information received during 
the running of the study that demonstrates an unexpected risk or absence of benefit to patients.  
This may for example follow the request of the IDMC or where additional information emerges 
either during the study or from other sources (eg, literature or Health Authorities).   
If the study is discontinued, where patients withdraw early or where IMP has been discontinued 
by the Investigator, patients will be required to be followed-up for a minimum of 140 days for 
safety evaluation. 
Further details of IMP discontinuation are provided in Section 9.1. 
3.6 
Randomisation  
The Investigator must follow the study randomisation procedures when assigning patients to 
treatment within the study. 
The patient randomisation list will be generated by PPD using Statistical Analysis System 
(SAS®). 
All patients who have completed all Screening assessments and are confirmed as eligible by 
the Investigator will be randomised to treatment at Baseline. In cases where screen failure 
occurs due to a laboratory abnormality and is due to reasons expected to change at re-screening 
and based upon the Investigator’s clinical judgment, the patient may be re-screened one time 
for this study following notification to the Sponsor. Randomisation may be performed up to 
24 hours prior to the first administration of KY1005 if all inclusion/exclusion criteria have been 
satisfied. Each of the 5 treatment regimens (see Table 5-1) will comprise approximately 
70 patients (based on 30% drop out rate to Day 169 [Week 24], it is assumed that 49 patients 
will complete the study) who will be allocated to treatment with KY1005 or Placebo in an equal 
(1:1:1:1:1) ratio.   
Patients will be centrally randomised. Once confirmed as eligible for the study, patients will 
be allocated a randomisation number using an IRT system, corresponding to the next available 
randomised treatment, in a consecutive order starting with the lowest number. 
The randomisation will be stratified by disease severity (moderate/severe) and region. 
Further randomisation will occur at Day 169 (Week 24) in those patients who achieve 
≥ EASI 75 or who attain IGA 0/1.  Patients will be randomised in a 3:1 ratio to either enter a 
withdrawal cohort (receiving Placebo Q4W) or to remain on their pre-Week 24 dose/interval. 
This Day 169 (Week 24) randomisation will be stratified by IGA response (IGA 0/1 or IGA 2, 
3, 4). 
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3.7 
Blinding  
The study is double-blind. All patients, the Investigators and their study teams, the Sponsor 
(with exception of Sponsor Chemistry and Manufacturing Controls [CMC] Clinical Supplies 
Manager), Clinical Contract Research Organisation (CRO) (with the exception of the 
unblinded statistician(s), PPD Drug Supply Manager and IRT team), clinical laboratories 
(except those responsible for drug concentration analysis) and the IDMC will be blinded to 
treatment regimen until Day 169 (Week 24) has been completed for all patients and the 
database has been locked for analysis for the Day 169 (Week 24) data. IDMC members can 
have access to unblinded data sooner than the mentioned timepoint if that is necessary to 
perform data monitoring activities, and for safety purposes. Thereafter, the study data up to 
Day 169 (Week 24) will be unblinded to everyone except the study site and patients.  
Re-randomisation from Day 169 (Week 24) will not be unblinded to the team (except for those 
team members listed above). 
Study sites and patients will not be unblinded at any stage until after the final Data Base Lock. 
If deemed necessary by the IDMC, PPD will select an unblinded statistician among its 
statisticians.   
The work of PPD unblinded staff in support of the IDMC will be performed on an unblinded 
portal with access to unblinded personnel only. 
PPD will generate the trial treatment randomisation codes and provide these to the IRT for 
inclusion in the IRT system.  Randomisation codes will be controlled in the IRT system and 
procedures for breaking the codes in an emergency will be made available to relevant members 
of study site staff, the PPD Medical Monitor and the Sponsor Study Responsible medical 
Officer.  
At the assay institutions charged for ADA and PK measurements, samples will be analysed 
prior to database lock leading to unblinding of responsible bioanalysts. Bioanalysts are 
excluded from the Operation’s Team and results will not be communicated to the sites during 
the study. 
Following written confirmation of database lock, assignment of patients to the analysis 
populations and finalisation of the study SAP, the study will be unblinded.  The date, time, 
signature and printed name of the persons responsible for database lock, for the assignment of 
patients to the analysis populations and for treatment code-break (unblinding) will be recorded 
in order to verify that unblinding occurred in the correct sequence. 
For procedures to unblind an individual patient treatment in an emergency, see Section 8.2.1. 
Following database lock, the randomisation codes will be made available to all members of 
Sponsor and CRO staff as required.  Randomisation codes will be made available to site staff 
once all patients have completed the study and the database has been locked. 
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3.8 
Independent Data Monitoring Committee  
An IDMC with members independent from the Sponsor and the investigators is implemented 
to make appropriate recommendations on the conduct of the clinical trial to ensure the 
protection and the safety of the enrolled patients on the study.  The IDMC reviews and analyses, 
on a regular basis, safety and, if requested, efficacy data throughout the study. Blinded data 
will primarily form the basis for the IDMCs review. Unblinded data will be available alongside 
blinded data at the request of the IDMC. Formal data review meetings will be conducted 
approximately every 2 months to evaluate safety and efficacy data (frequency may need to be 
reviewed depending on recruitment) and are projected to begin once 10% of participants have 
received the first dose of IMP or 3 months after first patient dosed, whichever occurs first.  
A detailed IDMC charter will be written to outline the working procedures and duties of the 
IDMC in detail.  The data to be considered by the IDMC, the process for quality control of 
reports and data, and the documentation of decisions will be described in detail in the mutually 
agreed charter prior to the study start.  The primary responsibility of the IDMC will be to protect 
the safety of the study patients and will make recommendations to the Sponsor regarding the 
ongoing conduct of the study.  The IDMC may make recommendations to stop the study, 
continue the study with changes or continue without changes. For example, the IDMC may 
make a recommendation to terminate a specific dose level, so that if a dose level is not tolerated 
then no further patients receive a dose that is not safe. 
4 
STUDY POPULATION  
Adult patients with moderate-to-severe AD who have a documented history, within 6 months 
prior to Baseline, of either inadequate response or inadvisability of topical treatments.  
4.1 
Number of Patients  
Up to 350 patients (approximately 70 patients per treatment arm at Baseline) will be 
randomised. 
4.2 
Inclusion Criteria  
Patients must fulfil all the following inclusion criteria for entry into the study: 
1. Adults (18 to <75 years of age) with AD as defined by the American Academy of 
Dermatology Consensus Criteria [Eichenfield et al., 2014] for 1 year or longer at Baseline 
(Day 1; prior to first administration of IMP). For United Kingdom, see Section 17.15.2 
(Appendix 15). 
2. EASI of 12 or higher at the Screening Visit and 16 or higher at Baseline. 
3. IGA of 3 or 4 at Baseline. 
4. AD involvement of 10% or more of body surface area (BSA) at Baseline. 
5. Baseline worst/maximum pruritus NRS of ≥4. The baseline weekly average of daily 
worst/maximum pruritus NRS will be calculated from the 7 consecutive days immediately 
preceding the Baseline visit.  A minimum of 4 daily scores out of the 7 will be required.  
6. Documented history, within 6 months prior to Baseline, of either inadequate response or 
inadvisability of topical treatments. 
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a) Acceptable documentation includes contemporaneous chart notes that record 
TCS/TCI prescription and treatment outcome, or Investigator documentation 
based on communication with the patient’s treating physician. 
b) Failure to achieve and maintain remission or low disease activity (eg, IGA 0, 
clear skin to 2, mild disease) despite treatment with TCS of medium to high 
potency (± topical calcineurin inhibitor as appropriate), applied daily for at least 
28 days or for the maximum duration recommended by the product prescribing 
information (eg, 14 days for super-potent TCS), whichever was shorter. 
NOTE: Patients who failed systemic therapies intended to treat AD within 
6 months preceding screening, such as cyclosporine, methotrexate, azathioprine, 
and mycophenolate will be also considered as surrogate for having inadequate 
response to topical therapy. Washout of prior systemic medications must be 
completed as per the protocol requirements.  
c) Important side effects or safety risks defined as those that outweigh the potential 
treatment benefits including (but not limited to) hypersensitivity reactions, 
significant skin atrophy, treatment intolerance and adverse systemic effects, as 
assessed by the investigator or treating physician. 
7. Must have applied a stable dose of topical bland emollient (simple moisturiser, no additives 
[eg, urea]) at least twice daily for a minimum of 7 consecutive days before Baseline. 
8. Able to complete patient questionnaires, including collection of NRS (pruritus) on each of 
the 7 days prior to Baseline.  For patients who do not have at least 4 daily scores reported 
during the 7 days immediately preceding the planned randomisation date, randomisation 
should be postponed until this requirement is met, but without exceeding the 28-day 
maximum duration for screening. 
9. Able and willing to comply with requested study visits/telephone visits and procedures. 
10. Able and willing to provide written informed consent. This document must also actually be 
presented at the time of inclusion. 
11. For patients who decide to join the biopsy sub-study at sites selected for skin biopsy 
collection, be able and willing to provide skin biopsies at required timepoints. 
4.3 
Exclusion Criteria  
Patients fulfilling any of the following exclusion criteria will be excluded from the study: 
1. Treatment with any of the following prior to first IMP administration (Baseline): 
• Systemic corticosteroids, and systemic calcineurin inhibitors (tacrolimus and 
cyclosporin) 
; 
• Leukotriene inhibitors 
; 
• Use of mycophenolate mofetil, azathioprine, methotrexate, cyclosporine, dapsone, 
intravenous immunoglobulin, Kineret (anakinra), Enbrel (etanercept), or any other 
immunosuppressant not mentioned in this exclusion criterion 
 
 
 
• Use of infliximab, adalimumab, golimumab, abatacept, tocilizumab, certolizumab, 
secukinumab, IFN-γ, and any other biologic or targeted-synthetic disease modifier drug 
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not mentioned in this exclusion criterion or in the exclusion criterion above, as well as 
plasmapheresis 
 
• Previous treatment with systemic janus kinase (JAK) inhibitors 
  
• Use of anti-CD20 drugs such as rituximab, ofatumumab, other long-acting biologics 
 
 
• Topical corticosteroids, tacrolimus or pimecrolimus, or topical phosphodiesterase-4 
(PDE4) inhibitor 
 
• Prescription or non-prescription moisturisers with additives (eg, urea, filaggrin) within 
 
• Phototherapy or allergen immunotherapy 
 
• Regular use (>2 visits/week) of a tanning booth/parlour 
 
• Dupilumab (aIL-4Rα) 
 
• Any prior use of any anti-OX40, anti-OX40L mAb including KY1005; 
• Investigational therapy for the treatment of AD or other conditions within 5 half-lives 
or the limit of PD effects or 12 weeks where the t1/2 is not known. 
2. Known history of or suspected significant current immunosuppression, including history 
of invasive opportunistic infections despite infection resolution or otherwise recurrent 
infections of abnormal frequency or prolonged duration. 
3. Weight <40 kg or >150 kg at Baseline. 
 
4. Treatment with a live (attenuated) immunisation within 12 weeks prior to Baseline; 
completion of required administrations of COVID-19 vaccine within 14 days prior to 
Baseline or within 14 days immediately prior to or following IMP administration. 
 
5. Men and women (of reproductive potential) unwilling to use birth control and women who 
are pregnant or breastfeeding (see Section 4.4 and Section 4.5). 
6. Any malignancies or history of malignancies prior to Baseline (except for non-melanoma 
skin cancer that has been excised and cured for more than 3 years prior to Baseline; in situ 
cervical carcinoma that has been excised and cured). 
 
 
7. Positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), 
hepatitis B core antibody (HBcAb) or hepatitis C antibody at the Screening Visit. 
 
8. History (within last 2 years prior to Baseline) of prescription drug or substance abuse, 
including alcohol, considered significant by the Investigator. 
9. Current or any past history of tuberculosis or non-tuberculous mycobacterial infections 
(including a positive QuantiFERON®-Tuberculosis (TB) Gold blood test at the Screening 
Visit). 
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10. Elective surgery planned to be scheduled for any time in the period from Screening up to 
12 weeks following the last dose of IMP that in the investigator’s opinion would impact the 
conduct of the trial. 
11. Anticipated initiation of prohibited medications from Screening up to 12 weeks following 
the last dose of IMP. 
12. Severe concomitant illness that would in the Investigator’s opinion inhibit the patient’s 
participation in the study, including for example, but not limited to, hypertension, renal 
disease, neurological conditions, heart failure and pulmonary disease. 
13. Skin co-morbidity that would adversely affect the ability to undertake AD assessments. 
14. Any medical or psychiatric condition which, in the opinion of the Investigator may present 
an unreasonable risk to the study patient as a result of his/her participation in this clinical 
study, may make patient’s participation unreliable, or may interfere with study assessments. 
15. Any active or chronic infection requiring systemic treatment within 2 weeks prior to 
Baseline (1 week in the event of superficial skin infections). 
16. Laboratory values at the Screening Visit: 
• 
 
• 
 
 
 
 
• In the Investigator’s opinion, any additional clinically significant laboratory results 
from the clinical chemistry, haematology or urinalysis tests at the Screening Visit. 
17. In the Investigator’s opinion, any significant abnormality on 12-lead electrocardiogram 
(ECG) at the Screening Visit. 
18. History of or known or suspected hypersensitivity to KY1005 or the matching placebo 
formulation, or excipients used in the presentation of KY1005 or placebo, or in preparation 
for administration. History of or known or suspected severe hypersensitivity reactions to 
other mAbs and/or their excipients.  
19. Patients for whom coercion by either the Investigator or the Sponsor (eg, employee, student 
or persons who have been placed in an institution on the basis of an official or court order) 
cannot be discounted. (No patients will be included who are related to, or in a relationship 
with, or employed by the Investigator, the Sponsor or any organisations contracted on 
behalf of the Sponsor in the design, setting up or running of the study). 
20. Concurrent participation in any other clinical study, including non-interventional studies. 
4.4 
Reproductive Status  
Women of childbearing potential (WOCBP) are permitted to participate in the study provided 
adequate birth control measures are taken during the whole length of the study, including the 
post-dose safety follow-up period (see Section 4.5).  A woman is considered WOCBP (fertile) 
from the time of menarche until becoming postmenopausal (see below) unless permanently 
sterile (see below). 
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• A postmenopausal state is defined as the period of time after a woman has experienced 
no menses for 12 consecutive months without an alternative medical cause. 
• A high follicle-stimulating hormone (FSH) level in the postmenopausal range should 
be used to confirm a postmenopausal state in women not using hormonal contraception 
or hormonal replacement therapy. However, in the absence of 12 months of 
amenorrhea, confirmation with more than one FSH measurement is required. 
Permanent sterilization methods include: 
• Documented hysterectomy; 
• Documented bilateral salpingectomy; 
• Documented bilateral oophorectomy; 
• For individuals with permanent infertility due to an alternate medical cause other than 
the above, (eg, Mullerian agenesis, androgen insensitivity, gonadal dysgenesis), 
investigator discretion should be applied to determining study entry eligibility. 
Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview. 
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before first administration of IMP, additional evaluation should be considered. 
The Investigator must consult the Medical Monitor if there is doubt whether a patient is of 
childbearing potential.  
See Section 4.5 for adequate birth control (contraception and sterilisation) for WOCBP.   
Males participating in the study with partners of childbearing potential must ensure adequate 
birth control measures are taken from Baseline and for a period after they last receive IMP (see 
Section 4.5). 
The Investigator must consult the Medical Monitor if there is doubt whether a patient qualifies 
as undertaking adequate birth control. 
4.5 
Contraceptive Precautions  
• WOCBP and males with partners of childbearing potential (see Section 4.4) must 
ensure adequate birth control precautions are undertaken from Baseline until 5 months 
after Day 337 (Week 48) or the early termination visit (if prior to Day 337) unless 
entering the LTE. WOCBP should agree to use a contraceptive method that is highly 
effective (with a failure rate of <1% per year), as described in Section 17.10 
(Appendix 10) Contraception and Barrier Guidance. 
• Adequate contraception includes the combined oral contraceptive pill (if judged by the 
Investigator to be taken regularly), intra-uterine devices and contraceptive implants.  
Periodic abstinence, single barrier methods of contraception and progesterone-only 
pills not associated with inhibition of ovulation, even in those aged over 40 years are 
examples of inadequate contraception. See Section 17.10 (Appendix 10) for further 
detail. 
• For both WOCBP and males with a partner of childbearing potential adequate 
sterilisation includes vasectomy and abdominal (including laparoscopic) and 
hysteroscopic female sterilisation. 
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• Male patients should be advised of the benefit for a female partner to use a highly 
effective method of contraception (as described in Section 17.10 (Appendix 10) 
Contraceptive and Barrier Guidance) as a condom may break or leak when having 
sexual intercourse with a woman of childbearing potential (WOCBP) who is not 
currently pregnant. 
• Male patients with a pregnant partner must undertake some barrier protection, such as 
a condom until 5 months after Day 337 (Week 48) or the early termination visit (if prior 
to Day 337).   
• Female patients must not breastfeed until 5 months after Day 337 (Week 48) or the 
early termination visit (if prior to Day 337).   
• Patients must not donate or cryopreserve sperm/ova until 5 months after Day 337 
(Week 48) or the early termination visit (if prior to Day 337).  If male patients with a 
pregnant partner enter the LTE study, then barrier protection should be used as per the 
study protocol. 
The Investigator must consult the Medical Monitor if there is doubt whether a patient qualifies 
as undertaking adequate birth control. 
4.6 
Screen Failures  
Screen failures are defined as patients who consent to participate in the clinical study but are 
not subsequently randomised.  A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure patients to meet the Consolidated Standards of Reporting 
Trials (CONSORT) publishing requirements and to respond to queries from regulatory 
authorities. Minimal information includes demography, screen failure reasons, eligibility 
criteria, and any SAE. 
In cases where original screen failure was as a result of a laboratory abnormality due to reasons 
expected to change at re-screening and based upon the Investigator’s clinical judgment, the 
patient may be re-screened one time for this study after notification of the Sponsor.  A different 
patient identification number will be issued.  There is no requirement for a waiting period 
between the screen-failure and the re-screening.  Patients that are re-screened will be required 
to sign a new consent form. 
4.7 
Strategies for Recruitment and Retention  
Recruitment for this study will be competitive.  
Patients may be selected from the participating sites patient databases (if applicable) in 
accordance with the study eligibility criteria (see Section 4.2 and Section 4.3).  Patients may 
be contacted by telephone, e-mail or in writing if applicable.  Advertisements may be used to 
aid patient recruitment; however, prior to implementation, all advertising and marketing 
material available to patients must be submitted to the Independent Ethics Committee 
(IEC)/Independent Review Board (IRB) for approval (see Section 12.1).  After provision of 
the Informed Consent Form (ICF), patients will be screened at the respective site. 
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5 
TREATMENT OF PATIENTS  
5.1 
Presentation of Investigational Medicinal Product(s)  
The IMPs are KY1005 (SAR445229), hereby known as KY1005, or matching Placebo. 
5.1.1 KY1005  
 
  
  
5.1.2 Matching Placebo  
 
 
 
5.1.3 Non-investigational Medicinal Products/Auxiliary Medicinal Products/ Ancillary 
Treatments  
There will be no Non-investigational Medicinal Products, Auxiliary Medicinal Products or 
Ancillary Treatments used in this study. 
5.2 
Study Treatment Administration  
All dosages prescribed and dispensed to patients and all dose changes during the study must be 
recorded in the patient’s hospital files and on the electronic case report form (eCRF). 
5.2.1 Treatment Regimen  
Patients may receive study treatment every 4 weeks from Day 1 to Day 337 (Week 48) 
according to the scheme in Figure 3-1.   
All study treatment regimens are presented in Table 5-1. Randomisation will occur 
pre-injection on Day 1, with re-randomisation pre-injection on Day 169 (Week 24) should the 
patient achieved an ≥ EASI 75 or attain IGA 0/1 (see Section 3.6). 
From Baseline up to Day 169 (Week 24) IMP will be administered at the following dose and 
intervals:  
• 500 mg loading at Baseline (
) followed 4 weeks later 
with 250 mg Q4W as 
 injection; 
Or  
• 250 mg (
) plus 
 Placebo at Baseline followed 4 weeks 
later with 250 mg Q4W 
 
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Or  
• 125 mg (as 
 injection) plus 
 Placebo at Baseline followed 4 weeks 
later with 125 mg Q4W as 
 
Or  
• 62.5 mg (
) plus 
 Placebo at Baseline followed 4 weeks 
later with 62.5 mg Q4W as 
 
Or 
• Placebo given 
 at Baseline followed 4 weeks later with 
 
placebo (0 mg).  
At Baseline, those patients not receiving a KY1005 loading dose will receive both KY1005 
and Placebo to maintain the study blind. 
• From Day 169 (Week 24) to Day 365 (Week 52) in patients who achieve ≥ EASI 75 
or who attain IGA 0/1 at Day 169 (Week 24) will be randomised 3:1 to either 
Withdrawal or will continue to receive their pre-Week 24 dosing. 
• Patients randomised to Withdrawal will receive Placebo Q4W.  Those patients not 
randomised to Withdrawal will continue to receive their pre-Week 24 dose/interval. 
• Re-randomisation from Day 169 (Week 24) will not be uncoded to the team, study 
sites or patients until after the final Data Base Lock.  Those patients who do not 
achieve ≥ EASI 75 or IGA 0/1 at Day 169 (Week 24) will have the possibility to enrol 
into the LTE where they will receive KY1005.  
Table 5-1 
TreatmentRegimes 
Arm 
Day 1  
Day 29 (Week 4) to Day 169 
(Week 24) 
Day 169 (Week 24) to Day 365 
(Week 52) in patients who 
achieve ≥ EASI 75 or who attain 
IGA 0/1at Day 169 (Week 24) 
IMP 
Dose (mg) 
IMP 
Dose 
(mg) 
Frequency 
IMP 
Dose 
(mg) 
Frequency 
1 
KY1005 
500 mg  
(
) 
KY1005 
250 mg 
Q4W 
KY1005 
250 mg 
Q4W or 
PBO 
0 
Q4W 
2 
KY1005 
250 mg plus 
PBO loading 
KY1005 
250 mg 
Q4W 
KY1005 
250 mg 
Q4W or 
PBO 
0 
Q4W 
3 
KY1005 
125 mg plus 
PBO loading 
KY1005 
125 mg 
Q4W 
KY1005 
125 mg 
Q4W or 
PBO 
0 
Q4W 
4 
KY1005 
62.5 mg plus 
PBO loading 
KY1005 
62.5 mg 
Q4W 
KY1005 
62.5 mg 
Q4Wor 
PB0 
0 
Q4W 
5 
Placebo 
NA plus 
PBO loading 
Placebo 
NA 
Q4W 
PBO 
0 
Q4W or 
PBO 
0 
Q4W 
IMP=investigational medicinal product; PBO= Placebo; NA=not applicable; Q4W=every 4 weeks.  
All doses of KY1005 and Placebo will be administered 
.  At Baseline 
, one injection at each side of the region to be injected, to 
maintain the integrity of the blind. 
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5.2.2 Administration of IMP  
 
  KY1005 or matching Placebo will be administered as a SC 
injection to the abdomen.  If IMP administration to the abdomen is not possible due to the 
extent of skin involvement, the outer thigh may be selected.  However, the same anatomical 
region must be used for IMP administration throughout study participation and documented 
in the eCRF.  IMP should not be administered at the site of a recent injection or in areas which 
in the Investigator's opinion are not suitable eg, tender, bruised, red or hard.  Details of 
administration will be documented in the study specific Pharmacy Manual. 
5.2.3 Precautions for Administration  
Only fully trained and qualified study site personnel should administer SC injections.  The 
injection must be administered at a constant pressure.   
5.2.4 Monitoring During Administration  
After treatment administration, check for local skin reactions will be performed.  Patients will 
be monitored with assessments of vital signs at the timepoints outlined in the Schedule of 
Assessments (Section 6.1, Table 6-1, Table 6-2, Table 6-3, Table 6-4). 
5.2.5 Treatment Duration  
All patients treated with KY1005 or matching Placebo will be randomised and begin study 
treatment on Day 1. Patients will initially receive SC injections of IMP Q4W to Day 169 
(Week 24).  The Day 113 (Week 16) primary analysis will occur once all patients have reached 
the Day 169 (Week 24) visit (or earlier in the event of termination).   
Those patients in the 500 mg loading with 250 mg Q4W treatment arm will 
 
 commence 250 mg Q4W on Day 29 (Week 4). 
 
 
 
 
As outlined previously, those patients who achieve ≥ EASI 75 or who attain IGA 0/1 at 
Day 169 (Week 24) will be re-randomised pre-injection at Day 169 (Week 24) to either the 
Withdrawal arm (and receive Placebo Q4W) or remain on their pre-Week 24 dose for the 
second study period. 
The duration of treatment will therefore be up to Day 365 (Week 52), with last dose 
administered on Day 337 for those patients who achieve ≥ EASI 75 or who attain IGA 0/1 at 
Day 169 (Week 24), irrespective of whether response is maintained to Day 365 (Week 52) and 
they enter safety follow-up or they experience loss of clinical response at or after Day 197 
(Week 28) and enter the LTE. 
Those patients who do not achieve ≥ EASI 75 or IGA 0/1 at Day 169 (Week 24) will have the 
possibility to enter the LTE at Day 169. 
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5.2.6 Guidance for Overdose  
Overdose is defined 
 In the unlikely event that an overdose of KY1005 is administered, the patient will 
be observed and treated symptomatically. The circumstances (ie, accidental or intentional) 
should be clearly specified in the verbatim and symptoms, if any, entered on separate AE forms.  
 
  If severe adverse 
reactions occur after an overdose of KY1005, then plasmapheresis (or infusion of albumin) to 
reduce the drug exposure may be considered. 
All instances of symptomatic overdose, both serious and non-serious, will be reported to the 
Sponsor (or designee) as AESIs within 24 hours of learning of the event (see Section 8.1.3). 
5.2.7 Dose Modification  
 
 
 
 
5.3 
Concomitant Medication and Dietary Supplements  
Any treatment (including nutritional supplements) or procedure administered from the time of 
consent to the EOS Visit is considered concomitant and will be recorded in the eCRF.  This 
includes permitted medications ongoing at the time of consent.  Concomitant medications and 
procedures are allowed, except for those listed in Section 5.3.2. 
Prior medications will not be recorded in the eCRF, except for prior use of systemic 
corticosteroids, systemic calcineurin inhibitors, and systemic treatment for AD or other 
indications with an immunosuppressive/immunomodulating substance including (but not 
limited to) dupilumab, JAKi and aIL13 mABs, with reason for discontinuation recorded where 
available.  
5.3.1 Permitted Concomitant Therapy  
Other than the prohibited medications listed in Section 5.3.2, treatment with concomitant 
medication is permitted during the study.  This includes treatment with oral contraceptives, 
nasal, otological, and inhaled corticosteroids for any duration, and oral or topical antibiotics 
for up to 2 weeks for AD-associated superficial skin infections. 
5.3.2 Prohibited Concomitant Therapy (and Procedures)  
Treatment with the following concomitant medications is prohibited during the study: 
• Dupilumab. 
• Topical or systemic tacrolimus and pimecrolimus (exceptions might apply, see 
Section 4.3 and Section 5.3.4, Section 5.3.5). 
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• Topical or systemic corticosteroids (exceptions might apply, see Section 4.3 and 
Section 5.3.4). 
• Leukotriene inhibitors. 
• Allergen immunotherapy. 
• Systemic treatment with an immunosuppressive/immunomodulating substance 
(including, but not limited to aIL13 mABs, JAKi, aOX40 mAbs, cyclosporine, 
mycophenolate-mofetil, IFN-γ, azathioprine, methotrexate, or biologics). 
• Treatment with a live (attenuated) immunisation (Note: immunisation with inactivated 
seasonal influenza vaccine and inactivated adenovirus COVID-19 vaccines is permitted 
(see Section 5.3.3).  COVID-19 vaccines should not be administered within 14 days 
prior to Baseline or within 14 days immediately prior to, or following, IMP 
administration. 
The following concomitant procedures are prohibited during study participation: 
• Elective surgical procedures. 
• Ultraviolet (UV) procedures (phototherapy [narrowband UVB, UVB, UVA1 
orpsoralen UVA]). 
• Tanning in a booth/parlour. 
• More than 2 bleach baths per week. 
5.3.3 COVID-19 Vaccination and Other Vaccines 
To allow for an optimal immune response as well as protection against COVID-19, it is 
strongly recommended that patients complete their COVID-19 vaccination schedule (per local 
requirements) a minimum of 14 days prior to receiving the first dose of IMP.
 
 
The safety profile and effectiveness of COVID-19 vaccines on people with compromised 
immune systems or therapies (such as KY1005) that modify or that suppress their immune 
response is not yet established. 
While vaccination with an approved COVID-19 vaccine (including booster dose) is widely 
recommended (AAD COVID-19 Vaccine Administration Guidance, 2021; EADV Task Force 
Covid Vaccination Advice, 2021), a patient’s decision to have a COVID-19 vaccination during 
the study should only be made after discussing with his/her physician and the Investigator to 
assess the benefits/risks of receiving a COVID-19 vaccination during this study.  In this 
instance, if the vaccine is authorised, available, and recommended by the local regulatory 
health authority, it may be administered during the study and should be administered according 
to the label or local health authority recommendations.  The vaccine should not be administered 
within 14 days immediately prior to, or following, IMP administration. Details of the 
COVID-19 vaccine should be recorded in the eCRF. 
The impact of KY1005 on overall vaccination response, new and recall response, for both 
COVID19 and other vaccines, has not been tested to date in AD. 
 
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5.3.4 Rescue Therapy  
No AD rescue therapy is permitted in the first 14 days following randomisation. Any AD rescue 
therapy administration either topical or systemic during this period will result in permanent 
discontinuation from the IMP. Bland emollients are not considered rescue therapy for AD, and 
should be maintained during this period as per protocol. 
If medically unavoidable after Day 14 (ie, to control intolerable AD symptoms), rescue 
treatment for AD may be provided to study patients at the discretion of the Investigator.  For 
the purpose of efficacy analysis, patients who receive rescue topical treatment during this study 
treatment period will be considered treatment failures but can continue study treatment if the 
rescue treatment consists of topical medications only.   
If topical corticosteroids (TCS) are needed, it is recommended that the investigator start with 
the least potent TCS for the face (eg, hydrocortisone 2.5% cream/ointment) and moderately 
potent TCS for the body (eg, triamcinolone acetonide 0.1% cream/ointment), applied up to 
twice daily. Where the use of moderate potency topical corticosteroids (TCS) are not 
considered clinically appropriate, low potency TCS or topical calcineurin inhibitors can be 
used, however, these should be reserved for problem areas only. Topical PDE4 inhibitors are 
also permitted.  
Participants should use topical rescue therapy only for as long as necessary to control 
problem areas on a maximum of 2 occasions during study participation, and for a 
maximum of 2 consecutive weeks on each occasion.  
If a patient receives rescue treatment with high potency TCS, systemic corticosteroids or 
non-steroidal 
systemic 
immunosuppressive 
drugs 
(cyclosporine, 
methotrexate, 
mycophenolate mofetil, azathioprine, etc) or receives more than 2 episodes of topical 
rescue treatment, study treatment will be immediately discontinued.   
Investigators should conduct efficacy and safety assessments immediately before 
administering any rescue treatment.  An unscheduled visit may be required.   
All patients should complete the schedule of study visits and assessments whether or not they 
complete study treatment and whether or not they receive rescue treatment for AD.  If a patient 
has IMP permanently discontinued due to the taking of systemic therapy rescue but consent is 
retained, study assessments may be continued until Day 169 (Week 24) for patients who 
discontinue IMP in the first study period, or until Day 365 (Week 52) or the end of the safety 
follow-up period (whichever is longer) in patients who discontinue IMP after Day 169 
(Week 24).   
5.3.5 Background Therapy  
Patients are required to apply a stable dose of a topical bland emollient (simple moisturiser) at 
least twice daily for a minimum of 7 consecutive days before the Baseline Visit (see 
Section 4.2) and to continue with the same emollient at the same dose twice daily throughout 
their participation in the study.   
To permit an adequate assessment of skin dryness, moisturisers should not be applied on area(s) 
of non-lesional skin, designated as such for assessment purposes, for at least 8 hours before 
each clinic visit. 
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Patients are permitted to use any simple bland prescription, over-the-counter or general 
purchase moisturiser providing it contains NO additives, such as corticosteroids or urea (even 
at low concentrations).  The type/brand of emollient will be recorded in the eCRF.  Prescription 
and non-prescription moisturisers with additives (eg, urea, filaggrin, niacinamide, ceramides, 
bisabolol) are not permitted within 2 weeks prior to first IMP administration (Baseline; see 
Section 4.3) or during the study. 
5.4 
Lifestyle Restrictions  
Patients must maintain a relatively constant level of exercise during study participation through 
to Day 365 (Week 52) and refrain from unusually strenuous physical activities to avoid a 
potentially confounding effect on safety assessments caused by exercise-related changes in 
serum enzymes of clinical importance (eg, creatine phosphokinase [CPK], lactate 
dehydrogenase, aspartate aminotransferase [AST], alanine aminotransferase [ALT]).  In 
addition, patients should avoid excessive alcohol intake and the use of drugs of abuse during 
the study.  
5.5 
Patient Numbering and Treatment Assignment  
Patients will be identified with unique patient numbers assigned by an IRT system at the time 
of screening.  This unique patient number will identify the patient in all study databases 
(eg, eCRF, central laboratory, etc) and will be linked to the patient’s name in an identification 
list retained in the Investigator Site File (ISF).  Patient numbers assigned by IRT will be 
retained regardless of whether the patient subsequently fulfils the eligibility criteria.  If a patient 
withdraws from the study the patient number will not be re-used. 
Patient eligibility will be established before IMP is allocated to individual patients by the IRT 
system.  
5.6 
Supply, Packaging, Labelling and Storage  
 
 
 
 
 
 
The KY1005 and Placebo will be provided by the Sponsor to the investigational sites in a 
blinded condition as kits in tamper-sealed cartons.  IMP kits will be packaged and labelled 
according to the randomisation list.  Each vial and each finished kit will be labelled in 
accordance with EudraLex, Volume 4 GMP Guidelines, Annex 13, IND and other local 
regulatory requirements.  Labels will be translated in local language as required.  Replacement 
supplies will be available at each site, in case of damage to the originally assigned kit.  The 
replacement kits will also be assigned to the patient via the IRT system. 
Procedures for breaking the codes in an emergency will be provided via the IRT system, to 
relevant members of study site staff and the PPD Medical Monitor.  This will be activated prior 
to or concurrent with receipt of the IMPs and will be described in the study specific Pharmacy 
Manual.  
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After release procedures have been completed in accordance with Sponsor or designee 
Standard Operating Procedures (SOPs), and as needed thereafter, IMPs will be shipped with 
temperature monitoring equipment to the responsible person at the investigational site in 
temperature-controlled shippers.  The responsible person will check the amount and condition 
of the IMP received and will acknowledge receipt in IRT. 
If the temperature monitoring device shows that shipment conditions have fallen outside the 
specified range, the site will take measures to prevent the IMPs being dispensed and contact 
the Sponsor as directed in the study specific Pharmacy Manual to discuss the potential 
implications and any action(s) that may be necessary. 
 
 
 
 
 
The responsible person at the investigational site will prepare blinded individual patient IMP 
doses using IMP kits assigned by the IRT system and in accordance with the instructions 
provided in the study specific Pharmacy or IRT Manuals.   
 
 
 
 
Records of the actual storage conditions during the period of the study must be maintained 
(eg, records of the date and time and initials of person checking, and the daily (weekday) 
temperatures of the area used for storage of study drug) and provided to the Sponsor for 
retention in the electronic Trial Master File (eTMF). 
5.7 
Procedures for Monitoring Patient Compliance  
The Investigator is responsible for the administration of the IMP.  The Study Monitor will 
assess compliance throughout the study by reviewing drug reconciliation/accountability 
records on a periodic basis as outlined in the monitoring plan and guidelines. 
Sites should also discuss study procedure compliance with the patients, as required.  
5.8 
Study Drug Accountability Records  
The Investigator is responsible for accountability of all used and unused IMP supplies at the 
site.  IMP must only be used for the purpose of the study in accordance with the protocol. 
IMP accountability will be recorded by the Investigator and filed in the ISF.  The IMP 
accountability details should be kept current and should contain the dates and quantities of drug 
received at site, kit number, patient number, date, time, and quantity of drug dispensed to each 
patient, and the name/initials of the authorised dispenser.  Any issues with the IMP 
administration (eg, spillage, blockage etc) must be recorded as per the study specific Pharmacy 
Manual. 
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All IMP accountability documents must be made available for inspection by the Study Monitor, 
Sponsor or Sponsor’s representatives and regulatory agency inspectors. 
At the end of the study all documents related to IMP lifecycle must be filed in the ISF and 
eTMF.  
Final IMP reconciliation must also be performed by the IMP distributers of stocks remaining 
at or returned to by the sites to all distribution centres.  The Sponsor or Sponsor’s 
representatives must be granted access on reasonable request to all distribution centres to check 
drug storage, dispensing procedures and accountability records. 
5.9 
Study Drug Destruction  
All IMP supplies including unused, partially used, or empty containers, will be retained at site 
prior to completion of accountability.  At the EOS, or as directed in writing by the Sponsor, 
and after final IMP reconciliation completed by study monitor, the Sponsor will give written 
approval for destruction of IMP locally or return to a central location for destruction. 
Local or institutional regulations may require immediate destruction of used study drug for 
safety reasons.  In these cases, it may be acceptable for the study site staff to destroy dispensed 
study drug prior to a monitoring inspection, if source document verification is performed on 
the remaining inventory and reconciled against the documentation of quality supplied, 
dispensed, returned, and destroyed.  Written authorisation must be obtained from the Sponsor 
prior to destruction. 
Proof of delivery, certificates of destruction and/or study drug return documentation will be 
filed in the eTMF. 
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6 
STUDY PROCEDURES  
6.1 
Study Schedule of Assessments  
The schedule of procedures and assessments during the study is summarised and presented in 
Table 6-1, Table 6-2 and Table 6-3 for all patients, plus Table 6-4 for patients who are not 
enrolled into the LTE and have additional safety follow-up. Where possible, the patient 
reported outcome (PRO) assessments completed at the study site are to be completed by 
patients prior to the completion of other study assessments and the administration of study 
drug. 
In general, and wherever possible, patients will be assessed at the approved study 
clinics/facilities. Section 17.14 (Appendix 14) details contingency procedures that are 
suggested for a regional or national emergency declared by a governmental agency that 
prevents access to the study site, to ensure the safety of the patients, to consider continuity of 
the clinical study conduct, protect trial integrity, and assist in maintaining compliance with 
GCP in Conduct of Clinical Trials Guidance. 
 
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Table 6-1: 
Schedule of Assessments Screening to Day 113(Week 16)  
 
Visit 
1 
2b 
3 
4 
5 
6a 
7a 
8a 
9a 
ET# 
Visit days 
-29 to -8 
-7 to 1 
1 
8 
15 
22 
29 
57 
85 
113 
- 
Visit weeks 
-4 to -1 
- 1 
0 
1 
2 
3 
4 
8 
12 
16 
- 
Visit window (days) 
0 
0 
0 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
- 
 
Screening 
Baseline 
Treatment 
 
Description 
Clinic 
Clinic 
Clinic 
Clinic 
Telephonem 
Clinic 
Clinic 
Clinic 
Clinic 
 Clinic 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
Concomitant medications - including 
emollients 
X 
 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
AEs (including SAEs) 
<=========================================================================> 
X 
Inclusion/exclusion criteria  
X 
 
X 
 
 
 
 
 
 
 
 
Physical examination  
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
Body weight and height (height at 
Screening only) 
X 
 
X 
 
 
 
 
 
 
X 
X 
Vital signsc 
X 
 
X 
 
 
 
X 
X 
X 
X 
X 
12-lead ECG 
X 
 
X 
 
 
 
 
X 
 
X 
X 
EASI 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
BSA 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
IGA 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
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Visit 
1 
2b 
3 
4 
5 
6a 
7a 
8a 
9a 
ET# 
Visit days 
-29 to -8 
-7 to 1 
1 
8 
15 
22 
29 
57 
85 
113 
- 
Visit weeks 
-4 to -1 
- 1 
0 
1 
2 
3 
4 
8 
12 
16 
- 
Visit window (days) 
0 
0 
0 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
- 
 
Screening 
Baseline 
Treatment 
 
Description 
Clinic 
Clinic 
Clinic 
Clinic 
Telephonem 
Clinic 
Clinic 
Clinic 
Clinic 
 Clinic 
SCORAD Indexl 
X 
 
X 
 
 
 
X 
X 
X 
X 
X 
DLQIl  
 
 
X 
 
X 
 
 
X 
 
X 
X 
ADCTl 
 
 
X 
 
 
 
 
 
 
X 
X 
HADSl 
 
 
X 
 
 
 
 
X 
 
X 
X 
Blood samples for virology (HIV, Hepatitis 
B and C) and TB (QuantiFERON®-TB Gold 
blood test)n 
X 
 
  
 
 
 
 
 
 
 
 
Safety tests (FBC, non-fasting biochemistry, 
electrolytes, urinalysis), FSH for 
post-menopausal women at Screening 
Xk 
 
X 
 
 
 
X 
X 
X 
X 
X 
Pregnancy test – females only (serum at 
Screening, urine thereafter)e 
X 
 
X 
 
 
 
X 
X 
X 
X 
X 
Blood samples for serum concentrations of 
KY1005 (PK)a 
 
 
Xa 
X 
X 
 
X 
X 
X 
X 
X 
Blood samples for serum concentrations of 
ADAsd 
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Visit 
1 
2b 
3 
4 
5 
6a 
7a 
8a 
9a 
ET# 
Visit days 
-29 to -8 
-7 to 1 
1 
8 
15 
22 
29 
57 
85 
113 
- 
Visit weeks 
-4 to -1 
- 1 
0 
1 
2 
3 
4 
8 
12 
16 
- 
Visit window (days) 
0 
0 
0 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
- 
 
Screening 
Baseline 
Treatment 
 
Description 
Clinic 
Clinic 
Clinic 
Clinic 
Telephonem 
Clinic 
Clinic 
Clinic 
Clinic 
 Clinic 
POEMl 
 
 
X 
 
 
 
X 
X 
X 
X 
X 
NRS (pruritus) – internet-enabled deviceg 
 
Xh 
X 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
Contact IRT 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Randomisationi 
 
 
X 
 
 
 
 
 
 
 
 
IMP administration and check of local 
skin reactionj, o 
 
 
X 
 
 
 
X 
X 
X 
X 
 
 
 
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ADA=anti-drug antibody; ADCT=atopic dermatitis control tool; AEs=adverse events; BSA=body surface area; DLQI=Dermatology Quality of Life Index; EASI=Eczema Area and Severity 
Index; ECG=electrocardiogram; FBC=full blood count; FSH=follicle-stimulating hormone; HADS= Hospital Anxiety and Depression Scale; HIV=human immunodeficiency virus; 
IgE=immunoglobulin E; IMP=Investigational Medicinal Product; NRS=Numerical Rating Scale; POEM=Patient Oriented Eczema Measure; PK=pharmacokinetics; PRO=patient reported 
outcome; SAE=serious adverse event; SCORAD=SCORing of Atopic Dermatitis; TB=tuberculosis; IGA= Investigator Global Assessment.  
# 
Early Termination could be done by the Investigator (see Section 3.4, Section 3.5 and Section 9). 
a On IMP administration days, all assessments, including taking blood samples, will be performed pre-injection unless stated otherwise. 
b Baseline assessments may be performed up to 24 hours prior to the first IMP injection (Day 1). 
c On IMP administration days up to and including Day 113 (Week 16) vital signs will be measured pre-injection and at 15-, 30- and 60-minutes post-injection. The tolerance on vital signs measurements after 
dosing is ±5 minutes.  
d 
 
   
e If urine pregnancy test is positive, a serum control must be done before IMP administration   
f 
 
 
g NRS (pruritus) will be recorded daily, ideally in the morning, based on the previous 24 hours, with worst (maximum) itch intensity recorded. 
h Patients will be asked to assess their worst itching due to atopic dermatitis over the last 7 days prior to Baseline on an NRS anchored by the terms “no itch” (0) and “worst itch imaginable” (10). 
i 
May be performed up to 24 hours prior to first injection as long as all inclusion/exclusion criteria are satisfied. 
j 
   
k Screening laboratory assessments may be repeated a maximum of once where initial results are in the Investigator’s opinion, clinically significant 
l 
Where possible, the PRO assessments completed at the study site are to be completed by patients prior to the completion of other study assessments and the administration of IMP. 
m A telephone visit is defined as a videoconference, video call or telephone call. 
n 
 
o 
  
 
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Table 6-2: 
Schedule of Assessments - Day 120 (Week 17) to Day 169 (Week 24) 
 
Visit 
10 
11a 
12 
13 
14 
15a 
ET# 
Visit days 
120 
141 
148 
155 
162 
169 
- 
Visit weeks 
17 
20 
21 
22 
23 
24k 
- 
Visit window (days) 
±1 
±3 
±1 
±1 
±1 
±3 
- 
 
Treatment 
- 
Description 
Clinic 
Clinic 
Telephoneh 
Telephoneh 
Telephoneh 
Clinic 
 Clinic 
Concomitant medications – including emollients 
X 
X 
X 
X 
X 
X 
X 
AEs (including SAEs) 
<=========================================================================> 
X 
Physical examination  
 
 
 
 
 
 
X 
Vital signsb 
 
X 
 
 
 
X 
X 
12-lead ECG 
 
 
 
 
 
X 
X 
EASI 
 
X 
 
 
 
X 
X 
BSA 
 
X 
 
 
 
X 
X 
IGA 
 
X 
 
 
 
X 
X 
SCORAD Indexg 
 
X 
 
 
 
X 
X 
DLQIg  
 
X 
 
 
 
X 
X 
ADCTg 
 
 
 
 
 
X 
X 
HADSg 
 
X 
 
 
 
X 
X 
Safety tests (FBC, non-fasting biochemistry, 
electrolytes, urinalysis) 
 
X 
 
 
 
X 
X 
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Visit 
10 
11a 
12 
13 
14 
15a 
ET# 
Visit days 
120 
141 
148 
155 
162 
169 
- 
Visit weeks 
17 
20 
21 
22 
23 
24k 
- 
Visit window (days) 
±1 
±3 
±1 
±1 
±1 
±3 
- 
 
Treatment 
- 
Description 
Clinic 
Clinic 
Telephoneh 
Telephoneh 
Telephoneh 
Clinic 
 Clinic 
Pregnancy test - females only (urine)i 
 
X 
 
 
 
X 
X 
Blood samples for serum concentrations of KY1005 
(PK)a 
X 
X 
 
 
 
X 
X 
Blood samples for serum concentrations of ADAsc 
POEMg 
 
X 
 
 
 
X 
X 
NRS (pruritus) – internet-enabled deviced 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
Contact IRT 
X 
X 
X 
X 
X 
X 
X 
Re-randomisation 
 
 
 
 
 
Xe 
 
IMP administration and check of local skin 
reactionf, g, j 
 
X 
 
 
 
X 
 
ADA=anti-drug antibody; ADCT=atopic dermatitis control tool; AEs=adverse events; BSA=body surface area; DLQI=Dermatology Quality of Life Index; EASI=Eczema Area and Severity 
Index; ECG=electrocardiogram; FBC=full blood count; IgE=immunoglobulin E; IMP=Investigational Medicinal Product; NRS=Numerical Rating Scale; POEM=Patient Oriented Eczema 
Measure; PK=pharmacokinetics; PRO=patient reported outcome; SAE=serious adverse event; SCORAD=SCORing of Atopic Dermatitis; IGA= Investigator Global Assessment; HADS= Hospital 
Anxiety and Depression Scale. 
# 
Early Termination Visit could be done by the Investigator (see Section 3.4, Section 3.5 and Section 9). 
a On IMP administration days, all assessments, including taking blood samples, will be performed pre-injection unless stated otherwise. 
b On IMP administration days vital signs will be measured pre-injection and 30 minutes post injection.  The tolerance on vital signs after dosing is ±5 minutes. 
c 
 
 
d NRS (pruritus) will be recorded daily, ideally in the morning, based on the previous 24 hours with worst (maximum) itch intensity recorded. 
e Where IMP administration occurs on a re-randomisation day the IMP injection is to be administered after re-randomisation (with the new regimen where applicable). 
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f 
 
g Where possible, the PRO assessments completed at the study site are to be completed by patients prior to the completion of other study assessments and the administration of IMP. 
h A telephone visit is defined as a videoconference, video call or telephone call. 
i 
If urine pregnancy test is positive, a serum control must be done before IMP administration   
j 
 
k The ICF from the DRI/Phase2b/parent study will not be valid as LTE informed consent. In order for patients to roll over to the LTE study, a specific LTE ICF will need to be applied, agreed upon and signed at the 
LTE study, as the LTE is a separated protocol. 
 
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Table 6-3: 
Schedule of Assessments - Day 176 (Week 25) to Day 365(Week 52)  
Visit 
16 
17a 
18 
19a 
20 
21a 
22a 
23 
24a 
25 
26a 
27 
28a 
ET# 
Visit days 
176 
197 
204 
225 
232 
253 
281 
288 
309 
316 
337 
344 
365 
Visit weeks 
25j 
28j 
29j 
32j 
33j 
36j 
40j 
41j 
44j 
45j 
48j 
49j 
52j 
Visit window (days) 
±1 
±3 
±1 
±3 
±1 
±3 
±3 
±1 
±3 
±3 
±3 
±1 
±3 
 
Treatment 
- 
Description 
Clinic 
Clinic 
Telephonef 
Clinic 
Telephonef 
Clinic 
Clinic 
Telephonef 
Clinic Telephonef 
Clinic 
Telephonef 
Clinic 
Clinic 
Concomitant 
medications - 
including emollients 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AEs (including 
SAEs) 
<========================================================================================================> 
X 
Physical 
examination  
 
X 
 
 
 
 
X 
 
 
 
 
 
X 
X 
Vital signsb 
 
X 
 
X 
 
X 
X 
 
X 
 
X 
 
X 
X 
12-lead ECG 
 
 
 
X 
 
 
X 
 
 
 
X 
 
X 
X 
EASI 
 
X 
 
X 
 
X 
X 
 
X 
 
X 
 
X 
X 
BSA 
 
X 
 
X 
 
X 
X 
 
X 
 
X 
 
X 
X 
IGA 
 
X 
 
X 
 
X 
X 
 
X 
 
X 
 
X 
X 
SCORAD Indexg 
 
X 
 
X 
 
X 
X 
 
X 
 
X 
 
X 
X 
DLQIg 
 
X 
 
X 
 
X 
X 
 
X 
 
X 
 
X 
X 
ADCTg 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
X 
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Visit 
16 
17a 
18 
19a 
20 
21a 
22a 
23 
24a 
25 
26a 
27 
28a 
ET# 
Visit days 
176 
197 
204 
225 
232 
253 
281 
288 
309 
316 
337 
344 
365 
Visit weeks 
25j 
28j 
29j 
32j 
33j 
36j 
40j 
41j 
44j 
45j 
48j 
49j 
52j 
Visit window (days) 
±1 
±3 
±1 
±3 
±1 
±3 
±3 
±1 
±3 
±3 
±3 
±1 
±3 
 
Treatment 
- 
Description 
Clinic 
Clinic 
Telephonef 
Clinic 
Telephonef 
Clinic 
Clinic 
Telephonef 
Clinic Telephonef 
Clinic 
Telephonef 
Clinic 
Clinic 
HADSg 
 
X 
 
X 
 
X 
X 
 
X 
 
X 
 
X 
X 
Safety tests (FBC, 
non-fasting 
biochemistry, 
electrolytes, 
urinalysis) 
 
X 
 
X 
 
X 
X 
 
X 
 
X 
 
X 
X 
Pregnancy test - 
females only (urine)i 
 
X 
 
X 
 
X 
X 
 
X 
 
X 
 
X 
X 
Blood samples for 
serum 
concentrations of 
KY1005 (PK)a 
X 
X 
 
X 
 
X 
X 
 
X 
 
X 
 
X 
X 
Blood samples for 
serum 
concentrations of 
ADAsc 
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Visit 
16 
17a 
18 
19a 
20 
21a 
22a 
23 
24a 
25 
26a 
27 
28a 
ET# 
Visit days 
176 
197 
204 
225 
232 
253 
281 
288 
309 
316 
337 
344 
365 
Visit weeks 
25j 
28j 
29j 
32j 
33j 
36j 
40j 
41j 
44j 
45j 
48j 
49j 
52j 
Visit window (days) 
±1 
±3 
±1 
±3 
±1 
±3 
±3 
±1 
±3 
±3 
±3 
±1 
±3 
 
Treatment 
- 
Description 
Clinic 
Clinic 
Telephonef 
Clinic 
Telephonef 
Clinic 
Clinic 
Telephonef 
Clinic Telephonef 
Clinic 
Telephonef 
Clinic 
Clinic 
POEMg 
 
 
 
X 
 
X 
X 
 
X 
 
X 
 
X 
X 
NRS (pruritus) - 
internet-enabled 
deviced 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
Contact IRT 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IMP 
administration and 
check of local skin 
reactione 
 
X 
 
X 
 
X 
X 
 
X 
 
X 
 
 
 
ADAs=anti-drug antibodies; ADCT=atopic dermatitis control tool; AEs=adverse events; BSA=body surface area; DLQI=Dermatology Quality of Life Index; EASI=Eczema Area and Severity Index; 
ECG=electrocardiogram; FBC=full blood count; IgE=immunoglobulin E; IMP=Investigational Medicinal Product; NRS=Numerical Rating Scale; POEM=Patient Oriented Eczema Measure; 
PK=pharmacokinetics; PRO=patient reported outcome; SAE=serious adverse event; SCORAD=SCORing of Atopic Dermatitis; IGA= Investigator Global Assessment; HADS= Hospital Anxiety and 
Depression Scale. 
 
# 
Early Termination could be done by the Sponsor or the Investigator (see Section 3.4, Section 3.5 and Section 9). 
a 
On IMP administration days in this time period, all assessments, including taking blood samples, will be performed pre-injection unless stated otherwise. 
b 
On IMP administration days in this time period, vital signs will be measured pre-injection and 30 minutes post- injection. The tolerance on vital signs after dosing is ±5minutes. 
c 
  
d 
NRS (pruritus) will be recorded daily, ideally in the morning, based on the previous 24 hours with worst (maximum) itch intensity recorded. 
e 
 
f 
A telephone visit is defined as a videoconference, video call or telephone call. 
g 
Where possible, the PRO assessments completed at the study site are to be completed by patients prior to the completion of other study assessments and the administration of IMP. 
i 
 If urine pregnancy test is positive, a serum control must be done before IMP administration. 
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j 
The ICF from the DRI/Phase2b/parent study will not be valid as LTE informed consent. In order for patients to roll over to the LTE a specific LTE ICF will need to be applied, agreed upon and signed at the LTE study, as 
the LTE is a separated protocol. 
Table 6-4: 
Schedule of Assessments - SafetyFollow-up  
Visit 
29a 
30a 
31a 
32a 
ET# 
Visit days 
393 
421 
449 
477 
Visit weeks 
56d 
60d 
64d 
68d 
Visit window (days) 
±7 
±7 
±7 
±7 
Description 
Clinic 
Telephoneb 
Clinic 
Clinic 
Clinic 
Concomitant medications - including 
emollients 
X 
X 
X 
X 
X 
AEs (including SAEs) 
-----------------------------------------------------------------------------------------------→ 
X 
Physical examination  
 
 
X 
X 
X 
Vital signs 
X 
 
X 
X 
X 
12-lead ECG 
X 
 
X 
X 
X 
Safety tests (FBC, non-fasting 
biochemistry, electrolytes, urinalysis) 
X 
 
X 
X 
X 
Pregnancy test – females only (urine)c 
X 
 
X 
X 
X 
Blood samples for serum concentrations of 
ADAs 
ADA=anti-drug antibody; AEs=adverse events; ECG=electrocardiogram; FBC=full blood count; SAE=serious adverse event. 
 
# 
Early Termination could be done by the Sponsor or the Investigator (see Section 3.4, Section 3.5 and Section 9). 
a For patients who are not enrolled into the LTE (LTS17367) and require additional safety follow-up. 
b A telephone visit is defined as a videoconference, video call or telephone call. 
c If urine pregnancy test is positive, a serum control must be done before IMP administration. 
d The ICF from the DRI/Phase2b/parent study will not be valid as LTE informed consent. In order for patients to roll over to the LTE a specific LTE ICF will need to be applied, agreed upon and signed at the LTE 
study, as the LTE is a separated protocol.
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6.2 
Screening Procedures  
6.2.1 Written Informed Consent  
Written informed consent for the study will be obtained from each patient before any 
protocol-specific assessments or procedures are carried out. 
At the Screening Visit (or at a prior interview), the Investigator will explain the aims, methods, 
anticipated benefits and potential risks of participating in the study and should inform the 
patient that participation is voluntary and that they can withdraw from the study at any time.  
Each patient will be given a study-specific Patient Information Sheet (PIS), as part of the 
informed consent process, to read and will be given adequate time to ask questions.  In 
accordance with ICH GCP and 21 CFR 50, informed consent shall be documented using an 
ICF approved by the IECs/ IRBs.  The ICF will be signed and personally dated by the patient 
(or patient’s legal representative) and by the person who conducted the informed consent 
discussion.  
In exceptional circumstances, such as a regional or national emergency declared by a 
governmental agency, consent may be collected through a remote solution if allowed through 
country and site regulations and following approval by the IEC/IRB.  Implementation must 
have prior approval from the Sponsor (or its designee).   
In case of ICF amendment while the patients are still included in the study, they must be 
re-consented to the most current version of the ICF(s).  Where patients are no longer in the 
study, teams in charge of the amendment must define if those patients must or not re-consent 
or be informed of the amendment (eg, if the processing of personal data is modified, if the 
Sponsor changes, etc). 
In addition to the ICF for the study, the patient will be asked if they would like to participate 
in the pharmacogenomic sampling section of the study.  Consent for this will be in addition to 
the main consent.  Lack of informed consent to participate in the pharmacogenomic sampling 
section of the study does not preclude patients from participating in the clinical study.  
At selected sites, patients will be asked to participate in a biopsy sub-study.  Consent for this 
will be in addition to the main study consent. Biopsies will not be conducted in patients if there 
is a contraindication to the procedure in the Investigator’s opinion. Lack of consent to 
participate in the biopsy sub-study does not preclude patients from participating in the main 
clinical study.  
In addition, the patient will be asked if the samples collected from them can be stored and used 
for possible future analyses.  Lack of informed consent for future analysis of samples does not 
preclude patients from participating in the clinical study.  
Informed consent will be documented in the patient’s medical records, as required by 21 CFR 
Part 312.62.  The patient should be given a copy of the PIS and their signed and dated ICF, and 
the original ICF should be filed in the ISF.  
6.2.2 Demographic Information  
Demographic information will be collected at the Screening Visit as follows: 
• Age. 
• Year of birth. 
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• Gender (sex). 
• Race. 
• Ethnicity. 
6.2.3 Medical History  
The Investigator will be responsible for review of the medical history (including AD history) 
of patients to ensure that they meet the criteria for eligibility for the study.  This will include a 
review of the study inclusion and exclusion criteria, including review for drugs of abuse (see 
Section 6.4.6), which will be repeated at the Baseline Visit.  
6.2.3.1 QuantiFERON®-TB Gold Blood Test  
A whole blood sample will be collected from each patient at the Screening Visit for the 
QuantiFERON®-TB Gold blood test (see Section 6.7).  
Detailed instructions for blood sample collection, preparation and shipping will be provided in 
a laboratory manual to be finalised before the samples are collected.  Samples will be shipped 
to and analysed by PPD Central Labs.  
Positive QuantiFERON®-TB Gold blood test is an exclusion criterion. If an indeterminate 
result is found at the first evaluable test, a retest should be performed as soon as possible. If the 
second evaluable test is negative, patient is not excluded. If the second evaluable test is either 
indeterminate or positive, patient is excluded. In the event of test cancelation, a retest should 
be performed as soon as possible, and the cancelation will not account as an evaluable test 
result for the procedure mentioned in this paragraph.  
6.2.4 Concomitant Medications  
Concomitant medications will be recorded at Screening and throughout the study at the 
timepoints outlined in the Schedule of Assessments (see Table 6-1, Table 6-2, Table 6-3 and 
Table 6-4). 
Data 
should 
be 
collected 
for 
all 
medicines 
(including 
emollients 
and 
natural/herbal/prescription/over-the-counter/contraceptive etc). The following information 
should be recorded on the eCRF: drug/therapy name (product name), route, dose and units, 
frequency, indication, reference to AE if applicable, start date, end date or ongoing at the EOS. 
6.3 
Efficacy Assessments  
The efficacy of KY1005 in the treatment of AD will be assessed using change in EASI, IGA, 
SCORAD Index and affected BSA.  Investigator performed assessments should be carried out 
by the same assessor on each occasion for an individual patient.  These assessments will be 
completed on an internet-enabled device. Patient reported outcomes will be assessed using the 
POEM, DLQI, HADS, ADCT and the NRS for pruritus.  Patients will be required to use an 
internet-enabled device (eg, computer, mobile phone or tablet device) to complete an electronic 
diary to record the PROs in local languages where validated.  Patients should bring their eDiary 
to visits and review with coordinators.  Patients will be encouraged to continue completing 
diary information until their last visit.  
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Where possible, the PRO assessments completed at the study site are to be completed by 
patients prior to the completion of other study assessments and the administration of study 
drug. 
All assessments will be performed at the timepoints outlined in the Schedule of Assessments 
(see Table 6-1, Table 6-2 and Table 6-3). 
Sites should discuss study procedure compliance with the patients, as required.  
6.3.1 Eczema Area Severity Index  
The EASI is an Investigator-assessed validated tool used to measure the extent (area) and 
severity of AD [Hanifin 2001 Exp Dermatol].  A copy of the EASI is included in Section 17.2 
(Appendix 2). This assessment will be completed using an internet-enabled device. 
The Investigator will assess the severity of 4 disease characteristics (erythema [E], 
induration/papulation [I], excoriation (X) and lichenification [L]) in 4 body regions on a scale 
of zero (absent) to 3 (severe).  In addition, the extent of involvement of 4 body regions 
(head/neck, trunk, upper extremities and lower extremities) will be assessed.  The possible 
highest score for extent of involvement in each region is 100%.  For each region, the percentage 
of BSA will be converted to an area score of zero (none in that region) to 6 (>90% to 100% of 
the entire region affected). 
For each major region of the body (head, upper extremities, trunk and lower extremities), EASI 
score = (E + I + X + L) × Area Score.  The total EASI score is the weighted total of the region 
EASI using the weights 10% (head), 20% (upper extremities), 30% (trunk) and 40% (lower 
extremities).  The minimum possible EASI score is 0 and the maximum possible EASI score 
is 72, where a higher score indicates increased extent and severity of AD. 
6.3.2 Investigator Global Assessment  
The IGA is an Investigator--lead assessment scale used to determine severity of AD and clinical 
response to treatment.  It is based on a 5-point scale, ranging from 0 (clear) to 4 (severe).  A 
copy of the IGA is also included in Section 17.3 (Appendix 3).  
This assessment will be completed using an internet-enabled device. 
6.3.3 SCORing of Atopic Dermatitis Index  
The SCORAD Index is a validated clinical tool that was developed to standardise the 
evaluation of the extent and severity of AD [SCORAD Dermatol Basel Switz 1993].  A copy 
of the SCORAD Index is included in Section 17.4 (Appendix 4). This assessment will be 
completed using an internet-enabled device. 
To determine the extent of AD, the affected area (A) as a percentage of the whole body is 
determined, with a maximum score of 100% (head and neck [9%], upper limbs [9% each], 
lower limbs [18% each], anterior trunk [18%], back [18%], genitals [1%]).  The severity (B) 
of 6 specific symptoms of AD (redness, swelling, oozing/crusting, scratch marks, skin 
thickening [lichenification], dryness [area where there is no inflammation]) is assessed on a 
4-point scale, with a maximum score of 18: none (0), mild (1), moderate (2) or severe (3).  
Subjective symptoms (ie, itch and sleeplessness; C) are recorded as scored by the patient or 
relative on a visual analogue scale (VAS), where 0 is no itch (or sleeplessness) and 10 is the 
worst imaginable itch (or sleeplessness), with a maximum possible score of 20. 
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The SCORAD score for each patient is calculated as: A/5 + 7B/2 + C. 
6.3.4 Body Surface Area Involvement of Atopic Dermatitis  
Body surface area (BSA) affected by AD will be assessed for each section of the body (the 
possible highest score for each region is: head and neck [9%], anterior trunk [18%], back 
[18%], upper limbs [18%], lower limbs [36%], and genitals [1%]) and will be reported as a 
percentage of all major body sections combined. 
6.3.5 Patient Oriented Eczema Measure  
The POEM is a tool used for monitoring atopic eczema severity.  It focuses on the illness as 
experienced by the patient.  This will be completed using an internet-enabled device.  A copy 
of the POEM form is included in Section 17.5 (Appendix 5).  The questionnaire consists of 
7 questions pertaining to the symptoms of AD and their frequency.  Scores are based on a scale 
of zero (no days) to 4 (every day in the last week) for each question, with a maximum score of 
28 possible for all questions.  A POEM total score is correlated to eczema severity (0-2 [clear 
or almost clear], 3-7 [mild], 8-16 [moderate], 17-24 [severe], 25-28 [very severe]). 
6.3.6 Dermatology Life Quality Index  
The DLQI is a dermatology-specific QoL instrument and is a simple, validated questionnaire.  
A copy of the DLQI is included in Section 17.6 (Appendix 6). This will be completed using an 
internet-enabled device. 
The instrument consists of 10 questions pertaining to the effect of AD on QoL.  Scores are 
based on a scale of “0” (not at all/not relevant/question unanswered) to “3” (very 
much/prevented work or studying), with a maximum score of 30 possible for all questions.  The 
total score is correlated to the detrimental effect of AD on QoL (0-1 [no effect at all on patient’s 
life], 2-5 [small effect], 6-10 [moderate effect], 11-20 [very large effect] and 21-30 [extremely 
large effect]). 
6.3.7 Atopic Dermatitis Control Tool  
The ADCT is a validated 6-item instrument with a 7-day recall period to measure AD disease 
control (Section 17.7 [Appendix 7]).  This will be completed using an internet enabled device. 
The following domains are assessed: overall severity of symptoms, frequency of intense 
episodes of itching, severity of bother of itching, frequency of sleep impact, severity of daily 
activities impact, severity of mood or emotions impact.  Each item is scored from 0 (none) to 
4 (extreme).  A total score of 7 or more points (derived by adding item scores) was identified 
during validation as an optimum threshold to identify patients whose AD is “not in control”. 
6.3.8 Hospital Anxiety and Depression Scale  
The HADS is a validated 14-item PRO measure used to assess states of anxiety and depression 
over the past week.  A copy of the HADS is included in Section 17.8 (Appendix 8). This will 
be completed using an internet-enabled device. 
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6.3.9 Numerical Rating Scale for Pruritus  
The NRS for pruritus is an assessment tool that will be used to assess the patient’s worst itch 
as a result of their AD in the previous 24 hours.  This will be recorded daily, ideally in the 
morning, using an internet-enabled device with patients asked, “On a scale of “0” (no itch) to 
“10” (worst imaginable itch), how was your worst itch in the past 24 hours?” according to 
Section 17.9 (Appendix 9).  Patients will additionally be asked to record NRS for 7 consecutive 
days immediately prior to Baseline.  Sites will be encouraged to contact patients who have 
missed 2 consecutive e-diary entries to encourage patient compliance. 
6.4 
Safety and Tolerability Assessments  
The Investigator will review results of safety assessments on a regular basis and the Sponsor 
must be kept fully informed of any clinically significant findings either at screening or 
subsequently during study conduct.  All assessments will be performed at the timepoints 
outlined in the Schedule of Assessments (see Table 6-1, Table 6-2, Table 6-3 and Table 6-4).   
6.4.1 Physical Examination  
The Investigator will perform physical examinations throughout the study, consisting of 
assessment of general appearance, ears, eyes, nose, throat, mouth, neck, thyroid, skin, 
cardiovascular, respiratory, abdomen, neurological, musculoskeletal, lymph nodes and 
extremities. 
6.4.2 Body Weight and Height  
Body weight will be measured in kilograms (kg) and height in metres (m), with patients in light 
clothing and without shoes.  Body weight will be assessed at Screening and during study 
treatment; height will be measured at Screening only. 
Body mass index (BMI) will be calculated as follows:  
BMI = Weight (kg) / Height (m)2 
6.4.3 Adverse Events  
Investigators must carefully monitor patients for the occurrence of AEs, including clinical 
laboratory, vital signs and ECG variables.  Assessments must be made of the seriousness, 
severity and relationship to the administration of study treatment (causality).  Serious adverse 
events and specific AESI will require expedited reporting to the Sponsor.  For details on 
definitions and reporting procedures see Section 8.1.  
Adverse event assessments must be made by the Investigator or delegated to an appropriately 
trained and experienced physician.  The Investigator is required to record the assessments in 
the eCRF and patient’s medical notes.  Any AEs already recorded and designated as 
“continuing” should be reviewed at each subsequent assessment. 
During and following a patient’s participation in this study, the Investigator must ensure that 
adequate medical care is provided to a patient for any AEs, including clinically significant 
laboratory values, related to the trial. 
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Adverse events and SAEs will be collected from the time of the patient signing the ICF until 
completion of the last visit.  If an event that starts after the safety follow-up period is due to a 
late onset toxicity to study treatment, then it should be reported as an AE or SAE as applicable. 
Investigators are not obligated to actively seek AE or SAE in former study patients.  However, 
if the Investigator learns of any SAE, including a death, at any time after a patient’s last visit 
and he/she considers the event to be reasonably related to the study treatment or study 
participation, the Sponsor should be notified. 
6.4.4 Standard Laboratory Safety Tests  
All standard safety laboratory parameters assessed will be evaluated centrally. 
The standard laboratory safety tests consisting of haematology (full blood count [FBC]), 
clinical chemistry (electrolytes and non-fasting biochemistry) and urinalysis assessments 
defined in Table 6-5 will be performed throughout the study.   
All WOCBP will also have a serum pregnancy test at Screening. Urine pregnancy tests will be 
performed pre-injection on IMP administration days, and at the early termination visit, 
Days 393 (Week 56), 449 (Week 64), and 477 (Week 68) of the safety follow-up period. These 
will be performed locally. If a urine pregnancy test result is positive, it must be confirmed by 
a serum pregnancy test. 
For post-menopausal women only, a blood sample will also be taken at Screening for FSH. 
Screening laboratory assessments may be repeated a maximum of once where initial results are 
in the Investigator’s opinion, clinically significant and only provided the initial result is 
considered a temporary anomaly and there is a documented explanation as to the likely cause 
of the result (Section 4.6).  
All laboratory reports should be reviewed, signed, and dated by a designated physician within 
24 hours of receipt.  These will be checked and verified by the Study Monitor during 
monitoring visits. 
Table 6-5: 
Standard Laboratory SafetyTests 
Category 
Parameter 
Haematology  
WBCC and differentials, RBCC, RDW, Hb, HCT, nucleated red blood cells, 
platelet count, MCH, MCHC, MCV, and MPV 
Clinical chemistry  
Albumin, sodium, potassium, chloride, bicarbonate, urea, creatinine, glucose, 
calcium, phosphate, ALT, AST, GGT, LDH, alkaline phosphatase, total protein, 
iron, total bilirubin and CPK 
Urinalysis 
pH, protein, glucose, ketones and blood 
ALT=alanine aminotransferase; AST=aspartate aminotransferase; CPK=creatine phosphokinase; GGT=gamma-glutamyl 
transferase; Hb=haemoglobin; HCT=haematocrit; LDH=lactate dehydrogenase; MCH=mean cell haemoglobin; MCHC=mean 
cell haemoglobin concentration; MCV=mean cell volume; MPV=mean platelet volume; RBCC=red blood cell count; 
RDW=red cell distribution width; WBCC=white blood cell count. 
Assay methodology and procedures will be described in a laboratory manual to be finalised 
before the samples are collected.  Samples will be shipped to and analysed by PPD Central 
Laboratory. 
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6.4.5 Virology  
Blood samples for HIV and hepatitis virology tests (HBsAg and HBcAb and hepatitis C 
antibody, will be taken at the Screening Visit. 
 
Any patients who are positive will be excluded from the study. 
Assay methodology and procedures will be described in a Laboratory Manual to be finalised 
before the samples are collected.  Samples will be shipped to and analysed by PPD Central 
Laboratory. 
6.4.6 Drugs of Abuse Testing  
History (within last 2 years) of current prescription drug or substance abuse, including alcohol, 
considered significant by the Investigator is an exclusion criterion for this study (see 
Section 4.3).  Drug abuse is a patterned use of a substance in which the patient uses amounts 
or methods that are harmful to themselves or others during the study period.  If the medical 
history suggests such abuse, then the Investigator should consider whether the patient meets 
the exclusion criteria.  Drugs of abuse screening, including breath test, may be performed at 
the Investigator’s discretion.   
6.4.7 Vital Signs  
Vital signs will be assessed throughout the study. On IMP administration Days 1 (Week 0), 
29 (Week 4), 57 (Week 8), 85 (Week 12), and 113 (Week 16), vital signs will be measured 
pre-injection and at 15-, 30-, and 60-minutes post-injection.  On all other IMP administration 
days, vital signs will be measured pre-injection and 30 minutes post-injection. 
Evaluations of systolic and diastolic blood pressure, heart rate, and tympanic temperature will 
be performed (other methods may be used but they must be consistently used throughout the 
study for each individual patient).  Heart rate and blood pressure will be taken after 5 minutes 
in the supine position. 
Any changes from Baseline in blood pressure and heart rate findings judged to be clinically 
significant by the Investigator will be recorded as AEs. In such cases, vital signs will be 
repeated at appropriate intervals until they return to Baseline or to a level deemed acceptable 
by the Investigator or until the abnormality can be explained by an appropriate diagnosis. 
Vital signs may be repeated a maximum of once where initial results are outside of the limits 
defined in the inclusion/exclusion criteria and only provided the initial result is considered a 
temporary anomaly and there is a documented explanation as to the likely cause of the result. 
6.4.8 12-lead ECG  
Standard 12-lead ECGs will be performed throughout the study after the patient has been 
supine for at least 5 minutes.  All ECGs should be recorded with the patient in the same physical 
position.  The ECG should be obtained either prior to the time of blood collection, or at least 
15 minutes afterwards.   
The ECG traces are to be reviewed by a qualified physician at the study site (physician to sign, 
date and record interpretation on ECG trace).  The Investigator will enter a signed and dated 
clinical interpretation of the ECG trace in the CRF. Any ECG traces on heat sensitive paper 
must be photocopied before archiving. 
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6.4.9 Local Skin Reactions  
 
  
Light pressure will be applied at the injection site and any pain, itchiness, tenderness, 
erythema, and induration will be recorded in the eCRF. Pain, itchiness and tenderness will 
be assessed according to the following scale: 
Definitions of pain and tenderness: 
• None  
nothing. 
• Mild 
 
easily tolerated. 
• Moderate 
interferes with daily activities. 
• Severe prevents normal everyday activities or sleep. 
The largest diameter of erythema and induration will be measured using a ruler, or a template 
supplied by the Sponsor. 
6.5 
Pharmacokinetic and Anti-drug Antibodies Assessments  
6.5.1 Pharmacokinetic Procedures  
Blood samples will be withdrawn periodically for KY1005 assay.  Pharmacokinetic and ADA 
samples will be collected from all patients including those receiving Placebo. 
6.5.1.1 Pharmacokinetic Sampling Schedule  
Serum concentrations of KY1005 will be assessed from blood samples taken during the study 
using validated enzyme-linked immunosorbent assay (ELISA) bioanalytical methods.  Assay 
methodologies and procedures will be described in analytical plans to be finalised before the 
start of sample analysis. 
Samples will be collected at the timepoints specified in the Schedule of Assessments (see 
Table 6-1, Table 6-2 and Table 6-3). On IMP administration days, samples for serum 
concentration of KY1005 will be withdrawn pre-dose. 
Tolerances for deviation from the nominal time of sampling are provided in the schedule of 
assessments (visit window).  These tolerances indicate the best time to allow interpretation of 
data. However, samples taken outside these tolerances will be evaluated so should be taken.  
The exact date and time of sampling will be recorded.  Samples may also be drawn for serum 
concentration, with prior agreement with the Medical Monitor, at unscheduled times.  
6.5.1.2 Pharmacokinetic Sample Preparation and Shipment  
The details of blood volume, type of tube, sample handling, storage and dispatch are described 
in the Laboratory Manual. 
6.5.1.3 Pharmacokinetic Parameter Derivation  
The following PK values will be derived for each patient receiving KY1005 and all KY1005 
regimens: 
• Cmax following the first, or any doses where sampling permits.  Peak concentrations 
following any doses where sampling permits. 
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• tmax following the first, or any doses where sampling permits. 
• Cmin following the first, second, third, fourth and any doses where sampling permits. 
6.5.2 Anti-drug Antibody Procedures  
Blood samples will be withdrawn periodically for anti-KY1005 antibody assays. 
6.5.2.1 Anti-drug Antibody Sampling Schedule  
Serum titres of anti-KY1005 antibodies will be assessed in blood samples taken during the 
study using a validated bioanalytical method.  Characterisation of positive ADA samples, eg, 
KY1005 neutralising capacity, may be performed if required. 
Samples will be collected at the timepoints specified in the Schedule of Assessments (see 
Table 6-1, Table 6-2, Table 6-3 and Table 6-4) and will be withdrawn before injection of IMP.  
Tolerances for deviation from the nominal time of sampling are provided in the schedule of 
assessments (visit window).  These tolerances indicate the best time to allow interpretation of 
data.  However, samples taken outside these tolerances will be evaluated and should therefore 
be collected.  The exact date and time of sampling will be recorded on the eCRF.   
 
 
6.5.2.2 Anti-drug Antibody Sample Preparation and Shipment  
The details of blood volume, type of tube, sample handling, storage and dispatch are described 
in the Laboratory Manual. 
 
 
6.6 
Assessment of Pharmacodynamics Markers  
 
 
 
  
 
 
 
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. 
 
 
 
 
   
 
 
6.7 
Total Blood Volume  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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7 
USE OF BIOLOGICAL SAMPLES AND DATA FOR 
FUTURE RESEARCH   
Future research may help further the understanding of disease subtypes, disease biology, 
related conditions, drug response and toxicity, and can help identify new drug targets or 
biomarkers that predict patient response to treatment.  Therefore, data and biological samples 
will be stored and used for future research when consented to by participants unless prohibited 
by local laws or IRBs/IECs (in such case, consent for future use of sample will not be included 
in the local ICF).  
 
 
 
 
 
 
Data and samples will be used in compliance with the information provided to patients in the 
section of the ICF related to future research. 
All study patient data and samples will be coded such that no patient direct identifiers will be 
linked to them. Coded data and samples may be transferred to a Sponsor site (or a 
sub-contractor site), which may be located outside of the country where the study is conducted.  
The Sponsor adopts safeguards for protecting participant confidentiality and personal data. 
The samples will be stored for a maximum of 25 years after the end of the study. Any samples 
remaining at the end of retention period will be destroyed.  If a participant requests destruction 
of his/her samples before the end of the retention period, the Investigator must notify the 
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Sponsor (or its CRO) in writing.  In such case, samples will be destroyed, and related coded 
data will be anonymised unless otherwise required by applicable laws. 
Study patient coded data will be stored for future research for up to 25 years after the end of 
the study. If data are still considered of important scientific value after this period, coded data 
already available will be anonymised unless otherwise required by applicable laws (the same 
will apply to the data of a study patient who has requested the destruction of his/her samples). 
Patient’s coded data sets provided to researchers for a specific research project will be available 
to the researchers for a maximum of 2 years after the end of their specific project (end of project 
is defined by publication of the results or finalisation of the future research project report). 
8 
SAFETY MONITORING AND REPORTING  
8.1 
Definition of an Adverse Event  
The ICH E6(R2) Good Clinical Practice Guideline defines an AE as any untoward medical 
occurrence in a patient or clinical investigation patient administered a pharmaceutical product, 
which does not necessarily have to have a causal relationship with this treatment.  An AE can, 
therefore, be any unfavourable and unintended sign (including an abnormal laboratory finding), 
symptom or disease temporally associated with the use of a medicinal (investigational) product, 
whether or not considered related to the medicinal (investigational) product. 
An AE can include an undesirable medical condition occurring at any time, even if no 
investigational medicinal product has been administered.  This includes an exacerbation of 
pre-existing conditions or events, intercurrent illnesses, drug interaction, or the significant 
worsening of the indication under investigation that is not recorded elsewhere on the eCRF 
under specific efficacy assessments.  Anticipated fluctuations of pre-existing conditions, 
including the disease under study, that do not represent a clinically significant exacerbation or 
worsening are not considered AEs and will not be captured as AEs.  Lack of efficacy or failure 
of expected pharmaceutical action per se will not be reported as an AE or a SAE.  Such 
instances will be captured under the efficacy assessments.  However, the signs symptoms and 
clinical sequelae resulting from lack of efficacy will be reported as an AE/SAE if they fulfil 
the definition of an AE or SAE. 
This definition includes events occurring from the time of the patient giving informed consent 
until the 140 days after the last dose of IMP. 
8.1.1 Adverse Events Categorisation, Recording, and Follow-up  
Investigators must carefully monitor patients for the occurrence of AEs, including clinical 
laboratory, vital signs and ECG variables. Assessments must be made of the seriousness, 
severity and relationship to the administration of study treatment (causality). These 
assessments must be made by the Investigator or delegated to an appropriately trained and 
experienced physician.  The Investigator must promptly record all identified AEs in the eCRF 
and patient medical notes. 
The Investigator should report a diagnosis or a syndrome rather than individual signs or 
symptoms, wherever possible. The Investigator should also try to separate a primary AE 
considered as the foremost untoward medical occurrence from secondary AEs which occurred 
as complications. 
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During and following a patient’s participation in this study, the Investigator must ensure that 
adequate medical care is provided to a patient for any AEs, including clinically significant 
laboratory values, related to the trial. 
8.1.1.1 Severity of Adverse Events  
Adverse events will be classified by the Investigator according to the following criteria: 
• Mild (Grade 1 Common Terminology Criteria for Adverse Events [CTCAE]): 
Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention 
not indicated. 
• Moderate (Grade 2 CTCAE): Minimal, local or noninvasive intervention indicated; 
limiting age-appropriate instrumental Activities of Daily Living (ADL). Instrumental 
ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, 
managing money, etc. 
• Severe (≥ Grade 3 CTCAE): Severe or medically significant but not immediately 
life-threatening; hospitalization or prolongation of hospitalization indicated; disabling, 
limiting self care ADL. Self care ADL refers to bathing, dressing and undressing, 
feeding self, using the toilet, taking medications, and not bedridden. Life-threatening 
consequences; urgent intervention indicated; Death related to AE. 
Changes in the severity of an AE should be documented to allow an assessment of the duration 
of the event at each level of severity to be performed.  Adverse events characterised as 
intermittent require documentation of onset and duration of each episode. 
8.1.1.2 Causality of Adverse Events  
The relationship of an AE to IMP administration will be classified by the Investigator according 
to the following: 
• Related: The temporal relationship of the AE to IMP administration makes a causal 
relationship possible, and other medications, therapeutic interventions, or underlying 
conditions do not provide a sufficient explanation for the observed event. 
• Not related: The temporal relationship of the AE to IMP administration makes a causal 
relationship unlikely or remote, and other medications, therapeutic interventions, or 
underlying conditions provide a sufficient explanation for the observed event. 
As this is a double-blind study, the causality assessment should be made under the assumption 
that the patient is receiving active study treatment.  If considering unblinding, this assessment 
should be made prior to unblinding to avoid bias. 
8.1.1.3 Follow-up of Adverse Events  
During the study, all AEs will be proactively followed up for each patient.  Every effort should 
be made to obtain a resolution for all events, even if the events continue after the patient 
discontinued the study.  
Any AEs already recorded and designated as “continuing” should be reviewed at each 
subsequent assessment for their final outcome. 
 
 
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For any AE which remains unresolved after completion of the trial, detailed evaluation and 
follow-up should be attempted until the AE has been resolved or a reasonable explanation for 
its persistence is found. 
8.1.2 Serious Adverse Event Assessment and Reporting to Sponsor  
The Investigator must pursue and obtain information adequate both to determine the outcome 
of the AE and to assess whether it meets criteria for classification as a SAE requiring immediate 
notification to the Sponsor (or designee). 
A SAE is any AE that: 
• Results in death. 
• Is life-threatening (ie, in the opinion of the Investigator, the patient is at immediate 
risk of death from the AE). 
• Results in inpatient hospitalisation or prolongation of existing hospitalisation 
(hospitalisation is defined as an inpatient admission, regardless of length of stay; 
hospital admissions for procedures planned before administration of IMP do not need 
to be reported). 
• Hospitalisation or prolongation of hospitalisation in the absence of a precipitating AE 
is not in itself an SAE.  Examples include: 
o Social admission (eg, patient has no place to sleep); 
o Protocol-specified admission during a clinical study (eg, for a procedure 
required by the study protocol); 
o Optional admission not associated with a precipitating AE (eg, for elective 
cosmetic surgery); 
o Surgery that was planned prior to study enrolment (appropriate documentation 
is required for these cases) and was not caused by worsening of a pre-existing 
condition. 
• Results in a persistent or significant disability/incapacity, where disability is a 
substantial disruption of a person's ability to conduct normal life functions. 
• Results in congenital anomaly/birth defect in the offspring of a patient who received 
the IMP. 
• Constitutes an important medical event that may not result in death, be 
life-threatening, or require hospitalisation when, based upon appropriate medical 
judgement, may jeopardise the patient and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition.  Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalisation, or the development of drug dependency or drug abuse. 
The Investigator must report all SAEs, regardless of treatment group or suspected relationship 
to investigational medicinal product, to the Sponsor or designee within 24 hours of knowledge 
of the event.   
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The following information is the minimum that must be provided: 
• Investigator/reporter’s name and contact details.  
• Patient identification number. 
• Description of the SAE, including criteria for seriousness and initial causality 
assessment. 
The additional information included in the SAE form must be provided to Sponsor or designee 
as soon as it is available.  The Investigator should always provide an assessment of causality 
for each event reported.  Upon receipt of the initial report, the Investigator’s causality 
assessment will be requested if it was not provided with the initial report. 
The procedures for completing and transmitting SAE reports are provided in Section 17.11 
(Appendix 11). 
8.1.3 Adverse Events of Special Interest  
Adverse events of special interest, defined below, will be reported to Sponsor or designee 
within 24 hours of learning of the event: 
• Systemic or localised allergic reactions that require immediate treatment*. 
• Severe injection site reactions that last longer than 24 hours.  
• Any severe or opportunistic viral, bacterial or fungal infection and/or any uncommon, 
unanticipated or persistent infection (viral, parasitic, bacterial, or fungal). 
• Any malignancy. 
• Increase in alanine transaminase (ALT) >3 × upper limit of normal (ULN); see the 
“Increase in ALT” flow chart in Section 17.12 (Appendix 12). 
The special situations of: 
• Symptomatic overdose (serious or non-serious) with IMP (any administration that is 
twice or more than the intended dose administered in less than 3 weeks [21 days]). 
• Pregnancy - discussed separately in Section 8.3. 
* In the event that a patient has a systemic allergic reaction that requires immediate treatment, 
blood samples should be withdrawn as soon as feasible (not to interfere with treatment of the 
reaction) for the analysis of ADA, serum tryptase, C1q, C1 inhibitor, C3 and C4, and repeated 
at 4 hours and 24 hours.  Detailed instructions for sample collection, preparation and shipping 
will be provided in a Laboratory Manual.   
8.1.4 
Deaths  
All AEs resulting in death during the study or follow-up period must be reported as SAEs 
irrespective of the causality, and the Investigator should supply the Sponsor and IRB/IEC if 
applicable, with as much detail of the events leading to death as possible immediately and any 
additional requested information (eg, autopsy reports and terminal medical reports).  
The convention for recording death is as follows: 
• AE term: lead/exact cause of death (eg, multiple organ failure, pneumonia, 
myocardial infarction). 
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• Outcome: fatal. 
• Causality assessment. 
The only exception is if the cause of death is unknown (ie, sudden or unexplained death), in 
which case the AE term may be “death” or “sudden death”.  As many details about the fatal 
cases should be provided as possible and available. 
8.1.5 Disease-related events and/or disease-related outcomes not qualifying as AEs or 
SAEs  
Not applicable. 
8.1.6 Regulatory reporting requirements for SAEs  
Prompt notification by the Investigator to the Sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of patients and the safety of a study 
intervention under clinical investigation are met.  
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety reporting 
to the regulatory authority, IRB/ IEC, and Investigators. 
Serious adverse events that are considered expected will be specified in the reference safety 
information (specify IB or label), as applicable.  
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
(SUSARs) according to local regulatory requirements and Sponsor policy and forwarded to 
Investigators as necessary. 
An Investigator who receives an Investigator safety report describing an SAE, SUSAR or any 
other specific safety information (eg, summary or listing of SAEs) from the Sponsor will 
review and then file it along with the IB and will notify the IRB/IEC, if appropriate according 
to local requirements. It is the responsibility of the Sponsor to assess whether an event meets 
the criteria for a SUSAR, and therefore, is expedited to regulatory authorities. 
8.1.7 Reporting to Regulatory Authorities, IECs/IRBs and other Investigators  
The Sponsor will ensure that processes are in place for submission of reports of SUSARs and 
special situations etc occurring during the study to the regulatory authorities, IECs/IRBs and 
other Investigators concerned by the investigational medicinal product, as applicable.  
Reporting will be performed by the Investigator or the Sponsor (or designee) in accordance 
with the applicable regulatory requirements. 
Details of procedures and responsibilities will be documented in a Safety/SAE management 
plan for the study. 
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8.2 
Emergency Procedures  
Each patient will be given an emergency card at the enrolment/randomisation visit and asked 
to carry it with them at all times in case of an emergency.  The card will include the following 
study information as a minimum: a patient identifier, investigational drug name and name and 
24-hour telephone number of the Investigator (or medically qualified designee).  Patients 
should be asked to destroy this card at the end of the study. 
If the Investigator needs urgent advice regarding the management of an SAE or any other safety 
issue, an ‘on call’ contracted medical advisor is available 24 hours a day by telephone, as per 
the details below. 
Emergency contact for medical monitor is specified in the STUDY PERSONNEL section. 
8.2.1 Emergency Treatment Code-break  
The IRT will be programmed with blind-breaking instructions. In case of an emergency, the 
Investigator has the sole responsibility for determining if unblinding of a participant’s 
intervention assignment is warranted (eg, in case of available antidote). Participant safety must 
always be the first consideration in making such a determination. If the Investigator decides 
that unblinding is warranted, he/she may, at his/her discretion, contact the Sponsor to discuss 
the situation prior to unblinding a participant’s intervention assignment unless this could delay 
emergency treatment of the participant. If a participant’s intervention assignment is unblinded, 
the Sponsor must be notified within 24 hours after breaking the blind. The date and reason that 
the blind was broken must be recorded in the source documentation and case report form, as 
applicable. If the code is broken upon Investigator’s request, the participant must withdraw 
from IMP administration and the patient should return for a final study assessment 
(see Section 9.2).  
8.3 
Pregnancy  
8.3.1 Maternal Exposure  
If a patient becomes pregnant during the study, IMP should be discontinued immediately. 
Although pregnancy is not considered an AE it does require reporting expeditiously with 
follow-up to an outcome, for up to 6 months post-partum, for mother and infant.  If any study 
patient is found to be pregnant while enrolled in the study, the Investigator must submit a 
pregnancy report form within 24 hours of becoming aware of confirmation of the pregnancy 
(see Section 17.10 - Appendix 10 for a flow chart of the process). 
Any event of pregnancy that occurs during the study (including long-term follow-up) or up to 
5 months following the last dose of IMP will be reported. Abnormal pregnancy outcomes (eg, 
spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are 
considered SAEs and will be reported as such. 
A follow-up report will be provided once the outcome of the pregnancy is definitive and the 
partner has given consent using a form approved by the relevant IEC for her personal medical 
information to be discussed, if applicable.  Follow-up of offspring for 6 months is desirable.  
In the event of any abnormality, the neonate will also be followed up if there is parental consent 
in place for such information to be discussed. 
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8.3.2 Paternal Exposure  
Pregnancy of a patient’s partner is not considered to be an AE.  However, any conception 
occurring from the date of dosing until 5 months after last dosing will be reported within 
24 hours on pregnancy report form and followed up for its outcome. 
9 
WITHDRAWAL OF PATIENTS FROM TREATMENT 
AND/OR THE STUDY  
Patients are free to withdraw from participation in the study at any time, without prejudice to 
their further care.  In some circumstances, patients may be discontinued from study treatment 
but continue certain study assessments.  
The Investigator should discontinue study treatment for a given patient if, on balance, he/she 
believes that continuation would be detrimental to the patient’s well-being. 
Study treatment will be discontinued and/or patients may be withdrawn from the study under 
the following circumstances: 
1. Withdrawal of consent. 
2. Severe noncompliance with the protocol as judged by the Investigator and/or the Sponsor. 
3. Patients incorrectly initiated on study treatment (eg, patient has been determined to have 
met one or more of the exclusion criteria for study participation at study entry and 
continuing study treatment might constitute a safety risk). 
4. AEs that, in the opinion of the Investigator or the Medical Monitor, contraindicate further 
dosing.   
5. Pregnancy. 
6. Disease progression in the investigator's point of view. 
7. Study terminated by the Sponsor. This includes any decision on study termination after 
IDMC recommendation. The IDMC reviews and evaluates accumulating blinded and 
unblinded if deemed necessary safety and efficacy data (including by treatment arm or 
patient) to ensure the safety of trial subjects (please refer to Section 3.8 of the protocol). 
8. Lost to follow-up.  
9.1 
Discontinuation of the Patient from Investigational Medicinal Product  
9.1.1 Reasons for Permanent Discontinuation of Investigational Medicinal Product   
The IMP will be permanently discontinued for any of the following reasons: 
1. Anaphylactic reaction or other severe systemic reaction to the IMP injection. 
2. Diagnosis of a malignancy during the study. 
3. Major surgery. 
4. Severe intercurrent illness. 
5. Evidence of confirmed pregnancy. 
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6. Any infection that is opportunistic, such as active TB, non-tuberculous mycobacterial 
infections 
and 
other 
infections 
whose 
nature 
or 
course 
may 
suggest 
an 
immunocompromised status. 
7. Severe laboratory abnormalities: 
• Absolute neutrophil count ≤0.5 × 109/L; 
• Platelet count ≤50 × 109/L; 
• Serum ALT >3 ULN and Total Bilirubin >2 ULN; 
• Serum ALT >5 ULN if baseline ALT ≤2 ULN or ALT >8 ULN if baseline 
ALT >2 ULN. 
Note: If the laboratory abnormality is considered causally related to the IMP, the IMP will 
be permanently discontinued.  In cases where a causal relationship to the IMP can be 
reasonably excluded (ie, an alternative cause is evident), the IMP will be discontinued but 
it may be resumed when the laboratory abnormality is sufficiently normalised.  
8.  If a subject experiences an adverse event assessed as ≥ Grade 3 CTCAE [severe; see 
Section 8.1.1.1] (or ≥ Grade 2 CTCAE [moderate; see Section 8.1.1.1] for the System 
Organ Classes of Cardiac disorders and Blood and Lymphatic disorders) per CTCAE v5.0, 
the subject should be discontinued from further dosing. Such subjects should not be 
discontinued from the study, but they should be monitored by their medical practitioner and 
study investigator until the adverse event (AE) resolves or stabilizes. 
Other reasons that may lead to the permanent discontinuation of IMP include: 
• Treatment with any prohibited systemic concomitant medication or procedure (see 
Section 5.3.2 and Section 5.3.4). 
• Treatment with any topical concomitant rescue therapy in the first 14 days from 
Baseline (see Section 5.3.4).  
• After Day 14, treatment with topical concomitant rescue therapy on more than 
2 occasions during study participation. The maximum permitted duration of topical 
concomitant rescue therapy on either occasion is 2 consecutive weeks. If duration of 
treatment is exceeded on either occasion this will also lead to permanent 
discontinuation of IMP.  
9.1.2 Reasons for Temporary Discontinuation of Investigational Medicinal Product  
Dosing of IMP should be temporarily interrupted for the following reasons: 
1. Clinically important laboratory abnormalities, such as: 
• Absolute neutrophil count ≤1.0 × 109/L but >0.5 × 109/L; 
• Platelet count ≤100 × 109/L but >50 × 109/L; 
• Creatine phosphokinase >10 × ULN. 
2. Other intercurrent illness. 
3. An infection requiring systemic treatment with antibiotic, antifungal, antiviral, antiparasitic 
or antiprotozoal agents, or requiring oral treatment with such agents for more than 2 weeks. 
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9.1.2.1 Re-challenge  
Reinitiation of intervention with the IMP will be done under close and appropriate clinical 
and/or laboratory monitoring once the Investigator will have considered according to his/her 
best medical judgment that the responsibility of the IMP(s) in the occurrence of the concerned 
adverse event was unlikely and if the selection criteria for the study are still met (refer to 
Section 4). 
If there is to be a delay to any dosing of IMP outside of the permitted visit windows as per the 
Schedule of Assessments (Section 6.1), the Investigator must consult with, and receive written 
confirmation that dosing can be rescheduled from, the Medical Monitor. 
9.1.2.1.1 Study intervention restart or rechallenge after liver stopping criteria met  
Study intervention restart or rechallenge after liver chemistry stopping criteria are met by any 
participant in this study is not allowed. 
9.1.3 Follow-up of Patients Off Treatment  
If a patient discontinues study treatment prematurely, she/he will be encouraged to remain in 
the study to complete all remaining study visits and to participate in all assessments according 
to the Schedule of Assessments.  Their study data collected during their continued involvement 
is important to the study efficacy analysis and study value.  
If a patient permanently withdraws from study treatment early but consent is retained, study 
assessments may be continued until Day 169 (Week 24) for patients who withdraw from study 
treatment in the first study period (and who are therefore no longer eligible for consideration 
for the LTE at Day 169 (Week 24) or progression to the next study period), or until Day 365 
(Week 52) in patients who withdraw from study treatment after Day 169 (Week 24) and who 
decide not to participate in or are not eligible for the LTE study.  This may be followed by the 
safety follow-up according to the Schedule of Assessments (Section 6.1).   
If a patient chooses not to attend remaining visits in the event of withdrawal from study 
treatment early before Day 169 (Week 24) or Day 365 (Week 52), they will instead enter the 
safety follow-up and complete their assessments as per the Schedule of Assessments 
(Section 6.1). 
Patients will be considered lost to follow-up only if no contact has been established by the time 
the study is completed, such that there is insufficient information to determine the patient’s 
status at that time.  Patients who refuse to continue participation in the study, including 
telephone contact, should be documented as “withdrawal of consent” rather than “lost to 
follow-up.”  Investigators should document attempts to re-establish contact with missing 
patients throughout the study period.  If contact with a missing patient is re-established, the 
patient should not be considered lost to follow-up, and evaluations should resume according to 
the protocol. 
The following actions must be taken if a patient fails to return to the clinic for a required study 
visit: 
• The site must attempt to contact the patient and reschedule the missed visit as soon as 
possible and counsel the patient on the importance of maintaining the assigned visit 
schedule. 
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• Before a patient is deemed lost to follow-up, the Investigator or designee must make 
every effort to regain contact with the patient or next of kin by, for example, repeat 
telephone calls, certified letter to the patient’s last known mailing address, or local 
equivalent methods.  These contact attempts should be documented in the patient’s 
medical record. 
• Efforts to reach the patient should continue until the end of the study.  Should the 
patient be unreachable at the end of the study, the patient should be considered to be 
lost to follow-up. 
9.1.4 Discontinuation of the Patient from Study  
Patients are free to withdraw from the study at any time without prejudice to further treatment.  
Patients who withdraw consent for further participation in the study will not receive any further 
IMP or further study assessments. 
A patient who withdraws consent will always be asked about the reason(s) for withdrawal and 
the presence of any AEs.  If a patient withdraws consent, they will be specifically asked if they 
are withdrawing consent for: all further participation in the study including any further 
follow-up (eg, telephone calls), and/or withdrawal of consent for the use of any samples. 
9.2 
End of Treatment and End of Study Procedures  
At the EOS Visit (defined in Section 3.4), patients will undergo the procedures specified in the 
Schedule of Assessments.  Following withdrawal for any reason, patients will attend an early 
termination visit and will undergo the procedures specified in the applicable Schedule of 
Assessments (Table 6-1, Table 6-2, Table 6-3 and Table 6-4), if possible.  All data available 
for the patient at the time of withdrawal and all reasons for withdrawal, must be recorded in 
the eCRF. 
9.3 
Study Discontinuation  
The Sponsor reserves the right to close the study site or terminate the study at any time for any 
reason at the sole discretion of the Sponsor.  The study may be stopped if, in the judgment of 
the Sponsor, patients are placed at undue risk because of clinically significant findings that: 
• Meet individual stopping criteria or are otherwise considered significant. 
• Are assessed as causally related to study treatment. 
• Are not considered to be consistent with continuation of the study. 
Regardless of the reason for termination, all data available for the patient at the time of 
discontinuation of follow-up must be recorded in the eCRF.  All reasons for discontinuation of 
treatment must be documented. 
In terminating the study, the Sponsor will ensure that adequate consideration is given to the 
protection of the patients’ interests. 
Study sites will be closed upon study completion.  A study site is considered closed when all 
required documents and study supplies have been collected and a study-site closure visit has 
been performed. 
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Reasons for the early closure of a study site by the Sponsor may include, but are not limited to, 
the following: 
• Failure of the Investigator to comply with the protocol, the requirements of the 
IEC/IRB or local health authorities, the Sponsor's procedures, or GCP guidelines. 
• Inadequate recruitment of participants by the Investigator. 
• Discontinuation of further study intervention development. 
9.4 
Patient Replacement Policy  
Patients who have been dosed will not be replaced. 
Patients who are ineligible for study enrolment for reasons that are temporary, or who are 
unable to receive the first dose of study drug within the allowed Screening window for 
administrative reasons may be rescreened once after agreement to do so has been obtained in 
writing from the Medical Monitor. 
10 
STATISTICAL CONSIDERATIONS  
An SAP based on the primary and secondary endpoints will be written and finalised before the 
study closure, ie, before database closure and unblinding of the randomisation code.  The SAP 
will provide full details of the analyses, the data displays and the algorithms to be used for data 
derivations.   
For all assessments, Baseline is defined as last recorded measurement prior to first IMP 
administration unless otherwise stated. 
All safety and statistical programming, including PK analysis, will be conducted with 
Statistical Analysis System (SAS)® version 9.4 or higher for Windows (SAS Institute Inc., 
Cary, North Carolina, United States of America [USA]). 
10.1 Sample Size Determination  
A sample size of 350 patients (70 patients / group) in the target population, (adult with 
moderate-to-severe AD who have a documented history, within 6 months prior to Baseline, of 
either inadequate response to topical treatments or inadvisability of topical treatments),  
randomised 1:1:1:1:1 to 4 KY1005 groups or matching Placebo group is estimated 
 
 to detect a pairwise difference in means between each KY1005 and Placebo 
with respect to the percentage change in EASI from Baseline to Day 113 (Week 16), based on 
a 2-sided 2-sample equal-variance t-test.   
 
 
 
10.2 Estimands and Intercurrent Event  
 
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10.3 Analysis Sets  
10.3.1 Full Analysis Set  
The full analysis set (FAS) includes all randomised patients.  Efficacy analysis will be based 
on treatment allocated at randomisation which will be stratified by disease severity 
(moderate/severe) and region.  
10.3.2 Safety Set  
The safety set (SAF) will consist of all patients who take at least one dose of study treatment, 
including Placebo.  Safety analysis will be based on actual treatment received. 
10.3.3 Pharmacokinetic Set  
The PK set will consist of all randomised and treated patients in the SAF with a Baseline 
assessment and at least one post-Baseline PK sample (with adequate documentation of dosing 
and sampling dates and times). 
10.3.4 Anti-drug Antibody Set  
The ADA set will consist of all randomised and treated patients in the SAF with a Baseline 
ADA result (positive, negative or inconclusive) and at least one post-Baseline ADA result 
(positive, negative or inconclusive). 
10.4 Statistical Analyses  
Full details of the statistical analyses of the data will be documented in an agreed SAP, which 
will be finalised prior to locking the database.  Analyses will be performed by treatment 
regimen. 
For continuous variables, descriptive statistics will include: the number of patients, mean, 
median, SD, minimum, and maximum. 
For categorical or ordinal data, frequencies and percentages will be displayed for each category. 
10.4.1 Demographic and Baseline Characteristics  
Demographic variables (age, gender and ethnicity) and medical history (coded according to the 
Medical Dictionary for Regulatory Activities [MedDRA]) will be summarised by treatment 
regime for FAS and SAF.  Body weight, height and BMI will also be summarised by treatment 
regimen. 
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10.4.2 Efficacy Analysis  
An overall test for the treatment effect of KY1005 will be conducted.  Pairwise comparisons 
of each KY1005 treatment group versus Placebo group will be performed. 
 
 
 
 
 
 
For the continuous endpoints  
An analysis of covariance (ANCOVA) model will be used.  This model includes treatment, 
randomisation strata (region, disease severity) as fixed effects, and baseline value as a 
covariate.  
 
 
 
 
 
 
  
A mixed-effect model with repeated measures (MMRM) will be used as a sensitivity analysis 
for primary and continuous key secondary endpoints.  This model includes the factors (fixed 
effects) for treatment, randomisation strata (region, disease severity), visit, treatment-by-visit 
interaction, and relevant baseline value.  Within the framework of MMRM, the treatment 
difference will be tested at the pre-specified primary timepoint, Day 113 (Week 16), as well as 
at the other timepoints by timepoint-specific contrasts from the MMRM model.  
 
 
For the categorical endpoints   
Cochran-Mantel-Haenszel test stratified by randomisation strata (region, disease severity) will 
be used at the analysis timepoint. 
   
Other sensitivity analysis might be performed and details will be specified in the SAP. 
Data will be presented graphically, where applicable, and with summary statistics by visit and 
by treatment regimen.   
10.4.2.1 Primary Analysis  
The primary efficacy endpoint is the percentage change in EASI from Baseline to Day 113 
(Week 16).  This will be assessed using an ANCOVA model. 
The primary analysis will be conducted on the FAS after all patients have reached the Day 169 
(Week 24) visit/early termination.   
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10.4.2.2 Secondary Analysis  
The key secondary efficacy endpoints for the study are: 
• Percentage change from Baseline in EASI at Day 169 (Week 24).  
• Percentage of patients with at least a 75% reduction from Baseline in EASI (EASI 75) 
 at Days 113 (Week 16) and 169 (Week 24). 
• Percentage of patients with a response of IGA 0 or 1 and a reduction from Baseline of 
 ≥2 points at Days 113 (Week 16) and 169 (Week 24). 
• Proportion of patients with improvement (reduction) of weekly average of pruritus 
NRS ≥4 with a Baseline pruritis NRS of ≥4 from Baseline to Days 113 (Week 16) and 
169 (Week 24). 
Additional secondary efficacy endpoints for the study are: 
• Absolute change from Baseline in EASI at Days 15 (Week 2), 29 (Week 4), 
57 (Week 8), 85 (Week 12), 113 (Week 16), 141 (Week 20) and 169 (Week 24). 
• Percentage change from Baseline in EASI at Days 15 (Week 2), 29 (Week 4), 
57 (Week 8), 85 (Week 12) and 141 (Week 20). 
• Percentage of patients with at least a 50% reduction from Baseline in EASI (EASI 50) 
at Days 15 (Week 2), 29 (Week 4), 57 (Week 8), 85 (Week 12), 113 (Week 16), 
141 (Week 20) and 169 (Week 24). 
• Percentage of patients with at least a 75% reduction from Baseline in EASI (EASI 75) 
at Days 15 (Week 2), 29 (Week 4), 57 (Week 8), 85  (Week 12)and 141 (Week 20). 
• Percentage of patients with at least a 90% reduction from Baseline in EASI (EASI 90) 
at Days 15 (Week 2), 29 (Week 4), 57 (Week 8), 85 (Week 12), 113 (Week 16), 
141 (Week 20) and 169 (Week 24). 
• Percentage of patients with a 100% reduction from Baseline in EASI (EASI 100) at 
Days 15 (Week 2), 29 (Week 4), 57 (Week 8), 85 (Week 12), 113 (Week 16), 
141 (Week 20) and 169 (Week 24). 
• Change in IGA from Baseline to Day 113 (Week 16) and over time. 
• Percentage of patients with a response of IGA 0 or 1 and a reduction from Baseline of 
≥2 points at Days 15 (Week 2), 29 (Week 4), 57 (Week 8), 85 (Week 12) and 
141 (Week 20). 
• Absolute and percentage change in SCORAD Index from Baseline to Day 169 
(Week 24) and over time. 
• Absolute and Percentage change in affected BSA from Baseline to Day 169 
(Week 24) and over time. 
• Absolute and Percentage change in POEM from Baseline to Day 169 (Week 24) and 
over time. 
• Absolute and Percentage change in DLQI from Baseline to Day 169 (Week 24) and 
over time. 
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• Absolute and Percentage change in ADCT from Baseline to Day 169 (Week 24) and 
over time. 
• Absolute and Percentage change in HADS from Baseline to Day 169 (Week 24) and 
over time. 
• Absolute and Percentage change in weekly average of pruritus NRS from Baseline to 
Day 169 (Week 24) and over time.  
• Proportion of patients with improvement (reduction) of weekly average of pruritus 
NRS ≥3 with a Baseline pruritis NRS of ≥3 from Baseline to Days 113 (Week 16) and 
169 (Week 24). 
• Time to loss of EASI 75 in patients randomised to withdrawal post-Week 24. 
• Time to loss of IGA 0/1 in patients randomised to withdrawal post-Week 24. 
• Time to loss of EASI 50 in patients randomised to withdrawal post-Week 24. 
10.4.2.3 Exploratory Analysis  
 
• 
 
• 
 
• 
 
• 
 
• 
 
  
10.4.2.4 Safety Analysis  
All safety data will be included in the patient data listings. 
Summaries will be presented by treatment regime and by timepoint and will be summarised for 
the SAF. 
10.4.2.4.1 Adverse Events  
The primary safety endpoint is the incidence of TEAEs. 
All AEs in the clinical trial database will be coded according to MedDRA, which will be used 
to summarise AEs by primary System Organ Class (SOC) and Preferred Term (PT).  All AEs 
will be displayed in listings. 
A TEAE is defined as an AE observed starting after the first administration of IMP up until 
140 days after the last IMP administration.  All TEAEs collected during the main study (to 
Day 169 [Week 24]) will be summarised.  Additionally, all TEAEs collected during the second 
study period in those patients who achieve ≥ EASI 75 or who attain IGA 0/1 response following 
24 weeks of treatment will be summarised (to Day 365 [Week 52]). 
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The number and percentage of patients with TEAEs and the number of TEAEs will be 
summarised in each KY1005 treatment regimen and in the Placebo group.   
The number and percentage of patients with TEAEs/AESIs will be further tabulated by 
causality and severity (mild, moderate and severe) in each KY1005 treatment regime and in 
the Placebo group. 
In addition, the number and percentage of patients with SAEs, TEAEs leading to treatment 
discontinuation, TEAEs leading to study discontinuation and AEs leading to death will be 
summarised in each KY1005 treatment regimen and in the Placebo group. 
Adverse events will be listed by treatment allocation, grouped by primary SOC and 
sub-grouped by PT and causality. 
10.4.2.4.2 Concomitant Medications  
Concomitant medications will be coded using the WHO Drug Dictionary and will be 
summarised in incidence tables by Drug Class and Preferred name, and by treatment regimen. 
10.4.2.5 Vital Signs  
At each timepoint, absolute values and change from Baseline of blood pressure, heart rate and 
temperature will be summarised with number of patients (n), mean, SD, median, minimum and 
maximum values.  The number of available observations and out of range values (absolute and 
percentage) will be presented.  Values outside the reference range will be flagged in the listing. 
10.4.2.6 Safety Laboratory Tests  
At each timepoint, absolute values and change from Baseline of clinical laboratory variables 
will be summarised with n, mean, SD, median, minimum and maximum values.  The number 
of available observations and out-of-range values (absolute and in percentage) will be 
presented.  All laboratory data (including re-check values if present) will be listed 
chronologically.   
10.4.2.7 Virology  
Positive samples for HIV, HBsAg, HBcAb and hepatitis C at the Screening Visit will be listed 
by patient. 
10.4.2.8 12-lead Electrocardiograms  
At each timepoint, absolute values and change from Baseline of ECG numeric variables will 
be summarised with n, mean, SD, standard error of the mean (SEM), median, minimum and 
maximum values.  The number of available observations and out-of-range values (absolute and 
in percentage) will be presented.  Values outside the reference range will be flagged in the 
listing.  The Investigator’s interpretation of 12-lead ECGs will be listed only. 
10.4.2.9 Physical Examination  
Physical examination findings will be listed by treatment regimen and by patient only. 
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10.4.2.10 Local Skin Reactions  
Findings from examination of local skin reactions will be listed by treatment regimen and by 
patient only. 
10.4.3 Pharmacokinetic Analysis  
Serum KY1005 concentrations will be summarised by treatment group and visit using 
descriptive statistics.  Serum concentration time profiles will be provided by treatment group.  
Additional plots will be prepared, as deemed necessary.  Serum KY1005 concentrations might 
be used for population PK modeling if considered necessary and the results of population PK 
modeling will be reported separately from the CSR. 
Further details will be provided in SAP. 
10.4.4 Pharmacodynamic Analysis  
The PD endpoint planned for this study is: 
• Anti-KY1005 antibody titre and number of patients with positive response. 
Data will be presented graphically, where applicable, and with summary statistics by visit and 
by treatment regime. 
Statistical analysis of this endpoint will be defined in the SAP. 
10.4.5 Handling of Withdrawals and Missing Data  
 
 
 
 
Other details for handling missing data will be specified in the SAP. 
10.4.6 Protocol Deviations  
Any inadvertent protocol deviations that occur during the conduct of the study must be fully 
documented by the Investigator or authorised designee and the Sponsor notified.  The statistical 
impact of important protocol deviations will be assessed, and the details provided in the SAP. 
10.4.7 Other analysis  
Data collected regarding the impact of the COVID-19 or other pandemics on the participants, 
will be summarized (eg, discontinuation due to COVID-19). Any additional analyses and 
methods required to investigate the impact of COVID-19 or other pandemics requiring public 
health emergency on the efficacy (eg, missing data due to COVID-19) and safety will be 
detailed in the SAP. 
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10.4.8 Interim analysis  
An interim analysis will be planned when approximately 
 participants in each arm 
complete the Week 16 assessments. The interim analysis will evaluate the percentage change 
in EASI from baseline to Day 113 (Week 16) and proportions of participants with EASI 75 at 
Day 113 (Week 16), as well as the other available data as needed. 
 
 In order to maintain the further double-blinded conduct of the study, the 
Study Team will be kept blinded on the individual participant's treatment group assignment. 
An independent team will be formed to perform this analysis. More details will be specified 
in the statistical analysis plan for the planned interim analysis 
 
11 
QUALITY CONTROL AND QUALITY ASSURANCE  
11.1 Monitoring  
The Sponsor will ensure the approval of the assignment of an appropriately qualified monitor(s) 
who will be responsible for visiting the site at intervals throughout the study in order to verify 
adherence to the protocol, completeness and accuracy of the data entered in the eCRFs and to 
perform source data verification (SDV) of data recorded in the eCRFs, in accordance with 
applicable regulations, SOPs and the monitoring plan.  
The monitoring plan will contain monitoring details describing strategy (eg, risk-based 
initiatives in operations and quality such as Risk Management and Mitigation Strategies and 
Analytical Risk-Based Monitoring), methods, responsibilities and requirements, including 
handling of noncompliance issues and monitoring techniques (central, remote, or on-site 
monitoring). 
The Investigator is responsible for the validity of all data collected at the site and should 
maintain adequate and accurate records and source data in accordance with the GCP principles 
of data integrity. Any source data changes should be traceable and original data not obscured. 
The eCRF is expected to be completed on an ongoing basis to allow regular review by the study 
monitor, both remotely and during site visits. 
The Study Monitor will communicate deviations from the protocol, SOPs, GCP and applicable 
regulations to the Investigator and should ensure that appropriate action designed to prevent 
recurrence of the detected deviations is taken and documented.  Additionally, the Study 
Monitor will provide a written report, including copies of correspondence with the Investigator 
and site study staff, to the Sponsor, following each visit. 
The frequency and nature of monitoring will be agreed with the Sponsor and documented prior 
to commencement of the study.  The monitor must have direct access to patient medical records 
and other study-related source documents.  The Investigator and study staff will be expected to 
co-operate with the monitor, to be available during the monitoring visit to answer questions 
and to ensure that any problems detected are resolved in a timely manner. 
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11.1.1 Audits and Inspections  
In accordance with the ICH E6(R2) GCP guideline, the Sponsor may select this study for audit.  
During the audit, the Sponsor/Sponsor representative will carry out an inspection of site 
facilities (eg, pharmacy, drug storage areas, laboratory) and review study-related records to 
evaluate the study compliance with the Sponsor/vendor SOPs, protocol, ICH E6(R2) GCP 
guideline, applicable parts of 21 CFR and local regulations.  The Investigator must also agree 
to inspection of all study documents by the regulatory authorities and the IEC/IRB.  
The Investigator and site personnel should be available to provide information and answer 
questions as necessary.  Should the Investigator be notified of a regulatory inspection involving 
this study, they must notify the Sponsor immediately. 
11.2 Data Quality Assurance  
Quality assurance and quality control systems will be implemented and maintained using 
written SOPs to ensure that the trial is conducted, and that the data are generated, recorded and 
reported in compliance with the protocol, GCP and the applicable regulatory requirements. 
Quality control procedures will be applied to each stage of data handling to ensure that all data 
are reliable and have been processed correctly. 
12 
REGULATORY AND ETHICAL CONSIDERATIONS  
The study will be conducted in compliance with the protocol, informed consent regulations, 
the general principles of the Declaration of Helsinki and the International Conference on 
Harmonisation (ICH) E6(R2) guidelines related to GCP.  In addition, the study will adhere to 
all applicable local regulatory requirements. IEC/IRB Approval. 
The study protocol, PIS, ICF, IB, available safety information, any patient-facing documents 
(eg, Patient Emergency Card), any patient recruitment materials (eg, advertisements), 
information about payments and compensation available to the patients and documentation 
evidencing the Investigator’s qualifications and any other written information regarding this 
study to be provided to a patient or patient’s legal representative will be submitted to the 
IEC/IRB for ethical review and approval if required by local regulations, prior to the study 
start.  The written approval should identify all documents reviewed by name and version. 
The Investigator/Sponsor will follow all necessary regulations to ensure appropriate, initial, 
and ongoing, IEC/IRB study review.  The Investigator/Sponsor (as appropriate) must submit 
and, where necessary, obtain approval from the IEC/IRB for all subsequent protocol 
amendments and changes to the informed consent document.  Investigators will be advised by 
the Sponsor whether an amendment is considered substantial or non-substantial and whether it 
requires submission for approval or notification only to an IEC/IRB. 
If applicable, the Investigator will notify the IEC/IRB within 90 days of the end of the study 
(as defined in Section 3.4), or if the study terminates early, the Investigator must notify the 
IEC/IRB within 15 days of the termination.  A reason for the early termination must be 
provided.  The Sponsor will either prepare or review all submission documents prior to 
submission to the IEC/IRB. 
Safety updates for KY1005 will be prepared by the Sponsor as required, for submission to the 
relevant IEC/IRB. Investigator/Sponsor will ensure all required safety updates including all 
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necessary SUSAR notifications are submitted to the IEC/IRB in accordance with relevant 
legislation and guidance. 
The Investigator will inform the Sponsor if the IEC/IRB suspends or terminates the trial. 
12.1 Regulatory Approval  
As required by local regulations, the Sponsor will ensure approval of the appropriate regulatory 
bodies is obtained prior to study initiation.  If required, the Sponsor will also ensure that the 
implementation of substantial amendments to the protocol and other relevant study documents 
happens only after approval by the relevant regulatory authorities. 
The Sponsor will notify the relevant regulatory authorities about end of study or early study 
termination within required timelines and in case of early termination will provide the reasons 
for it. 
Safety updates for KY1005 will be prepared by the Sponsor as required, for submission to the 
relevant regulatory authority. 
12.2 Patient Confidentiality and Data Protection  
All personal data collected and/or processed in relation to this study will be handled in 
compliance with all applicable Privacy and Data Protection laws and regulations, including the 
GDPR (General Data Protection Regulation).  The Sponsor is responsible for ensuring 
compliance with this matter, when processing data from any individual who may be included 
in the Sponsor databases, including Investigators, nurses, experts, service providers, Ethics 
Committee members, etc.  
When archiving or processing personal data pertaining to the Investigator and/or to the patients, 
the Sponsor will take all appropriate measures to safeguard and prevent access to this data by 
any unauthorised third party. 
Protection of patient data 
Data collected must be adequate, relevant and not excessive, in relation to the purposes for 
which they are collected.  Each category of data must be properly justified and in line with the 
study objective. 
Patient race and ethnicity will be collected in this study because they may modify the drug 
response and are required by regulatory agencies.  They will not be collected in countries where 
this is prohibited by local regulation. 
• Patients will be assigned a unique identifier by the Sponsor. Any patient records or 
datasets that are transferred to the Sponsor or its service providers will be identifiable 
only by the unique identifier; participant names or any information which would make 
the participant identifiable will not be transferred to the Sponsor. For all patients 
enrolled into the trial, the Investigator must maintain a list of names and identifying 
information (eg, date of birth, patient identification code, date of study enrolment).  The 
patient identification code list will be kept by the Investigator in the ISF. 
• The patient will be informed that his/her personal study-related data will be used by the 
Sponsor in accordance with applicable data protection laws. The level of disclosure 
must also be explained to the participant as described in the informed consent. 
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• The patient will be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorised personnel appointed by the Sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. The 
patient’s consent to direct access to his/her original medical records for data verification 
purposes must be obtained prior to a patient’s participation in the study. 
• Patients must be informed that their study-related data will be used for the whole “drug 
development programme”, ie, for this trial as well as for the following steps necessary 
for the development of the investigational product, including to support negotiations 
with payers and publication of results. 
Protection of data related to professionals involved in the study  
• Personal data (eg, contact details, affiliation(s) details, job title and related professional 
information, role in the study, professional resume, training records) are necessary to 
allow the Sponsor to manage involvement in the study and/or the related contractual or 
pre-contractual relationship.  They may be communicated to any Sponsor service 
providers, where needed. 
• Personal data can be processed for other studies and projects.  At any time, objection to 
processing can be made by contacting the Sponsor (via link available on Sponsor 
website), although this may limit a professional’s ability to participate in the study.  
• Personal data can be communicated to the following recipients:  
o Personnel within the Sponsor or partners or service providers involved in the study;  
o Judicial, administrative and regulatory authorities, in order to comply with legal or 
regulatory requirements and/or to respond to specific requests or orders in the 
framework of judicial or administrative procedures.  Contact details and identity 
may also be published on public websites in the interest of scientific research 
transparency. 
• Personal data may be transferred towards entities located outside the Economic 
European Area, in countries where the legislation does not necessarily offer the same 
level of data protection or in countries not recognised by the European Commission as 
offering an adequate level of protection.  Those transfers are safeguarded by the sponsor 
in accordance with the requirement of European law.  
• Professionals have the possibility to lodge a complaint relating to data protection with 
a competent local regulatory authority. 
• Personal data of professionals will be retained by the Sponsor for up to thirty (30) years, 
unless further retention is required by applicable regulations. 
• Professionals have the right to request the access to and the rectification of their 
personal data, as well as their erasure (where applicable) by contacting the Sponsor via 
the link provided on the Sponsor’s website.   
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12.3 Protocol Amendments  
The Investigator will not implement any changes to the protocol without approval from the 
Sponsor, the regulatory authority and IRB/IEC (and other approving bodies), if required, except 
where necessary to eliminate immediate hazards to the study patients, or when the changes 
involve only logistical or administrative aspects of the study. 
The Sponsor will not permit or approve any waivers from the approved protocol. 
Modifications to the protocol will be made as a protocol amendment. 
Substantial amendments to the protocol are those likely to have a significant impact on: 
• The safety, or physical or mental integrity of the patients. 
• The scientific value of the trial. 
Non-substantial amendments (eg, changes in telephone numbers, etc) will not require prior 
submission to the regulatory authority and the IRB/IEC or other approving body unless 
requested. 
12.4 Principal Investigator Responsibilities  
Principal Investigator responsibilities are set out in the ICH E6(R2) Guideline for GCP, 
applicable parts of 21 CFR and in the local regulations.  Sponsor staff or an authorised 
representative will evaluate and approve all Investigators who in turn will select their staff. 
The PI must show that they are appropriately qualified, registered and have the time, resources 
and expertise needed to carry out the study.  
If there are changes to the Investigator’s status or a change in PI, the Sponsor should be 
informed. 
The PI must ensure that all persons assisting with the study are appropriately qualified and 
trained for the role they will perform and are adequately informed about the protocol, 
amendments, study treatments, as well as study-related duties and functions.  The PI must 
ensure that the facilities and number of staff available are adequate to conduct the trial properly 
and safely. 
The PI is responsible for supervising any individual or party to whom he/she delegates trial 
related duties and functions and will maintain a list of sub-Investigators and other appropriately 
qualified persons to whom he or she has delegated significant study-related duties. 
If the PI contracts any vendors to work on the study, he/she must ensure appropriate oversight 
of said vendors and must obtain approval from the Sponsor for such work to be subcontracted.  
The PI is responsible for the validity of all data collected at site (see Section 13). 
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13 
DATA HANDLING AND RECORD KEEPING  
13.1 Data Capture  
Data collection is the responsibility of the clinical trial staff at the site under the supervision of 
the site PI.  The PI is responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported and should ensure that study staff are adequately trained and 
have sufficient time to fulfil their responsibilities.  
The PI must ensure that adequate and accurate records and source data are maintained in 
accordance with the GCP principles of data integrity.  Any source data changes should be 
traceable and original data not obscured. 
An eCRF, Rave, a 21 CFR Part 11-compliant data capture system provided by Medidata will 
be used for this study.  
In addition, patients will be asked to enter data into electronic patient-reported outcome 
(ePRO), which will form patient diaries and enable recording of patient daily assessments.  
The results from screening and data collected during the study will be entered into Medidata 
Rave by the Investigator or delegate.  The data system includes password protection and 
internal quality checks, such as automatic range checks, to identify data that appear 
inconsistent, incomplete, or inaccurate.  The Investigator will electronically sign the eCRF 
indicating that the data in the eCRF have been assessed and agreed.  
At the Sponsor’s discretion, SDV may be performed on all data items or a percentage thereof.  
The study monitoring plan will document the approach to be taken for SDV. 
13.2 Data Management  
Detailed data entry instructions will be provided in the eCRF Completion Guidelines. 
Data management and handling of the data will be conducted according to Data Validation 
Manual, the CRO equivalent of the study-specific data management plan (DMP), ICH 
guidelines and PPD SOPs. 
The electronic data capture (EDC) system, Medidata Rave will be used to capture data on 
eCRFs in the study.  Authorised study site personnel will perform data entry.  Changes to the 
data in the eCRF will be made at the site by study site personnel.  The PPD Data Management 
Team will perform data cleaning and handling of queries.  The data will be subjected to data 
review according to PPD SOPs to ensure accuracy of the collected data.   
Medidata Rave includes full audit trail with functionality for data capture, tracking and 
documentation of any changes to identify the person and timing of entering or changing the 
data.  Electronic signatures will be used to sign off the eCRFs. 
Results of clinical laboratory and PK analyses will be sent electronically to PPD and merged 
with the clinical datasets for inclusion in Study Data Tabulation Model (SDTM) transfers.   
Before database lock, a reconciliation will be performed between the SAEs entered in the safety 
database and the study clinical database.  After the database has been declared complete and 
accurate, the database will be locked and the database will be exported as SAS® datasets for 
statistical analysis.  Any deviations (ie, discrepancies and additions from the process defined 
in the DMP) will be described in an appropriate study plan).   
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13.3 Record Archiving and Retention  
The PI and study staff are responsible for maintaining a comprehensive ISF of all study-related 
(essential) documentation, suitable for inspection at any time by representatives from the 
Sponsor and/or applicable regulatory authorities.  The ISF must consist of those documents 
that individually or collectively permit evaluation of the conduct of the study and the quality 
of the data produced at the site.  
In addition, all original source documents supporting entries in the eCRF must be included in 
the patient’s medical file and retained so that integrity and accessibility are maintained for at 
least 5 years after the end of the study and in accordance with the maximum period of time 
permitted by the hospital, institution or private practice.  This requirement applies to both 
hardcopy (paper) and electronic source data. 
The ISF must be retained in accordance with ICH E6(R2) GCP, 21 CFR 312.62(c) or longer if 
required by applicable regulatory requirements or by the Sponsor.  The PI or his/her institution 
should retain essential documents until written instructions for their destruction are obtained 
from the Sponsor and must take adequate measures to prevent accidental or premature 
destruction of trial related records.  If the PI wishes to assign the study records to another party 
or to another location, they must obtain prior approval in writing from the Sponsor.  Any 
transfer of records must be fully documented. 
14 
FINANCING AND INSURANCE  
The financing and insurance for this study will be subject to a separate written agreement 
between the Sponsor and applicable parties. 
This study will be financed by Kymab Ltd, a Sanofi Company, the Sponsor of the study.  
Individual site financing and insurance will be subject to a separate written agreement between 
the Sponsor and applicable parties.  Patients will not be paid for participating in this study; 
however, allowances and reimbursements for patient and family travel may be provided, as 
included in the site-specific written agreement/budget/Clinical Trial Agreement. 
Investigators are required to provide financial disclosure information to the Sponsor to permit 
the Sponsor to fulfill its obligations under 21 CFR Part 54.  In addition, Investigators must 
commit to promptly updating this information if any relevant changes occur during the study 
and for a period of 1 year after the end of the study. 
15 
PUBLICATION POLICY  
All information provided regarding the study, as well as all information collected/documented 
during the course of the study, will be regarded as confidential.  
The Sponsor is committed to publish the data arising from this study at a suitable time 
irrespective of the study outcome.  Results from the study will be published/presented at 
scientific meetings as per the Sponsor’s publication policy. 
This is a multi-site study, and publication of the results of the study conducted at any individual 
site may not be made before multi-site publication(s) by Sponsor.  Once the Sponsor’s 
multi-site publication(s) have taken place, each site will have the right to publish its results 
from the study, subject to the following notice requirements:  
• At least 60 days prior to submitting or presenting a manuscript relating to the study for 
publication a copy must be provided to the Sponsor for review and comment. 
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• The Sponsor may request further delay to publication or presentation for a period of up 
to 120 days to allow the protection of any proprietary information, intellectual property 
or inventions.   
• If there is no multi-site publication within 18 months after the study has been completed 
or terminated at all study sites, and all data has been analysed, sites will have the right 
to publish their own results from the study. 
• Any publication made by a site must refer to the relevant Multi-Centre Trial publication 
where applicable. 
The Sponsor will ensure that any applicable requirements to register the study or publish the 
results arising on public databases are met. 
 
 
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16 
REFERENCES  
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American Academy of Dermatology Association (AAD). COVID-19 Vaccine administration 
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8549216409841c/AAD-COVID-19-Vaccine-administration-guidance.pdf 
Brunner PM, Guttman-Yassky E, Leung DYM. The immunology of atopic dermatitis and its 
reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol. 
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Charman CR, Venn AJ, Ravenscroft JC, Williams HC. Translating Patient-Oriented Eczema 
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anchor-based methods.  Br J Dermatol. Dec 2013;169(6):1326-32. 
Charman CR, Venn AJ, Williams HC. The Patient-Oriented Eczema Measure: Development 
and Initial Validation of a New Tool for Measuring Atopic Eczema Severity From the 
Patients' Perspective. Arch Dermatol. 2004;140:1513-9. 
Croft M. Control of Immunity by the TNFR-Related Molecule OX40 (CD134). Annu Rev 
Immunol. 2010 Mar;28(1):57-78.  
Drucker AM, Wang AR, Li WQ, Sevetson E, Block JK, Qureshi AA. The Burden of Atopic 
Dermatitis: Summary of a Report for the National Eczema Association. J Invest Dermatol. 
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Force Covid Vaccination Advice. 2021 [cited 2021 July]. Available from: 
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%20TF%20ADVICE_02-10-2021-13-12-40.pdf 
Eichenfield LF, Tom WL, Chamlin SL, Feldman SR, Hanifin JM, Simpson EL, et al. 
Guidelines of care for the management of atopic dermatitis: Section 1. Diagnosis and 
assessment of atopic dermatitis. J Am Acad Dermatol. 2014;70(2):338-51. 
Garmhausen D, Hagemann T, Bieber T, Dimitriou I, Fimmers R, Diepgen T, et al. 
Characterization of different courses of atopic dermatitis in adolescent and adult patients. 
Allergy. 2013 Apr;68(4):498-506.  
Gauvreau GM, Boulet LP, Cockcroft DW, FitzGerald JM, Mayers I, Carlsten C, et al. OX40L 
blockade and allergen-induced airway responses in subjects with mild asthma. Clin Exp 
Allergy. 2013 Jan;44(1):29-37.  
Gittler JK, Shemer A, Suárez-Fariñas M, Fuentes-Duculan J, Gulewicz KJ, Wang CQF, et al. 
Progressive activation of TH2/TH22 cytokines and selective epidermal proteins characterizes 
acute and chronic atopic dermatitis. J Allergy Clin Immunol. 2012 Dec;130(6):1344-54. 
Guttman-Yassky E, Pavel AB, Estrada Y, Zhou L, Salhi Y, Gudi G, et al. 453 GBR 830 induces 
progressive and sustained changes in atopic dermatitis biomarkers in patient skin lesions. J 
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Guttman-Yassky E, Pavel AB, Zhou L, Estrada YD, Zhang N, Xu H, et al. GBR 830, an 
anti-OX40, improves skin gene signatures and clinical scores in patients with atopic dermatitis. 
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Guttman-Yassky E, Blauvelt A, Eichenfield LF, Paller AS, Armstrong AW, Drew J, et al. 
Efficacy and Safety of Lebrikizumab, a High-Affinity Interleukin 13 Inhibitor, in Adults With 
Moderate to Severe Atopic Dermatitis: A Phase 2b Randomized Clinical Trial. JAMA 
Dermatol. 2020;156(4):411-20.  
Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M, et al. The eczema area 
and severity index (EASI): assessment of reliability in atopic dermatitis: EASI: assessment of 
reliability in AD. Exp Dermatol. 2001 Feb;10(1):11-8. 
Ilves T, Harvima IT. OX40 ligand and OX40 are increased in atopic dermatitis lesions but do 
not correlate with clinical severity: OX40/OX40L in atopic dermatitis. J Eur Acad Dermatol 
Venereol. 2013 Feb;27(2):e197-205.  
Kay J, Gawkrodger DJ, Mortimer MJ, Jaron AG. The prevalence of childhood atopic eczema 
in a general population. J Am Acad Dermatol. 1994 Jan;30(1):35-9.  
Kitamura N, Murata S, Ueki T, Mekata E, Reilly RT, Jaffee EM, et al. OX40 costimulation 
can abrogate Foxp3+ regulatory T cell-mediated suppression of antitumor immunity. Int J 
Cancer. 2009;125(3):630-8.  
Langan SM, Irvine AD, Weidinger S. Atopic dermatitis. Lancet. 2020 
Aug 1;396(10247):345-60. Erratum in: Lancet. 2020 Sep 12;396(10253):758.  
Papp KA, Gooderham MJ, Girard G, Raman M, Strout V. Phase I randomized study of 
KHK4083, an anti-OX40 monoclonal antibody, in patients with mild to moderate plaque 
psoriasis. J Eur Acad Dermatol Venereol. 2017 Aug;31(8):1324-32.  
Perkin MR, Strachan DP, Williams HC, Kennedy CTC, Golding J, the ALSPAC Study Team. 
Natural history of atopic dermatitis and its relationship to serum total immunoglobulin E in a 
population-based birth cohort study. Pediatr Allergy Immunol. 2004 Jun;15(3):221-9.  
Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the European 
Task Force on Atopic Dermatitis. Dermatol Basel Switz. 1993;186(1):23-31. 
Silverberg JI, Hanifin JM. Adult eczema prevalence and associations with asthma and other 
health and demographic factors: A US population-based study. J Allergy Clin Immunol. 2013 
Nov;132(5):1132-8.  
Stalder J-F, Barbarot S, Wollenberg A, Holm EA, De Raeve L, Seidenari S, et al. 
Patient-Oriented SCORAD (PO-SCORAD): a new self-assessment scale in atopic dermatitis 
validated in Europe: PO-SCORAD self-assessment scale validation. Allergy. 2011 
Aug;66(8):1114-21. 
Ständer S, Zeidler C, Riepe C, Steinke S, Fritz F, Bruland P, et al. European EADV network 
on assessment of severity and burden of Pruritus (PruNet): first meeting on outcome tools. J 
Eur Acad Dermatol Venereol. 2016 Jul;30(7):1144-7. 
Thaçi D, Simpson EL, Beck LA, Bieber T, Blauvelt A, Papp K, et al. Efficacy and safety of 
dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by 
topical treatments: a randomised, placebo-controlled, dose-ranging Phase 2b trial. The Lancet. 
2016;387(10013):40-52. 
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Webb GJ, Hirschfield GM, Lane PJL. OX40, OX40L and Autoimmunity: a Comprehensive 
Review. Clin Rev Allergy Immunol. 2016 Jun;50(3):312-32.  
Weidinger S, Beck LA, Bieber T, Kabashima K, Irvine AD. Atopic dermatitis. Nat Rev Dis 
Primer [Internet]. 2018 Dec [cited 2018 Jul 26];4(1). Available from: 
http://www.nature.com/articles/s41572-018-0001-z. 
Weidinger S, Novak N. Atopic dermatitis. The Lancet. 2016 Mar;387(10023):1109-22. 
 
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17 
APPENDICES  
17.1 Appendix 1 - Protocol Amendments  
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the STUDY PERSONNEL. 
This is the ninth version of the protocol. Details of the key changes made in each version are 
provided below. 
 
  
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17.1.2 Amended Clinical Trial Protocol 04 (14 December 2021)  
This amended clinical trial protocol 04 is considered non-substantial based on the criteria set 
forth in Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of 
the European Union, because it does not significantly impact the safety or physical/mental 
integrity of participants, nor the scientific value of the study. 
OVERALL RATIONALE FOR THE AMENDMENT 
The primary reason for this amendment to Protocol KY1005-CT05 is to fulfil requirement from 
Pharmaceuticals and Medical Devices Agency (PMDA), Japan. 
 
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17.1.3 Amended Clinical Trial Protocol 05 (18 January 2022)  
This amended clinical trial protocol 05 is considered substantial based on the criteria set forth 
in Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union. 
OVERALL RATIONALE FOR THE AMENDMENT 
The primary reason for this amendment to Protocol KY1005-CT05 is to fulfil requirement from 
the Medicines and Healthcare products Regulatory Agency (MHRA), UK. 
 
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17.1.4 Amended Clinical Trial Protocol 06 (03 February 2022)  
This amended clinical trial protocol 06 is considered non-substantial based on the criteria set 
forth in Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of 
the European Union. 
OVERALL RATIONALE FOR THE AMENDMENT 
The primary reason for this amendment to Protocol KY1005-CT05 is to fulfil requirement from 
the Hungary Ethics Committee for Clinical Pharmacology, Emberi Erőforrások Minisztériuma, 
Ministry of Human Capacities. 
 
 
17.1.5 Amended Clinical Trial Protocol 07 (10 February 2022)  
This amended clinical trial protocol 07 is considered non-substantial based on the criteria set 
forth in Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of 
the European Union. 
OVERALL RATIONALE FOR THE AMENDMENT 
The primary reason for this amendment to Protocol KY1005-CT05 is to fulfil requirements 
from the German authorities Paul-Ehrlich-Institut (PEI) and Ethics Committee (EC) of the 
State of Berlin (Ethik-Kommission des Landes Berlin). 
 
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17.2 Appendix 2 - Eczema Area and Severity Index  
 
Source: Hanifin et al (2001) [Hanifin Exp Dermatol 2001]; reproduced with permission of Wiley (© Munksgaard 2001, 
managed by Wiley). 
 
 
 
 
 
 
 
 
 
 
 
 
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17.3 Appendix 3 - Investigator Global Assessment Scale  
Investigator Global Assessment scale for Atopic 
 
 
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17.4 Appendix 4 - SCORing of Atopic Dermatitis Index (SCORAD Index)  
 
Source: European Task Force on Atopic Dermatitis (2003)  
 
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POEM for self-completion 
17.5 Appendix 5 - Patient Oriented Eczema Measure  
 
 
Please circle one response for each of the seven questions below about your eczema. Please 
leave blank any questions you feel unable to answer.  
1. Over the last week, on how many days has your skin been itchy because of your eczema?  
No days  
1-2 days  
3-4 days  
5-6 days  
Every day  
2. Over the last week, on how many nights has your sleep been disturbed because of your 
eczema?  
No days  
1-2 days  
3-4 days  
5-6 days  
Every day  
3. Over the last week, on how many days has your skin been bleeding because of your eczema?  
No days  
1-2 days  
3-4 days  
5-6 days  
Every day  
4. Over the last week, on how many days has your skin been weeping or oozing clear fluid because 
of your eczema?  
No days  
1-2 days  
3-4 days  
5-6 days  
Every day  
5. Over the last week, on how many days has your skin been cracked because of your eczema?  
No days  
1-2 days  
3-4 days  
5-6 days  
Every day  
6. Over the last week, on how many days has your skin been flaking off because of your eczema?  
No days  
1-2 days  
3-4 days  
5-6 days  
Every day  
7. Over the last week, on how many days has your skin felt dry or rough because of your eczema? 
No days  
1-2 days  
3-4 days  
5-6 days  
Every day  
Total POEM Score (Maximum 28): 
_________________
© The University of Nottingham  
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POEM for self-completion 
 
 
 
 
 
How is the scoring done? 
Each of the seven questions carries equal weight and is scored from 0 to 4 as follows: 
 
 
 No days 
= 0 
 
1-2 days 
= 1 
 
3-4 days 
= 2 
 
5-6 days 
= 3 
 
Every day 
= 4 
 
Note: 
 
• If one question is left unanswered this is scored 0 and the scores are summed and 
expressed as usual out of a maximum of 28 
  
• If two or more questions are left unanswered the questionnaire is not scored 
   
• If two or more response options are selected, the response option with the highest score 
should be recorded 
 
References 
Charman CR, Venn AJ, Williams HC. The Patient-Oriented Eczema Measure: Development and Initial Validation of a New 
Tool for Measuring Atopic Eczema Severity From the Patients' Perspective. 
Arch Dermatol. 2004;140:1513-1519 
Charman CR, Venn AJ, Ravenscroft JC, Williams HC. Translating Patient-Oriented Eczema Measure (POEM) scores into 
clinical practice by suggesting severity strata derived using anchor-based methods.   
Br J Dermatol. Dec 2013; 169(6): 1326–1332. 
© The University of Nottingham  
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17.6 Appendix 6 - Dermatology Quality of Life Index  
The aim of this questionnaire is to measure how much your skin problem has affected your life OVER 
THE LAST WEEK.  Please tick  one box for each question. 
 
1. 
Over the last week, how itchy, sore,  
 
 
Very much 
 
 
painful or stinging has your skin   
 
 
A lot 
 
 
 
been?   
 
 
 
 
 
A little  
 
 
 
 
 
 
 
 
 
Not at all 
 
 
2. 
Over the last week, how embarrassed 
 
 
Very much 
 
 
or self conscious have you been because   
 
A lot 
 
 
 
of your skin? 
 
  
 
 
 
A little  
 
 
 
 
 
 
 
 
 
Not at all 
 
 
3. 
Over the last week, how much has your  
 
 
Very much 
 
 
skin interfered with you going 
 
  
 
A lot 
 
 
 
shopping or looking after your home or   
 
A little  
 
 
garden? 
 
 
 
 
 
Not at all 
 
Not relevant  
 
4. 
Over the last week, how much has your  
 
 
Very much 
 
 
skin influenced the clothes  
 
 
 
A lot 
 
 
 
you wear? 
 
 
 
 
 
A little  
 
 
 
 
 
 
 
 
 
Not at all 
 
Not relevant  
 
5. 
Over the last week, how much has your  
 
 
Very much 
 
 
skin affected any social or  
 
 
 
A lot 
 
 
 
leisure activities? 
 
 
 
 
A little  
 
 
 
 
 
 
 
 
 
Not at all 
 
Not relevant  
 
6. 
Over the last week, how much has your  
 
 
Very much 
 
 
skin made it difficult for   
 
 
 
A lot 
 
 
 
you to do any sport? 
 
 
 
 
A little  
 
 
 
 
 
 
 
 
 
Not at all 
 
Not relevant  
 
7. 
Over the last week, has your skin prevented 
 
Yes 
 
 
 
you from working or studying?  
 
 
No 
 
 
Not relevant  
 
 
 
If "No", over the last week how much has   
 
A lot 
 
 
 
your skin been a problem at  
 
 
 
A little  
 
 
work or studying? 
 
 
 
 
Not at all 
 
 
8. 
Over the last week, how much has your  
 
 
Very much 
 
 
skin created problems with your   
 
 
A lot 
 
 
 
partner or any of your close friends 
 
 
A little  
 
 
or relatives?  
 
 
 
 
 
Not at all 
 
Not relevant  
 
9. 
Over the last week, how much has your  
 
 
Very much 
 
 
skin caused any sexual   
 
 
 
A lot 
 
 
 
difficulties? 
 
 
 
 
 
A little  
 
 
 
 
 
 
 
 
 
Not at all 
 
Not relevant  
 
10. 
Over the last week, how much of a  
 
 
Very much 
 
 
problem has the treatment for your 
 
 
A lot 
 
 
 
skin been, for example by making  
 
 
A little  
 
 
your home messy, or by taking up time?   
 
Not at all 
 
Not relevant  
 
Please check you have answered EVERY question. Thank you.  
AY Finlay, GK Khan, April 1992 www.dermatology.org.uk, this must not be copied without the permission of the authors. 
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17.7 Appendix 7 - Atopic Dermatitis Control Tool  
 
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17.8 Appendix 8 - Hospital Anxiety and Depression Scale  
 
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17.9 Appendix 9 - Pruritus Numeric Rating Scale  
 
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17.10 Appendix 10 - Contraceptive and Barrier Guidance  
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
Highly effective methodsb that have low user dependency Failure rate of <1% per year when used consistently 
and correctly. 
• Implantable progestogen-only hormone contraception associated with inhibition of ovulation 
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS) 
• Bilateral tubal occlusion 
• Azoospermic partner (vasectomized or due to a medical cause) 
Azoospermia is a highly effective contraceptive method provided that the partner is the sole sexual partner of 
the woman of childbearing potential and the absence of sperm has been confirmed. If not, an additional highly 
effective method of contraception should be used.  
Note: documentation of azoospermia for a male participant can come from the site personnel’s review of the 
participant’s medical records, medical examination, or medical history interview. 
Highly effective methodsb that are user dependent Failure rate of <1% per year when used consistently and 
correctly. 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation 
- oral 
- intravaginal 
- transdermal 
- injectable 
Progestogen-only hormone contraception associated with inhibition of ovulation 
- oral 
- injectable 
Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of risk associated with the study intervention. The reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of 
the participant. 
a) Contraceptive use by men or women should be consistent with local regulations regarding the use of 
contraceptive methods for those participating in clinical studies. 
b) Failure rate of <1% per year when used consistently and correctly. Typical use failure rates differ from those 
when used consistently and correctly. 
 Note: Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhea method (LAM) are not acceptable methods of contraception for 
this study. Male condom and female condom should not be used together (due to risk of failure from friction) 
 
 
 
 
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17.11 Appendix 11 - Reporting of Serious Adverse Events  
SAE reporting to the Sponsor via an electronic data collection tool 
• The primary mechanism for reporting an SAE to the Sponsor’s representative will be 
the electronic data collection tool. 
• If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) to report the event within 24 hours. 
• The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
• After the study is completed at a given site, the electronic data collection tool will be 
taken off-line to prevent the entry of new data or changes to existing data. 
• If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form (see next 
section) or to the Sponsor’s representative by telephone. 
• Contacts for SAE reporting can be found in the Investigator Site File. 
Serious adverse event reporting to the Sponsor via paper data collection tool (In case of 
failure of electronic reporting of SAE via the EDC system) 
• Facsimile transmission of the SAE paper data collection tool is the preferred method 
to transmit this information to the Sponsor’s representative. 
• In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by overnight 
mail or courier service. 
• Initial notification via telephone does not replace the need for the Investigator to 
complete and sign the SAE data collection tool within the designated reporting time 
frames. 
• Contacts for SAE reporting can be found in the Investigator Site File. 
 
 
 
 
 
 
 
 
 
 
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17.12 Appendix 12 - Liver safety: suggested actions and follow-up 
assessments  
 
*If unable to retest in 72 hours, use original lab results to decide on further reporting/monitoring/discontinuation.  
Note: 
“Baseline” refers to ALT sampled at the Baseline Visit; or if the Baseline value unavailable, to the latest ALT 
sampled before the Baseline Visit.  The algorithm does not apply to the instances of increase in ALT during 
screening. 
See Section 17.10 (Appendix 10) for guidance on safety reporting. 
Normalisation is defined as ≤ ULN or baseline value, if the Baseline value is > ULN. 
INCREASE IN ALT
ALT > 3 ULN
Confirm ALT > 3 ULN
Retest within 72 hours of initial 
sample*
No
Yes
COMPLETE the specific CRF forms for 
„ALT Increase” and inform the 
Monitoring Team within 24 hours
Total Bilirubin > 2 ULN 
No
Yes
ALT > 5 ULN (if baseline ALT ≤ 2 ULN), or 
ALT >8 ULN (if baseline ALT > 2 ULN)
Continue IMP administration
No
Monitor LFTs every 72 hours
IMP administration can be continued as 
long as – under close monitoring –
conditions for permanent 
discontinuation or temporary 
interruption per protocol are not met
Yes
Permanent Discontinuation of IMP
In ANY CASE, FOLLOW the instructions listed in the box below: 
1.
INFORM the Site Monitor who will forward the information to the Study Manager
2.
INVESTIGATE specifically for malaise with or without loss of consciousness, dizziness, and/or hypotension and/or episode of 
arrhythmia in the previous 72 hours; rule out muscular injury
3.
PERFORM the following tests:
- LFTs: AST, ALT, alkaline phosphatase, total and conjugated bilirubin and prothrombin time / INR
- CPK, serum creatinine, complete blood count
- Anti-HAV IgM, anti-HBc IgM (HBV-DNA if clinically indicated), anti-HCV and HCV RNA, anti-
CMV  IgM and anti-HEV IgM antibodies
- Depending on the clinical context, check for recent infection with EBV, herpes viruses, and toxoplasma
- Hepatobiliary ultrasonography (or other imaging investigations if needed)
4.
CONSIDER Auto-antibodies: antinuclear, anti-DNA, anti-smooth muscle, anti-LKM
5.
CONSIDER consulting with hepatologist
6.
CONSIDER patient hospitalisation if INR>2 (or PT<50%) and/or central nervous system disburbances suggesting hepatic 
encephalopathy
7.
MONITOR LFTs after discontinuation of IMP:
- As closely as possible (or every 48 hours) until stabilization, then every 2 weeks until return to normal/baseline or clinical 
resolution.
8.
FREEZE serum sample (5ml x 2)
9.   In case of SUSPICION of GILBERT Syndrome, a DNA diagnostic test should be done
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• 
 
 
 
  
• 
 
 
 
   
• 
 
 
   
• 
 
 
  
• 
  
• 
 
  
• 
 
 
 
  
 
 
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17.14 Appendix 14 - Contingency Measures for a Regional or National 
Emergency That is Declared by a Governmental Agency  
Contingency procedures are suggested for an emergency that prevents access to the study site, 
to ensure the safety of the patients, to consider continuity of the clinical study conduct, protect 
trial integrity, and assist in maintaining compliance with GCP in Conduct of Clinical Trials 
Guidance. 
The following contingencies may be implemented for the duration of the emergency (after 
Sponsor agreement is obtained). Contingencies implemented due to emergency will be 
documented. 
Informed consent 
In exceptional circumstances, such as a regional or national emergency declared by a 
governmental agency, consent may be collected through a remote solution if allowed through 
country and site regulations and following approval by the Independent Ethics Committees 
(IEC)/ Institutional Review Boards (IRB). Implementation must have prior approval from the 
Sponsor (or its designee).  Contingency procedures may be implemented for the duration of 
the emergency.  
The patient or their legally authorised representative should be verbally informed prior to 
initiating any changes that are to be implemented for the duration of the emergency (eg, study 
visit delays/treatment extension). 
Study drug administration 
During the initial part of the study (up to and including Day 57 [Week 8]), study drug must be 
administered in accordance with Section 1.5.4, Section 1.7 and Section 5.2. At all other times, 
consideration may be given to administration of study drug at home if all conditions in the 
Pharmacy manual are adhered to and prior Sponsor agreement is obtained. 
Temporary IMP discontinuation may apply in exceptional cases, under regional or national 
emergencies (eg, natural disaster, epidemic diseases, terrorist attack) due to which a visit at the 
clinical study site is no longer feasible.  
In the case of an exceptional temporary treatment discontinuation, the discontinuation should 
be approved by the Sponsor.  The Sponsor should also be notified to determine if treatment 
should be resumed. If deemed safe, the treatment can be resumed at the next scheduled or 
unscheduled visit.  During the discontinuation period, remote checks (eg, telephone/video 
calls) will take the place of on-site visits per the Schedule of Assessments (Section 6.1). 
Study assessments and procedures 
Attempts should be made to perform all assessments in accordance with the approved protocol 
to the extent possible.  In case this is not possible due to a temporary disruption caused by a 
government declared regional or national emergency, focus should be given to assessments 
necessary to ensure the safety of patients and those important to preserving the main scientific 
value of the study. 
Use of local clinic or laboratory locations may be allowed when central labs analyses cannot 
be performed due to a government declared regional or national emergency.  These local 
laboratory results will only be performed to ensure patient safety and will not be used for the 
purpose of statistical analyses. 
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If onsite visits are not possible the implementation of remote visits (eg, phone call, virtual 
consultation, televisit, etc) or home visits (eg, home nurses, etc) may be planned for the 
collection of possible safety and/or efficacy data. 
A Televisit is defined as a videoconference, video call or telephone call.  
The following conditions must be met at a site level before such visits can be authorised. 
• The visit must be performed by appropriately delegated study site staff or a home 
healthcare service.  
• 
The correct equipment necessary to perform the required assessments must be taken to 
the visits. 
• 
Home visits or televisits must be permitted by the site, local regulations, relevant ethics 
committee, relevant regulatory authority.  
• 
The patient must have given consent via informed consent.  
• Prior to implementing remote study visits for patients, notification to the Sponsor (or 
its designee) must be provided. The notification should include justification and 
expected patients and visits that may be impacted.  
Visit windows may be extended for assessment of safety and/or efficacy data that cannot be 
obtained remotely.  Possibility of visit extension and duration of such extension must be 
discussed on a case-by-case basis with the Sponsor considering first of all patients’ safety and 
best interests. 
If the above emergency scenario occurs during the follow-up period, one or more follow up 
visits can be performed remotely (eg, via telephone calls or video calls), but at least one 
follow-up visit should be performed on site (EOS visit), even if the visit window needs to be 
extended.  Remote follow-up should be conducted according to local regulations and approved 
by the Sponsor. 
If the above emergency scenario leads to site closure or complete regional or national 
lock-down, the study may be suspended for the affected sites.  
 
 
 
 
 
 
 
 
 
 
 
 
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17.15 Appendix 15 - Country-specific Requirements  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
  
 
 
 
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