Clinical trial NCT03985943
Conditions: Moderate-to-Severe Atopic Dermatitis
Keywords: CD14152 Nemolizumab Atopic Dermatitis
Sponsor: Galderma R&D
Start date: 2019-06-27; Completion date: 2022-08-11
Enrollment: 941 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The main purpose of the study was to assess the efficacy and safety of nemolizumab after a 16-week treatment period in adult and adolescent subjects with moderate-to-severe atopic dermatitis (AD) not adequately controlled with topical treatments.

Detailed description:
This was a randomized, double-blind, placebo-controlled, multi-center, parallel-group study in adult and adolescent subjects of age 12 years and above with moderate-to-severe AD. Eligible subjects had a documented history of inadequate response to topical AD medication(s). Approximately 750 subjects were randomized in 2:1 to receive either nemolizumab or placebo, stratified by baseline disease severity (Investigator's Global Assessment (IGA) = 3, moderate; IGA = 4, severe) and peak pruritus numeric rating scale (PP NRS) severity (PP NRS \>= 7; PP NRS \< 7). A minimum of 250 subjects were randomized in each PP NRS strata. All nemolizumab-treated subjects who were clinical responders at Week 16 (i.e., the end of initial treatment \[Initial Treatment Period\]/beginning of Maintenance Period) were re-randomized (1:1:1) to different treatment regimens (nemolizumab injections Q4W or every 8 weeks (Q8W) \[with placebo injections at Weeks 20, 28, 36, and 44 to maintain the blind\] or placebo Q4W). A clinical responder was defined as a subject at Week 16 with an IGA of 0 (clear) or 1 (almost clear) or a \>= 75% improvement in EASI from baseline (EASI-75). All placebo-treated subjects who responded to placebo during the Initial Treatment Period continued to receive placebo Q4W in the Maintenance Period.

Arms: arm 1: Placebo arm 2: Nemolizumab Active
Interventions: intervention 1: Placebo intervention 2: Nemolizumab
Intervention descriptions: intervention 1: Placebo intervention 2: Nemolizumab

Protocol documents:
Prot_000.pdf: 
CLINICAL STUDY PROTOCOL
A Randomized, Double-Blind, Placebo-Controlled Study to Assess the 
Efficacy and Safety of Nemolizumab (CD14152) in Subjects with 
Moderate-to-Severe Atopic Dermatitis 
Protocol Number:
RD.06.SPR.118161
EudraCT Number:
2019-001887-31
Syneos Health Study Number:
1008782
Investigational Product:
Nemolizumab (CD14152)
IND Number:
117122
Phase:
3
Sponsor:
Galderma S.A.
Avenue Gratta-Paille 2
1018 Lausanne
Switzerland
Galderma Research & Development, LLC
14501 North Freeway
Fort Worth, TX 76177
United States
Contract Research Organization:
Syneos Health
1030 Sync Street
Morrisville, NC 27560
United States
Protocol Date:
4 Nov 2021
Protocol Version:
Version 8.0
CONFIDENTIAL
This document contains confidential, proprietary information, and may not be 
reproduced or communicated to a third party without the written permission of 
Galderma S.A./Galderma R&D, LLC
 
              
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Medical Director, Asia
Name:
Title:
Senior Medical Director
Telephone No.:
Mobile No.: 
Email: 
 
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3
SYNOPSIS
Protocol Number:
RD.06.SPR.118161
Title:
A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of 
Nemolizumab (CD14152) in Subjects with Moderate-to-Severe Atopic Dermatitis 
Investigational Product:
Nemolizumab (CD14152)
IND Number:
117122
Study Centers:
Approximately 150 study centers are planned in Europe, Americas, and Asia-Pacific.
Phase:
3
Objectives:
Primary objective: The primary objective is to assess the efficacy and safety of nemolizumab (CD14152) 
after a 16-week treatment period in adult and adolescent subjects with moderate-to-severe atopic 
dermatitis (AD) not adequately controlled with topical treatments.
Secondary objective: The secondary objective is to evaluate the efficacy and safety of maintenance 
treatment with nemolizumab (CD14152) for up to an additional 32 weeks.
Study Design:
This is a randomized, double-blind, placebo-controlled, multicenter, parallel-group study in adult and 
adolescent subjects with moderate-to-severe AD. Eligible subjects must have a documented history of 
inadequate response to topical AD medication(s).
Approximately 750 total subjects will be randomized (2:1) to receive either nemolizumab (CD14152) 
or placebo, stratified by baseline disease severity (Investigator’s Global Assessment [IGA]; moderate:
IGA = 3; severe: IGA = 4) and peak pruritus numeric rating scale (PP NRS) severity (PP NRS ≥7; 
PP NRS < 7). A minimum of 250 subjects will be randomized in each PP NRS strata. Clinical 
responders at Week 16 (ie, the end of initial treatment/beginning of maintenance) will be re-
randomized (1:1:1) to different treatment regimens (injections every 4 weeks [Q4W] or every 8 weeks 
[Q8W] of nemolizumab [CD14152] or placebo Q4W). 
Subjects will apply a moisturizer at least once daily, beginning at screening. Subjects will also be 
provided or prescribed background topical therapy for AD (including a medium-potency topical 
corticosteroid [TCS] for the body and a low-potency TCS or topical calcineurin inhibitor (TCI) for 
sensitive areas such as the face, neck, intertriginous areas, etc for use throughout the study. If deemed to 
be medically necessary by the investigator (eg, to control intolerable AD signs/symptoms), rescue 
therapies can be prescribed to the subjects during the study, except during the run-in period (ie, at least 
2 weeks [14 days] before Day 1/baseline).
 
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The study consists of 4 periods over approximately 60 weeks: screening (including run-in), initial 
treatment, maintenance, and follow-up (unless the subject is a non-responder at Week 16, at which 
their participation could last up to 28 weeks). Refer to Figure 1 for an overview of the treatment/study
design.
An independent data monitoring committee (IDMC) will review and monitor subject safety throughout 
the study, and an independent adjudication committee (IAC) will review all asthma-related events 
throughout the study. Details on the IDMC and IAC, including the plan of analysis for outputs; the 
composition of the committees; and the procedures, roles, responsibilities, and communications are 
provided in the respective IDMC and IAC charters.
Screening Period (Screening to Initial Randomization/Baseline)
The screening period (approximately 2-4 weeks before planned Day 1/baseline) will evaluate subject 
eligibility and introduce standardized background topical therapy over a run-in period of at least 2 weeks 
(ie, 14 days) before Day 1/baseline.
Initial Treatment Period (Baseline/Day 1 to Week 16 Pre-dose)
The initial treatment period is defined as Day 1/baseline through Week 16 (before the Week 16 dose,
with last dose at Week 12). Eligible subjects will be randomized in a ratio of 2:1 at baseline to receive 
subcutaneous injections of nemolizumab (CD14152) or placebo Q4W.
Subjects will continue to use background topical therapy, which should be adjusted according to the 
disease activity and tolerability, including tapering when signs and symptoms improve, discontinuation 
when lesions clear, and restarting if signs and symptoms recur, based on investigator clinical judgment. 
Table 1: Initial Treatment Period Randomized Group Assignments
Group
Treatment
Loading dose 
(Day 1/Baseline)
Dose at Week 4, 8, 12
Route
Schedule
1
Nemolizumab
(CD14152)
60 mg (two 30-mg 
injections)
30 mg
sc
Q4W
2
Placebo
Placebo (two 
injections)
Placebo
sc
Q4W
Abbreviation(s): Q4W = every 4 weeks; sc = subcutaneous.
Clinical assessments will occur according to the schedule of assessments through the Week 16 visit (see 
Section 8.1.2 ). Subjects who are clinical responders at Week 16 will continue to the maintenance period.
Subjects who are non-responders at Week 16 may be eligible to enroll into a long-term extension (LTE) 
study (Protocol 118163). Subjects who require rescue therapy for clinical worsening of AD before Week 
16 may also be considered for the LTE study but will be required to continue with study visits until the 
Week 16 visit. The follow-up visit is not required for subjects who participate in the LTE study.
Subjects who decline or are not eligible to enter into the LTE study will complete a follow-up visit 12
weeks after their last study drug injection.
Subjects who discontinue the initial treatment period prematurely should complete an early termination
(ET) visit and a follow-up visit 12 weeks after the last study drug injection. 
Initial treatment period results may be analyzed after all subjects have either completed the 
Week 16 visit or have withdrawn or been discontinued from the study before Week 16. To 
maintain the blind during the maintenance period, personnel directly involved with the ongoing 
 
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conduct of the study from the sponsor, contract research organization, or investigational study centers
will not have access to any information that may lead to unblinding.
Maintenance Period (Re-Randomization: Week 16 to Week 48)
The maintenance period is defined as Week 16 (maintenance baseline) to Week 48. All nemolizumab
(CD14152)-treated subjects (ie, group 1) who are clinical responders at Week 16 will be re-randomized 
(1:1:1) to study medication, as follows: group 1A, nemolizumab (CD14152) 30 mg Q4W; group 1B,
nemolizumab 30 mg Q8W; or group 1C, placebo Q4W.
Clinical responders are defined as: 

IGA of 0 (clear) or 1 (almost clear) at Week 16
OR

Eczema Area and Severity Index (EASI)-75 at Week 16
All placebo-treated subjects (ie, subjects in group 2 from the initial treatment period) who responded to 
placebo during the initial treatment period will continue to receive placebo Q4W in the maintenance 
period. 
Subjects who receive rescue therapy will be considered non-responders.
Based on the phase 2b results (Protocol 114322), it is estimated that 15% of subjects will drop out from 
the initial treatment period. Assuming a 45% responder rate in active treatment and 12% with placebo, 
approximately 216 subjects will participate in the maintenance period (190 nemolizumab and 26 placebo 
subjects).
Table 2: Maintenance Period Re-Randomized Group Assignments
Group
Treatment
Dose
Week(s)
Route
Schedule
1A
Nemolizumab
(CD14152)
30 mg
16, 20, 24, 28, 32, 36, 40, 44
sc
Q4W
1B
Nemolizumab
(CD14152)
30 mg
16, 20*, 24, 28*, 32, 36*, 40, 44*
sc
Q8W*
1C 
Placebo
Placebo
16, 20, 24, 28, 32, 36, 40, 44
sc
Q4W
*with placebo Q4W at Week 20, 28, 36, and 44 to maintain blind
Abbreviation(s): Q4W=every 4 weeks; Q8W=every 8 weeks; sc=subcutaneous.
Beginning at Week 16, subjects in group 1A will receive active (ie, nemolizumab [CD14152]) study drug 
injections Q4W up to Week 44. Subjects in group 1B will receive active study drug injections Q8W, 
with placebo at alternating visits to maintain the blind. Group 1B subjects will receive the last active
study drug injection at Week 40 (final injection at Week 44 will be placebo). Group 1C subjects will 
receive placebo Q4W (ie, through Week 44).
Subjects should continue the same background topical therapy used in the initial treatment period 
leading up to the Week 16 visit, including tapering or complete cessation (no use), if applicable. 
Throughout the maintenance period, adjustments to background topical therapy, as determined by the 
investigator, are permitted based on the subject’s clinical response.
Primary maintenance effect will be evaluated based on Week 48 assessments. All maintenance 
endpoints will be analyzed independently from each pivotal study and by using pooled data after the 
completion of both trials.
 
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Subjects requiring rescue therapy before the Week 32 visit must undergo a required wait period (with 
continued study visits) until the Week 32 visit, at which time they may be considered for LTE
eligibility/participation. Thereafter, no wait period is required. 
Subjects who complete the Week 48 visit may be eligible to enroll into the LTE study (Protocol 118163). 
Subjects requiring rescue medication before the Week 48 visit may be considered for LTE eligibility.
The follow-up visit is not required for subjects who participate in the LTE study.
Subjects who decline or are not eligible for the LTE study will be asked to complete the follow-up visit.
Subjects who discontinue the maintenance period prematurely should complete an ET visit and a follow-
up visit 12 weeks after the last study drug injection. 
Follow-up 
The follow-up visit will be conducted 12 weeks after the last study drug injection for subjects who 
decline or are not eligible to enter the LTE study. (Twelve weeks corresponds to approximately 5 half-
lives when nemolizumab 30 mg is dosed subcutaneously Q4W.) The follow-up visit is not required for 
subjects who participate in the LTE study.
Number of Subjects: 
Approximately 750 total subjects are planned to be randomized, including a minimum of 130
adolescent subjects aged 12 to 17 years.
Treatment:
Nemolizumab (CD14152) or placebo will be provided as lyophilized powder for solution for injection
for subcutaneous use only after reconstitution in a single-use, pre-filled, dual-chamber syringe (DCS).
During the initial treatment period, eligible subjects will be randomized to receive either 30 mg of 
nemolizumab (CD14152) in group 1 or placebo in group 2, administered as a subcutaneous injection 
only after reconstitution Q4W for 16 weeks (last injection at Week 12), with a loading dose of 60 mg 
on Day 1/baseline. 
Subjects (and/or their caregivers) will have the option to self-inject study drug while at the study center 
under staff supervision. Subjects (and/or their caregivers) will be trained on injecting the study drug at 
Day 1 and will be allowed to inject study drug at all subsequent visits, while at the study center, under 
staff supervision. If the subject (and/or caregivers) is unwilling to perform the injections, study staff can 
administer study drug at each visit.
In the maintenance period, group 1 subjects who are clinical responders will be re-randomized to 
receive either 30 mg of nemolizumab (CD14152) or placebo for 32 weeks. Subjects in group 1A will 
receive a subcutaneous injection of nemolizumab Q4W (last injection at Week 44); group 1B will 
receive an injection of nemolizumab Q8W, with alternating placebo Q8W (last active injection at Week 
40 and last placebo injection at Week 44); and group 1C will receive placebo Q4W. Subjects in group 2 
who are clinical responders will continue to receive placebo Q4W. 
Moisturizer
Subjects will apply a moisturizer at least once daily, and liberally as needed, to dry skin and AD lesions 
beginning at screening, and throughout the study. The subjects’ current moisturizer or a moisturizer 
recommended by the investigator may be used. To allow for accurate assessment of skin dryness, use 
should not occur within 8 hours before each clinic/office visit. Whenever possible, subjects should use 
the same moisturizer throughout the study.
 
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Background topical therapies
Subjects will be provided or prescribed authorized background topical therapy for use during the study, 
beginning at screening:

Medium-potency TCS therapy for non-sensitive areas: Subjects will apply the authorized medium-
potency TCS background therapy in areas of the body where use of medium-potency TCS is 
considered safe (eg, trunk and extremities), beginning within the screening period and ≥14 days 
before Day 1 (ie, run-in). Refer to the current version of the pharmacy manual for a listing of 
permitted medium-potency TCS medications that are commercially available in planned countries.

Low-potency TCS or TCI therapy for sensitive areas: Subjects will apply an authorized background 
therapy (ie, low-potency TCS or TCI) to areas of the body considered TCS-sensitive (eg, face, neck, 
intertriginous areas) or in cases where medium-potency TCS is not tolerated, beginning within the 
screening period and ≥14 days before Day 1 (ie, run-in). The investigator may select either low-
potency TCS or TCI for each subject, per investigator discretion. The subject may only apply one
medication to each affected area; concomitant use of low-potency TCS and TCI on the same lesion 
is not permitted. Refer to the current version of the pharmacy manual for a listing of permitted low-
potency TCS and TCI medications that are commercially available in planned countries.
Subjects will apply a thin layer of authorized background topical therapy on all AD lesions at a 
frequency that is necessary to ensure disease stability and prevent AD flare but which does not exceed 
the daily frequency recommended in the product labeling. Refer to the current version of the pharmacy 
manual for the authorized topical medications and permitted daily frequency of use. “As needed” 
(PRN) use of TCS or TCI is not permitted. Only topical therapies specifically provided or prescribed 
for use in this study are permitted.
Background therapy use should be adjusted to the disease activity and tolerability of the subject, 
including tapering when signs and symptoms improve, discontinuation when lesions clear, and 
restarting if signs and symptoms recur, at the discretion of the investigator.
Rescue Therapies
If deemed to be medically necessary by the investigator (eg, to control intolerable AD signs/symptoms), 
rescue therapies can be prescribed to the subjects at any time during the study except during the run-in 
period. Subjects receiving rescue therapies during the run-in period are not eligible to participate in the
study. 
As a general guideline and per individual investigator judgment, rescue therapy should not be prescribed 
within the first 2 weeks after baseline (ie, Week 2) to allow a minimum time for study drug exposure in 
the presence of background therapy. 
Investigator assessments of efficacy should be performed before initiating rescue therapy. Subjects 
requiring rescue therapy between scheduled visits should return to the clinic (unscheduled visit) for 
investigator assessment of efficacy before starting rescue therapy.
Rescue treatments are only treatments that directly treat AD (mainly those that are approved or are 
standard of care) and include topical and systemic treatments as outlined. Rescue therapies include:

Higher potency of TCS (equivalent to class I-II according to the United States classification)2

Oral corticosteroids

Biologics (including their biosimilars)

Systemic nonsteroidal immunosuppressants/immunomodulators

Phototherapy
 
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Antihistamines, sleep aids, topical and systemic antibiotics, and anti-itch creams are not considered to 
be rescue therapy because they do not directly treat AD.
Whenever possible, investigators should first use topical medications as rescue therapy before escalating 
to systemic therapies. If subjects receive topical treatments or phototherapy as rescue therapy, study drug 
administration should be continued unless there is a safety concern according to the investigator’s 
judgment. If subjects receive systemic rescue therapy, the study drug administration must be permanently 
discontinued.
Study Duration:
The expected duration for each subject’s participation in the study depends on the clinical response and
may be:

Up to 28 weeks (including a 4-week screening period, a 16-week initial treatment period and an 8-
week follow-up period [12-weeks after the last study medication injection]) for subjects who are 
non-responders at the completion of the initial treatment period (Week 16)

Up to 60 weeks (including a 4-week screening period, a 16-week initial treatment period, a 32-
week maintenance period, and an 8-week follow-up period [12-weeks after the last study 
medication injection]) in subjects who are clinical responders at the completion of the initial 
treatment period (Week 16)
The 12-week follow-up visit is not required for subjects who will continue in the LTE study (Protocol 
118163).
Study Population:
Inclusion Criteria: To be eligible for study entry, subjects must satisfy all of the following inclusion 
criteria.
1.
Male or female subjects aged ≥12 years at the screening visit. 
Note: Enrollment of subjects aged 12 to 17 years has been opened after the IDMC has assessed 
interim safety data from the phase 2 study (Protocol 116912) and provided recommendations to the 
sponsor, who then determined the eligibility of this age group for enrollment in the study. The 
sponsor sent a written communication to the site confirming that the study is open for enrollment of 
adolescents. Adolescents could not be enrolled in the study until such communication was received.
2.
Chronic AD for at least 2 years before the screening visit, and confirmed according to American 
Academy of Dermatology Consensus Criteria (Appendix 1)2 at the time of the screening visit. 
3.
EASI score ≥16 at both the screening and baseline visits.
4.
IGA score ≥3 (based on the IGA scale ranging from 0 to 4, in which 3 is moderate and 4 is severe) 
at both the screening and baseline visits.
5.
AD involvement ≥10% of body surface area (BSA) at both the screening and baseline visits.
6.
Peak (maximum) pruritus NRS score of at least 4.0 at the screening and baseline visit.
Screening PP NRS score will be determined by a single PP NRS assessment (score ranging from 0 
to 10) for the 24-hour period immediately preceding the screening visit.
Baseline PP NRS score will be determined based on the average of daily PP NRS scores (score 
ranging from 0 to 10) during the 7 days immediately preceding baseline (rounding is not permitted). 
A minimum of 4 daily scores out of the 7 days immediately preceding baseline is required for this 
calculation.
 
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7.
Documented recent history (within 6 months before the screening visit) of inadequate response to 
topical medications (TCS with or without TCI). All subjects must demonstrate inadequate 
response to TCS. All subjects who have used TCI within 6 months of the screening visit, or for 
whom TCI is selected as background therapy for sensitive areas, must also demonstrate inadequate 
response to TCI. Acceptable documentation includes patient records with information on TCS 
(with or without TCI) prescription and treatment outcome, or written documentation of the 
conversation with the subject’s treating physician, if different than the investigator. 
Inadequate response to TCS treatments (with or without TCI) is defined as:
7a. Failure to achieve or maintain remission or low disease activity (equivalent to IGA ≤ 2) despite 
treatment with a regimen of a medium-, high-, or very high-potency TCS (Class I-III according 
to the US classification)2 (with or without TCI), applied for at least 4 weeks or for the maximum 
duration per prescribing information;
or
7b. Requirement of a long-term treatment (> 4 weeks) with a high- or very high-potency TCS (Class 
I-II according to the US classification)2 (with or without TCI) to achieve or maintain remission 
or low disease activity (equivalent to IGA ≤ 2);
or 
7c. If documentation of inadequate response to topical treatments is not available, subjects with a 
documented recent course of systemic treatment or phototherapy for AD (within 6 months 
before the visit) will also be considered as inadequate responders to topical treatments.
If documentation is inadequate, subjects may be re-screened after such documentation is obtained.
8.
Agree to apply a moisturizer throughout the study from the screening visit; agree to apply authorized 
topical therapy from the screening visit and throughout the study as determined appropriate by the 
investigator.
9.
Female subjects of childbearing potential (ie, fertile, following menarche and until becoming post-
menopausal unless permanently sterile) must agree either to commit to true abstinence throughout 
the study and for 12 weeks after the last study drug injection, when this is in line with the preferred 
and usual lifestyle of the subject, or to use an adequate and approved method of contraception 
throughout the study and for 12 weeks after the last study drug injection. This criterion also applies 
to a prepubertal female subject who begins menses during the study. *In Germany only, if a 
subject has reached Tanner stage 3 breast development, even if not having menarche, the subject 
will be considered a female of childbearing potential.
Adequate and approved methods of contraception applicable for the subject and/or her partner are 
defined below:

Progestogen-only oral hormonal contraception

Combination of male condom with cap, diaphragm, or sponge with spermicide (double barrier 
methods) (*In Germany only, double barrier methods are not considered a highly effective
method of contraception)
Note: “Double barrier methods” refers to simultaneous use of a physical barrier by each partner. 
Use of a single barrier method (eg, condom) together with a spermicide is not acceptable.

Combined (estrogen- and progestogen-containing) oral, intravaginal, or transdermal hormonal 
contraception

Injectable or implanted hormonal contraception

Intrauterine devices or intrauterine hormone-releasing system

Bilateral tubal ligation or tube insert (such as the Essure system) at least 3 months before the 
study
 
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
Bilateral vasectomy of partner at least 3 months before the study
10. Female subjects of non-childbearing potential must meet one of the following criteria:

Absence of menstrual bleeding for 1 year prior to screening without any other medical reason, 
confirmed with follicle-stimulating hormone (FSH) level in the postmenopausal range

Documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy at least 3 
months before screening
Note: Bilateral tubal ligation is not accepted as a reason for non-childbearing potential.
11. Subject (and guardian, when applicable) willing and able to comply with all of the time 
commitments and procedural requirements of the clinical study protocol, including daily diary 
recordings by the subject using an electronic handheld device provided for this study.
12. Understand and sign an informed consent form (and assent form, when applicable) before any 
investigational procedure(s) are performed.
Exclusion Criteria: Subjects will be excluded from the study if 1 or more of the following exclusion 
criteria are applicable.
1.
Body weight < 30 kg.
2.
Subjects meeting 1 or more of the following criteria at screening or baseline:
2a. Had an exacerbation of asthma requiring hospitalization in the preceding 12 months.
2b. Reporting asthma that has not been well-controlled (ie, symptoms occurring on > 2 days per 
week, nighttime awakenings 2 or more times per week, or some interference with normal 
activities) during the preceding 3 months.
2c. Asthma Control Test ≤19 (only for subjects with a history of asthma).
2d. Peak expiratory flow < 80% of the predicted value.
3.
Subjects with a current medical history of chronic obstructive pulmonary disease and/or chronic 
bronchitis.
4.
Cutaneous infection within 1 week before the baseline visit, any infection requiring treatment with 
oral or parenteral antibiotics, antivirals, antiparasitics or antifungals within 2 weeks before the 
baseline visit, or any confirmed or suspected coronavirus disease (COVID)-19 infection within 2 
weeks before the screening or baseline visit. Subjects may be rescreened once the infection has 
resolved. Resolution of COVID-19 infection can be confirmed by recovery assessment methods, as 
described in Section 8.3.4.2.
Note: Subjects with chronic, stable use of prophylactic treatment for recurrent herpes viral infection 
can be included in this study.
5.
Requiring rescue therapy for AD during the run-in period or expected to require rescue therapy 
within 2 weeks following the baseline visit.
6.
Positive serology results (hepatitis B surface antigen [HBsAg] or hepatitis B core antibody [HBcAb], 
hepatitis C antibody, or human immunodeficiency virus antibody) at the screening visit. 
Note: Subjects with a positive HBcAb and a negative HBsAg can be included in this clinical study 
if hepatitis B surface antibody is positive (considered immune after a natural infection).
7.
Having received any of the following treatments in Table 3 within the specified timeframe before
the baseline visit:
 
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10. Pregnant women (positive serum pregnancy test result at the screening visit or positive urine 
pregnancy test at the baseline visit), breastfeeding women, or women planning a pregnancy during 
the clinical study.
11. History of lymphoproliferative disease or history of malignancy of any organ system within the 
last 5 years, except for (1) basal cell carcinoma, squamous cell carcinoma in situ (Bowen’s 
disease), or carcinomas in situ of the cervix that have been treated and have no evidence of 
recurrence in the last 12 weeks before the baseline visit, or (2) actinic keratoses that have been 
treated.
12. History of hypersensitivity (including anaphylaxis) to an immunoglobulin product (plasma-derived 
or recombinant, eg, monoclonal antibody) or to any of the study drug excipients.
13. History of intolerance to TCS or for whom TCS is not advisable (eg, hypersensitivity, significant 
skin atrophy).
14. Known active or untreated latent tuberculosis infection.
Note: Subjects who have a documented history of completion of an appropriate TB treatment 
regimen for active or latent TB with no history of re-exposure to TB since their treatment was 
completed are eligible to participate in the study.
15. Known or suspected immunosuppression or unusually frequent, recurrent, severe, or prolonged 
infections as per investigator judgment.
16. Presence of confounding skin condition that may interfere with study assessments (eg, Netherton 
syndrome, psoriasis, cutaneous T-cell lymphoma [mycosis fungoides or Sezary syndrome], contact 
dermatitis, chronic actinic dermatitis, dermatitis herpetiformis).
17. Any medical or psychological condition or any clinically relevant laboratory abnormalities, such 
as but not limited to elevated ALT or AST (> 3 × upper limit of normal [ULN]) in combination 
with elevated bilirubin (> 2 × ULN), during the screening period that may put the subject at 
significant risk according to the investigator’s judgment, if he/she participates in the clinical study, 
or may interfere with study assessments (eg, poor venous access or needle-phobia).
18. Planned or expected major surgical procedure during the clinical study.
19. Subjects unwilling to refrain from using prohibited medications during the clinical study (see 
Section 8.4.9.2).
20. Currently participating or participated in any other study of a drug or device, within the past 8 
weeks before the screening visit, (or 5 half-lives of the investigational drug, whichever is longer), 
or is in an exclusion period (if verifiable) from a previous study.
21. History of alcohol or substance abuse within 6 months of the screening visit.
Endpoints:
Co-Primary Endpoints:

Proportion of subjects with an IGA success (defined as an IGA of 0 [clear] or 1 [almost clear] and a 
≥2-point reduction from baseline) at Week 16

Proportion of subjects with EASI-75 (≥ 75% improvement in EASI from baseline) at Week 16
Key Secondary Endpoints:

Proportion of subjects with an improvement of PP NRS ≥ 4 at Week 16

Proportion of subjects with PP NRS < 2 at Week 16
 
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Primary Endpoint:
The 2 co-primary endpoints will be analyzed using a Cochran-Mantel-Haenszel test adjusted for 
randomized stratification variables (IGA severity and PP NRS).
Key Secondary Endpoints:
All key secondary endpoints will be analyzed similar to the analysis of primary endpoint using a stratified 
Cochran-Mantel-Haenszel test.
Secondary Endpoints during Initial Period
Binary endpoints will be analysed with the same method as primary endpoint using non-responder 
imputation.
Continuous and QoL endpoints will be analyzed using an analysis of covariance (ANCOVA) including 
treatment group and randomization stratification factors as factors and appropriate baseline values as a 
covariate, if applicable. Missing values will be imputed using MI under MAR assumption. In addition, 
EASI, PP NRS, BSA and SCORAD will be analyzed using a mixed-effect model for repeated measures 
(MMRM) approach, including terms of treatment group, stratification factors, and appropriate baseline 
values. An unstructured covariance will be used to model the within-patient errors in the analysis. A 
linear contrast will be used, within the MMRM framework, to estimate difference between nemolizumab
and placebo. Treatment difference between nemolizumab and placebo will be estimated along with 
associated 95% confidence intervals.
Secondary Endpoints during Maintenance Period
All secondary endpoints during the maintenance period will be descriptively summarized.
Multiplicity Adjustment: 
The primary comparison of interest is nemolizumab 30 mg compared to placebo for the co-primary 
endpoints in both populations (baseline PP NRS 4; baseline PP NRS 7). 
To control the type I error at 5% significance level, a serial gatekeeping approach will be implemented. 
The co-primary endpoints will be tested at 2.5% significance level for each population. If both co-primary 
endpoints are statistically significant at 2.5% significance level, the key secondary endpoints will be 
tested sequentially following hierarchical testing procedure using the pre-specified order of endpoints 
for each population. The comparisons for key secondary endpoints will be made sequentially, and the 
subsequent tests will be stopped when no statistical difference is found.
Other secondary endpoint comparisons will not be adjusted for multiplicity.
Sample Size
To achieve at least 90% power for both co-primary endpoints at 2.5% significance level, 150 subjects 
per group will be required to detect the following differences between treatment groups for 2 co-
primary endpoints with 1:1 randomization ratio, assuming 15% dropout rate during the initial treatment 
period.
With a 2:1 randomization, 180 subjects in nemolizumab and 90 subjects in placebo will be required to 
detect the differences in both co-primary endpoints to achieve 90% power.
IGA Success: To detect a difference of 18%, assuming IGA response for nemolizumab 30% and 
placebo 12% at Week 16.
EASI-75 Response: To detect a difference of 30%, assuming EASI-75 response for nemolizumab 49% 
and placebo 19% at Week 16.
 
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To ensure sufficient exposure with nemolizumab and to ensure sufficient size of the safety database, 
the sample size is increased to 750 subjects in total with randomization ratio 2:1. This sample size will 
provide more than 99% power to detect the treatment difference for both co-primary endpoints at 2.5% 
significance level.
Figure 1: Study Visit Schema (Synopsis)
Abbreviations: BL=baseline; q4wk=every 4 weeks; q8wk=every 8 weeks; W=week.
 
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4
TABLE OF CONTENTS
CLINICAL STUDY PROTOCOL.............................................................................1
1
PROTOCOL APPROVAL SIGNATURES ................................................2
2
STUDY PERSONNEL ..................................................................................3
3
SYNOPSIS......................................................................................................5
4
TABLE OF CONTENTS ............................................................................21
TABLE OF FIGURES...............................................................................................27
TABLE OF TABLES.................................................................................................28
5
LIST OF ABBREVIATIONS.....................................................................29
6
INTRODUCTION .......................................................................................32
6.1
Background & Rationale ............................................................................32
6.2
Clinical Studies.............................................................................................35
6.2.1
Phase 1 Single-Dose Safety Study................................................35
6.2.2
Phase 2a Multi-Dose Safety and Efficacy Study..........................36
6.2.3
Phase 2b Dose-Ranging Study......................................................37
6.2.4
Phase 2 Safety Study in Adolescents............................................39
6.3
Risk/Benefit Assessment..............................................................................39
6.4
Drug Profile..................................................................................................41
6.5
Dose Selection Rationale .............................................................................42
7
STUDY OBJECTIVES & ENDPOINTS...................................................43
7.1
Primary Objective .......................................................................................43
7.2
Co-Primary Endpoints................................................................................43
7.3
Secondary Objective....................................................................................43
7.4
Key Secondary Endpoints:..........................................................................43
7.5
Secondary Endpoints...................................................................................44
7.6
Safety Endpoints..........................................................................................48
7.7
Other Endpoints...........................................................................................48
 
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7.7.1
Pharmacokinetics..........................................................................48
7.7.2
Immunogenicity............................................................................48
8
INVESTIGATIONAL PLAN .....................................................................49
8.1
Overall Study Design and Plan: Description.............................................49
8.1.1
Study Visit Schema.......................................................................53
8.1.2
Schedule of Assessments..............................................................54
8.2
Discussion of Study Design .........................................................................62
8.2.1
Study Design.................................................................................62
8.3
Selection of Study Population.....................................................................64
8.3.1
Number of Planned Subjects ........................................................64
8.3.2
Inclusion Criteria ..........................................................................64
8.3.3
Exclusion Criteria.........................................................................67
8.3.4
Removal of Subjects From Therapy or Assessments ...................71
8.3.4.1
Pregnancy .....................................................................................72
8.3.4.2
COVID-19 Infection.....................................................................73
8.4
Investigational Products..............................................................................74
8.4.1
Investigational Products Administered.........................................74
8.4.1.1
Study Drug Dosing – Initial Treatment Period.............................74
8.4.1.2
Study Drug Dosing – Maintenance Treatment Period..................75
8.4.1.3
Study Drug Preparation ................................................................75
8.4.1.4
Study Drug Injection.....................................................................76
8.4.2
Identity of Investigational Products..............................................77
8.4.3
Packaging and Labeling................................................................79
8.4.4
Study Drug Management..............................................................79
8.4.4.1
Storage of Study Drug ..................................................................79
8.4.4.2
Study Drug Accountability...........................................................79
8.4.4.3
Dispensing and Return of Study Drug..........................................80
8.4.4.4
Treatment Compliance..................................................................80
8.4.5
Method of Assigning Subjects to Treatment Groups: 
Randomization and Re-Randomization........................................81
8.4.6
Selection of Doses in the Study....................................................81
8.4.7
Dose Modification ........................................................................81
8.4.8
Blinding ........................................................................................82
8.4.9
Prior and Concomitant Therapy....................................................83
8.4.9.1
Permitted Concomitant Therapy...................................................84
8.4.9.1.1 Moisturizer....................................................................................85
8.4.9.1.2 Background Topical Therapy .......................................................85
 
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10
STATISTICAL METHODS.....................................................................122
10.1 Statistical and Analytical Plans................................................................122
10.1.1
Datasets or Populations Analyzed ..............................................122
10.1.1.1
Intent-to-Treat Population ..........................................................122
10.1.1.2
Safety Population........................................................................122
10.1.1.3
PK Analysis Population..............................................................122
10.1.1.4
Per-Protocol Population..............................................................122
10.1.1.5
PD Analysis Population..............................................................123
10.1.2
Demographic and Other Baseline Characteristics ......................123
10.1.3
Efficacy Variables ......................................................................123
10.1.4
Safety Variables..........................................................................126
10.1.4.1
Extent of Exposure .....................................................................126
10.1.4.2
Adverse Events ...........................................................................127
10.1.4.3
Clinical Laboratory.....................................................................127
10.1.4.4
Vital Signs ..................................................................................127
10.1.4.5
Peak Expiratory Flow .................................................................127
10.1.4.6
Physical Examination .................................................................128
10.1.4.7
Electrocardiogram.......................................................................128
10.1.5
Pharmacokinetic Parameters and Anti-Drug Antibody 
Analyses......................................................................................128
10.1.6
Biomarker Analyses....................................................................128
10.1.7
Subject Interview Analysis.........................................................128
10.1.8
Psychometric Validation Analyses.............................................129
10.1.9
Interim Analyses.........................................................................129
10.1.10
Handling of Missing Data...........................................................129
10.1.11
Sensitivity Analyses for Primary and Key Secondary 
Endpoints....................................................................................130
10.2 Determination of Sample Size...................................................................131
10.3 Protocol Deviations....................................................................................132
11
QUALITY ASSURANCE AND QUALITY CONTROL.......................133
11.1 Audit and Inspection .................................................................................133
11.2 Monitoring..................................................................................................133
11.3 Personnel Training ....................................................................................133
11.4 Data Management......................................................................................134
11.5 Clinical Study Conduct .............................................................................134
11.6 Amendments...............................................................................................134
 
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11.7 Quality Management and Risk Evaluation.............................................134
12
ETHICS ......................................................................................................135
12.1 Independent Ethics Committee or Institutional Review Board ............135
12.2 Regulatory Authorities..............................................................................135
12.3 Ethical Conduct of the Study....................................................................135
12.4 Informed Consent......................................................................................135
12.5 Subject Confidentiality..............................................................................136
12.6 Financing and Insurance...........................................................................137
13
REPORTING AND PUBLICATION, INCLUDING 
ARCHIVING..............................................................................................138
14
REFERENCES ..........................................................................................139
15
APPENDICES............................................................................................144
Appendix 1: American Academy of Dermatology Consensus Criteria 
for AD Diagnosis........................................................................................144
Appendix 2: Specific Guidance for Study Conduct and Subject Safety 
during the COVID-19 Pandemic..............................................................146
Appendix 3: CYP Substrates with Narrow Therapeutic Index......................157
Appendix 4: Investigator’s Global Assessment (IGA).....................................158
Appendix 5: Eczema Area and Severity Index (EASI)....................................159
Appendix 6: Pruritus (Peak and Average) Numeric Rating Scale (PP 
NRS and AP NRS) .....................................................................................160
Appendix 7: Sleep Disturbance Numeric Rating Scale (SD NRS)..................161
 
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TABLE OF TABLES
Table 1: Initial Treatment Period Randomized Group Assignments.............................6
Table 2: Maintenance Period Re-Randomized Group Assignments .............................7
Table 3: Prior Treatments ............................................................................................13
Table 4: Initial Treatment Period Randomized Group Assignments...........................50
Table 5: Maintenance Period Re-Randomized Group Assignments ...........................51
Table 6: Prior Treatments ............................................................................................68
Table 7: Initial Treatment Period Dosing By Treatment Group..................................74
Table 8: Maintenance Period Dosing By Treatment Group ........................................75
Table 9: Description and Usage of Investigational Product ........................................78
Table 10: Prohibited Medication/Therapy...................................................................87
 
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5
LIST OF ABBREVIATIONS 
ACT
Asthma Control Test
AD
atopic dermatitis
ADA
anti-drug antibody
AE
adverse event
AESI
adverse event of special interest
ALT
alanine aminotransferase
AP
Average pruritus
AST
aspartate aminotransferase
BL
baseline
BSA
body surface area
cDLQI
Children’s Dermatology Life Quality Index
CI
confidence interval
COVID-19
coronavirus disease-19
CPK
creatine phosphokinase
CRF
case report form
CRO
contract research organization
CS
clinically significant
CYP450
cytochrome P450
DCS
dual chamber, single-use syringe
DLQI
Dermatology Life Quality Index
DNA
deoxyribonucleic acid
EASI
Eczema Area and Severity Index
ECG
electrocardiogram
ELISA
enzyme-linked immunosorbent assay
EQ-5D
EuroQoL 5-Dimension 
ET
early termination
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
HADS
Hospital Anxiety and Depression Scale 
HBcAb
hepatitis B core antibody
HBsAg
hepatitis B surface antigen
HIPAA
Health Insurance Portability and Accountability Act 
HIV
human immunodeficiency virus
IAC
independent adjudication committee
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonisation of Technical Requirements for
Pharmaceuticals for Human Use
IDMC
independent data monitoring committee
IEC
Independent Ethics Committee
IGA
Investigator’s Global Assessment
IgE
immunoglobulin E
IL
interleukin
IRB
Institutional Review Board
 
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IRR
injection-related reaction
IRT
interactive response technology
ITT
intent-to-treat
JAK
Janus kinase
LDH
lactate dehydrogenase
LOCF
last observation carried forward
LTE
long-term extension
MI
multiple imputation
miRNA
micro ribonucleic acid
MMRM
mixed-effect model for repeated measures
mRNA
messenger ribonucleic acid
NAb
neutralizing antibody
NCA
non-compartmental analysis
NCS
not clinically significant
NRS
numeric rating scale
OC
observed case
PCS
Pruritus Categorical Scale
PD
pharmacodynamics
PDE
phosphodiesterase
PEF
peak expiratory flow
PGAD
Patient Global Assessment of Disease
PGAT
Patient Global Assessment of Treatment
PGIC-P
Patient Global Impression of Change - Pruritus
PGIC-SD
Patient Global Impression of Change - Sleep Disturbance
PGIS-P
Patient Global Impression of Severity - Pruritus
PGIS-SD
Patient Global Impression of Severity - Sleep Disturbance
PGx
pharmacogenomics
PIQ
PROMIS® Itch Questionnaire 
PK
pharmacokinetics
POEM
Patient-Oriented Eczema Measure
PP NRS
peak pruritus numeric rating scale
PRN
pro re nata (when necessary or as needed)
PRO
patient-reported outcome
PROMIS®
Patient-Reported Outcomes Measurement Information System
PTC
product technical complaint
Q4W (q4wk)
every 4 weeks
Q8W (q8wk)
every 8 weeks
QoL
quality of life
RA
receptor A
RNA
ribonucleic acid
RTSM
randomization and trial supply management
SAE
serious adverse event
SAP
statistical analysis plan
sc
subcutaneous
SCORAD
SCORing Atopic Dermatitis
SD NRS
sleep disturbance numeric rating scale
 
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SIN
subject identification number
SNRI
serotonin-norepinephrine reuptake inhibitor
SSRI
selective serotonin reuptake inhibitor
SUSAR
suspected unexpected serious adverse reaction
TARC
thymus and activation-regulated chemokine
TB
tuberculosis
TCI
topical calcineurin inhibitor
TCS
topical corticosteroid
TEAE
treatment-emergent adverse event
Th2
type 2 helper T [cell]
TMF
Trial Master File
ULN
upper limit of normal
UPT
urine pregnancy test
US
United States
VAS
visual analogue scale
WASO
wakefulness after sleep onset
WOCBP
women of childbearing potential
WPAI:AD
Work Productivity and Activity Impairment: Atopic Dermatitis
 
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6
INTRODUCTION
6.1
Background & Rationale
Atopic dermatitis (AD) is a chronic inflammatory skin disease estimated to occur in 
10% to 20% of the population1 and up to 25% of children.2 The disease is 
characterized by pruritus (itching), xerosis (skin dryness), and eczematous lesions 
whose features include erythema, infiltration/papulation, oozing with crusting, 
excoriations, and lichenification. Approximately 60% of AD patients have another 
concomitant atopic condition (eg, asthma, allergic rhinitis, food allergy) and AD often 
constitutes the first step of atopic march (progression from 1 atopic disease to 
another). Although not a life-threatening disease, AD has a marked negative impact 
on patients’ quality of life (QoL), and depression and anxiety have been reported as 
comorbidities in AD patients.3 Existing literature suggest that the prevalence of AD is 
highest in young children and gradually reduces with age. Prevalence is higher in 
developed countries.
The overall lifetime prevalence of AD has increased over the past 30 years.2 In most 
countries, there has been an increase in AD prevalence over a 5- to 10-year period.4 In 
the United States (US), the prevalence of AD in children has been reported between 
10% and 13% in 2 studies.5,6 Many environmental and geographic factors were shown 
to contribute to incidence rate and severity in both studies. These variables included 
urban living, household income, parental education level, and race.
The majority of AD cases can be regarded as “mild”, with 10% to 20% of patients 
suffering from severe eczematous skin lesions, although the percentage of individuals 
experiencing severe disease appears to be higher in the adult AD population.7 Whereas 
the prevalence of moderate-to-severe AD is up to 71% in adults suffering from AD, the 
prevalence of moderate and severe AD in children with AD was found to be 14% and 
2%, respectively.8 Evaluation of AD data collected through the US 2007 National 
Survey of Children’s Health showed that 67% of pediatric AD patients had mild
disease, 26% had moderate disease, and 7% had severe disease, which translates to 
approximately 5.6, 2.2, and 0.6 million US children, respectively.6
The clinical manifestations of AD vary with age.9 The eczematous changes and its 
morphology are seen in different locations, depending on the age of the patient (child, 
adolescent, or adult).
Atopic dermatitis occurs in 3 main age-related stages10 that may be separated by 
periods of remission or overlap: the first, the infantile stage up to age 2 years, is 
typified by highly pruritic, red, scaly, crusted, and sometimes weeping patches on 
both cheeks and on the extensor parts of the extremities. Eczematous changes of the 
scalp and wheal formation may also be seen. The diaper area is generally spared, and 
 
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early infantile AD may be difficult to distinguish from seborrheic dermatitis on 
clinical grounds alone. The childhood stage from 2 years to 12 years shows papulation 
rather than exudation and occurs in the flexural areas, especially the antecubital and 
popliteal fossae, the volar aspect of the wrists, ankles, and neck. Thickened plaques 
show lichenification and excoriation. In the adult stage, from puberty onward, patients 
may have had few or no skin problems since infancy or may have suffered a chronic 
relapsing course with periods of remission. Lichenification occurring in the flexural 
areas and facial involvement is common, especially the forehead and periorbital 
regions. The wrists, hands, ankles, feet, fingers, and toes are often involved.
The cause of AD, although still not completely understood, is probably multifactorial 
and involves complex interrelation between susceptibility genes, immunological 
factors, infections, and environmental factors to produce a skin barrier disturbance as 
well as immunologic dysregulation and inflammation.11 Abnormal protein (filaggrin 
and related proteins) and lipid (ceramide) metabolism may also play a key role. Upon 
stimulation with allergens, dendritic cells in the skin stimulate type 2 helper T cells
(Th2) and cause the subsequent release of pro-inflammatory cytokines, including 
interleukin (IL)-4, IL-5 and IL-13. High levels of Th2 cytokines in AD skin increase 
serine protease, which leads to further skin barrier dysfunction, and IL-31, which 
leads to pruritus and further inflammation and barrier dysfunction.12,13 The 
pathophysiology also involves Th1 cells in the chronic phase of AD. Involvement of 
Th17 and Th22 cells in AD pathogenesis has been more recently reported.14 Of note, 
non-lesional skin already shows signs of subclinical inflammation with increased 
numbers of Th2 cells, Th22 cells, and to a lesser degree, Th17 cells, and a pro-
inflammatory cytokine milieu.15
The scratching behavior associated with pruritus is believed to exacerbate AD lesions 
by causing mechanical damage to the skin, allowing the penetration of foreign 
antigens, triggering inflammatory responses, and leading to further aggravation of 
dermatitis and itching. This vicious circle of scratching exacerbation of dermatitis 
aggravation of itching is known as the “itch-scratch cycle”.16
IL-31 is involved in both primary AD pathophysiology and perpetuation of the itch-
scratch cycle. IL-31 is preferentially produced by Th2 cells, following induction by 
IL-4, and its expression is consistently increased in the skin lesions of AD 
patients.12,17,18 Furthermore, the IL-31 receptor A (IL-31 RA) was found to be 
expressed in several tissues including the dorsal root spinal ganglia, which contain 
sensory nerve cells,19 and keratinocytes.20 Through interaction with its receptor, IL-31 
promotes pruritus, Th2-driven inflammation, and keratinocyte proliferation and 
differentiation, which are crucial for skin barrier function.12,13,21,22 Together, these 
findings suggest that IL-31 is involved in the pathogenesis of pruritus and is 
implicated in the inflammation of AD.
 
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Atopic dermatitis is currently managed with topical and systemic treatments, as well 
as phototherapy. Topical agents are the mainstay of AD therapy. Moisturizers are 
used to improve skin dryness and skin barrier dysfunction. Topical corticosteroids 
(TCS) are widely prescribed in adults and children for their anti-inflammatory effect, 
but their long-term use can lead to side effects, such as skin atrophy and risks 
associated with systematic absorption (eg, hypothalamic pituitary axis suppression 
and Cushing’s syndrome). Topical calcineurin inhibitors (TCI) are effective for acute 
and chronic treatment in adults and children, particularly in selected anatomical areas. 
Stinging and burning are frequent local reactions, and both tacrolimus and 
pimecrolimus carry a warning in the US prescription information that long-term 
safety has not been established due to reports of (rare cases of) malignancy. 
Crisaborole (Eucrisa®; Pfizer) is a topical phosphodiesterase (PDE)-4 inhibitor with 
an acceptable safety profile in adults and children but is most commonly used in the 
treatment of mild-to-moderate AD. Hypersensitivity reactions at or near the 
application site have also been observed.23
Despite the demonstrated efficacy of topical treatments, they are not always sufficient 
to control moderate-to-severe AD in some patients, who therefore require the addition 
of phototherapy or a systemic treatment to achieve sufficient control of AD.24 There 
are various forms, doses, and treatment protocols of phototherapy, which lead to 
heterogeneous treatment outcomes, including common side effects such as actinic 
damage, local erythema and tenderness, pruritus, burning and stinging, as well as the 
long-term risk of skin cancer. Systemic corticosteroids, while effective at controlling 
disease temporarily, should be avoided due to an overall unfavorable risk-benefit 
safety profile, particularly in pediatric populations. Oral antihistamines (including 
both sedating and non-sedating medications) have been studied in the management of 
AD but there is insufficient evidence of treatment benefit. Cyclosporine, 
methotrexate, azathioprine, or mycophenolate mofetil may be considered when 
systemic treatment is required.24 Most of these systemic immunosuppressants, except 
cyclosporine, have not been approved for the treatment of AD and are used off-label 
in both adults and pediatric patients. Cyclosporine is approved for treatment of severe 
AD in the European Union and in a few other countries (eg, Japan), but not in the US. 
However, given the high response variability and the known secondary adverse 
effects of these drugs, there is a need for new drugs to better control the disease while 
decreasing the risk of secondary adverse effects.
Several biological agents are currently being used or developed for the treatment of 
AD. Dupilumab, a human monoclonal antibody that blocks the signaling pathway of 
both IL-4 and IL-13, is approved in adults with moderate-to-severe AD not 
adequately controlled with topical medications25 and is being developed for use in 
 
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pediatric populations. Two other anti-IL-13 therapies, lebrikizumab and tralokinumab, 
are also currently in development.
Nemolizumab, a humanized anti-human IL-31 RA monoclonal antibody, inhibits the 
binding of IL-31 to IL-31 RA and subsequent signal transduction. Transgenic mice 
overexpressing IL-31 exhibited skin lesions resembling those of AD and scratching 
behavior, which could be suppressed by treatment with an anti-mouse IL-31 
antibody.26,27 In dogs, lokivetmab, a caninized, anti-canine IL-31 antibody, has been 
shown to reduce pruritus in a dose-dependent manner with a rapid onset of effect and 
decrease in dermatitis score compared to placebo.28 In cynomolgus monkeys, 
nemolizumab suppressed IL-31-induced scratching.29 In a phase 2a study 
(CIM003JG) in adult subjects with AD, nemolizumab improved both pruritus and 
lesional AD, while demonstrating an acceptable safety profile.30 In a randomized, 
placebo-controlled, double-blind, parallel-group (10 mg, 30 mg, 90 mg, and placebo),
phase 2b dose-finding study, the 30-mg dose was selected as the final dose for further 
evaluation in phase 3. Nemolizumab has not been previously studied in subjects under 
the age of 18 years. The safety and pharmacokinetic (PK) profile of the 30-mg dose, 
selected for further development based on the results of the phase 2b study conducted 
in adult subjects, will be investigated in adolescent subjects with moderate-to-severe 
AD.
In conclusion, nemolizumab may present a new treatment option for AD in pediatric 
as well as adult patients. Atopic dermatitis patients with associated pruritus and an 
insufficient response to topical therapies could particularly benefit from such a 
therapy. The objective of this phase 3 pivotal study is to evaluate the safety and 
efficacy of nemolizumab administered concomitantly with background topical therapy
in adult and adolescent subjects with moderate-to-severe AD who are not adequately 
controlled with topical treatments.
6.2
Clinical Studies
The Investigator’s Brochure (IB) contains detailed information on clinical and non-
clinical studies. Results of 3 completed clinical studies of nemolizumab in AD are 
summarized below.
6.2.1 Phase 1 Single-Dose Safety Study
The safety, tolerability, and PK of a single subcutaneous dose of nemolizumab were 
evaluated in a randomized, double-blind, placebo-controlled phase 1 study including 
80 healthy adult volunteers and 36 Japanese subjects with moderate-to-severe AD.31
Doses ranged from 0.003 to 3.0 mg/kg in healthy volunteers and from 0.3 to 3.0 
mg/kg in AD subjects. There were no deaths or serious adverse events (SAEs) 
 
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reported in the study, and no dose-dependent increase in the incidence of adverse 
events (AEs) was observed. 
Pharmacokinetic assessments following a single subcutaneous dose of nemolizumab 
showed a dose-dependent increase in serum nemolizumab concentration, AUCinf, and 
maximum drug concentration. Peak serum concentrations were observed 4 to 6 days 
after nemolizumab administration, after which the drug gradually disappeared over a 
half-life of approximately 2 weeks.
6.2.2 Phase 2a Multi-Dose Safety and Efficacy Study
The safety, tolerability, and efficacy of nemolizumab monotherapy was evaluated in 
264 moderate-to-severe AD subjects who were inadequately controlled by or 
intolerant to topical therapy in a phase 2a study (CIM003JG).30,32 The study included 
a 12-week, randomized, double-blind, placebo-controlled period (Part A) and a 52-
week extension (Part B). At Week 12, various doses of nemolizumab (0.1 mg/kg, 0.5 
mg/kg, or 2.0 mg/kg) administered subcutaneously every 4 weeks (Q4W) were 
statistically significantly more effective than placebo in reducing pruritus visual 
analogue scale (VAS) score, with 0.5 mg/kg and 2.0 mg/kg doses being more 
effective than 0.1 mg/kg. No additional benefit was observed with the 2.0 mg/kg 
Q4W or every 8 weeks (Q8W) doses compared to 0.5 mg/kg Q4W.
During the entire study (Parts A and B), AEs that occurred in 5% or more of the 
nemolizumab-treated patients (all groups pooled) were nasopharyngitis, AD, 
increased blood creatine phosphokinase (CPK), upper respiratory tract infection, 
headache, peripheral edema, and impetigo. The majority of AEs were mild or 
moderate in intensity. No clinically relevant findings were observed during the study 
for laboratory tests, vital signs, physical examination, or electrocardiogram (ECG). 
Pharmacokinetic assessments after subcutaneous injections of various doses showed a 
dose-proportional increase of nemolizumab serum concentrations after repeated 
injections. Limited accumulation was observed, with median actual accumulation 
index below 2, and steady-state concentrations were achieved at Week 16 of
treatment. The PK profile of nemolizumab is predictable: It is not affected by the 
number of administrations. This might be partly due to the low occurrence and 
minimal effect of serum anti-nemolizumab antibodies (ADA), with ADA-positive 
subjects representing 7.1% of all subjects treated with nemolizumab. In addition, in 
this study, 1 subject in the 0.1 mg/kg Q4W group with anti-nemolizumab antibodies 
from baseline developed neutralizing ADA at Week 64. Importantly, serum 
nemolizumab concentrations in ADA-positive subjects were not different from those 
in the ADA-negative subjects. Four subjects had treatment-emergent nemolizumab-
 
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specific immunoglobulin E (IgE) antibodies. No AEs possibly related to 
nemolizumab-specific IgE antibodies were observed.
6.2.3 Phase 2b Dose-Ranging Study
The phase 2b study was a randomized, placebo-controlled, double-blind, parallel-
group, dose-ranging study to evaluate the efficacy and safety of various doses of 
nemolizumab in moderate-to-severe AD subjects with severe pruritus (peak pruritus 
numeric rating scale [PP NRS] ≥ 7). 
A total of 226 adult subjects were randomized (1 subject in the placebo group was 
randomized but not treated): 57 subjects were randomized to placebo and 169 subjects 
were randomized to nemolizumab arms (55 subjects to 10 mg, 57 subjects to 30 mg,
and 57 subjects to 90 mg). There were 176 subjects (77.9%) who completed the 
treatment and 44 subjects (19.5%) who discontinued the study. Overall, all 
demographic and baseline disease characteristics were similar in all treatment groups.
At the Week 24 visit, a greater percent change reduction in Eczema Area and Severity 
Index (EASI) was observed with the nemolizumab 30-mg dose (least squares mean 
difference vs placebo = 16.7%) and the difference was statistically significant (95% 
confidence interval [CI] = -30.2, -3.2; p < 0.05) compared to placebo. The 
nemolizumab 10-mg dose showed marginally significant difference vs placebo (least 
squares mean difference = 13.6%; 95% CI = -27.3, 0.0; p = 0.05). However, the 
difference between the nemolizumab 90-mg dose and placebo did not achieve 
statistical significance.
The secondary endpoint of Investigator’s Global Assessment (IGA) success 
(clear/almost clear and 2-point reduction) was not statistically significant at Week 24 
(25.5% in nemolizumab 10 mg, 36.8% in 30 mg, 22.8% in 90 mg, and 21.1% in 
placebo). However, the difference was statistically different for the 30-mg dose 
compared to placebo at Week 16 (33.3% vs 12.3%; p = 0.008). The PP NRS 
responder (PP NRS improvement ≥ 4) rate was statistically significant (p < 0.05) for 
the nemolizumab 10-mg and 30-mg doses at Week 24, and all nemolizumab doses 
were statistically significantly superior to placebo at Week 16 (p < 0.05). 
Nemolizumab demonstrated an early onset of action in pruritus as early as Week 1. In 
addition, the proportion of EASI-75 responders was statistically significantly greater 
for nemolizumab 30 mg at Week 24 and for both the 30-mg and 90-mg doses at Week 
16 compared to placebo (p < 0.05). The sleep disturbance NRS was highly 
statistically significant for all 3 nemolizumab doses at Week 24 (p < 0.001) vs 
placebo.
Among all nemolizumab doses, the 30-mg dose showed statistically significant and 
greater difference compared to placebo for all AD and pruritus endpoints at Week 16. 
 
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Probably due to TCS background therapy, there was increasing placebo effect in the 
study, shrinking the deltas between active arms and placebo as the study progressed 
from Week 16 to Week 24. The dose-effect was closer to the maximum efficacy
model, achieving the maximum efficacy at the 30-mg dose and lower efficacy with
the 10-mg and 90-mg doses.
There was 1 non-related AE with a fatal outcome (82-year-old subject treated with the 
10-mg dose died due to non–study drug related aspiration pneumonia and 
cardiopulmonary arrest). Three suspected unexpected serious adverse reactions
(SUSARs) were recorded in the study: exacerbation of AD (10-mg dose, withdrawal 
from study), septic shock (90-mg dose, sepsis, Staphylococcus aureus–positive blood 
culture, recovered/resolved without sequelae), and phlegmon/cellulitis of the right 
cheek (30-mg dose, recovered/resolved without sequelae). All doses of nemolizumab 
were associated with a slightly higher incidence of serious treatment-emergent AEs 
(TEAEs) (1 [1.8%], 3 [5.5%], 2 [3.5%], and 2 ([3.5%] in placebo, 10 mg, 30 mg, and 
90 mg, respectively) but not severe TEAEs (6 [10.7%], 3 [5.5%], 5 [8.8%], and 2 
[3.5%] in placebo, 10 mg, 30 mg, and 90 mg, respectively) when compared to 
placebo. There was a comparable percentage of subjects discontinuing treatment due 
to TEAE in the placebo and active treatment arms. All doses of nemolizumab were 
associated with a slightly higher incidence of TEAEs when compared to placebo. 
There was no increase in the incidence of skin infections in the nemolizumab 
compared to the placebo groups, although there was a higher incidence of non-skin 
infections with nemolizumab (mainly rhinopharyngitis and upper respiratory tract 
infections). There was a dose-dependent increase of asthma flares (1 [1.8%], 2 
[3.6%], 7 [12.3%], and 10 [17.5%] in placebo, 10 mg, 30 mg, and 90 mg, 
respectively) in subjects with pre-existing asthma. Events were mostly mild or 
moderate (1 severe event with highest dose), manageable, and reversible under 
treatment with study drug. Further, a higher incidence of AD exacerbation in the 
placebo arm compared to the nemolizumab treatment arms was observed. Local and 
systemic injection-related reactions (IRRs) occurred more frequently in the placebo 
compared to the active treatment groups. Finally, there was a low incidence of 
peripheral edema, with no serious cases and no imbalance with the placebo arm. 
The safety and efficacy data generated in the phase 2b dose-finding study supported 
the selection of the 30-mg dose as the treatment dose for the phase 3 studies.
Based on the safety data from the 3 completed studies, no additional risks for 
nemolizumab have been identified. Potential important risks to be monitored closely 
include newly diagnosed asthma or worsening of asthma and infections. 
 
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6.2.4 Phase 2 Safety Study in Adolescents
A 16-week, open-label, phase 2 study (N = 20) will evaluate the safety, efficacy, and 
PK of nemolizumab 30 mg Q4W, administered concomitantly with background TCS, 
in adolescent subjects (12-17 years old) with moderate-to-severe AD who are not 
adequately controlled with topical treatments. 
Nemolizumab has not been previously studied in subjects under the age of 18 years. 
The safety and PK profile of the 30-mg dose, selected for further development based 
on the results of the phase 2b study conducted in adult subjects, will be investigated in 
adolescent subjects with moderate-to-severe AD. 
An interim analysis is planned to support enrollment of adolescent subjects in the 
current phase 3 pivotal study for AD. 
6.3
Risk/Benefit Assessment
Topical medications are the mainstay of AD therapy. Treatment options are however,
limited for patients with moderate-to-severe AD whose disease cannot be adequately 
controlled with topical medications.
Results of previous clinical studies in adults demonstrated that treatment with 
nemolizumab had a marked effect on AD, pruritus, and pruritus-related sleep loss. 
Improvements in the symptoms of AD were consistent with the observed 
improvement in sleep quality (evaluated subjectively) and QoL (evaluated using 
Dermatology Life Quality Index [DLQI]). Continuous treatment for up to 64 weeks 
led to improvements in overall AD severity, evaluated with various validated scales 
commonly used in dermatology clinical trials (ie, EASI, SCORing Atopic Dermatitis 
[SCORAD], and IGA). Nemolizumab was also well tolerated overall when used as 
monotherapy or concomitantly with a TCS. 
Based on the currently available information on nemolizumab and the risks associated 
with biologic agents in general, the potential risks of nemolizumab treatment include 
local or systemic IRRs, newly diagnosed asthma or worsening of asthma, 
exacerbation of atopic dermatitis, and skin or non-skin infections. The following 
specific risk-minimization and safety follow-up measures have been planned in this 
clinical study: 
a.
In the phase 2b (114322) dose-ranging study, a dose-dependent increase of asthma 
flares (1 [1.8%], 2 [3.6%], 7 [12.3%], and 10 [17.5%] in placebo, 10-mg, 30-mg,
and 90-mg treatment arms, respectively) in subjects with pre-existing asthma was 
observed. Events were mostly mild or moderate (1 severe event with highest 
dose), manageable, and reversible under treatment with study drug. The protocol 
 
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will exclude subjects with asthma exacerbation requiring hospitalization in the 
preceding 12 months before screening, subjects whose asthma has not been well 
controlled (ie, symptoms > 2 days per week, nighttime awakenings 2 or more
times per week, or some interference with normal activities) during the last 3 
months before the screening visit, Asthma Control Test (ACT) score ≤19, and 
subjects with peak expiratory flow (PEF) below 80% of the predicted value. At all
visits, all subjects will be asked about respiratory changes and a respiratory 
examination will be performed. Peak expiratory flow measurements will be 
performed for all subjects at screening, baseline, and regular intervals throughout 
the study. For subjects with a history of asthma, PEF measurements and ACT will 
be administered at all visits. Subjects diagnosed with de novo asthma will perform 
PEF and ACT assessments at all visits starting with the visit in which the 
diagnosis was confirmed. Subjects with a medical history of asthma will be 
referred to the physician managing their asthma if ACT ≤ 19, PEF < 80% of the 
predicted value, and/or unexpected worsening of asthma is observed or reported. 
Subjects without a medical history of asthma will be referred to a respiratory 
specialist if respiratory changes suggestive of asthma are observed or reported. An 
independent adjudication committee (IAC) will review all asthma adverse events 
reported during the course of the study.
b. The exclusion criteria of this clinical study (ie, restricting entry of subjects with 
recent/current infections or known/suspected immunosuppression or unusually 
frequent, recurrent, severe, or prolonged infections) will prevent non-eligible
patients from receiving nemolizumab. As no data are available in pregnant or 
breastfeeding women, these patients are not eligible for this study. Patients who 
have recently received live vaccines may be considered for enrollment after an 
appropriate time has elapsed before baseline/Day 1. Administration of live 
vaccines is prohibited during the study. Administration of non-live vaccines is
permitted including coronavirus disease 2019 (COVID-19) vaccination.
c.
A slight trend of dose-dependent increase of peripheral edema was reported in the 
nemolizumab phase 2a study (CIM003JG). Most events were mild (11 of 21), no 
case was serious, and none resulted in premature treatment discontinuation; no 
case was associated with renal or cardiac AEs. The EASI values and thymus and 
activation-regulated chemokine (TARC) levels were relatively higher in subjects
with peripheral edema indicating that peripheral edema might be related to more 
severe AD. There were a few subjects reporting peripheral edema in the phase 2b 
(114322) study (2 [3.6%], 2 [3.6%], 4 [7%], and 2 [3.5%] in placebo, 10-mg, 30-
mg, and 90-mg groups, respectively). Peripheral edema will be followed as an AE
of special interest (AESI) in this study.
 
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d. Based on the Sponsor’s and IDMC analysis of the data in 12 to 17-year-old 
adolescents obtained in the PK/safety study (SPR.116912), it was decided to allow 
recruitment of adolescent subjects.
e.
An independent data monitoring committee (IDMC) will monitor the safety data 
regularly throughout the study, including AESIs, which were defined based on the 
currently available safety information on nemolizumab and the risks associated 
with biologic agents in general. AESIs for this study are: 

IRRs
o
Anaphylactic reactions
o
Acute allergic reactions requiring treatment
o
Severe injection site reactions with a duration greater than 24 hours

Newly diagnosed asthma or worsening of asthma

Infections
o
Any severe infection or any infection requiring treatment with 
parenteral antibiotics or with oral antibiotics/antivirals/antifungals
for > 2 weeks
o
Any confirmed or suspected coronavirus disease (COVID-19)
infection

Peripheral edema: limbs, bilateral

Facial edema

Elevated ALT or AST (> 3 × ULN) in combination with elevated bilirubin 
(> 2 × ULN)
In conclusion, when taking into consideration the currently available data of 
nemolizumab and the risk-minimization approaches to be implemented, the 
benefit/risk ratio of nemolizumab is considered to be favorable in this study.
6.4
Drug Profile
Nemolizumab is a humanized monoclonal modified immunoglobulin G 2 antibody 
comprising a structure of 2 H-chains (445 amino acid residues) and 2 L-chains (214 
amino acid residues) connected by 16 disulfide bonds. Study drug will be supplied as 
a lyophilized powder for solution in a pre-filled, dual chamber, single-use syringe 
(DCS). The lyophilized CD14152 powder (39 mg) and solution for reconstitution 
(0.595 mL) are stored in separate syringe chambers, with each DCS designed to 
deliver a 30-mg dose of CD14152. The placebo will be supplied as a lyophilized 
powder for solution in a pre-filled, single-use DCS.
 
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6.5
Dose Selection Rationale
Based on the outcome of the phase 2b dose-ranging study in adults, the 30-mg dose 
(with 60-mg loading dose), when administered Q4W, provided the best benefit/risk 
ratio of the 3 doses evaluated and is therefore selected as the final dose to be 
developed for the treatment of AD. Across the full range of subject body weights in 
the phase 2b study, the 30-mg dose (with 60-mg loading dose) provided a comparable 
observed exposure with respect to the body weight-based dose of 0.5 mg/kg tested 
during the phase 2a study.
Adolescent subjects will be enrolled after the sponsor confirms the safety of the 30-
mg Q4W dose in adolescents in a separate clinical study (Protocol 116912).
The current study includes a 32-week maintenance period whereby clinical responders 
on nemolizumab 30 mg Q4W at Week 16 will be re-randomized (1:1:1) to 30 mg 
Q4W, 30 mg Q8W, or placebo to evaluate maintenance of effect. The nemolizumab 
30 mg Q8W regimen is proposed to evaluate whether a clinical response can be 
maintained with a lower dosing frequency. 
PK/pharmacodynamic (PD) modeling was performed on three clinical endpoints 
(EASI, IGA, and PP NRS) to support selection of the additional Q8W dose regimen 
for Phase 3 maintenance. The medians of the active treatment arms were not 
contained within the range of the placebo for all clinical endpoints, indicating a 
benefit with active treatment over placebo in both dose regimens (Q4W and Q8W). 
While higher efficacy on all clinical endpoints was observed with the Q4W dose 
regimen, it was evidenced that subcutaneous nemolizumab Q8W for 16 weeks will 
maintain clinical benefit compared to placebo. 
PK/PD modeling provides the rationale to evaluate and compare the safety and 
efficacy of Q4W and Q8W dosing of 30 mg nemolizumab in the maintenance phase 
of the pivotal studies.
 
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8
INVESTIGATIONAL PLAN
8.1
Overall Study Design and Plan: Description
This is a randomized, double-blind, placebo-controlled, multicenter, parallel-group 
study in adult and adolescent subjects with moderate-to-severe AD. Eligible subjects 
must have a documented history of inadequate response to topical AD medications. 
Approximately 150 study centers are planned in Europe, Americas, and Asia-Pacific.
Beginning at screening, subjects will apply a moisturizer at least once daily and an
authorized background topical therapy (including a medium-potency TCS for the 
body and a low-potency TCS or a TCI for sensitive areas such as the face, neck, 
intertriginous areas, etc) for use throughout the study. If deemed to be medically 
necessary by the investigator (eg, to control intolerable AD signs/symptoms), rescue 
therapies can be prescribed to the subjects during the study, except during the run-in 
period (ie, at least 2 weeks [14 days] before Day 1/baseline).
The study consists of 4 periods over approximately 60 weeks: screening (including 
run-in), initial treatment, maintenance, and follow-up (unless the subject is a non-
responder at Week 16, at which their participation could last up to 28 weeks). Refer to
Figure 2 for an overview of the treatment/study design.
An IDMC will review and monitor subject safety throughout the study. The IDMC 
will provide recommendations on the safety of subjects. Details on the IDMC, 
including the plan of analysis for IDMC outputs, the composition of the IDMC, the 
procedures, roles, responsibilities and their communications are provided in the 
IDMC charter.
Screening Period (Screening to Initial Randomization/Baseline)
The screening period (approximately 2-4 weeks before planned Day 1/baseline) will 
evaluate subject eligibility and introduce standardized background topical therapy over 
a run-in period of at least 2 weeks (ie, 14 days) before Day 1/baseline.
Subjects may be rescreened once unless the reason for screen failure is related to disease 
severity inclusion criteria (IGA, EASI, BSA, and PP NRS). The latter subjects are not 
permitted to rescreen.
Initial Treatment Period (Baseline/Day 1 to Week 16 Pre-dose)
The initial treatment period is defined as Day 1/baseline through Week 16 (before the
Week 16 dose, with last dose at Week 12). Approximately 750 total subjects will be 
randomized (2:1) to receive either nemolizumab (CD14152) or placebo, stratified by 
baseline disease severity (IGA; moderate: IGA = 3; severe: IGA = 4) and PP NRS 
severity [PP NRS ≥7; PP NRS < 7). A minimum of 250 subjects will be randomized 
in each PP NRS strata. Table 4 summarizes study drug dosing during the initial 
treatment period.
 
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Subjects will continue to use background topical therapy, which should be adjusted 
according to the disease activity and tolerability, including tapering when signs and 
symptoms improve, discontinuation when lesions clear, and restarting if signs and 
symptoms recur, based on investigator clinical judgment. Any adjustments to 
background topical therapy are to be recorded in the appropriate case report form
(CRF).
Table 4: Initial Treatment Period Randomized Group Assignments
Group
Treatment
Loading dose 
(Day 1/Baseline)
Dose at Week 4, 8, 12
Route
Schedule
1
Nemolizuma
b(CD14152)
60 mg (two 30-mg 
injections)
30 mg
sc
Q4W
2
Placebo
Placebo (two 
injections)
Placebo
sc
Q4W
Abbreviation(s): Q4W=every 4 weeks; sc=subcutaneous.
A pharmacist (or other qualified personnel) will prepare study drug for injection 
throughout the study, including confirmation of complete reconstitution, prior to 
delivery of study medication for injection. The pharmacist (or other qualified 
personnel) preparing study medication should not discuss any aspects of study drug 
preparation with the subject/caregivers or study staff involved in subject interviews or 
study assessments.
Subjects (and/or their caregivers) will have the option to self-inject study drug while 
at the study center under staff supervision. Subjects (and/or their caregivers) will be 
trained on injecting the study drug at Day 1 and will be allowed to inject study drug at 
all subsequent visits. If the subject (and/or caregiver) is unwilling to perform 
injections, study staff can administer study drug at each visit.
Clinical assessments will occur according to the schedule of assessments through the 
Week 16 visit (see Section 8.1.2 ). Subjects who are clinical responders at Week 16 will 
continue to the maintenance period. Subjects who are non-responders at Week 16 may 
be eligible to enroll into the LTE study (Protocol 118163). Subjects who require rescue 
therapy for clinical worsening of AD before Week 16 may also be considered for LTE
study participation but will be required to continue with study visits until the Week 16 
visit is due. The follow-up visit is not required for subjects who participate in the LTE
study.
Subjects who decline or are not eligible to enter into the LTE study will complete a 
follow-up visit 12 weeks after their last study drug injection.
 
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Subjects who discontinue the initial treatment period prematurely should complete an 
early termination (ET) visit and a follow-up visit 12 weeks after the last study drug 
injection. 
Initial treatment period results may be analyzed after all subjects have either 
completed the Week 16 visit or have withdrawn or been discontinued from the study 
before Week 16. To maintain the blind during the maintenance period, personnel 
directly involved with the ongoing conduct of the study from the sponsor, contract 
research organization (CRO), or investigational study centers will not have access to 
any information that may lead to unblinding.
Maintenance Period (Re-Randomization: Week 16 to Week 48)
The maintenance period is defined as Week 16 (maintenance baseline) to Week 48. All 
nemolizumab (CD14152)-treated subjects (ie, group 1) who are clinical responders at 
Week 16 will be re-randomized (1:1:1) to study medication, as follows: group 1A, 
nemolizumab (CD14152) 30 mg Q4W; group 1B, nemolizumab (CD14152) 30 mg 
Q8W; or group 1C, placebo Q4W (Table 5). 
Clinical responders are defined as: 

IGA of 0 (clear) or 1 (almost clear) at Week 16
OR

EASI-75 at Week 16
All placebo-treated subjects (ie, subjects in group 2 from the initial treatment period) 
who responded to placebo during the initial treatment period will continue to receive 
placebo Q4W in the maintenance period. 
Subjects who receive rescue therapy will be considered non-responders.
Based on the phase 2b results (Protocol 114322), it is estimated that 15% of subjects 
will drop out from the initial treatment period. Assuming a 45% responder rate with 
active treatment and 12% with placebo, approximately 216 subjects will participate in 
the maintenance period (190 nemolizumab and 26 placebo subjects). 
Table 5: Maintenance Period Re-Randomized Group Assignments
Group
Treatment
Dose
Week(s)
Route
Schedule
1A
Nemolizumab 
(CD14152)
30 mg
16, 20, 24, 28, 32, 36, 40, 44
sc
Q4W
1B
Nemolizumab 
(CD14152)
30 mg
16, 20*, 24, 28*, 32, 36*, 40, 44*
sc
Q8W*
1C 
Placebo
Placebo
16, 20, 24, 28, 32, 36, 40, 44
sc
Q4W
*with placebo Q4W at Week 20, 28, 36, and 44 to maintain blind
Abbreviation(s): Q4W=every 4 weeks; Q8W=every 8 weeks; sc=subcutaneous.
 
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Beginning at Week 16, subjects in group 1A will receive active (ie, nemolizumab 
[CD14152]) study drug injections Q4W up to Week 44. Subjects in group 1B will 
receive active (ie, nemolizumab [CD14152]) study drug injections Q8W, with placebo 
at alternating visits to maintain the blind. Group 1B subjects will receive the last active 
study drug injection at Week 40 (final injection at Week 44 will be placebo). Group 1C 
subjects will receive placebo Q4W (ie, through Week 44). 
Clinical assessments will occur according to the schedule of assessments through the 
Week 48 visit (see Section 8.1.2 ). Subjects should continue the same background 
topical therapy used in the initial treatment period leading up to the Week 16 visit, 
including tapering or complete cessation (no use), if applicable. Throughout the 
maintenance period, adjustments to background topical therapy, as determined by the 
investigator, are permitted based on the subject’s clinical response.
Primary maintenance effect will be evaluated based on Week 48 assessments. All 
maintenance endpoints will be analyzed independently from each pivotal study and by 
using pooled data after the completion of both trials.
Subjects requiring rescue before the Week 32 must undergo a required wait period (with 
continued study visits) until Week 32, at which time they may be considered for LTE
eligibility/participation. Thereafter, no wait period is required. See Section 8.5.1 for 
details.
Subjects who complete the Week 48 visit may be eligible to enroll into the LTE study 
(Protocol 118163). The follow-up visit is not required for subjects who participate in 
the LTE study.
Subjects who decline or are not eligible for the LTE study will be asked to complete 
the follow-up visit.
Subjects who discontinue the maintenance period prematurely should complete an ET
visit and a follow-up visit 12 weeks after the last study drug injection.
Follow-up
The follow-up visit will be conducted 12 weeks after the last study drug injection for 
subjects who decline or are not eligible to enter the LTE study. The follow-up visit is 
not required for subjects who participate in the LTE study. (Twelve weeks 
corresponds to approximately 5 half-lives when nemolizumab 30 mg is dosed 
subcutaneously Q4W.)
 
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8.1.1 Study Visit Schema
Figure 2: Study Visit Schema
Abbreviations: BL=baseline; q4wk=every 4 weeks; q8wk=every 8 weeks; W=week.
 
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be performed per investigator’s judgement.. Subjects requiring rescue therapy between scheduled visits should return to the clinic for an unscheduled visit for investigator 
assessments of efficacy before starting rescue therapy.
c 
 
 
d Subjects discontinued prematurely should complete ET assessments according to: Visit 6/Week 16 if during the initial treatment period or Visit 14/Week 48 if during the
maintenance period and a final/follow-up visit 12 weeks after the last study drug injection (for subjects not participating in the LTE study). Subjects who require rescue
therapy (with or without study medication discontinuation) must continue with study visits until: Visit 6/Week 16 if during the initial treatment period or until Visit 
10/Week 32 if during the maintenance period to be considered for LTE eligibility. (If during the maintenance period, rescue is needed after the Week 32 visit, no wait 
period is required.) See Section 8.5.1 for details.
e The follow-up visit will be conducted for subjects who decline or are not eligible to enter the LTE study and should be conducted 12 weeks after the last study drug injection.
(The follow-up visit is not required for subjects who will rollover to the LTE study.)
f The run-in period begins at least 2 weeks (ie, 14 days) before Day 1/baseline. Subjects receiving rescue therapies during the run-in period are not eligible to participate in the 
study.
g Patient-reported outcome assessments and designated safety measurements should occur before investigator assessments, laboratory sample collections, and study drug 
administration.
h
 
 
 
 
 
 
 
k Assessments to be completed by subjects for 7 consecutive days before the designated target visit dates during study treatment.
l Optional subject interviews will be conducted at the end of the initial treatment period between Week 16 and Week 18. See Section 9.7.15 for details.
m Optional photographs of AD lesions will be performed only for consenting subjects at selected sites. See Section 9.8 for details.
n Subjects with a history of asthma will complete the ACT (and PEF testing) at each scheduled visit. Subjects with de novo asthma will complete the ACT (and PEF testing) 
beginning from de novo diagnosis and at all subsequent scheduled visits. See Section 9.2.9.1 for details.
o At screening, the investigator should specifically question all subjects about any medical history of asthma and their respiratory health (eg, wheezing, coughing, allergies, 
infections). A respiratory examination will be required for all subjects at all scheduled visits. See Section 9.2.9.2 for details.
 
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p PEF testing will be performed for all subjects at screening, baseline, Week 8, 16, 32, 48, and follow up visits. For subjects reporting a medical history of asthma, PEF testing
(and ACT) will be performed at all visits during the clinical study. For subjects diagnosed with de novo asthma, PEF testing (and ACT) will be performed at all visits,
starting with the visit in which the diagnosis was confirmed. Subjects should be asked to withhold asthma medication on study visit days until after PEF testing is 
complete, to the extent it does not pose an undue risk to the subject. See Section 9.2.9.3 for details.
q Complete PE should be performed at designated visits. See Section 9.2.8 for PE details.
r Contraceptive counseling should occur at screening or at applicable visits when pre-pubertal subjects begin menses.
s Height collection will be performed for all subjects at screening. Height collection is only required for adolescents (ages 12-17) at designated post-screening visits.
t 12-lead ECGs should be performed in the supine position, before any scheduled vital sign measurements and blood draws. See Section 9.2.10 .
u Vital signs will include pulse rate, systolic and diastolic blood pressure (after the subject has been sitting for at least 5 minutes), and body temperature. See Section 9.2.6 .
v At scheduled visits with laboratory, PK, and ADA assessments, samples are to be collected before study drug injection(s). See Section 9.2.2.1, 9.2.2.2, and 9.2.2.3 for 
hematology, clinical chemistry (including FSH for postmenopausal subjects), and urinalysis testing details, respectively.
w TB screening: QuantiFERON-TB Gold test for all subjects. See Section 9.2.5 for details.
x Only for WOCBP. Pregnancy test results must be available prior to the administration of the study drug. Serum pregnancy test to be performed at the screening visit;
UPT at all other visits. For prepubertal subjects, reconfirm pre-menses status at every visit and, in case of status change, collect information on contraceptive measures 
and perform a UPT according to the schedule for WOCBP.
y For postmenopausal subjects (ie, no menses for 12 consecutive months), confirm status with a high FSH level in the postmenopausal range. Blood chemistry sample at the 
screening visit (V1) will also be used for an FSH test for the confirmation of postmenopausal status.
z See Section 9.3 for details on PK assessments. As a guideline, PK samples should be collected at approximately the same time of day throughout the study, to the extent 
possible, before study drug injection (pre-dose samples). 
aa See Section 9.4 and Section 9.5 for details on ADA and PD/biomarker assessments, respectively.
bb Optional PGx sample collection is only for subjects who provide additional consent. See Section 9.5.1 for details.
cc All nemolizumab (CD14152)-treated subjects who are clinical responders at Week 16 (defined as 1. IGA of 0 [clear] or 1 [almost clear]; OR 2. EASI-75) will be re-
randomized (1:1:1) to receive nemolizumab (CD14152) Q4W, Q8W, or placebo Q4W.
dd Study drug reconstitution will be performed by the pharmacist (or other qualified personnel) throughout the study, and complete reconstitution confirmed, prior to delivery 
for injection. Study center staff will provide study drug injection training for subjects willing and able to self-inject (or have their caregiver inject) study medication. 
Subjects and/or caregivers will then be allowed to inject medication at subsequent visits. Based on the subject’s preference, study center staff can also perform all 
injections.
ee After study drug administration, subjects will be monitored closely for any signs or symptoms of hypersensitivity reaction before being discharged. Subjects should remain at 
the study center for at least 30 minutes after the first 2 injections during the study. *In Germany only, subjects must undergo a 60 minute observation period after the first 
3 injections and a 30 minute observation period after all subsequent doses.
ff Subjects will receive a loading dose on Day 1 (ie, 2 injections of nemolizumab 30 mg or placebo).
gg Subjects will apply a moisturizer daily, and liberally as needed, to dry skin and AD lesions throughout the study. The subject’s current moisturizer or a moisturizer 
recommended by the investigator may be used. Use should not occur within 8 hours before clinic/office visits.
 
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hh Authorized topical therapy use beginning ≥ 14 days before Day 1. See Section 8.4.9.1.2. The investigator should adjust background topical therapy use during the 
study, according to the disease activity and tolerability, including tapering when signs and symptoms improve, discontinuation when lesions clear, and restarting 
if signs and symptoms recur, based on investigator clinical judgment.
ii Appropriate amounts of TCS and/or TCI should be dispensed or prescribed at each visit, according to investigator judgement. Containers of previously dispensed/prescribed 
TCS and/or TCI should be collected at each visit. Collected containers with remaining medication may be re-dispensed back to the subject, when applicable.
jj No dispensation of TCS and/or TCI should occur at the final study visit. Collection only.
 
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8.2
Discussion of Study Design
8.2.1 Study Design
This study will evaluate the safety and efficacy of nemolizumab (CD14152) in adolescent 
and adult subjects with AD. The rationale for the general study design is based upon the 
prior phase 2b design conducted in adult subjects with AD, with background TCS therapy. 
The rationale for the nemolizumab dose/dose regimen is provided in Section 6.5. 
Eligible subjects for this clinical study will be adolescents and adults with moderate-to-
severe AD whose disease is not adequately controlled by topical treatments. The study 
population is selected based on the current unmet need in the management of AD in 
pediatric populations, the mode of action of nemolizumab (CD14152), and the need to 
understand the safety and long-term exposure of nemolizumab (CD14152) in the 
adolescent and adult population. The inclusion criteria for IGA, BSA, and EASI are 
consistent with the disease severity targeted in the study and in nemolizumab (CD14152) 
studies in adults: An IGA of 3 or 4 corresponds to moderate or severe AD, respectively; 
BSA of at least 10% is usually observed in these more severe AD patients. An EASI 
threshold of 16 is generally recognized to be representative of moderate-to-severe AD and 
is consistent with the published analyses correlating IGA and EASI assessments in patients 
with AD.33,34 Finally, subjects with associated pruritus are targeted because of prior studies
with nemolizumab (CD14152) and its marked effect on pruritus. Specifically, subjects with 
a PP NRS score of ≥ 7 were included based on the population evaluated in the phase 2b 
study; a lower PP NRS threshold of ≥ 4 was selected for this study based on anticipated 
benefits for subjects with less severe pruritus as well.
The study includes a 16-week initial treatment period, a 32-week maintenance period, and 
an 8-week follow-up period (ie, 12 weeks after last study drug administration) for subjects 
who decline or are not eligible to enter the LTE study. A 16-week treatment is considered 
adequate to evaluate the safety and efficacy of nemolizumab based on the results of the 
phase 2b study (114322) and other registrational studies for the treatment of AD. The 
maintenance period will compare the maintenance of effect of 2 nemolizumab dosing 
regimens (30 mg Q4W and 30 mg Q8W) compared to placebo. The nemolizumab 30 mg 
Q8W regimen is proposed to evaluate whether a clinical response can be maintained with 
a lower dosing frequency. Subjects who are clinical responders at Week 16 will be re-
randomized (1:1:1) to 1 of 3 maintenance treatment groups. 
 
              
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Clinical responders are defined as: 

IGA of 0 (clear) or 1 (almost clear) at Week 16
OR 

EASI-75 at Week 16
Subjects who are non-responders at the Week 16 visit can be considered for LTE study 
eligibility. All subjects who complete the maintenance period (Week 48 visit) can be 
considered for LTE study eligibility.
The selected endpoints for assessing the PK and safety of nemolizumab (CD14152) are in 
accordance with current standards, as are the safety endpoints of the trial. Blinding subjects 
and the designated study team to the treatment assignment(s) ensures objectivity and 
minimizes bias. Randomization through the interactive response technology (IRT) guards 
against selection bias.
A follow-up visit is scheduled for subjects who decline participation in the LTE study or 
are not eligible to participate. The duration of the follow-up period from the final 
nemolizumab dose (12 weeks) corresponds to approximately 5 half-lives of nemolizumab,
which is considered adequate to ensure subject safety. The follow-up visit is not required 
for subjects who participate in the LTE study as its primary objective is long-term 
evaluation of safety.
Differences may be detectable during the study drug reconstitution process between active 
study drug and placebo but appear similar after reconstitution is complete (approximately 
10 minutes). Throughout the study, a pharmacist (or other qualified personnel) will prepare 
study medication for injection, including confirmation of complete reconstitution, prior to 
delivery of study medication for injection. The pharmacist (or other qualified personnel) 
preparing study medication should not be involved with any study assessments and should 
not discuss any aspects of study drug reconstitution with the subject/caregiver or study staff 
involved in subject interviews or study assessments. 
Background topical therapy includes the use of authorized TCS ± TCI throughout this 
study. This is in line with the current practice to use topical agents in conjunction with 
systemic treatment in more severe cases.2 Background topical therapy will be started from 
the screening visit to ensure disease stability and avoid flares. The potency of TCS selected 
for this study is clinically justified: a medium-potency TCS will be used on the body, where 
considered safe (eg, trunk and extremities). A low-potency TCS or a TCI will be used in 
 
              
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sensitive areas considered unsafe for medium-potency TCS (eg, face, neck, intertriginous 
areas) or where medium-potency TCS is not tolerated. The prescribed background therapy
use should be within daily limits according to the product labeling. The protocol includes 
guidelines to adjust background therapy usage according to disease activity and tolerability 
of the subject, including tapering when signs and symptoms improve, discontinuation when 
lesions clear, and restarting if signs and symptoms recur, based on investigator clinical 
judgment.
The placebo-control design includes a provision for rescue therapy for clinical worsening 
of AD or lack of improvement in AD based on investigator clinical judgment. Subjects 
requiring rescue therapy may be eligible for the LTE study but will be required to continue 
scheduled study visits until the Visit 6/Week 16 visit during the initial treatment period or 
the Week 32 visit for those participating in the maintenance period before LTE eligibility 
will be assessed. After Week 32, no wait period is required. The required wait periods for 
considering LTE study eligibility are intended to discourage inappropriate use of rescue 
medication for the sole purpose of accessing open-label, active study medication. 
Initial treatment period results may be analyzed after all subjects have either completed the 
Visit 6/Week 16 visit or have withdrawn or been discontinued from the study before Visit 
6/Week 16.
To avoid bias and to ensure the integrity of the blind, personnel directly involved with the 
ongoing conduct of the study from the sponsor, CRO, or other investigational study centers 
will not have access to any information that may lead to unblinding.
8.3
Selection of Study Population
8.3.1 Number of Planned Subjects 
Approximately 750 total subjects are planned to be randomized, including a minimum of 
130 adolescent subjects aged 12 to 17 years.
Refer to Section 10.2 for the statistical considerations on which the sample size is based.
8.3.2 Inclusion Criteria
To be eligible for study entry, subjects must satisfy all of the following inclusion criteria:
1. Male or female subjects aged ≥ 12 years at the screening visit. 
 
              
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Note: Enrollment of subjects aged 12 to 17 years has been opened after the IDMC has 
assessed interim safety data from the phase 2 study (Protocol 116912) and provided 
recommendations to the sponsor, who then determined the eligibility of this age group 
for enrollment in the study. The sponsor sent a written communication to the site 
confirming that the study is open for enrollment of adolescents. Adolescents could not 
be enrolled in the study until such communication was received.
2. Chronic AD for at least 2 years before the screening visit and confirmed according to 
American Academy of Dermatology Consensus Criteria (Appendix 1)2 at the time of 
the screening visit. 
3. EASI score ≥ 16 at both the screening and baseline visits.
4. IGA score ≥ 3 (based on the IGA scale ranging from 0 to 4, in which 3 is moderate and 
4 is severe) at both the screening and baseline visits.
5. AD involvement ≥ 10% of BSA at both the screening and baseline visits.
6. Peak (maximum) pruritus NRS score of at least 4.0 at the screening and baseline visit.
Screening PP NRS score will be determined by a single PP NRS assessment (score 
ranging from 0 to 10) for the 24-hour period immediately preceding the screening visit.
Baseline PP NRS score will be determined based on the average of daily PP NRS scores 
(score ranging from 0 to 10) during the 7 days immediately preceding baseline 
(rounding is not permitted). A minimum of 4 daily scores out of the 7 days immediately 
preceding baseline is required for this calculation.
7. Documented recent history (within 6 months before the screening visit) of inadequate 
response to topical medications (TCS with or without TCI). All subjects must 
demonstrate inadequate response to TCS. All subjects who have used TCI within 6 
months of the screening visit, or for whom TCI is selected as background therapy for 
sensitive areas, must also demonstrate inadequate response to TCI. Acceptable 
documentation includes patient records with information on TCS (with or without 
TCI) prescription and treatment outcome, or written documentation of the 
conversation with the subject’s treating physician, if different than the investigator. If 
documentation is inadequate, subjects may be re-screened after such documentation is 
obtained.
Inadequate response to TCS treatments (with or without TCI) is defined as:
7a. Failure to achieve or maintain remission or low disease activity (equivalent to IGA 
≤ 2) despite treatment with a regimen of a medium-, high-, or very high-potency 
 
              
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TCS (Class I-III according to the US classification)2 (with or without TCI), applied 
for at least 4 weeks or for the maximum duration per prescribing information;
or
7b. Requirement of a long-term treatment (> 4 weeks) with a high- or very high-potency 
TCS (Class I-II according to the US classification)2 (with or without TCI) to 
achieve or maintain remission or low disease activity (equivalent to IGA ≤ 2);
or 
7c. If documentation of inadequate response to topical treatments is not available, 
subjects with a documented recent course of systemic treatment or phototherapy 
for AD (within 6 months before the visit) will also be considered as inadequate 
responders to topical treatments.
8. Agree to apply a moisturizer throughout the study from the screening visit; agree to 
apply authorized topical therapy from the screening visit and throughout the study as 
determined appropriate by the investigator.
9. Female subjects of childbearing potential (ie, fertile, following menarche and until 
becoming post-menopausal unless permanently sterile) must agree either to commit to 
true abstinence throughout the study and for 12 weeks after the last study drug 
injection, when this is in line with the preferred and usual lifestyle of the subject, or to 
use an adequate and approved method of contraception throughout the study and for 
12 weeks after the last study drug injection. This criterion also applies to a 
prepubertal female subject who begins menses during the study. *In Germany only, if 
a subject has reached Tanner stage 3 breast development, even if not having 
menarche, the subject will be considered a female of childbearing potential.
Adequate and approved methods of contraception applicable for the subject and/or 
her partner are defined below:

Progestogen-only oral hormonal contraception

Combination of male condom with cap, diaphragm, or sponge with spermicide
(double barrier methods) (*In Germany only, double barrier methods are not 
considered an adequate and approved method of contraception)
Note: “Double barrier methods” refers to simultaneous use of a physical barrier by 
each partner. Use of a single barrier method (eg, condom) together with a 
spermicide is not acceptable.

Combined (estrogen-
and progestogen-containing) oral, intravaginal, or 
transdermal hormonal contraception

Injectable or implanted hormonal contraception

Intrauterine devices or intrauterine hormone-releasing system
 
              
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
Bilateral tubal ligation or tube insert (such as the Essure system) at least 3 months 
before the study

Bilateral vasectomy of partner at least 3 months before the study
10. Female subjects of non-childbearing potential must meet one of the following criteria:

Absence of menstrual bleeding for 1 year prior to screening without any other 
medical reason, confirmed with follicle-stimulating hormone (FSH) level in the 
postmenopausal range

Documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy at 
least 3 months before screening
Note: Bilateral tubal ligation is not accepted as a reason for non-childbearing 
potential
11. Subject (and guardian, when applicable) willing and able to comply with all of the 
time commitments and procedural requirements of the clinical study protocol, 
including daily diary recordings by the subject using an electronic handheld device 
provided for this study.
12. Understand and sign an informed consent form (ICF) (and assent form, when 
applicable) before any investigational procedure(s) are performed.
8.3.3 Exclusion Criteria
Subjects will be excluded from the study if 1 or more of the following criteria are 
applicable:
1. Body weight < 30 kg.
2. Subjects meeting 1 or more of the following criteria at screening or baseline:
2a. Had an exacerbation of asthma requiring hospitalization in the preceding 12 
months.
2b. Reporting asthma that has not been well-controlled (ie, symptoms occurring on >
2 days per week, nighttime awakenings 2 or more times per week, or some 
interference with normal activities) during the preceding 3 months.
2c. ACT ≤ 19 (only for subjects with a history of asthma).
2d. PEF < 80% of the predicted value.
 
              
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3. Subjects with a current medical history of chronic obstructive pulmonary disease 
and/or chronic bronchitis.
4. Cutaneous infection within 1 week before the baseline visit, any infection requiring 
treatment with oral or parenteral antibiotics, antivirals, antiparasitics, or antifungals 
within 2 weeks before the baseline visit, or any confirmed or suspected COVID-19 
infection within 2 weeks before the screening or baseline visit. Subjects may be 
rescreened once the infection has resolved. Resolution of COVID-19 infection can be 
confirmed by recovery assessment methods, as described in Section 8.3.4.2.
Note: Subjects with chronic, stable use of prophylactic treatment for recurrent herpes 
viral infection can be included in this study.
5. Requiring rescue therapy for AD during the run-in period or expected to require rescue 
therapy within 2 weeks following the baseline visit.
6. Positive serology results (hepatitis B surface antigen [HBsAg] or hepatitis B core 
antibody [HBcAb], hepatitis C antibody, or human immunodeficiency virus [HIV] 
antibody) at the screening visit. 
Note: Subjects with a positive HBcAb and a negative HBsAg can be included in this 
clinical study if hepatitis B surface antibody is positive (considered immune after a 
natural infection).
7. Having received any of the following treatments in Table 6 within the specified 
timeframe before the baseline visit:
Table 6: Prior Treatments
Treatment(s)
Timeframe
Coal tar products
2 weeks
Topical PDE-4 inhibitor
2 weeks
Non-authorized TCS
2 weeks
Topical medications, including authorized TCS/TCI, with occlusive 
dressings (eg, wet wraps)
2 weeks
Systemic corticosteroids (corticosteroid inhalers are permitted)
4 weeks 
Phototherapy or tanning beds
4 weeks
 
              
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Treatment(s)
Timeframe
Immunosuppressive or immunomodulatory drugs (eg, cyclosporine A, 
oral tacrolimus, cyclophosphamide, azathioprine, methotrexate, 
mycophenolate mofetil, Janus kinase inhibitors)
4 weeks or 5 
half-lives 
(whichever is 
longer)
Biologics and their biosimilars (eg, etanercept, adalimumab, 
infliximab, omalizumab, etc)
8 weeks or 5 
half-lives 
(whichever is 
longer)
Dupilumab
10 weeks
Live attenuated vaccine
12 weeks
Drugs with a sedative effect such as benzodiazepines, 
imidazopyridines, barbiturates, sedative anti-depressants (eg, 
amitriptyline), SSRIs (eg, paroxetine), or SNRIs, except if these 
treatments were taken at a stable dose for at least 3 months before 
screening
(Stable treatment with antihistamines with sedative effect is allowed at 
a dose that, based on previous experience, is well tolerated by the 
subject.)
1 week
Gabapentinoids (eg, gabapentin, pregabalin)
4 weeks
Cannabinoids
2 weeks
Alternative medicine for AD (eg, traditional Chinese medicine)
2 weeks
Abbreviation(s): AD=atopic dermatitis; PDE-4=phosphodiesterase-4; SNRI= serotonin-
norepinephrine reuptake inhibitor; SSRI=selective serotonin reuptake inhibitor; TCI=topical 
calcineurin inhibitor; TCS=topical corticosteroid.
Note: Subjects should not interrupt ongoing treatment with medications important for the subject’s 
health for the sole purpose of participating in this study.
8. Previous treatment with nemolizumab.
9. Subjects who, after a full treatment course of 16 weeks with dupilumab, experienced 
worsening of their AD or failed to achieve minimal improvement (eg, ≤ 10% 
reduction in EASI or no reduction in IGA).
 
              
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10. Pregnant women (positive serum pregnancy test result at the screening visit or 
positive urine pregnancy test [UPT] at the baseline visit), breastfeeding women, or 
women planning a pregnancy during the clinical study.
11. History of lymphoproliferative disease or history of malignancy of any organ system 
within the last 5 years, except for (1) basal cell carcinoma, squamous cell carcinoma 
in situ (Bowen’s disease), or carcinomas in situ of the cervix that have been treated 
and have no evidence of recurrence in the last 12 weeks before the baseline visit, or 
(2) actinic keratoses that have been treated.
12. History of hypersensitivity (including anaphylaxis) to an immunoglobulin product 
(plasma-derived or recombinant, eg, monoclonal antibody) or to any of the study drug 
excipients.
13. History of intolerance to TCS or for whom TCS is not advisable (eg, hypersensitivity, 
significant skin atrophy).
14. Known active or untreated latent tuberculosis (TB) infection.
Note: Subjects who have a documented history of completion of an appropriate TB 
treatment regimen for active or latent TB with no history of re-exposure to TB since 
their treatment was completed are eligible to participate in the study.
15. Known or suspected immunosuppression or unusually frequent, recurrent, severe, or 
prolonged infections as per investigator judgment.
16. Presence of confounding skin condition that may interfere with study assessments 
(eg, Netherton syndrome, psoriasis, cutaneous T-cell lymphoma [mycosis fungoides 
or Sezary syndrome], contact dermatitis, chronic actinic dermatitis, dermatitis 
herpetiformis). 
17. Any medical or psychological condition or any clinically relevant laboratory 
abnormalities, such as but not limited to elevated ALT or AST (> 3 × ULN) in 
combination with elevated bilirubin (> 2 × ULN), during the screening period that 
may put the subject at significant risk according to the investigator’s judgment, if 
he/she participates in the clinical study, or may interfere with study assessments (eg, 
poor venous access or needle-phobia).
18. Planned or expected major surgical procedure during the clinical study.
19. Subjects unwilling to refrain from using prohibited medications during the clinical 
study (see Section 8.4.9.2).
 
              
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20. Currently participating or participated in any other study of a drug or device, within 
the past 8 weeks before the screening visit, (or 5 half-lives of the investigational drug, 
whichever is longer), or is in an exclusion period (if verifiable) from a previous study.
21. History of alcohol or substance abuse within 6 months of the screening visit.
8.3.4 Removal of Subjects From Therapy or Assessments
Although the importance of completing the entire clinical study will be explained to the 
subjects, any subject is free to discontinue his/her participation in the study at any time 
and for whatever reason, specified or unspecified, and without any prejudice. No 
constraints are to be imposed on the subject, and when appropriate, a subject may be 
treated with other conventional therapy when clinically indicated. Investigators or the 
sponsor can also withdraw subjects from the clinical study if deemed to be necessary.
Reasons for discontinuing study drug include:

Subject request (ie, consent withdrawal)

Non-compliance with the study drug or study schedule

Lost to follow-up

Occurrence of AEs, including laboratory abnormalities, not compatible with the
continuation of subject participation in the study, in the investigator’s opinion, or 
unacceptable to the subject to continue, including but not limited to the following:
o
Serious immediate-type allergic manifestations including anaphylactic 
reaction
o
Serious worsening of asthma considered related to study drug 
administration
o
Diagnosis of a malignancy (except curatively treated in situ cervical 
carcinoma, squamous cell carcinoma [Bowen’s disease] or basal cell 
carcinoma)
o
Opportunistic infections such as but not limited to active TB and other 
infections whose nature or course suggest an immune-compromised or 
immune-suppressed status
o
Any serious infection or any severe infection requiring treatment with 
parenteral antibiotics or oral antibiotics/antivirals/antifungals for > 2 
weeks considered related to study drug administration
o
Confirmed or suspected COVID-19 infection (temporary discontinuation 
may be acceptable; for instructions on resuming study drug administration, 
see Section 8.3.4.2).
 
              
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
Pregnancy

Use of non-permitted concurrent therapy (unless discussed and agreed upon with 
the investigator and medical monitor)

Use of systemic rescue therapy, as specified in Table 10 of Section 8.4.9.2 and
Section 8.4.9.1.3

Treatment failure

Investigator request

Sponsor request, including any of the above criteria
The reason(s) for withdrawal will be documented in the CRF. Subjects who have been 
enrolled and treated will not be replaced by another subject.
Subjects who prematurely discontinue study drug will be encouraged to complete the 
scheduled study visits.
When a subject discontinues study drug, he/she will be fully assessed whenever possible, 
and followed according to guidelines presented in Section 8.5.1 (Early Termination
Visit). 
Reasonable efforts will be made to contact subjects who are lost to follow-up. These 
efforts must be documented in the subject’s file. 
The sponsor has the right to terminate the study at any time in case of SAEs or if special 
circumstances concerning the investigational product or the company itself occur, making 
further treatment of subjects impossible. In this event, the investigator(s) will be informed 
of the reason for study termination.
8.3.4.1
Pregnancy
Subjects will be instructed that known or suspected pregnancy occurring during the study
should be confirmed and reported to the investigator. If a subject becomes pregnant, 
the investigator must withdraw the subject from the study without delay. The 
subject must not receive any further injection(s) of the study drug.
The investigator must:

Follow the procedures for reporting/follow-up of a pregnancy within 24 hours (see 
Section 9.2.1.5) of receipt of the information.

Complete as fully as possible the applicable Pregnancy Surveillance Form(s) (see 
Section 9.2.1.5).
 
              
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
Monitor and record the progress of the pregnancy until its outcome. Contact the 
subject’s regular physician (general practitioner or gynecologist) or hospital staff to 
obtain further details and ask for regular follow-up information.

Provide tri-monthly updates until the final outcome of the pregnancy. If the subject 
can no longer be reached (lost to follow-up), documentation of the non-
response/contact with 2 phone calls and a letter (certified with return receipt) is 
required.

If the pregnancy leads to an abortion (ie, voluntary abortion, spontaneous abortion, or 
therapeutic abortion), in utero death, or congenital anomaly, follow the procedure for 
declaration of/reporting an SAE (Section 9.2.1.3). 
The investigator should also be notified of pregnancy occurring during the study (and 
within 12 weeks [± 5 days] after the last dose of study drug) but confirmed after 
completion of the study. In the event that a subject is subsequently found to be pregnant 
after inclusion in the study, any pregnancy will be followed to term, and the status of 
mother and child will be reported to the sponsor after delivery.
Full details will be recorded on the withdrawal page (exit form), or an SAE report will be 
completed if the subject has completed the study. Pregnancy is not to be considered as an 
AE; however, it must be monitored and reported as described in Section 9.2.1.5.
8.3.4.2
COVID-19 Infection
Study drug administration will be discontinued in a subject in whom a COVID-19 
infection is confirmed or suspected. COVID-19 must be specified as the reason for study 
drug discontinuation.
Study drug administration may resume in subjects with confirmed or suspected COVID-
19 infection based on investigator judgement after discussion with the medical monitor or 
Sponsor and only if the following minimum conditions are met:

For symptomatic subjects: At least 14 days have passed since recovery, defined as 
resolution of fever without the use of fever-reducing medications and improvement in 
respiratory symptoms (e.g. cough, shortness of breath)

For asymptomatic subjects: At least 21 days have passed since the positive PCR test 
and no symptoms
 
              
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Note: The above should be considered minimum criteria. Where the local guidelines are 
more stringent for infection resolution criteria, those must be applied.
See Appendix 2 for additional guidance for management of subjects and study conduct 
during the COVID-19 pandemic.
8.4
Investigational Products
“Study drug” or “study medication” refers to nemolizumab (CD14152) or placebo drug 
product for purposes of this double-blind study. The list of excipients are detailed in the 
IB.
8.4.1 Investigational Products Administered
Study drug will be supplied as a lyophilized powder for solution for injection for 
subcutaneous use only after reconstitution in a pre-filled, single-use DCS. The 
lyophilized nemolizumab (CD14152) powder (39 mg) and solution for reconstitution 
(0.595 mL) are stored in separate syringe chambers, with each DCS designed to deliver a 
30-mg dose of nemolizumab (CD14152) after reconstitution. 
8.4.1.1
Study Drug Dosing – Initial Treatment Period
Table 7 summarizes study drug dosing for the initial treatment period, which includes 
Day 1/baseline to Visit 6/Week 16.
Table 7: Initial Treatment Period Dosing By Treatment Group
Group
Treatment
Loading Dose 
(Day 1/Baseline)
Dose at Week 4, 8, 
12
Route
Schedule
1
Nemolizumab
(CD14152)
60 mg (two 30-mg 
injections)
30 mg
sc
Q4W
2
Placebo
Placebo (2 placebo 
injections)
Placebo 
sc
Q4W
Abbreviation(s): Q4W=every 4 weeks; sc=subcutaneous.
At Visit 6/Week 16, subjects who are clinical responders to nemolizumab (CD14152)
treatment will be re-randomized (1:1:1) for participation in the maintenance period, and 
assigned by IRT to nemolizumab (CD14152) 30 mg Q4W, nemolizumab (CD14152) 30
 
              
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mg Q8W, or placebo Q4W. The Q8W group will receive alternating injections of placebo 
to maintain the blind. Refer to the study design in Section 8.1 for the definition of clinical 
responders. Subjects responding to placebo treatment will be assigned by IRT to receive 
placebo Q4W in the maintenance period.
Subjects who are non-responders at the Visit 6/Week 16 visit can be considered for LTE
study eligibility. Similarly, subjects who require rescue therapy for clinical worsening of 
AD or lack of improvement in AD may be considered for LTE study eligibility but must
continue study visits until the Visit 6/Week 16 visit is due.
8.4.1.2
Study Drug Dosing – Maintenance Treatment Period
Table 8 summarizes study drug dosing for the maintenance period, which spans the Week 
16 to Week 48 visits.
Table 8: Maintenance Period Dosing By Treatment Group
Group
Treatment
Dose
Week(s)
Route
Schedule
1A
Nemolizumab 
(CD14152)
30 mg
16, 20, 24, 28, 32, 36, 40, 44
sc
Q4W
1B
Nemolizumab 
(CD14152)
30 mg
16, 20*, 24, 28*, 32, 36*, 40, 
44*
sc
Q8W*
1C 
Placebo
Placebo
16, 20, 24, 28, 32, 36, 40, 44
sc
Q4W
*with placebo injections at Week 20, 28, 36, and 44 to maintain blind
Abbreviation(s): Q4W=every 4 weeks; Q8W=every 8 weeks; sc=subcutaneous.
Subjects who complete the Week 48 visit can be considered for LTE study eligibility. 
Similarly, subjects requiring rescue therapy prior to the Week 48 visit may be considered 
for LTE eligibility. A wait period with continued study visits is required if rescue occurs 
before the Week 32 visit. Thereafter, no wait period is required. Subjects must complete 
the final study/ET visit prior to rollover to the LTE study.
8.4.1.3
Study Drug Preparation
A pharmacist (or other qualified personnel) will prepare study medication for injection 
according to instructions provided in the current version of the pharmacy manual and the 
instructions for use. Study medication preparation should be conducted in a secured and 
 
              
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clean area with limited access to only designated personnel at the time of the preparation. 
Good hygiene practices and clean techniques must apply at all times.
Differences may be detectable during the study drug reconstitution process between active 
and placebo, but active and placebo appear similar after reconstitution is complete 
(approximately 10 minutes). Throughout the study, a pharmacist (or other qualified 
personnel) will prepare study medication for injection, including confirmation of complete 
reconstitution, prior to delivery of study medication for injection. The pharmacist (or other 
qualified personnel) preparing study medication should not be involved with any study 
assessments and should not discuss any aspects of study drug reconstitution with the 
subject/caregiver or study staff involved in subject interviews or study assessments. 
The study drug does not contain preservatives. From a microbiological point of view, the 
preparation of the study drug has to be done as close to subject administration as possible, 
and the study drug should be used immediately (less than 1 hour) after reconstitution. If 
not used immediately, the study drug has to be used within 4 hours maximum after 
reconstitution stored at room temperature (below 30°C) and only if the preparation has 
taken place applying strictly good hygiene practices and clean techniques to ensure 
controlled aseptic conditions.
8.4.1.4
Study Drug Injection
All study drug injections will occur at the study center, following instructions provided in 
the current versions of the pharmacy manual and Instruction for Use. After confirming that 
the study drug is fully reconstituted, the pharmacist (or other qualified personnel) will 
deliver the DCS to the investigator or other qualified personnel, for subcutaneous injection 
in the subject’s abdomen or alternative injection site. A different injection site should be 
selected for each injection. Refer to the current versions of the pharmacy manual and 
Instruction for Use for further details. The site of injection should be recorded in the 
subject’s treatment record as well as the CRF at each time point.
For subjects willing and able to self-inject, or to have their caregiver inject study 
medication, study center staff will provide training on study medication injections. Subjects 
or caregivers will be allowed to inject medication at subsequent visits under supervision 
by study center clinic staff (with DCS preparation including reconstitution performed by 
the pharmacist or other qualified personnel and delivered for injection after reconstitution 
is complete). Study center/clinic staff can perform all injections if the subject (or caregiver)
is unwilling or unable to perform injections. The CRF will record who performed study 
drug injection at each visit.
 
              
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After study drug administration, subjects will be monitored closely for any signs or 
symptoms of hypersensitivity reaction before being discharged. Subjects should remain at 
the study center for at least 30 minutes after the first 2 injections during the study. *In 
Germany only, subjects must undergo a 60 minute observation period after the first 3 
injections and a 30 minute observation period after all subsequent doses.
8.4.2 Identity of Investigational Products
Table 9 provides a description and overview of study medication usage.
 
              
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Table 9: Description and Usage of Investigational Product
Investigational Product
Initial Treatment
Maintenance
Name (internal code)
Nemolizumab (CD14152)
Nemolizumab (CD14152)
Pharmaceutical form
Lyophilized powder in a DCS 
for solution for injection
Lyophilized powder in a 
DCS for solution for 
injection
Dosage
30 mg (with a loading dose of 
60 mg at baseline) 
30 mg 
Dose regimen
Q4W
Q4W or Q8W
Route*
Subcutaneous use by subjects, 
caregivers, or clinic staff after 
reconstitution
Subcutaneous use by 
subjects, caregivers, or clinic 
staff after reconstitution
Duration of treatment 
16 weeks: baseline to Week 
16
32 Weeks: Week 16 to Week 
48
Comparator
Initial Treatment
Maintenance
Name (internal code)
CD14152 placebo (N/A)
CD14152 placebo (N/A)
Pharmaceutical form
Lyophilized powder in a DCS 
for solution for injection 
Lyophilized powder in a 
DCS for solution for 
injection 
Dosage
N/A 
(2 injections at baseline, to 
maintain the blind)
N/A
Dose regimen
Q4W
Q4W 
(Note: CD14152 Q8W dose 
regimen uses placebo 
injections to maintain the 
blind)
Route*
Subcutaneous use by subjects, 
caregivers, or clinic staff after 
reconstitution
Subcutaneous use by 
subjects, caregivers, or clinic 
staff after reconstitution
Duration of treatment
16 weeks: baseline to Week 
16
32 Weeks: Week 16 to Week 
48
Abbreviation(s): DCS=dual-chamber, single-use syringe; N/A=not applicable; Q4W=every 4 
weeks; Q8W=every 8 weeks.
Note(s):
* All injections are performed at the study center clinic office. Injections by subjects or caregivers 
are performed under supervision by clinic staff, after appropriate training. 
 
              
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8.4.3 Packaging and Labeling
All packaging and labeling operations will be performed according to Good 
Manufacturing Practice for Medicinal Products in the local language, national 
regulations/guidelines, and the relevant regulatory requirements, specifying that the drug 
is for use in a clinical study. Each DCS will be packaged in an individual carton, 
including a 27G 1/2” needle and a plunger rod (not assembled). Local adaptation of the 
kit design may be required; specific details for each country are provided in the pharmacy 
manual.
8.4.4 Study Drug Management
8.4.4.1
Storage of Study Drug
All DCS units must be stored together in a safe and secure area with restricted access. 
Upon receipt, the DCS must be removed from the shipping cooler, kept in the outer 
carton until use, and stored in a refrigerator between 2°C to 8°C (36°F to 46°F), protected 
from light and protected from freezing.
The refrigerator must be monitored daily, and if a temperature excursion occurs, the 
designated personnel should promptly inform the study monitor, as specified in the 
current version of the pharmacy manual.
8.4.4.2
Study Drug Accountability
Study drug will be provided to the investigational site and site personnel will acknowledge 
receipt of the study drug using IRT to confirm the shipment condition and content. If a 
damaged shipment is received and/or a temperature excursion has been experienced, he/she 
will notify the sponsor/CRO and follow the guidelines according to the current version of 
the pharmacy manual. 
The designated personnel will also maintain accurate records of the study drug throughout 
the clinical study, including the inventory delivered to the study center, the use by each 
subject, the reconciliation of all delivered and received DCS units, and the 
return/destruction of unused study drug as specified in the current version of the pharmacy 
manual. No unauthorized use is permitted. Used DCS units will be properly documented 
in drug accountability records. Unless a product technical complaint (PTC) is detected or 
an event occurs before, during, or just after the injection, the used DCS can be disposed in 
 
              
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an appropriate sharps container and according to waste regulation(s) in the country. A DCS 
involved in a malfunction or an investigator or subject complaint must be retained on site 
and designated personnel must proceed as defined in the current version of the pharmacy 
manual. Refer to Section 8.4.10 for product technical complaints.
The study monitor may check the study supplies at each study center at any time during 
the study. It is the responsibility of the study monitor to ensure that the investigator (or 
designee) has correctly documented the amount of the study drug received, dispensed, 
and returned/destroyed on the dispensing log that will be provided. A full drug 
accountability log will be maintained at the study center at all times. The study monitor 
will arrange collection of any unused study drug not destroyed by the site. The study 
monitor will also perform an inventory of study drug at the close-out visit to the study 
center. All discrepancies must be accounted for and documented.
8.4.4.3
Dispensing and Return of Study Drug
All drug preparation must be appropriately performed and documented by the designated 
personnel. Any error in the preparation of dosing solution must be reported to the study 
monitor promptly and be properly documented. At the end of the study, the 
reconciliation/return/destruction process for all unused study drug will be conducted 
according to the sites’ SOPs, local regulations, and best practices, as described in the 
current version of the pharmacy manual. If the site does not have the capability to destroy 
drug, then the unused study drug will be returned to the CRO/drug depot for destruction.
8.4.4.4
Treatment Compliance
Treatment compliance will be assessed through the treatment records and drug 
dispensation logs.
As study drug is administered in the clinic, treatment compliance will be overseen and 
documented by the investigator and study staff (using the treatment records and drug 
accountability records). At a minimum, date, time, dose, injector (subject, caregiver, or
site staff), and site of injection should be accurately recorded to confirm that each dose of 
study treatment was properly administered.
 
              
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8.4.5 Method of Assigning Subjects to Treatment Groups: Randomization and Re-
Randomization
Upon confirmation of eligibility for a given subject to participate in the study, a unique 
randomization number will be assigned to that subject via IRT at the baseline visit.
Subjects will be randomized (2:1) to receive treatment of nemolizumab (CD14152) Q4W 
or placebo. Randomization will be stratified by disease severity (IGA=3, IGA=4) and 
pruritus severity (PP NRS ≥ 7, PP NRS < 7).
Subjects who were randomized to nemolizumab in the initial period and achieved clinical 
response (EASI-75 or IGA 0/1) at Week 16 will be re-randomized (1:1:1) to receive 
nemolizumab Q4W, nemolizumab Q8W, or placebo via IRT in the maintenance period.
8.4.6 Selection of Doses in the Study
The 30-mg dose (Q4W or Q8W) proposed for this study is supported by the results of the 
nemolizumab phase 2b study (114322) and other supportive data. Refer also to Section
6.5 for further details.
8.4.7 Dose Modification
Dose modification of the study drug will not be permitted during the clinical study. 
Any inadvertent dose modification(s) should be reported to the sponsor/CRO. 
In the event of a missed dose (ie, temporary discontinuation of the study drug), it will be 
documented in the CRF that the drug has not been administered at the study visit, 
together with the reason (eg, for safety). Subjects will be asked to return to the study 
centers for all remaining visits and complete all study assessments and procedures as 
described in Section 8.1.2 .
Dosing frequency is scheduled for Q4W, based on the baseline/Day 1 visit date. If a 
study visit occurs outside the visit window, study drug can be administered provided 
there is a minimum of 3 weeks since the last injection. Future visits should be scheduled 
within the required windows based on the baseline/Day 1 visit date, while maintaining 
the minimum 3-week interval between 2 injections.
 
              
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8.4.8 Blinding
All attempts will be made to keep the study center staff and subjects blinded throughout 
the study. Members of the study center staff, including those responsible for DCS 
preparation, will not have access to the randomized treatment assignment. 
To ensure double-blind administration of study drug the study center pharmacist(s) or 
other qualified personnel will prepare all nemolizumab (CD14152) or placebo treatments, 
according to the current versions of the pharmacy manual and Instruction for Use and 
assigned DCS provided by the IRT system.
As there may be detectable differences between active and placebo during the 
reconstitution process, the DCS is delivered for injection after the reconstitution is 
complete. The pharmacist (or other qualified personnel) preparing study medication 
should not be involved with any study assessments and should not discuss any aspects of 
study drug reconstitution with the subject/caregiver or study staff involved in subject 
interviews or study assessments.
To maintain the integrity of the study blinding, the bioanalytical laboratory staff who 
process/analyze the PK/PD/PGx samples will not provide any information to sponsor, 
CRO, or investigational study center personnel directly involved with the ongoing 
conduct of the study that may lead to unblinding. 
Unblinding of a subject’s individual treatment code should occur only in case of a 
medical emergency or in the event of a serious medical condition that necessitates 
identification of the study drug for the welfare of that subject, as judged by the 
investigator. The emergency unblinding process utilizes IRT to allow the investigator to 
have unrestricted, immediate, and direct access to the subject’s individual study 
treatment. When possible (ie, when the health of the subject is not immediately at risk), 
the investigator or sub-investigator is encouraged to consult with the medical monitor and 
the sponsor before breaking the blind.
If emergency unblinding is required:
•
Only the investigator will make the decision to unblind the treatment assignment.
•
Only the affected subject will be unblinded.
•
The IRT system will provide the treatment assignment to the investigator.
 
              
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Refer to the Randomization and Trial Supply Management (RTSM) User Guide for 
information on the steps for breaking the blind in the IRT system.
When the blinding code is broken, the reason must be fully documented. If the code is 
broken by the investigator, the subject must be withdrawn from the study and must also 
be appropriately followed for a minimum of 12 weeks after the last dose of study drug.
The reporting requirements for unblinding are the same for reporting an SAE. See also 
Section 9.2.1.3.
The randomization code will remain blinded to all study sites and study team members 
until completion of the study and after the study database has been locked. Although 
initial treatment period results may be analyzed after all subjects have either completed 
the Week 16 visit, or have withdrawn or been discontinued from the study before Week 
16, personnel from sponsor, CRO, and investigational sites directly involved with the 
ongoing conduct of the study will not have access to any information that may lead to 
unblinding for the ongoing maintenance evaluation.
The IDMC will review data at periodic intervals throughout the study as defined in the 
IDMC charter. The IDMC charter will specify the procedures for unblinding to ensure 
that treatment assignment remains undisclosed to all individuals involved in the direct 
execution and management of the study until the final database is locked.
8.4.9 Prior and Concomitant Therapy
Prior therapies are defined as therapies that have been stopped within the 3 months before 
the screening visit, unless relevant to the inclusion/exclusion criteria. Whenever possible, 
prior therapies for AD should be documented. 
Concomitant therapies/medications are defined as follows:

Any existing therapies ongoing at the time of the screening visit,

Any changes to existing therapies (such as changes in dose, formulation or application 
frequency) during the course of the study, or

Any new therapies received by the subject since the screening visit
The following 2 categories are to be considered for prior and concomitant therapies: 

Drugs/Therapies include but are not limited to prescription, over-the-counter, birth 
control pills/patches/hormonal devices, vitamins, moisturizers, sunscreens, herbal 
medicines/supplements, and homeopathic preparations.
 
              
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
Medical and surgical procedures (eg, phototherapy, exodontia, etc). Procedures whose 
sole purpose is diagnosis (non-therapeutic) are not included.
Prior and concomitant therapies for drugs/therapies or for medical/surgical procedures are 
to be recorded in the appropriate CRF. 
Concomitant therapies are to be recorded, reviewed, and updated at each visit. 
At each visit, investigators should also confirm concomitant therapies for contraception. 
Contraceptive counseling should occur at screening (or at applicable visits when pre-
pubertal subjects begin menses). 
Any new concomitant therapy or modification of an existing therapy may be linked to an 
AE. In such cases, a corresponding AE form should be completed to account for the new 
therapy or change in therapy, except in some cases such as dose modification for a 
chronic condition (see Section 8.4.7 ), in which case the medication will be linked to an 
item in the subject’s medical history.
8.4.9.1
Permitted Concomitant Therapy
Unless specified as prohibited therapies (see Section 8.4.9.2), all therapies are authorized,
including basic skin care (cleansing and bathing), moisturizers, bleach baths, topical 
anesthetics, and antihistamines without a sedative effect.
The formation of cytochrome P450 (CYP450) metabolic enzymes can be altered by 
increased levels of certain cytokines (eg, IL-1, IL-6, IL-10) during chronic inflammation. 
Although there is no known evidence suggesting that IL-31 affects the level or activity of 
CYP450 enzymes, the impact of nemolizumab (CD14152) on such enzymes has not been 
studied. Therefore, investigators should consider observing for clinical or laboratory 
signs that might indicate a potential effect of nemolizumab (CD14152) in subjects using 
concomitant therapies that are CYP450 substrates, particularly those with a narrow 
therapeutic index. Typical examples of substrates with a narrow therapeutic range include 
warfarin, drugs that may cause torsade de pointes, almost all cytotoxic antineoplastic 
drugs, and aminoglycoside antibiotics. A list of representative CYP450 substrates with 
narrow therapeutic index can be found in Appendix 3.
 
              
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8.4.9.1.1 Moisturizer
Subjects will apply a moisturizer at least once daily, and liberally as needed, to dry skin 
and AD lesions beginning at screening, and throughout the study. The subject’s current 
moisturizer or a moisturizer recommended by the investigator may be used. Use should 
not occur within 8 hours before each clinic/office visit. Whenever possible, subjects 
should use the same moisturizer throughout the study. Moisturizer use and any 
adjustments should be documented in the CRF.
8.4.9.1.2 Background Topical Therapy
Subjects will apply the authorized background topical therapy to all AD lesions 
beginning within the screening period and ≥ 14 days before Day 1 (ie, run-in). 
Medium-potency TCS Therapy for Non-Sensitive Areas: Subjects will apply a 
medium-potency TCS in areas of the body where use of medium-potency TCS is 
considered safe (eg, trunk and extremities). 
Low-potency TCS or TCI Therapy for Sensitive Areas: A low-potency TCS or a TCI 
will be used in sensitive areas considered unsafe for medium-potency TCS (eg, face, 
neck, intertriginous areas) or in cases where medium-potency TCS is not tolerated. The 
investigator may select either low-potency TCS or TCI for each subject, per investigator 
discretion. The subject may only apply 1 medication to each affected area; concomitant 
use of low-potency TCS and TCI on the same lesion is not permitted.
The prescribed use of background therapies and any adjustments should be documented 
in the CRF. Subjects will apply a thin layer of authorized topical therapy on all AD 
lesions at a frequency that is necessary to ensure disease stability and prevent AD flare 
but which does not exceed the daily frequency recommended in the product labeling. 
Refer to the current version of the pharmacy manual for authorized topical therapies and 
permitted daily frequency of use. “As needed” (PRN) use of TCS or TCI is not permitted.
Only topical therapies specifically dispensed or prescribed for use in this study are 
permitted.
The investigator should adjust background therapy use during the study, according to the 
disease activity and tolerability of the subject, including tapering when signs and 
symptoms improve, discontinuation when lesions clear, and restarting if signs and 
symptoms recur.
 
              
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In transitioning to the maintenance period, subjects should generally continue the same 
background topical therapy used in the initial treatment period leading up to the Week 16 
visit, including tapering or complete cessation (no use), if applicable. Throughout the 
maintenance period, adjustments to background topical therapy, as determined by the 
investigator, are permitted based on the subject’s clinical response.
8.4.9.1.3 Rescue Therapy
If deemed to be medically necessary by the investigator (eg, to control intolerable AD
signs/symptoms), rescue therapies can be prescribed to the subjects at any time during the 
study, except during the run-in period. (Subjects receiving rescue therapies during the 
run-in period are not eligible to participate in the study.)
As a general guideline and per individual investigator judgment, rescue therapy should 
not be prescribed within the first 2 weeks after baseline (ie, Week 2) to allow a minimum 
time for study drug exposure in the presence of background therapy. 
Rescue treatments are only treatments that directly treat AD (mainly those that are 
approved or are standard of care) and include topical and systemic treatments as outlined.
Rescue therapies include:

Higher potency of TCS (equivalent to class I-II according to the US 
classification)2

Oral corticosteroids

Biologics (including their biosimilars)

Systemic nonsteroidal immunosuppressants/immunomodulators

Phototherapy 
Antihistamines, sleep aids, topical and systemic antibiotics, and anti-itch creams are not
considered to be rescue therapy because they do not directly treat AD.
Whenever possible, investigators should first use topical medication as rescue therapy 
before escalating to systemic therapies. If subjects receive topical treatments or 
phototherapy as rescue therapy, study drug administration should be continued unless 
there is a safety concern according to the investigator’s judgment. If subjects receive 
systemic rescue therapy, the study drug administration must be permanently 
discontinued.
 
              
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administration of COVID-19 vaccinations within 1 week of study drug dosing. A 
different anatomical location should be used for study drug administration and vaccine 
administration.
8.4.10 Product Technical Complaints
All DCS units must be inspected prior to preparation/injection by the persons 
performing the preparation/injection to ensure absence of visual defects that could lead 
to a DCS PTC. This also includes the needle and plunger rod. In case of doubt, the DCS 
should not be used, and the deficiency must be reported as defined in the pharmacy 
manual.
All PTCs should be reported to the sponsor/designee by filing the relevant forms 
available in the Investigator Site File and the pharmacy manual and as required by local 
regulations. A PTC is any written, electronic, or oral communication that alleges 
deficiencies related to the identity, quality, reliability, safety, durability, effectiveness, or
performance of a drug or delivery system. Examples may include but are not limited to 
appearance issues, discoloration, odor, broken/cracked syringe, missing parts, damaged 
stoppers, and foreign matter in lyophilized powder or diluent. These complaints may or
may not represent a potential risk to the subject. For these types of events, a form must 
be completed as per the specific instruction by the site personnel, pictures of the 
defective DCS must be attached, and forwarded to the sponsor/designee at the latest on 
the next working day. Reporting to health authorities will be in accordance with local 
regulations. The defective DCS/items must be kept in case of investigation need as 
defined in the pharmacy manual and may be requested to be sent to the 
Sponsor/designee in accordance with regulations.
Refer to the current version of the pharmacy manual for further details.
8.5
Duration of Subject Participation
The expected duration for each subject’s participation in the study depends on the clinical 
response and may be:

Up to 28 weeks (including a 4-week screening period, a 16-week initial treatment 
period, and an 8-week follow-up period [12-weeks after the last study medication 
injection]) for subjects who are non-responders at the completion of the initial 
treatment period (Week 16)
 
              
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
Up to 60 weeks (including a 4-week screening period, a 16-week initial treatment 
period, a 32-week maintenance period, and an 8-week follow-up period [12-weeks 
after the last study medication injection]) in subjects who are clinical responders at 
the completion of the initial treatment period (Week 16)
The 12-week follow-up visit is not required for subjects who will continue in the LTE
study (Protocol 118163).
 
              
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8.5.1 Early Termination Visit
Subjects may discontinue from the study or discontinue the study treatment only and 
continue to participate in the study.
Subjects who prematurely discontinue from the study should undergo final study 
assessments according to the following guidelines:

Subjects discontinued from the study during the initial treatment period on/before the 
Week 16 visit should attend an ET visit. A follow-up/final visit is required 12 weeks 
after the last study drug administration.

Subjects discontinued from the study during the maintenance period should attend an 
ET visit.
A follow-up/final visit is required 12 weeks after the last study drug administration.
Subjects who prematurely discontinue the study drug will be asked to continue 
participation in the study and return for all remaining visits and assessments (including 
daily assessment of pruritus, sleep disturbance, etc). Participation will continue until the 
subject completes the final study visit or otherwise discontinues study participation. 
Subjects requiring rescue medication (with or without study medication discontinuation) 
may be eligible for LTE study participation: 

Subjects requiring rescue medication during the initial treatment period should 
continue with study visits including the Visit 6/Week 16. A follow-up/final visit is not 
required for subjects participating in the LTE study.

During the maintenance period, for subjects requiring rescue medication before the 
Week 32 visit, a wait period with continuing study visits until the Week 32 visit is 
due is required. Thereafter, no wait period is required. Subjects must complete the 
final study/ET assessments prior to rollover to the LTE study.
A follow-up visit is not required for subjects who will participate in the LTE.
 
              
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8.5.2 Unscheduled Visit
The subject should be reminded to adhere to the study schedule. Unscheduled visits are 
defined as visits to repeat testing for abnormal laboratory results, for follow-up of AEs, or
to conduct efficacy assessments for subjects requiring rescue medication between 
regularly scheduled study visits. Visits occurring outside of the visit window are not 
considered unscheduled visits.
Assessments to be conducted at the unscheduled visit will depend on the reason for the 
visit: Any of the procedures/assessments listed in Section 8.1.2 may be conducted, but 
not all are required. Blood sample collection for PK and ADA analyses are only required
during unscheduled visits that are conducted for safety reasons.
 
              
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9
STUDY ASSESSMENTS
A written, signed ICF, assent form, and Health Insurance Portability and Accountability 
Act (HIPAA) authorization is required before any study-related procedures are 
performed.
Upon provision of the signed ICF/assent form, each subject will be assigned a unique 
SIN. For the duration of the entire clinical study, the subject will be identified using the 
SIN in all documentations and discussion.
The planned study assessments are in Section 8.1.2 . At each visit, 
assessments/procedures should be performed in the following order: 
1. Patient-reported efficacy and safety measurements
2. Investigator assessments (including efficacy and safety)

ECG should be done before vital signs measurements (and blood draws). 
See Section 9.2.10 
3. Sample collections for laboratory assessments
4. Sample collections for correlative assessments (PK, ADA, PD, and optional PGx)
5. Administration of study drug injections
9.1
Efficacy Assessments
Efficacy measurements should be conducted by the investigators (or trained designees) 
and subjects (for patient-reported efficacy measurements) according to Section 8.1.2 . 
Whenever possible, the same evaluator should make the assessment throughout the study.
Refer to Section 7.2 and Section 7.3 for efficacy endpoints. 
9.1.1 Investigator’s Global Assessment
The IGA is a 5-point scale ranging from 0 (clear) to 4 (severe) used by the investigator or 
trained designee to evaluate the global severity of AD and the clinical response to a 
treatment. Treatment success is defined as 0 (clear) or 1 (almost clear) and a 2-point 
improvement from baseline (see Appendix 4).35
9.1.2 Eczema Area and Severity Index 
The EASI is a validated measure commonly used in clinical trials and clinical practice to 
assess the severity and the extent of AD signs. The EASI score is a composite score 
 
              
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ranging from 0 to 72 (see Appendix 5).36 The severity of erythema, induration/papulation, 
excoriation, and lichenification will be assessed by the investigator or trained designee on 
a scale of 0 (absent) to 3 (severe) for each of the 4 body areas: head/neck, trunk, upper 
limbs, and lower limbs, with half points allowed. In addition, the extent of AD 
involvement in each of the 4 body areas will be assessed as a percentage by body area of 
head, trunk, upper limbs, and lower limbs, and converted to a score of 0 to 6. The EASI 
score will be calculated in the CRF.
9.1.3 Pruritus Numeric Rating Scale
The Pruritus NRS is a scale to be used by the subjects to report the intensity of their 
pruritus (itch) during the last 24 hours (see Appendix 6). Two measures of Pruritus NRS 
will be assessed (average and peak/maximum itch intensity). The PP NRS has been 
validated in other AD clinical trials in adults, and the minimum clinically important 
difference was shown to be 4.25
The average pruritus NRS (AP NRS) provides a measure of overall pruritus intensity 
over a given period and has clinical relevance to both subjects and physicians because 
peak pruritus may show higher intensity but short duration.
Subjects will be asked the following questions:

For average itch intensity (AP NRS): “On a scale of 0 to 10, with 0 being ‘no itch’ 
and 10 being the ‘worst itch imaginable’, how would you rate your itch overall during 
the previous 24 hours?”

For maximum itch intensity (PP NRS): “On a scale of 0 to 10, with 0 being ‘no itch’ 
and 10 being the ‘worst itch imaginable’, how would you rate your itch at the worst 
moment during the previous 24 hours?”
The screening PP NRS will be determined by a single assessment using the PP NRS 
(score ranging from 0 to 10) for the 24-hour period immediately preceding the screening 
visit. The baseline PP NRS will be determined based on the average of daily PP NRS 
(score ranging from 0 to 10) during the 7 days immediately preceding baseline (rounding 
to nearest whole number is not permitted). A minimum of 4 daily scores out of the 7 days 
immediately preceding baseline is required for this calculation. Subjects will receive 
instructions on how to record their pruritus NRS scores and will complete the assessment 
once daily in the evening throughout the clinical study (including the run-in and the 
follow-up period). 
 
              
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9.2.1 Adverse Events
Adverse Event Definition
An AE is defined as any untoward medical occurrence in a clinical study subject 
administered a medicinal product which does not necessarily have a causal relationship 
with this treatment. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated 
with the use of a medicinal (investigational) product, whether or not it is related to the 
medicinal (investigational) product. 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 in the CRF under 
specific efficacy assessments. 
Note(s): 

Any new sign or symptom reported by the subject that appears after accidental or 
intentional overdose or misuse should be reported as an AE.

Whenever possible, a diagnosis should be reported on the AE form, instead of 
signs, symptoms, or abnormal laboratory values. 

Pregnancy is not to be considered an AE; however, it must be monitored and 
reported as described in Section 9.2.1.5.

Each worsening of a chronic disease from the screening visit should be reported 
as a new AE.
The investigator or designee will report all AEs that occur from the time the ICF is signed 
until the end of the study. The sponsor/CRO should be informed if the investigator 
becomes aware of any safety information that appears to be drug related, even after the 
subject has completed the clinical study.
At each post-enrollment visit, the investigator (or sub-investigator) will question the 
subject about AEs using an open non-persuasive question to elicit reporting of AEs (for 
example, “Have you noticed any change in your health since the last visit?”). Directed 
questioning and examination will then be performed as appropriate. 
During optional subjects interviews, the subject will be queried on changes in his or her 
condition and perceived effects of the study treatment. Any unfavorable changes reported 
by the subjects will be reported to the Investigator or designee by the designated CRO 
responsible for the interviews. The Investigator will be responsible for reporting all AEs,
 
              
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including those reported during the interviews following the process described in the 
protocol. 
Any AE occurring during the AE reporting period, whether it is related to the study 
drug(s) or not, will be recorded immediately in the source document and described on the 
Adverse Event Form (“AE Form”) along with the date of onset, severity, relationship to 
the study drug(s), and outcome, without omitting any requested and known information. 
Additional information will be requested under certain circumstances.
Adverse events assessed as related to the treatment or study procedure will be monitored 
until they have resolved or reached a stable condition. Other AEs will be monitored until 
the last visit if they have not resolved or reached a stable condition. 
The investigator will obtain and maintain in the subject’s files all pertinent medical 
records, information and medical judgment from colleagues who assisted in the treatment 
and follow-up of the subject. If necessary, the investigator will contact the subject’s 
personal physician or hospital staff to obtain further details.
Assessment of Severity
Each AE will be assigned a category by the investigator as follows:
Mild:
An AE that is easily tolerated by the subject, causes minimal discomfort,
and does not interfere with everyday activities.
Moderate:
An AE that is sufficiently discomforting to interfere with normal everyday 
activities; intervention may be needed.
Severe:
An AE that prevents normal everyday activities; treatment or other 
intervention usually needed.
If there is a change in severity of an AE, it must be recorded as a separate event.
Assessment of Causality
The investigator is to determine whether there is a reasonable causal relationship between 
the occurrence of the AE, and exposure to the study drug (ie, nemolizumab or placebo) 
and/or study procedure (eg, injection, topical background therapy, blood sample 
collection). Medical judgment should be used to determine the relationship, considering 
all relevant factors including the pattern of the reaction, temporal relationships, relevant 
medical history, and confounding factors such as co-medication or concurrent diseases.
 
              
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The expression “reasonable causal relationship” is meant to convey in general that there 
are facts or arguments to suggest a causal relationship (ICH E2A, Section IIIA 1).
The relationship assessment for an AE is to be completed using the following definitions
as a guideline for all AEs occurring during this clinical study:
Reasonable possibility:
According to the reporting investigator, there is a reasonable possibility (ie, suggestive 
evidence or arguments) that there is a causal relationship irrespective of the dose 
administered:

Between the study drug (nemolizumab) and the AE, and/or

Between the clinical study protocol procedure (eg, injection, topical background 
therapy, blood sample collection) and the AE
No Reasonable Possibility:
No suggestive evidence or arguments can be identified regarding a causal relationship 
between the study drug or the clinical study protocol procedure and the AE.
Action Taken
The investigator will describe the action taken in the appropriate section of the CRF, as 
follows:

None

Study drug stopped

Study drug temporarily interrupted

Concomitant medication (any additions or discontinuations)

Other, specify
Follow-up of Adverse Events
All investigators should follow-up with subjects with AEs until the event is resolved or 
until, in the opinion of the investigator, the event is stabilized or determined to be 
chronic. Details of AE resolution must be documented in the CRF.
 
              
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Subjects should be followed up for 12 weeks (± 5 days) after receiving the last dose of 
study drug, and any AEs that occur during this time should be reported according to the 
procedures outlined above.
Documentation and Reporting of Adverse Events
Adverse events should be reported and documented in accordance with the procedures 
outlined below. All AEs occurring during the study must be documented on the relevant 
CRF pages. The following data should be documented for each AE:

Description of the symptom event

Classification of “serious” or “not serious”

Severity

Date of first occurrence and date of resolution (if applicable)

Action taken

Causal relationship

Outcome of event (unknown, recovered, not yet recovered, recovered with 
sequelae, death [with date and cause reported])
9.2.1.1
Adverse Events of Special Interest
An AESI is a noteworthy treatment-emergent event for the study drug that should be 
monitored closely and reported promptly. See Section 9.2.1.4 for reporting procedure. An 
AESI can be either serious or non-serious.
Based on the potential risks of nemolizumab (CD14152) and the risks associated with 
biologics (and their biosimilar equivalents) in general (ie, class effects), the following 
AEs will be considered AESIs: 

Injection-related reactions (IRRs)
o
Anaphylactic reactions
o
Acute allergic reactions requiring treatment
o
Severe injection site reactions with a duration greater than 24 hours

Newly diagnosed asthma or worsening of asthma
o
More specifically, subjects with a medical history of asthma will be referred 
to the physician who manages their asthma when:
▪
ACT score ≤ 19: An ACT score ≤ 19 conveys asthma that may not 
be adequately controlled. An AESI is reported based on the 
 
              
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investigator’s clinical judgment, including consideration of the 
managing physician’s report.
▪
PEF < 80% of the predicted value: An AESI should be reported.
▪
Unexpected worsening of asthma is observed or reported. An AESI 
is reported based on the investigator’s clinical judgment. 
o
Subjects without a medical history of asthma will be referred to an 
appropriate respiratory physician/specialist when:
▪
Signs and/or symptoms suggestive of asthma have been observed or 
reported. An AESI is reported based on the investigator’s clinical 
judgment of the specialist’s report.
▪
Respiratory assessments (eg, examination, PEF) suggest a decline in 
the subject’s respiratory health. An AESI is reported based on the 
investigator’s clinical judgment of the specialist’s report.

Infections
o
Any severe infection or any infection requiring treatment with parenteral 
antibiotics or oral antibiotics/antivirals/antifungals for > 2 weeks
o
Any confirmed or suspected COVID-19 infection

Peripheral edema: limbs, bilateral

Facial edema

Elevated ALT or AST (> 3 × ULN) in combination with elevated bilirubin (> 2 × 
ULN)
9.2.1.2
Serious Adverse Events
An SAE is any untoward medical occurrence or effect that, at any dose,

Results in death.

Is life-threatening (an AE is life-threatening if the subject was at immediate risk of 
death from the event as it occurred, ie, it does not include a reaction that might have 
caused death if it had occurred in a more serious form).

Requires or prolongs inpatient hospitalization. (Complications occurring during 
hospitalization are AEs and SAEs if they cause prolongation of the current 
hospitalization. Inpatient hospitalization is considered to have occurred if the 
subject has had to stay for a night at the hospital. The criterion for prolongation of 
hospitalization is also defined as an extra night at the hospital. Hospitalization may 
not constitute sufficient grounds to be considered as an SAE if it is solely for the 
purpose of diagnostic tests [even if related to an AE], elective hospitalization for an 
intervention that was already planned before subject enrollment in the clinical 
 
              
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study, admission to a day care facility, social admission [eg, if the subject has no 
place to sleep], or administrative admission [eg, for a yearly examination]. The 
details of such hospitalizations must be recorded on the medical history or physical 
examination CRF.)

Results in persistent or significant disability/incapacity. (An AE is incapacitating or 
disabling if it results in a substantial and/or permanent disruption of the subject’s 
ability to carry out normal life functions.)

Results in a congenital anomaly/birth defect.

An important medical event that may not result in death, be life-threatening, or 
require hospitalization, may be considered an SAE when, based upon appropriate 
medical judgment, the event may jeopardize the safety of the subject, and may 
require medical or surgical intervention to prevent 1 of the outcomes listed above in 
this definition. Examples of such events are intensive treatment in an emergency 
room or at home for allergic bronchospasm, blood dyscrasia, or convulsions that do 
not result in hospitalization.
9.2.1.3
Procedure for Reporting a Serious Adverse Event
For any SAE occurring during the clinical study, regardless of whether or not related to 
the study drug and/or procedure, the investigator must:
1. Take prompt and appropriate medical action, if necessary. The safety of the subject is 
the first priority.
2. Ensure that the event is evaluated as an SAE. Immediately notify (within 24 hours of 
receipt of the event) the Syneos Health Safety and Pharmacovigilance group of an 
SAE report, by email or fax:
Fax Number: 001-877-464-7787 
Safety email: SafetyReporting@SyneosHealth.com
Note: Immediate SAE reporting is required by the investigator if it occurs during the 
clinical study or within 12 weeks (± 5 days) of receiving the last dose of study drug, 
whether or not the event is considered to be related to the investigational product.
The demographics, medical history, drugs/therapies, and medical and surgical 
procedures forms must also be available for review in CRF, at that time.
 
              
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3. Send any relevant information or anonymized medical records (eg, laboratory test 
results) to the Syneos Health Safety and Pharmacovigilance group (see contact 
details above), within 24 hours of receipt of this relevant information.
4. Monitor and record the progress of the event until it resolves or reaches a stable 
condition, with or without sequelae. For all additional follow-up evaluations, 
complete an updated SAE report within 24 hours of receipt of the updated 
information.
5. Obtain and maintain in the subject files all pertinent medical records, information, 
and medical judgments from colleagues who participate in the treatment and follow-
up of the subject. If necessary, contact the subject’s personal physician or hospital 
staff to obtain further details.
6. When the outcome of the event is known, complete an updated SAE report, if 
appropriate.
7. Prompt notification of SAEs by the investigator is essential so that legal obligations 
and ethical responsibilities toward the safety of subjects are met. The sponsor has a 
legal responsibility to notify both the local regulatory authority and other regulatory 
agencies about the safety of a product under clinical investigation. The sponsor or its 
delegate (ie, the CRO) will comply with country-specific regulatory requirements 
relating to safety reporting to regulatory authorities, Institutional Review Board 
(IRB)/Independent Ethics Committee (IEC) and investigators. Investigator safety 
reports are prepared for SUSARs according to local regulatory requirements, and are 
forwarded to investigators as necessary.
An investigator who receives an investigator safety report describing a SAE(s) or 
other specific safety information (eg, summary or listing of SAEs) from the sponsor 
or its delegate (ie, the CRO) will file it accordingly (ie, within the Trial Master File 
[TMF]), and will notify the IRB/IEC, if appropriate according to local requirements.
8. Comply with the applicable regulatory requirement(s) related to the reporting of 
SAEs to the IRB/IEC.
9.2.1.4
Procedure for Reporting an Adverse Event of Special Interest
For any AESI occurring during the clinical study, regardless of whether or not related to 
the treatment, the investigator must:
 
              
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1. Take prompt and appropriate medical action, if necessary. The safety of subjects is 
the first priority.
2. Ensure that the event is evaluated as an AESI. Notify (within 3 days of receipt of the 
event) the Syneos Health Safety and Pharmacovigilance group of an AESI report, by 
email or fax. Refer to Section 9.2.1.3. 
Note: AESI reporting is required by the investigator if it occurs during the clinical 
study following the first dose of study drug or within 12 weeks (± 5 days) of 
receiving the last dose of study drug, whether or not the event is considered to be 
related to the investigational product.
The demographics, medical history, drugs/therapies, and medical and surgical 
procedures forms must also be available for review in CRF, at that time.
3. Send any relevant information or medical records (eg, laboratory test results) to the 
Syneos Health Safety and Pharmacovigilance group within 3 days of receipt of this 
relevant information.
4. Monitor and record the progress of the event until it resolves or reaches a stable 
condition, with or without sequelae. For all additional follow-up evaluations, update 
the AESI form within 3 days of receipt of the updated information.
5. Obtain and maintain in the files all pertinent medical records, information, and 
medical judgments from colleagues who participate in the treatment and follow-up of 
the subject. If necessary, contact the subject’s personal physician or hospital staff to 
obtain further details.
6. When the outcome of the event is known, update the AESI form, if appropriate.
9.2.1.5
Procedure for Reporting Pregnancies
Any pregnancy occurring during clinical studies where the fetus could have been exposed 
to the study drug must be monitored until its outcome in order to ensure the complete 
collection of safety data. If a subject becomes pregnant, the investigator must:
1. Withdraw the subject from the clinical study. The subject must not receive any further
injection of the study drug.
 
              
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2. Complete as fully as possible the Pregnancy Surveillance Form – Part I: History and 
Start of Pregnancy. Send by email or fax along with the exit form within 24 hours of 
receipt of the information, to the Syneos Health Safety and Pharmacovigilance group. 
Refer to Section 9.2.1.3. 
Note: Immediate pregnancy reporting is required by the investigator if it occurs 
during the clinical study or within 12 weeks (± 5 days) of receiving the last dose of 
study drug, whether or not the event is considered to be related to the investigational 
product.
3. Monitor and record the progress of the pregnancy until its outcome. Contact the 
subject’s regular physician (general practitioner or gynecologist) or hospital staff to 
obtain further details and ask for regular follow-up information.
4. Provide tri-monthly updates until the final outcome of the pregnancy, by completing 
the Pregnancy Surveillance Form – Part II: Course and Outcome of Pregnancy. For 
all additional follow-up evaluations, send the form by email or fax to the 
Syneos Health Safety and Pharmacovigilance group within 24 hours of receipt of the 
information. If the subject can no longer be reached (ie, lost to follow-up), 
documentation of the non-response/contact with 2 phone calls and a letter (certified 
with return receipt) is required.
5. At the outcome of the pregnancy, complete as fully as possible the Pregnancy 
Surveillance Form – Part II: Course and Outcome of Pregnancy. Print and send the 
form by email or fax to the Syneos Health Safety and Pharmacovigilance group
within 24 hours of receipt of the information.
6. If the pregnancy leads to an abortion (ie, voluntary abortion, spontaneous abortion, or 
therapeutic abortion), in utero death or congenital anomaly, follow the procedure for 
declaration of/reporting an SAE (see Section 9.2.1.3).
9.2.1.6
Unexpected Adverse Reactions
Unexpected Adverse Reaction Definition
An unexpected adverse reaction is any untoward and unintended response that is related 
to the administration of the study drug at any dose, the nature or severity of which is not 
 
              
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consistent with the applicable product information (eg, reference safety information in the 
investigator’s brochure for nemolizumab, study protocol, etc).
The sponsor or its delegate (ie, Syneos Health) will comply with country-specific 
regulatory requirements relating to safety reporting to regulatory authorities, IRB/IEC 
and investigators. Investigator safety reports are prepared for SUSARs according to local 
regulatory requirements and sponsor policy, and are forwarded to investigators as 
necessary.
An investigator who receives an investigator safety report describing a SAE(s) or other
specific safety information (eg, summary or listing of SAEs) from the sponsor or its
delegate (ie, Syneos Health) will file it accordingly (ie, with the TMF), and will notify the 
IRB/IEC, if appropriate according to local requirements.
9.2.2 Clinical Laboratory Evaluation
The hematology laboratory analyses, clinical chemistry laboratory analyses, and 
urinalyses will be performed at a central laboratory. Reference ranges will be supplied by 
the central laboratory and used by the investigator to assess the laboratory data for 
clinical significance and pathological changes. 
The investigator or medically qualified sub-investigator must review and evaluate 
laboratory values for each subject in a timely manner. Study centers should refer to the 
current version of the laboratory manual for laboratory values outside of normal limits.
For each out-of-range laboratory result, the investigator or designee will evaluate whether 
he/she considers it to be clinically significant, defined as meeting at least 1 of the 
following conditions: 

The abnormality suggests a disease and/or organ toxicity, or

The abnormality is of a degree that requires additional active management, eg,
discontinuation of the drug, close observation, more frequent follow-up assessments, 
or further diagnostic investigation. 
If the investigator observes a clinically significant laboratory result, the test will be 
repeated as soon as possible and the subject will be monitored until the value returns to 
normal and/or an adequate explanation for the abnormality is found. 
Investigators will also be allowed to repeat specific laboratory test(s) or procedure(s)
where the investigator suspects an inaccuracy or false result and that which may impact 
 
              
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the safety of the subject or the interpretation of the trial results; only after discussion with 
medical monitor.
All clinically significant out-of-range laboratory values at the screening visit will be 
recorded in the medical history form (report a diagnosis rather than the laboratory value 
whenever possible). All clinically significant out-of-range laboratory values after the 
screening visit are to be reported as an AE if this abnormality was not present at the 
screening visit or is assessed as having worsened since the screening visit (ie, changed 
significantly from the screening visit). Whenever possible, the investigator should 
provide a diagnosis of an AE when reporting the abnormal laboratory value.
Subjects should be reminded to be well hydrated before all visits for phlebotomy 
purposes. Subjects should fast for at least 8 hours before the visits when blood chemistry 
testing is planned, except for the screening visit. The screening visit laboratory values 
must be available before the baseline visit. Laboratory testing conducted in a nonfasting 
state will not be a protocol deviation.
Total blood volumes to be drawn at each visit are provided in the clinical laboratory 
manual and in Appendix 11. Additional samples may be required if medically indicated 
(eg, at unscheduled visits for safety reasons, when an abnormal laboratory value is 
observed and requires a re-test).
See Sections 9.2.3 , 9.2.4 , and 9.2.5 for details regarding pregnancy testing, virology, 
and TB testing samples, respectively. (See Sections 9.3, 9.4, 9.5, and 9.6, for details 
regarding PK, ADA, PD/biomarkers, and optional PGx sampling, respectively.)
The following laboratory safety tests will be performed as specified in Section 8.1.2 :
9.2.2.1
Hematology
Hemoglobin, hematocrit, white blood cell count (with differential including eosinophils), 
red blood cell count, platelet count, and mean cell volume.
9.2.2.2
Clinical Chemistry
Creatinine, AST, ALT, gamma glutamyltransferase, alkaline phosphatase, lactate 
dehydrogenase, total bilirubin, direct bilirubin, albumin, total protein, uric acid, sodium, 
potassium, calcium, chloride, glucose, urea, total cholesterol, triglycerides, low-density 
lipoprotein, high-density lipoprotein (HDL), creatine phosphokinase (CPK). CPK 
 
              
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isoenzyme test will be performed only if CPK is elevated to > 2.5 × ULN. The 
investigator should also contact the medical monitor in such situations. 
For postmenopausal subjects (ie, no menses for 12 consecutive months), postmenopausal
status will be confirmed with a high follicle-stimulating hormone level in the 
postmenopausal range.
9.2.2.3
Urinalysis
pH, glucose, ketones, blood, protein, leukocytes, nitrites, bilirubin, urobilinogen, and 
specific gravity.
9.2.3 Pregnancy Testing
All women of childbearing potential will have a serum pregnancy test at the screening 
visit and UPTs at subsequent visits according to Section 8.1.2 . Pregnancy test results 
must be available prior to the administration of the study drug.
Subjects with a positive serum pregnancy test result at screening must not be enrolled. 
Urine pregnancy tests with a sensitivity < 25 IU/L will be provided to the study centers 
for use in the trial.
UPTs will be performed at the study centers, and all other samples will be sent to central 
laboratory for analysis. 
If the result of a UPT is positive, it must be confirmed with a serum pregnancy test, and 
no study drug should be administered pending the serum pregnancy test result. Subjects 
with a positive serum pregnancy test result during the trial must discontinue treatment 
and be withdrawn from the trial.
9.2.4 Virology
Virology including HBsAg, HBcAb, hepatitis C, HIV-1, and HIV-2 antibody will be 
assessed at the screening visit. Subjects with a positive HBcAb and a negative HBsAg 
will also be assessed for hepatitis B surface antibody.
 
              
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9.2.5 Tuberculosis Testing
Immunosuppressant biologic treatments have been shown to increase the risk of TB 
infection or to cause conversion from latent to active TB in some circumstances. Because 
of this, subjects will be screened for active or latent TB before entry into this study.
9.2.5.1
Definitions
Active TB is a disease caused by Mycobacterium tuberculosis in any part of the body and 
that is in an active state as determined by either a smear or culture taken from any source 
in the person’s body which tests positive for TB or by radiographic evidence. Individuals 
with active TB are symptomatic, depending upon the location of the disease (most 
commonly in the lungs but also possibly in the brain, kidneys, spine, or elsewhere), and 
can spread the infection to others. 
Latent TB is said to exist when an individual is infected with M tuberculosis, as 
evidenced by a positive Interferon Gamma Release Assay,39 such as QuantiFERON-TB 
Gold, but is asymptomatic and has no evidence of active infection on screening pathology 
or radiographic tests. Such individuals do not pass the disease to others and should 
commence a course of prophylactic antimycobacterial treatment to eliminate the infection 
and commit to completing the course of treatment.
9.2.5.2
Tuberculosis Screening
Ideally, as part of the medical history, the subject should be asked if they have presented 
with active or latent TB in the past and whether they have received a bacillus Calmette-
Guérin (or BCG) vaccination. They should also be asked if they have been in contact 
with any individuals known to have active TB or been placed in any circumstances that 
may have exposed them to an increased risk of TB infection, such as travel to TB 
endemic regions, close contact with persons with active TB, or workplace risk (eg, 
prison, hospitals). 
A subject who tests positive for latent TB (with a positive QuantiFERON-TB gold test)
should be referred to the subject’s treating physician for appropriate follow-up. If the 
result is indeterminate, the test may be repeated once. If confirmed indeterminate, the 
subject should then be managed as though he/she has a positive test result.
 
              
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9.2.6 Vital Signs
Vital signs will be evaluated at the screening visit and at each subsequent visit according 
to Section 8.1.2 . Vital signs will include pulse rate, systolic and diastolic blood pressure 
(after the subject has been sitting for at least 5 minutes), and body temperature. All 
abnormal values at the screening visit identified as clinically significant by the 
investigator will be recorded in the medical history form. Any clinically significant 
changes from the screening visit will be recorded as an AE.
9.2.7 Height and Weight
Height and weight will be measured, according to Section 8.1.2 . 
Subjects must be at least 30 kg at both screening and baseline visits in order to be 
enrolled into this clinical study.
After the screening visit, additional height assessments will only be conducted for 
adolescent subjects (age 12-17).
9.2.8 Physical Examination
Complete physical examination should be performed at the screening, baseline, and 
certain subsequent scheduled visits, according to Section 8.1.2 . A complete physical 
examination will include assessments of the head, ears, eyes, nose, throat, neck 
(including thyroid), skin/integumentary system, cardiovascular system, respiratory 
system (for additional respiratory assessments, see Section 9.2.9 ), gastrointestinal 
system, musculoskeletal system, lymph nodes, nervous system, and extremities. 
Investigator should assess all abnormal findings for clinical significance. All clinically 
significant abnormal findings at the screening visit will be recorded in the medical history 
form. Any clinically significant changes from the screening visit will be recorded as an 
AE.
9.2.9 Respiratory Assessments
At screening, the investigator should specifically question all subjects about any medical 
history of asthma and their respiratory health (eg, wheezing, coughing, allergies, 
infections). Subjects with a history of asthma will be questioned about the seasonality of 
 
              
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their asthma and known triggers, such as allergens. Newly diagnosed asthma or 
worsening of asthma during the study will be reported as an AESI.
9.2.9.1
Asthma Control Test
Subjects with a medical history of asthma will take the ACT at visits according to Section 
8.1.2 before questioning and physical examination by the investigator. Subjects with a 
new (de novo) diagnosis of asthma will take the ACT beginning at the visit the diagnosis 
was first confirmed and at all subsequent study visits thereafter. Subjects with an 
ACT score ≤19 will be referred to the physician managing their asthma. 
The ACT is an assessment to determine if a subject’s asthma symptoms are well
controlled. The ACT is designed for adults and adolescents 12 years or older, and is 
composed of 5 questions. For each question, the subject will choose the best answer out 
of 5 possible answers. The test provides a numerical score ranging from 5 to 25 to assess 
asthma control; a higher score indicates better asthma control while a score of 19 or less 
indicates the subject’s asthma may not be under control. See Appendix 12.
9.2.9.2
Respiratory Examination
A respiratory examination will be required to be performed for all subjects at all 
scheduled visits, according to Section 8.1.2 . The ACT will aid the investigator’s 
questioning of subjects with a medical history of asthma and should be completed before 
the clinical questioning. After the screening visit, all subjects will be asked non-leading 
questions about any respiratory changes. The investigator or designee will then perform a 
respiratory examination of all subjects at all visits. 
Subjects with a medical history of asthma will be referred to the physician managing their 
asthma if unexpected worsening of asthma is observed or reported. Subjects without a 
medical history of asthma who experience respiratory changes (examination findings or 
newly reported signs and/or symptoms suggestive of asthma) will be referred to a 
respiratory specialist. 
9.2.9.3
Peak Expiratory Flow
All subjects will undergo PEF testing at screening, baseline, and specified visits 
according to Section 8.1.2 . For subjects reporting a medical history of asthma, PEF 
testing will be conducted at all visits.
 
              
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Subjects with a new (de novo) diagnosis of asthma will undergo PEF testing at all visits 
after the diagnosis is first made according to Section 8.1.2 .
PEF testing during the clinical study will be performed under the supervision of qualified 
study personnel. PEF measurements should consist of 3 good efforts, with the best result 
documented. It is preferable that the PEF measurement be performed before noon or at 
the same time during each study visit whenever possible. Obtained PEF values will be 
compared to predicted values based on the subject’s age, sex and height.40,41
Subjects should be asked to withhold asthma medication on study visit days until after 
PEF testing is complete, to the extent it does not pose an undue risk to the subject, to 
avoid interference with PEF measurements. 
Subjects with a medical history of asthma will be referred to the physician managing their 
asthma if PEF < 80% of the predicted value.
9.2.9.4
Respiratory Referrals
Subjects with a medical history of asthma will be referred to the physician who manages 
their asthma when:

PEF < 80% of the predicted value. 

ACT score ≤ 19 (an ACT score ≤ 19 conveys asthma that may not be adequately 
controlled).

Unexpected worsening of asthma is observed or reported at any time during the 
study.
At any study visit, subjects without a medical history of asthma will be referred to an 
appropriate specialist physician whenever: 

Signs and/or symptoms suggestive of asthma are newly observed or reported.

Respiratory assessments (eg, examination, PEF) suggests a decline in the 
subject’s respiratory health.
9.2.10 Electrocardiogram
A 12-lead Electrocardiogram (ECG) will be performed and read centrally according to 
visits specified in Section 8.1.2 using the ECG machine provided. ECGs for each subject 
 
              
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should be obtained using the same electrocardiograph machine whenever possible. ECGs 
will be performed in the supine position at the time points described in the schedule of 
assessments and before any scheduled vital sign measurements and blood draws. Subjects 
should be monitored for potentially clinically significant ECG results (refer to the current 
version of the central laboratory manual). Tests with abnormal results that are deemed 
clinically significant should be repeated to ensure reproducibility of the abnormality. 
ECG abnormalities present at screening should be recorded in the medical history form.
Any abnormalities considered by the investigator to be clinically significant after the 
screening visit are to be recorded as AEs and discussed with the medical monitor, as 
needed.
9.3
Pharmacokinetics
9.3.1 Blood Sampling
Blood samples will be collected according to Section 8.1.2 , Appendix 11, and the 
clinical laboratory manual to determine the PK profile of nemolizumab. At each sampling 
time point for PK assessment, the collected blood will be placed to clot at room 
temperature (no more than 60 minutes after collection) and then centrifuged. The serum 
will be collected into storage tubes. 
As a guideline, PK samples should be collected at approximately the same time of day 
throughout the study, to the extent possible, before study drug injection (pre-dose 
samples). The date and the time of each sample collection will be recorded in the CRF, 
together with the time of study drug injection at the same visit (or missed injection if 
applicable). 
9.3.2 CD14152 Quantification in Biological Sampling
Concentration of nemolizumab (CD14152) in the serum will be determined by the 
designated CRO using a validated enzyme-linked immunosorbent assay (ELISA) method. 
Details related to the processing of serum samples and the assessments of nemolizumab
will be described in the bioanalytical plan, which will be finalized before the beginning 
of sample analysis. Results will be described in the bioanalytical report, which will be 
included as an appendix in the final clinical study report.
 
              
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9.3.3 Pharmacokinetic Parameters
Pharmacokinetic parameters of nemolizumab (CD14152) in the serum may be calculated, 
if needed, by a designated CRO using 2 analyses:

PK parameters may be derived, if needed, using a non-linear mixed effect modeling 
approach with NONMEM. A pre-specified population PK model based on existing 
information from previous studies in adults and adolescents (first-order absorption 
and a 1-compartment distribution model) will be updated with the nemolizumab 
serum concentrations obtained in this study.

In addition, a static analysis based on serum concentration may be performed, if 
needed, using a noncompartmental analysis, for each subject based on concentration 
before dosing, to obtain areas under the curve. Data from subjects with missing 
concentration values (missing samples) may be used if PK parameters can be 
estimated using the remaining data points. 
If the population PK and non-compartmental analyses will be performed, details will be 
specified in an ad hoc Modeling Analysis Plan and PK Analysis Plan, respectively.
9.4
Immunogenicity
Blood samples will be collected according to Section 8.1.2 , Appendix 11, and the 
clinical laboratory manual to assess anti-nemolizumab ADA. The ADA will be 
determined by the designated CRO using a validated ELISA screening assay. The serum 
concentration will be assessed using a multi-tiered approach. 
Details related to the processing of serum samples and the assessments of ADA will be 
described in the bioanalytical plan, which will be finalized before the beginning of 
sample analysis. Results will be described in the bioanalytical report, which will be 
included as an appendix in the final clinical study report.
If serum circulating ADA is detected, presence will be confirmed and characterized (eg,
for neutralizing potential) using a validated assay. Incidence of positive ADA results will 
be summarized (absolute occurrence and percent of subjects). 
 
              
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9.5
Pharmacodynamic Biomarkers
Blood and stratum corneum (D-Squames) samples will be collected at selected sites to 
investigate the effect of nemolizumab (CD14152) on RNA and protein biomarkers, 
including but not limited to TARC, IgE, and IL-31. Samples will be collected according 
to Section 8.1.2 . The recruitment of subjects for this part of the study will continue until 
the end of recruitment period of the study.
The details of the procedures for PD samples and storage conditions are further described 
in the clinical laboratory manual. Samples will be shipped to the designated CRO for 
biomarker assessment, unless otherwise specified. Samples will be stored by the sponsor 
or designated CRO for up to 15 years after the end of the study.
9.5.1 Blood Samples for PD
Blood samples will be collected for assessment of TARC and IgE by the central 
laboratory. Additional blood samples will be collected and shipped to the designated
CRO for RNA and protein biomarkers assessment. Total blood volumes to be drawn at 
each visit are provided in the clinical laboratory manual and in Appendix 11.
9.5.2 D-Squames Samples
Stratum corneum samples will be collected using D-Squames (ie, tape strips) to evaluate 
biomarker expression levels.42,43,44 As much as possible, skin sampling should be 
performed in similar body areas (eg, upper arms) for all samples in all subjects, with a 
selected area at baseline, and recorded in the CRF. 
At baseline prior to administration of study drug, 1 lesional and 1 non-lesional area will 
be identified, and 20 consecutive D-squames will be collected from each area, making 40
D-squames in total (20 from lesional skin and 20 from non-lesional skin). At week 16, 20
consecutive D-squames will be collected from the exact anatomical location of the
lesional area identified at baseline, regardless if the lesion has regressed (20 D-squames 
in total). The samples will be shipped to the designated CRO for analysis of protein and 
RNA biomarkers. 
9.6
Optional Pharmacogenomic Testing
Pharmacogenomic testing (deoxyribonucleic acid [DNA] analysis) is optional for this 
study, and will apply to subjects who provide written consent for this procedure. Subjects 
 
              
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are not required to participate in the DNA analysis sub-study in order to enroll in the 
main study.
DNA analysis will be performed using a blood sample collected at baseline (see 
Appendix 11 for total blood volume). If inadvertently not collected at baseline, the 
sample may be collected at a post-baseline visit.  
Samples will be stored by the sponsor or designated CRO for up to 15 years after the end 
of the study. Candidate sequences in DNA analysis may include but are not limited to 
genes that encode IL-31 and its receptor (IL-31 RA). DNA analysis will be conducted for 
the purpose of understanding inter-individual variability in nemolizumab (CD14152) 
efficacy, safety, and PK. These data may be used or combined with data collected from 
other studies to identify genomic markers that may predict response and elucidate 
mechanisms of disease. Analyses may include sequence variation or single nucleotide 
polymorphism identification within candidate genes and surrounding genomic regions. 
Genome-wide studies may also be performed.
It is the intent of the sponsor to assure that PGx information obtained remains 
confidential. The sponsor maintains rigorous confidentiality standards for clinical studies 
by “coding” (ie, assigning a unique patient ID number at the investigational study center) 
for all subjects enrolled in the study. All samples taken for DNA analysis will undergo a
second level of “coding” (each sample will receive a double-coded ID), according to 
ICH15 standards. Records will exist to trace double-coded samples to individual subjects 
for destruction if a subject provides a written request to withdraw their sample for DNA 
analysis. The data from samples that have already been analyzed will not be destroyed.
Blood samples for DNA analysis will be destroyed after 15 years have elapsed from the 
completion of this study.
9.7
Patient Reported Outcome Assessments
9.7.1 Asthma Control Test
For this study, the ACT will be completed as part of the respiratory assessments. See 
Section 9.2.9.1 and Appendix 12 for details. 
 
              
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9.7.15 Optional Subject Interviews
Subject interviews are optional and will be conducted with approximately 75 consenting 
subjects, including adolescents. Subjects are not required to participate in the interview 
sub-study to enroll in the main study. Interviews will be conducted by the designated 
CRO in English-speaking countries (the US, the United Kingdom [UK], Canada, and 
Australia).
Subjects will be invited to participate in the subject interviews by the study investigators 
during the screening process. A patient information brochure that explains participation 
in the interview process will be given to the subjects (see Appendix 27). Acceptance to 
participate in the interviews will be documented on the ICF. Upon acceptance, the subject 
will be asked to complete a subject contact form (Appendix 27). This form will be sent to 
the designated CRO by the study staff. The designated CRO will be responsible for 
managing the interviews, scheduling, and interviewing the subjects. 
Qualitative telephone interviews will be scheduled to take place between week 16 and 
week 18. The interview will last approximately 60-90 minutes and will collect subjects’ 
current and past experience with their disease and their experience of participating in the 
trial. Perceived treatment effects and perceived changes in daily life since baseline will 
also be explored. Interviewers will follow a semi-structured interview guide specifically
designed for the current trial (see Appendix 27). The interviews will be audio recorded
and serve as source documents for archiving in the TMF. The audio recordings will be 
transcribed for analysis purposes. The details of the interview analysis are further 
described in a subject interview analysis plan.
9.8
Optional Clinical Photographs
Clinical photographs are optional for this study and will apply only to subjects who 
provide written consent at selected sites. Photographs of AD lesions will be captured 
from approximately 50 subjects using standardized photographic methods. Subjects are 
not required to provide photographs to enroll in the main study. Additional details will be 
provided in the photographic manual.
 
              
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9.9
Independent Data Monitoring Committee 
An IDMC will review and monitor subject safety throughout the study. The IDMC will 
provide recommendations on the safety of subjects. Details on the IDMC, including the 
plan of analysis for IDMC outputs, the composition of the IDMC, the procedures, roles, 
responsibilities, and their communications are provided in the IDMC charter.
9.10 Independent Adjudication Committee
An IAC will review all asthma-related adverse events throughout the study. Details on 
the IAC, including the plan of analysis for IAC outputs, the composition of the IAC, the 
procedures, roles, responsibilities, and their communications are provided in the IAC
charter.
 
              
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10
STATISTICAL METHODS
A statistical analysis plan (SAP) will be developed as a separate document. The SAP will 
contain detailed and technical descriptions of specific data conventions, calculations, and 
statistical procedures for executing the analyses that are specified in the sections of the 
clinical study protocol below.
10.1 Statistical and Analytical Plans
10.1.1 Datasets or Populations Analyzed
For initial and maintenance period, the following populations will be defined for analysis. 
Only subjects who are re-randomized after initial period will be included for the analysis 
of maintenance period.
10.1.1.1 Intent-to-Treat Population
The intent-to-treat (ITT) population will consist of all randomized subjects. All primary 
and secondary efficacy endpoints will be analyzed based on the ITT population. The ITT 
population will be the primary population for all efficacy analyses. All analyses on the ITT 
population will be analyzed under the treatment group ‘as randomized’.
10.1.1.2 Safety Population
The safety population will comprise all subjects in ITT population who receive at least 1 
dose of study drug. All safety data will be summarized based on the safety population under 
the treatment group ‘as treated’.
10.1.1.3 PK Analysis Population
The PK analysis population will include all subjects in the safety population who provide 
at least 1 post-baseline evaluable drug concentration value. All PK and ADA endpoints 
will be analyzed using the PK analysis population under the treatment group ‘as treated’.
10.1.1.4 Per-Protocol Population
The per-protocol population will comprise all subjects in the ITT population who have no 
major protocol deviations that would have a significant effect on the efficacy of the study 
treatment. Only primary and key secondary endpoints will be analyzed using the per-
protocol population.
 
              
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10.1.1.5 PD Analysis Population
The PD analysis population(s) will be described in a separate pharmacodynamic plan.
10.1.2 Demographic and Other Baseline Characteristics
Subject disposition, demographics, baseline characteristics, previous therapies, and 
concomitant therapies by treatment will be summarized by descriptive statistics.
10.1.3 Efficacy Variables
Both primary and key secondary endpoints will be evaluated for the following populations:

Baseline PP NRS 4 (full population)

Baseline PP NRS 7
Primary inference for all the efficacy analyses will be based on the ITT population at the 
Week 16 endpoint. The per-protocol analysis will be carried out as supportive analyses for 
the primary and key secondary endpoints. 
All efficacy variables will be summarized by treatment at each visit.
The categorical variables will be summarized by frequency and percentage for each 
response category (N, %). The continuous variables will be summarized using means, 
medians, minimum, maximum, and standard deviations for the data collected at each 
visit.
Primary Efficacy Endpoint
Primary efficacy endpoint consists of 2 co-primary endpoints. Both co-primary endpoints 
will be analyzed using a Cochran-Mantel-Haenszel test adjusted for the randomized 
stratification variables (IGA severity and PP NRS) for both populations (baseline PP NRS 
4; baseline PP NRS 7) to compare the proportion of subjects achieving success between 
treatment groups. The estimate of treatment difference, the corresponding 2-sided 95% 
confidence interval, and p-values will be presented. 
Any subjects with missing data at Week 16 will be regarded as a non-responder. If a subject 
received any rescue therapy, the data after receipt of rescue therapy will be set to missing 
and subsequently regarded as a non-responder for the respective primary endpoint.
 
              
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10.1.4.2 Adverse Events
Treatment-emergent AEs, defined as those AEs occurring after the first administration of 
study treatment until the last study visit, will be tabulated in frequency tables by system 
organ class and preferred term based on the Medical Dictionary for Regulatory Activities 
for each study phase. Additional summary tables will be provided for SAEs, AEs related 
to the study drug(s) (reasonable possibility, no reasonable possibility), AEs related to the 
study procedure, AESIs, and AEs leading to treatment discontinuation and study 
withdrawal. For a given AE, a subject will be counted once even if he/she has experienced 
multiple episodes of that particular AE. 
Pretreatment AEs will be listed separately.
10.1.4.3 Clinical Laboratory
Laboratory data (absolute values and change from baseline) will be summarized by visit 
and treatment group for each study phase. In addition, the number and percentage of 
subjects below, within, and above the laboratory reference ranges and the number and 
percentage of subjects who met criteria of potential clinically significant value will be 
summarized by treatment group. Shift tables will be generated using the reference ranges. 
Reference ranges will be provided in the laboratory manual.
Abnormal laboratory values from tests on baseline visit will not be considered as TEAEs, 
as the sample collection will be conducted before study drug administration.
10.1.4.4 Vital Signs
All vital signs and weight data (absolute values and change from baseline) will be 
summarized by visit and treatment group. In addition, the number and percent of subjects 
with clinically significant abnormal values (of clinical concern as identified by the 
investigator) will be summarized by treatment group.
10.1.4.5 Peak Expiratory Flow 
The PEF measurements (absolute values and change from baseline) will be summarized 
by visit, treatment group, and medical history of asthma. 
Further details on safety analyses will be provided in the SAP.
 
              
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10.1.4.6 Physical Examination
The number and percentage of subjects who are normal, abnormal (clinically significant
[CS]), and abnormal (not clinically significant [NCS]) will be displayed by treatment at 
each visit.
10.1.4.7 Electrocardiogram
The number and percentage of subjects who have ECGs that are abnormal/CS and 
normal/NCS will be displayed by treatment at each visit.
10.1.5 Pharmacokinetic Parameters and Anti-Drug Antibody Analyses
Descriptive statistics (n, arithmetic mean, standard deviation, minimum, median, 
maximum) by treatment group will be calculated for all derived PK endpoints.
The concentration at each time point will be summarized as arithmetic mean, standard 
deviation, median, minimum, maximum, and number below the limit of quantification.
Incidence of positive ADA results will be summarized (absolute occurrence, percent of 
subjects, and treatment-related ADA). The ADA results presentation will be detailed in the 
SAP.
The population PK and PKPD modeling will be detailed in a separate Modeling Analysis 
Plan.
10.1.6 Biomarker Analyses
Biomarker analysis will be conducted by the designated CRO based on a separate 
pharmacodynamic plan.
10.1.7 Subject Interview Analysis
De-identified transcripts of subject interviews will be analyzed by the designated CRO 
using a qualitative thematic analysis using ATLAS.ti version 7.0 software. Qualitative 
data (eg, subjects’ perceptions of the nature, magnitude, and impact of symptom changes) 
and quantitative data (eg, the actual changes experienced by the subjects on relevant 
PROs) will be combined to help interpret clinically meaningful within-patient score 
 
              
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changes. Further details of the analysis of subject interviews will be provided in a 
separate subject interview analysis plan.
10.1.8 Psychometric Validation Analyses
Psychometric analyses will be conducted on the Phase 3 data for the evaluation of the PP 
NRS, SD NRS, and Subject Sleep Diary in both adult and adolescent subjects. These 
blinded analyses will be performed by the designated CRO after approximately half of 
adult and adolescent subjects complete the initial treatment period, on the basis of a 
separate psychometric validation statistical analysis plan.
10.1.9 Interim Analyses
No interim analysis is planned.
Week 16 Analysis: Primary analysis may be carried out once all subjects have completed 
the Week 16 visit or have withdrawn from the study. No personnel directly involved with 
the conduct of the study shall have access to the unblinded data before the completion of 
the trial in order to avoid introducing bias to the remaining study data.
10.1.10 Handling of Missing Data
The primary method to impute the missing values will be as follows:
Continuous Endpoints: For continuous endpoints during initial period, the MI under 
MAR assumption approach and the MMRM approach will be used to handle the missing 
data for the selected secondary endpoints. QoL endpoints (eg, DLQI/cDLQI, EQ-5D, 
PIQ) may be imputed using last observation carried forward (LOCF), where applicable.
Binary Endpoints: All missing values will be treated as a non-responder for the binary 
endpoints. To assess the robustness of non-responder analysis, a tipping point analysis 
will be performed. The MI under MAR assumption, LOCF, and OC will be used as 
sensitivity analysis to impute the missing values for the primary and key secondary
endpoints.
Use of rescue therapy: All efficacy data, except OC, will be set to missing after rescue 
medication is used. In OC analysis, no observed data after subject has received rescue 
treatment will be excluded. There will be no imputations for missing data.
 
              
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10.1.11 Sensitivity Analyses for Primary and Key Secondary Endpoints
The following sensitivity analyses will be conducted for the robustness of the analyses. 

Same analysis on Per-protocol population

Tipping point analysis will be performed by converting non-responders due to 
missing data to responders in successive increments (∆) for both treatment groups to 
assess the robustness of analysis. The value of ∆ that overturns (ie, non-significant) 
the primary results will represent the tipping point. A graphic display of all possible 
combination of the number of responders among both treatment groups will be 
presented.

Multiple imputation (MI) methods for missing data: The MI imputation will be 
carried out as follows.
1. Imputation Phase
a.
A 50 imputed datasets with a monotone missing pattern will be created 
using SAS MI procedure based on the observed data (Markov-Chain-
Monte-Carlo method, MCMC). The seed to be used is 118161 (the 
Protocol number). Pattern of missing data will be evaluated and it is 
expected that the pattern of missing data will be monotonic. For non-
monotone missing data patterns, MCMC method of MI procedure will be 
used to impute enough data so that the remaining missing data is 
monotone.
b. Each of the imputed datasets will be used to generate 50 complete 
datasets, using the following approaches:
i. Ordinal data (eg, IGA score): A logistic regression method to 
impute the ordinal missing data, including treatment, 
randomization strata, and assessments from earlier time points as 
covariates. Response or total score of the subjects will be derived 
using these imputed data. 
ii. Continuous data (eg, EASI score): A linear regression model 
including treatment, randomization strata, and assessments from 
earlier time points as covariates will be used to impute the score. 
Response or total score of the subjects will be derived using these 
imputed data. 
2. Analysis Phase: The analysis will be conducted using the complete datasets.
a.
Binary endpoint: The complete datasets will be modelled for the endpoint 
using CMH method as per analysis described in Section 10.1.3 . 
 
              
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Proportion of responders in each treatment arm, difference and standard 
error will be calculated.
b. Continuous endpoint: The complete datasets will be analysed using 
ANCOVA including treatment group and randomization stratification 
factors as factors and appropriate baseline values as a covariate, if 
applicable. LSMeans in each treatment arm, difference and standard errors 
will be calculated.
3. Pooling Phase: The results from the analysis phase will be combined as follows. 
a.
Binary endpoint: The results from the CMH analysis of the multiple 
imputed datasets will be combined using the Rubin (1987) and Li et al 
(1991) approach to produce pooled CMH statistics and p-value. Proportion 
of responders in each treatment arm, difference and standard error will be 
combined using the MIANALYZE procedure in SAS.
b. Continuous endpoint: The LSMeans in each treatment arm, difference and 
standard errors from the ANCOVA of the multiple imputed datasets will 
be combined using the MIANALYZE procedure in SAS.

Last Observation Carried Forward (LOCF) imputation method for missing data 
(or where rescue medication is received)

Observed Case (OC) - No data will be imputed. For this analysis, if any rescue 
medication is received, and data are collected post rescue receipt, data post-rescue 
will be analyzed as observed (ie, not set to missing).
Sensitivity analyses may be performed to evaluate the impact COVID-19 deviations. 
Further details will be provided in SAP.
10.2 Determination of Sample Size
To achieve at least 90% power for each co-primary endpoint at 2.5% significance level, 
150 subjects per group will be required to detect the following differences between 
treatment groups for 2 co-primary endpoints with 2:1 randomization ratio, assuming 15% 
dropout rate during the initial treatment period.
With 2:1 randomization, 180 subjects in nemolizumab and 90 subjects in placebo will be 
required to detect the differences in both co-primaries to achieve 90% power.
IGA Success: To detect a difference of 18%, assuming IGA response for nemolizumab 
30% and placebo 12% at Week 16.
EASI-75 Response: To detect a difference of 30%, assuming EASI-75 response for 
nemolizumab 49% and placebo 19% at Week 16.
 
              
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To ensure sufficient exposure with nemolizumab and to ensure sufficient size of safety 
database, sample size is increased to 750 subjects in total with a randomization ratio of
2:1. This sample size will provide more than 99% power to detect the treatment 
difference for both co-primary endpoints at 2.5% significance level.
10.3 Protocol Deviations
Major deviations are categorized into the following categories:

Eligibility deviations (inclusion/exclusion criteria)

Improper reconstitution and administration of study medication

Noncompliance with study medication per the investigator’s discretion

Noncompliance with study procedures if the consequence of noncompliance would 
compromise either the subject’s safety and/or the study integrity, primary endpoint, 
and/or is not in line with Good Clinical Practice (GCP)/ICH guidelines

Use of prohibited concomitant therapies
All protocol deviations will be identified, evaluated, and closed before the respective 
database lock (final analysis) and will be described in the clinical study report. Protocol 
deviations incurred as a direct result of the COVID-19 pandemic should be specifically 
recorded as a COVID-19 deviation. Further details of protocol deviations will be 
provided in the Protocol Deviation and Non Compliance Management Plan.
 
              
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11
QUALITY ASSURANCE AND QUALITY CONTROL
11.1 Audit and Inspection
Study centers and study documentation may be subject to Quality Assurance audit during 
the course of the study by the sponsor or its nominated representative. In addition, 
inspections may be conducted by regulatory authorities at their discretion.
11.2 Monitoring
Data for each subject will be recorded on CRFs. Data collection must be completed for 
each subject who signs an ICF and is administered study drug.
In accordance with current GCP and ICH guidelines, the study monitor will carry out 
source document verification at regular intervals to ensure that the data collected in the 
CRF are accurate and reliable. 
The investigator must permit the monitor, the IEC/IRB, the sponsor’s internal auditors,
and representatives from regulatory authorities direct access to all study-related 
documents and pertinent hospital or medical records for confirmation of data contained 
within the CRFs.
11.3 Personnel Training
Study monitors and all relevant personnel will be trained before study initiation on the 
condition to be treated, the standard operating procedures to be used in this clinical study, 
the protocol, and all study-specific procedures. Team organization, communication, and 
operational issues will also be discussed and agreed upon.
Investigators, evaluators, study coordinators, pharmacists, and other applicable personnel 
are recommended to attend an investigator meeting. During the meeting, participants will 
be trained on the protocol, ICH/GCP, study-specific procedures (including efficacy 
assessment scales and instruction for use of the study drug), IRT, and CRF completion. 
All personnel involved in the study conduct will receive training before participating in 
any procedure and/or evaluation. Each study center will have a training record as part of 
the site file and TMF.
 
              
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11.4 Data Management
The designated CRO will be responsible for activities associated with the data 
management of this study. This will include, but is not limited to, setting up a relevant 
database and data transfer mechanisms, along with appropriate validation of data and 
resolution of queries. All data management activities will be detailed in the data 
management plan. 
Study centers will enter data directly into an electronic data capture system by 
completing the CRF via a secure internet connection. Data entered into the CRF must be 
verifiable against source documents at the study center or remotely if applicable. Data to 
be recorded directly on the CRF will be identified and the CRF will be considered the 
source document. Any changes to the data entered into the electronic data capture system 
will be recorded in the audit trail.
11.5 Clinical Study Conduct
With the exception of avoiding an immediate risk to a subject, the investigator should not 
deviate from the clinical study protocol or implement any changes without written 
approval from the sponsor and prior review and documented approval/favorable opinion 
from the IRB/IEC of a protocol amendment.
Changes that involve only logistical or administrative changes to the clinical study 
protocol are authorized. The investigator should document and explain any deviation 
from the clinical study protocol.
11.6 Amendments
The sponsor may modify the clinical study protocol at any time for ethical, medical, or 
scientific reasons. Any amendments will be handled according to applicable local 
regulations.
The sponsor does not have to notify non-substantial amendments to the competent 
authorities or IRB/IEC. However, non-substantial amendments will be recorded and 
detailed in subsequent submissions (eg, in the subsequent notification of a substantial 
amendment).
11.7 Quality Management and Risk Evaluation
Details will be provided in a separate Integrated Quality Risk Management Plan.
 
              
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12
ETHICS
12.1 Independent Ethics Committee or Institutional Review Board
Before initiation of the study at each study center, the protocol, the ICF, other written 
material given to the subjects, and any other relevant study documentation will be 
submitted to the appropriate IEC/IRB. Written approval of the study and all relevant 
study information must be obtained before the study center can be initiated or the study 
drug is released to the investigator. Any necessary extensions or renewals of IEC/IRB 
approval must be obtained for changes to the study such as amendments to the protocol, 
the ICF or other study documentation. The written approval of the IEC/IRB together with 
the approved ICF must be filed in the study files.
The investigator will report promptly to the IEC/IRB any new information that may 
adversely affect the safety of the subjects or the conduct of the study. The investigator 
will submit written summaries of the study status to the IEC/IRB as required. On 
completion of the study, the IEC/IRB will be notified that the study has ended.
12.2 Regulatory Authorities
Relevant study documentation will be submitted to the regulatory authorities of the 
participating countries, according to local/national requirements, for review and approval 
before the beginning of the study. On completion of the study, the regulatory authorities 
will be notified that the study has ended.
12.3 Ethical Conduct of the Study
The investigator(s) and all parties involved in this study should conduct the study in 
adherence to the ethical principles based on the Declaration of Helsinki, GCP, ICH 
guidelines, and the applicable national and local laws and regulatory requirements.
12.4 Informed Consent
The process of obtaining informed consent must be in accordance with applicable 
regulatory requirement(s) and must adhere to GCP.
The investigator is responsible for ensuring that no subject undergoes any study-related 
examination or activity before that subject has given written informed consent to 
participate in the study.
 
              
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All minor subjects who participate in this clinical study must be accompanied by a 
parent/guardian. Subjects and parent/guardians are required to be fully informed about 
the clinical study in accordance with GCP guidelines, federal regulations (for the US, 
HIPAA),52 and guidelines and in accordance with local requirements.
The investigator or designated personnel will inform the subject of the objectives, 
methods, anticipated benefits and potential risks and inconveniences of the study. The 
subject should be given every opportunity to ask for clarification of any points she/he 
does not understand and, if necessary, ask for more information. At the end of the 
interview, the subject will be given ample time to consider the study. Subjects will be 
required to sign and date the ICF. After signatures are obtained, the ICF will be kept and 
archived by the investigator in the investigator’s study file. A signed and dated copy of 
the subject ICF will be provided to the subject or his/her authorized representative.
It should be emphasized that the subject may refuse to enter the study or to withdraw 
from the study at any time, without consequences for their further care or penalty or loss 
of benefits to which the subject is otherwise entitled. Subjects who refuse to give or who 
withdraw written informed consent should not be included or continue in the study.
If new information becomes available that may be relevant to the subject’s willingness to 
continue participation in the study, a new ICF will be approved by the IEC(s)/IRB(s) (and 
regulatory authorities, if required). The study subjects will be informed about this new 
information and reconsent will be obtained.
12.5 Subject Confidentiality
Monitors, auditors, and other authorized agents of the sponsor and/or its designee, the 
IEC(s)/IRB(s) approving this research, and the US Food and Drug Administration, as 
well as that of any other applicable agency(ies), will be granted direct access to the study 
subjects’ original medical records for verification of clinical study procedures and/or 
data, without violating the confidentiality of the subjects to the extent permitted by the 
law and regulations. In any presentations of the results of this study or in publications, the 
subjects’ identities will remain confidential.
All personal data collected and processed for the purposes of this study should be 
managed by the investigator and his/her staff with adequate precautions to ensure 
confidentiality of those data, and in accordance with the applicable national and/or local 
laws and regulations (HIPAA for the US) 52 on personal data protection.
 
              
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For subjects participating in the qualitative interviews, audio files of the interviews will 
be transcribed and de-identified (any identifying information such as names and locations 
will be removed). The de-identified transcripts will be delivered for analysis, and a single
audio file will be kept as a source document in the TMF. Any copies of the audio file will 
be destroyed immediately upon confirmation of receipt of the transcript.
Data protection and privacy regulations will be observed in capturing, forwarding, 
processing, and storing subject contact details and data. Subjects will be informed 
accordingly and will be requested to give their consent on contact details data handling 
procedures in accordance with national regulations. Patient contact details will be sent to 
the designated CRO using a secure server, independently from study sponsor, monitor, 
data management and data analysis structures, and other study stakeholders. The subject 
contact form will not include health data and will be destroyed after completion of the 
interview.
12.6 Financing and Insurance
Financing and insurance of this study will be outlined in a separate agreement between 
the designated CRO and the sponsor.
 
              
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13
REPORTING AND PUBLICATION, INCLUDING ARCHIVING
Essential documents are those documents that individually and collectively permit 
evaluation of the study and quality of the data produced. After completion of the study
(end of study defined as the date of the last visit of the last subject), all documents and 
data relating to the study will be kept in an orderly manner by the investigator in a secure 
study file. This file will be available for inspection by the sponsor or its representatives. 
Essential documents should be retained for 2 years after the final marketing approval in 
an ICH region or for at least 2 years since the discontinuation of clinical development of 
the investigational product. It is the responsibility of the sponsor to inform the study
center when these documents no longer need to be retained. The investigator must contact 
the sponsor before destroying any study-related documentation. In addition, all subject 
medical records and other source documentation will be kept for the maximum time 
permitted by the hospital, institution, or medical practice.
The sponsor must review and approve any results of the study or abstracts for 
professional meetings prepared by the investigator(s). Published data must not 
compromise the objectives of the study. Data from individual study centers in multicenter
studies must not be published separately.
 
              
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REFERENCES
Weidinger S, Novak N. Atopic dermatitis. Lancet. 2016;387(10023):1109-22.
Eichenfield LF, Tom WL, Berger TG, et al. Guidelines of care for the management 
of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with 
topical therapies. J Am Acad Dermatol. 2014;71(1):116-32.
Linnet J, Jemec GB. An assessment of anxiety and dermatology life quality in 
patients with atopic dermatitis. Br J Dermatol. 1999;140(2):268-72.
Williams H, Stewart A, von Mutius E, Cookson W, Anderson HR; International 
Study of Asthma and Allergies in Childhood (ISAAC) Phase One and Three Study 
Groups. Is eczema really on the increase worldwide? J Allergy Clin Immunol. 
2008;121(4):947-54.e15.
Shaw TE, Currie GP, Koudelka CW, Simpson EL. Eczema prevalence in the United 
States: data from the 2003 National Survey of Children's Health. J Invest Dermatol. 
2011;131(1):67-73.
Silverberg JI, Simpson EL. Associations of childhood eczema severity: a US 
population-based study. Dermatitis. 2014;25(3):107-14.
Silverberg JI. Public Health Burden and Epidemiology of Atopic Dermatitis. 
Dermatol Clin. 2017;35(3):283–289.
Emerson RM, Williams HC, Allen BR. Severity distribution of atopic dermatitis in 
the community and its relationship to secondary referral. Br J Dermatol. 
1998;139(1):73-6. 
Wasserbauer N, Ballow M. Atopic dermatitis. Am J Med. 2009;122(2):121-5.
Rudikoff D, Lebwohl M. Atopic dermatitis. Lancet. 1998;351(9117):1715-21.
Rutkowski K, Sowa P, Rutkowska-Talipska J, Sulkowski S, Rutkowski R. Allergic 
diseases: the price of civilisational progress. Postepy Dermatol Alergol.
2014;31(2):77-83.
Stott B, Lavendar P, Lehmann S, Pennino D, Durham S, Schmidt-Weber CB. Human 
IL-31 is induced by IL-4 and promotes Th2-driven inflammation. J Allergy Clin 
Immunol. 2013;132(2):446-54.e5.
Singh B, Jegga AG, Shanmukhappa KS, et al. IL-31-driven skin remodeling involves 
epidermal cell proliferation and thickening that lead to impaired skin-barrier 
function. PLoS One. 2016;11(8):e0161877.
 
              
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Gittler JK, Shemer A, Suárez-Fariñas M, et al. Progressive activation of 
T(H)2/T(H)22 cytokines and selective epidermal proteins characterizes acute and 
chronic atopic dermatitis. J Allergy Clin Immunol. 2012;130(6):1344-54.
Suárez-Fariñas M, Tintle SJ, Shemer A, et al. Nonlesional atopic dermatitis skin is 
characterized by broad terminal differentiation defects and variable immune 
abnormalities. J Allergy Clin Immunol. 2011;127(4):954-64.e1-4.
Wahlgren CF. Itch and atopic dermatitis: an overview. J Dermatol. 1999;26(11):770-
9.
Szegedi K, Kremer AE, Kezic S, et al. Increased frequencies of IL-31-producing T 
cells are found in chronic atopic dermatitis skin. Exp Dermatol. 2012;21(6):431-6.
Neis MM, Peters B, Dreuw A, et al. Enhanced expression levels of IL-31 correlate 
with IL-4 and IL-13 in atopic and allergic contact dermatitis. J Allergy Clin Immunol.
2006;118(4):930-7.
Sonkoly E, Muller A, Lauerma AI, et al. IL-31: a new link between T cells and 
pruritus in atopic skin inflammation. J Allergy Clin Immunol. 2006;117(2):411-7.
Kato A, Fujii E, Watanabe T, et al. Distribution of IL-31 and its receptor expressing 
cells in skin of atopic dermatitis. J Dermatol Sci. 2014;74(3):229-35.
Saito S, Aoki A, Arai I, et al. Regulation of Th2 responses by different cell types 
expressing the interleukin-31 receptor. Allergy Asthma Clin Immunol. 2017;13:23.
Hänel KH, Pfaff CM, Cornelissen C, et al. Control of the physical and antimicrobial 
skin barrier by an IL-31-IL-1 signaling network. J Immunol. 2016;196(8):3233-44.
Eucrisa® [package insert]. New York, NY: Pfizer Inc; 2018.
Sidbury R, Davis DM, Cohen DE, et al; American Academy of Dermatology.
Guidelines of care for the management of atopic dermatitis: section 3. Management 
and treatment with phototherapy and systemic agents. J Am Acad Dermatol.
2014;71(2):327-49.
Simpson EL, Bieber T, Guttman-Yassky E, et al; SOLO 1 and SOLO 2 Investigators. 
Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med.
2016;375(24):2335-48.
Dillon SR, Sprecher C, Hammond A, et al. Interleukin 31, a cytokine produced by 
activated T cells, induces dermatitis in mice. Nat Immunol. 2004;5(7):752-60.
 
              
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Grimstad O, Sawanobori Y, Vestergaard C, et al. Anti-interleukin-31-antibodies 
ameliorate scratching behavior in NC/Nga mice: a model of atopic dermatitis. Exp 
Dermatol. 2009;18(1):35-43.
Michels GM, Ramsey DS, Walsh KF, et al. A blinded, randomized, placebo-
controlled, dose determination trial of lokivetmab (ZTS-00103289), a caninized, 
anti-cannine IL-31 monoclonal antibody in client owned dogs with atopic dermatitis. 
Vet Dermatol. 2016;27(6):478-e129.
Oyama S, Kitamura H, Kuramochi T, et al. Cynomolgus monkey model of 
interleukin-31-induced scratching depicts blockade of human interleukin-31 receptor 
A by a humanized monoclonal antibody. Exp Dermatol. 2018;27(1):14-21.
Ruzicka T, Mihara R. Anti-interleukin-31 receptor A antibody for atopic dermatitis. 
N Engl J Med. 2017;376(21):2093.
Nemoto O, Furue M, Nakagawa H, et al. The first trial of CIM331, a humanized 
antihuman interleukin-31 receptor A antibody, in healthy volunteers and patients 
with atopic dermatitis to evaluate safety, tolerability and pharmacokinetics of a single 
dose in a randomized, double-blind, placebo-controlled study. Br J Dermatol.
2016;174(2):296-304.
CIM003JG Clinical study report: A phase II, randomized, double-blind, placebo-
controlled, multiple-dose study to evaluate the safety, tolerability, and efficacy of 
CIM331 in atopic dermatitis patients who are inadequately controlled by or intolerant 
to topical therapy. 2017.
Leshem YA, Hajar T, Hanifin JM, Simpson EL. What the Eczema Area and Severity 
Index score tells us about the severity of atopic dermatitis: an interpretability study. 
Br J Dermatol. 2015;172(5):1353-7.
Barbier N, Paul C, Luger T, et al. Validation of the Eczema Area and Severity Index 
for atopic dermatitis in a cohort of 1550 patients from the pimecrolimus cream 1% 
randomized controlled clinical trials programme. Br J Dermatol. 2004;150(1):96-
102.
Paller AS, Tom WL, Lebwohl MG, et al. Efficacy and safety of crisaborole ointment, 
a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment 
of atopic dermatitis (AD) in children and adults. J Am Acad Dermatol.
2016;75(3):494-503.e6.
 
              
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Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M. The Eczema 
Area and Severity Index (EASI): assessment of reliability in atopic dermatitis. EASI 
Evaluator Group. Exp Dermatol. 2001;10(1):11-8.
Carney CE, Buysse DJ, Ancoli-Israel S, et al. The consensus sleep diary: 
standardizing prospective sleep self-monitoring. Sleep. 2012;35(2):287-302. 
European Task Force on Atopic Dermatitis. Severity scoring of atopic dermatitis: the 
SCORAD index. Consensus Report of the European Task Force on Atopic 
Dermatitis. Dermatology. 1993;186(1):23-31.
Centers for Disease Control and Prevention. Updated guidelines for using interferon 
gamma release assays to detect Mycobacterium tuberculosis infection—United 
States, 2010. MMWR. 2010;59(RR05);1-25.
Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC. Lung 
volumes and forced ventilatory flows. Eur Respir J. 1993;6 Suppl 16:5-40.
Polgar G, Weng TR. The functional development of the respiratory system from the 
period of gestation to adulthood. Am Rev Respir Dis. 1979;120(3):625-95.
Guttman-Yassky E, Diaz A, Pavel AB, et al. Use of tape strips to detect immune and 
barrier abnormalities in the skin of children with early-onset atopic dermatitis. JAMA 
Dermatol. 2019; 155(12):1358-1370.
Dyjack N, Goleva E, Rios C, et al. Minimally invasive skin tape strip RNA 
sequencing identifies novel characteristics of the type 2-high atopic dermatitis 
disease endotype. J Allergy Clin Immunol. 2018; 141(4):1298-1309.
Olesen CM, Fuchs CSK, Philipsen PA, et al. Advancement through epidermis using 
tape stripping technique and Refectance Confocal Microscopy. Sci Rep. 2019;
9(1):12217.
Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)–a simple practical 
measure for routine clinical use. Clin Exp Dermatol. 1994;19(3):210-6.
Lewis-Jones MS, Finlay AY. The Children’s Dermatology Life Quality Index 
(CDLQI): initial validation and practical use. Br J Dermatol. 1995;132(6):942-9.
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(12):1513-9.
Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr 
Scand. 1983;67(6):361-70.
 
              
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Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work 
productivity 
and 
activity 
impairment 
instrument. 
Pharmacoeconomics. 
1993;4(5):353-65.
EuroQoL Group. EuroQoL—a new facility for the measurement of heath-related 
quality of life. Health Policy. 1990;16(3):199-208.
Silverberg JI, Hinami K, Trick WE, Cella D. Itch in the general internal medicine 
setting: a cross-sectional study of prevalence and quality-of-life effects. Am J Clin 
Dermatol. 2016;17(6):681-90.
US Department of Health and Human Services. Health insurance portability and 
accountability act of 1996 (P.L.104-191) [HIPAA]. 
http://aspe.hhs.gov/admnsimp/pl104191.htm. Effective August 21, 1996.
 
              
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APPENDICES
Appendix 1: American Academy of Dermatology Consensus Criteria for AD 
Diagnosis
Features to be considered in diagnosis of patients with atopic dermatitis:
ESSENTIAL FEATURES; must be present:

Pruritus 

Eczema (acute, subacute, chronic):
o
Typical morphology and age-specific patterns* 
o
Chronic or relapsing history
*Patterns include:
1) Facial, neck, and extensor involvement in infants and children; 
2) Current or prior flexural lesions in any age group; 
3) Sparing of groin and axillary regions.
IMPORTANT FEATURES; seen in most cases, adding support to the diagnosis:

Early age of onset 

Atopy
o
Personal and/or family history
o
IgE reactivity 

Xerosis
ASSOCIATED FEATURES; these clinical associations help to suggest the diagnosis of 
AD but are too non-specific to be used for defining or detecting AD for research and 
epidemiologic studies:

Atypical vascular responses (eg, facial pallor, white dermographism, delayed blanch 
response)

Keratosis pilaris / pityriasis alba / hyperlinear palms / ichthyosis 

Ocular / periorbital changes

Other regional findings (eg, perioral changes / periauricular lesions) 

Perifollicular accentuation / lichenification / prurigo lesions
EXCLUSIONARY CONDITIONS; it should be noted that a diagnosis of AD depends 
on excluding conditions such as:

Scabies

Seborrheic dermatitis

Contact dermatitis (irritant or allergic)
 
              
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
Ichthyoses

Cutaneous T-cell lymphoma

Psoriasis

Photosensitivity dermatoses

Immune deficiency diseases

Erythroderma of other causes
Source: Eichenfield LF, Tom WL, Berger TG, et al. Guidelines of care for the management of atopic dermatitis: 
section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71(1):116-
32.
 
              
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Appendix 2: Specific Guidance for Study Conduct and Subject Safety during the 
COVID-19 Pandemic
This guidance applies during the COVID-19 pandemic, as defined by regional and/or 
local authorities. The updates summarized below are relevant to the referenced sections 
of the protocol.
Section 6.3
Risk/Benefit Assessment
During the COVID-19 pandemic, additional risks to participants may exist, including 
general environmental risks (eg, being outside the home, possible contact with 
unsanitized surfaces) and study-related activities (eg, interaction with study staff). 
Potential new subjects with known or suspected COVID-19 infection are ineligible for 
study enrollment until the infection has resolved. Furthermore, potential new subjects in a 
high-risk population for COVID-19 (e.g. 60 years and older or with comorbidities), 
should be temporarily deferred until the COVID-19 risk has subsided at the location of 
the enrolling site, according to investigator judgement. Risk mitigation measures to be 
implemented for enrolled subjects and for new subjects during the COVID-19 pandemic 
are detailed in Additional Measures for Subjects Amidst COVID-19 Pandemic below. 
Subjects with a known or suspected COVID-19 infection will immediately discontinue 
study drug; instructions for resuming treatment are described in Section 8.3.4.2 and 
below in Guidance for Existing Subjects. Known or suspected COVID-19 infection will 
also be followed as an AESI.
New Subsection to Section 8.1, Overall Study Design and Plan:
Additional Measures for Subjects Amidst COVID-19 Pandemic
All investigational sites should act according to applicable site regulations, to 
guidelines and restrictions implemented by local authorities, and to best practices 
for conducting clinical research during the COVID-19 pandemic. 
- Guidance for New Subjects:
Best practices currently in place must be followed when evaluating eligibility of 
subjects to participate in the study during the COVID-19 pandemic.
For potential subjects in a high-risk population for COVID-19 as defined by the 
American Academy of Dermatology (AAD) (e.g. 60 years and older or with 
 
              
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comorbidities) or local guidelines, deferring participation in the study should be 
considered. Deferment of enrollment is based on the potential risk posed by 
general environmental risks (e.g. being outside home, possible contact with 
unsanitized surfaces) and study-related activities (e.g. interaction with study staff).
For potential subjects in the low-risk population for COVID-19 (e.g. less than 60 
years of age and without comorbidities), the risks and benefits of participation in 
the study should be assessed on a case by case basis. 
If at the time of screening, in the opinion of the Investigator, the subject will not 
be willing and able to reach the investigational site and comply with all of the time 
commitments and requirements of the clinical study protocol, the subject should
not be considered for enrollment. The subject may be rescreened at a later time.
Pre-screening phone calls should be conducted to exclude potential 
candidates/subjects who display possible symptoms of COVID-19 or are at high 
risk of having been exposed to COVID-19.
- Guidance for Enrolled Subjects:
If the local situation allows for subjects to reach the clinical investigational site 
and complete all study procedures, the following measures should be taken:
-
Implement and document in the subject records regular 
communication with the subject between visits to attempt to ensure 
early detection of potential signs/symptoms of COVID-19 infection, 
and provide adequate advice, as per local medical practice and public 
health guidelines for suspected COVID-19 infection. Please refer to 
the Centers for Disease Control (CDC; https://www.cdc.gov/ 
coronavirus/2019-ncov/symptoms-testing/symptoms.html)/European 
CDC (https://www.ecdc.europa.eu/en/covid-19/questions-
answers)/local disease prevention agency and applicable local 
guidelines for assessment of subjects’ COVID-19 status.
-
Following the same guidelines, implement and document in the subject 
records an additional communication to the subject just before the 
scheduled visit. 
-
Discontinue study drug administration in case of confirmed or 
suspected COVID-19 infection until the infection is resolved. See 
Section 8.3.4.2. 
 
              
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
Study drug administration may resume in subjects with 
confirmed or suspected COVID-19 infection based on 
investigator judgement after discussion with the medical 
monitor or Sponsor and only if the following minimum 
conditions are met:
- For symptomatic subjects: At least 14 days have passed 
since recovery, defined as resolution of fever without the 
use of fever-reducing medications and improvement in 
respiratory symptoms (e.g. cough, shortness of breath)
- For asymptomatic subjects: At least 21 days have passed 
since the positive PCR test and no symptoms.
Note: The above should be considered minimum criteria. 
Where the local guidelines are more stringent for infection 
resolution criteria, those must be applied.
-
Report any COVID-19 infection (confirmed or suspected) as an AE 

if any seriousness criterion is met, also report as an SAE 
(see Section 9.2.1.3). 

if it occurs during the clinical study following the first 
dose of study drug administration, also report as AESI (see 
Section 9.2.1.4). 
-
Implement preventive infection control measures against COVID-19 
infection following local guidelines (e.g. good hygiene practice, clean 
techniques, and use of personal protective equipment such as gloves, 
goggles, and masks).
-
Implement preventive measures in handling all subject-facing study-
mandated assessment devices and parts: 

PEF meter device body is to be cleaned after each use, with 
recommended wipes, as per user manual 

PEF meter flow sensor is to be disposed of after each set of 
measurements is taken

Approved bacterial/virus filters may be used; if used, they must 
be disposed of after each set of measurements taken
 
              
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
Offer protective gloves to subjects for use while filling out 
assessments on a tablet and provide training on hygienic 
removal and disposal of gloves
If the local situation allows for subjects to reach the investigational site and 
complete only some study procedures where visit duration needs to be limited, the 
above measures also apply. All assessments should be conducted if possible. 
Subject-reported assessments that would usually be collected on the site tablet (e.g. 
ACT, PGAD, PGAT, EQ-5D, DLQI, AD-associated pain intensity and frequency) 
may be collected remotely (e.g. completed over the phone), as available.
Subjects can be dosed only if, taking into account the local situation and risk of 
exposure to COVID-19, the site considers that:
-
The study drug subcutaneous injection can be performed at the 
investigational site according to the instructions in the protocol, 
pharmacy manual and instruction for use, including preparation of 
study drug by an independent pharmacist or other qualified personnel.
-
ACT (for subjects with medical history of asthma) and PEF (all 
subjects) can be performed according to the protocol.
o
Exceptionally, if sites cannot perform PEF safely on site, the subjects 
should perform it at home prior to the onsite visit, on the same day. 
See section below for remote PEF testing instructions.
-
All other safety assessments are to be performed as per protocol: 
physical exam, vital signs, ECG, laboratory assessments, pregnancy 
test, monitoring of AEs and concomitant medications.
-
All missing assessments should be appropriately documented with 
COVID-19 recorded as the reason, where applicable.
If the local situation does not allow for subjects to reach the investigational site:
-
See New Subsection to Section 8.4.7
, Dose Modification:
Management of Subjects with Missed Doses of Study Drug due to 
COVID-19 Pandemic (below) for guidance on further dosing of
subjects.
-
Remote collection of data by Investigator or delegate is still to be done 
for the following assessments at the regularly scheduled visit time, by 
phone or video call:
 
              
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
AE collection,

ACT (for subjects with history of asthma),

Concomitant therapies used,

Moisturizer use/background topical therapy,

UPT results (for WOCBP),

PEF results,
Note: For remote PEF measurements the following should be done:
-
To prepare subjects to do remote PEF measurement at home 
in case it is needed during the course of the study, all 
subjects should be previously trained onsite 
-
During the remote visits, subjects can receive additional 
support (if needed) over the phone or video call by site staff 
when performing PEF 
-
If a subject has a PEF <80% of the predicted value:

Site staff can try to evaluate whether this is due to 
poor technique and ask the subject to repeat the set 
of measurements

If the subject’s best PEF measurement is still <80% 
of the predicted value or if there are other concerns 
regarding the subject’s respiratory health, refer to 
appropriate physician and report an AESI (see 
Section 9.2.1.4)

All laboratory samples should be collected at the site and 
analyzed at the central lab. Only in exceptional situations when 
subject safety cannot be assured otherwise and subject cannot 
reach the site, a local laboratory test (i.e. hematology, blood 
chemistry, urinalysis) can be performed and reported, based on 
investigator judgement. 

Subject-reported assessments that would usually be collected 
on the site tablet (e.g., ACT, PGAD, PGAT, EQ-5D, DLQI, 
AD-associated pain frequency and intensity), may be 
completed over the phone, as available.
 
              
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All missing assessments should be appropriately documented with COVID-19 recorded 
as the reason, where applicable.
New Subsection to Section 8.4.7 , Dose Modification:
Management of Subjects with Missed Doses of Study Drug due to COVID-19 
Pandemic
If a subject misses a dose of study drug due to the COVID-19 pandemic, study drug 
administration may be continued. The following dosing schedules apply. 
For subjects with a missed dose(s) during the initial treatment period (Baseline to Week 
16), study drug administration can be continued based on one of the following scenarios 
(see also Diagram 1, below):
1) Subject has missed one or more doses between Baseline and Week 16 but can 
come to the clinical site at Week 16 (see also Diagram 2a):
-
Subjects who are clinical responders (IGA of 0/1 or EASI-75) at Week 16 
can continue into the maintenance period.
-
Subjects who are non-responders at Week 16 may be eligible to enroll in 
the long-term extension (LTE) study RD.06.SPR.118163.
-
Subjects who required rescue therapy before Week 16 may be considered
for the LTE study but will be required to continue with study visits until 
Week 16 visit is due.
2) Subject has no missed doses through Week 12 but cannot reach the clinical site at 
Week 16 (see also Diagram 2b):
-
The Week 16 visit can be delayed by up to 8 weeks from the originally 
planned date. A remote Unscheduled visit should be planned between 
Week 12 and the delayed Week 16 visit for safety follow-up.
o
Subjects who are clinical responders (IGA of 0/1 or EASI-75) at 
the rescheduled Week 16 visit can continue into the maintenance 
period.
o
Subjects who are non-responders at the rescheduled Week 16 visit
may be eligible to enroll in the LTE study.
-
If the subject still cannot come to the delayed Week 16 visit within 8 
weeks of the originally planned date, the delayed Week 16 visit should be 
performed remotely at the rescheduled date. A remote Unscheduled visit 
 
              
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should be planned between Week 12 and the delayed Week 16 visit for 
safety follow-up. The subject may be considered for rollover into the LTE 
study after the delayed Week 16 visit is complete.
3) Subject has missed one or more doses between Baseline and Week 16 and cannot 
reach the clinical site at Week 16:
-
For subjects who cannot come to the clinical site at week 12 but with an 
administered dose at Week 8 (with or without Week 4), the Week 12 visit 
can be delayed up to 3 weeks, and the Week 16 visit can be delayed up to 
4 weeks from the rescheduled Week 12 visit (see also Diagram 2c). 
-
For subjects with an administered dose at week 12 but with a missed dose 
at Week 4 and/or Week 8, the Week 16 visit can be delayed by up to 4 
weeks from the originally planned date (see also Diagram 2d).
o
Subjects who are clinical responders (IGA of 0/1 or EASI-75) at 
the rescheduled Week 16 visit can continue into the maintenance 
period.
o
Subjects who are non-responders at the rescheduled Week 16 visit 
may be eligible to enroll in LTE study.
-
For subjects with a missed dose at week 12, the Week 16 visit will be 
performed remotely at Week 16 (cannot be delayed) and the subject may 
be considered for rollover into the LTE study (see also Diagram 2d).
For subjects with a missed dose(s) during the maintenance treatment period (Week 16 to 
Week 48), study drug administration can be continued. Any visits where the subject 
cannot reach the site should be done remotely. If a subject misses three doses, the 
investigator must contact the Sponsor for further guidance.
-
Subjects may be eligible to enroll in the LTE study at Week 48.
-
Subjects who required rescue therapy may be considered for the LTE 
study but will be required to continue with study visits until the Week 32 
visit is due.
 
              
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In all scenarios, study drug can be administered provided that there is a minimum 3 week 
interval between injections. If a subject cannot come to a planned visit due to COVID-19, 
the visit should be conducted remotely according to Additional Measures for Subjects 
Amidst COVID-19 Pandemic. Enrolment of subjects into the LTE study must be done 
in accordance with the LTE study protocol. Subjects who decline or are not eligible to 
enter into the LTE study will complete a follow-up visit 12 weeks after the last study 
drug injection.
11.2 Monitoring
On-site interim monitoring visits may not be feasible during COVID-19 restrictions; 
therefore, remote monitoring will be completed until on-site monitoring can be conducted 
again. Site monitoring activity will comply with the processes documented within the 
COVID-19 Site Management Risk Assessment Form.
 
              
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Diagram 1. Flow Chart of Management of Subjects with Missed Visits Before Week 
16 due to COVID-19
Diagram 2. Management of Subjects Based on Missed Dosing Scenarios
a. Diagram of Management of Subjects due to Scenario 1
 
              
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b. Diagram of Management of Subjects due to Scenario 2
c. Diagram of Management of Subjects due to Scenario 3: Cannot reach site at Visit 
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d. Diagram of Management of Subjects due to Scenario 3: Cannot reach site at Visit 
16
 
              
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Appendix 3: CYP Substrates with Narrow Therapeutic Index
CYP enzymes 
Substrates with narrow therapeutic index(1)
CYP1A2
Theophylline, Tizanidine
CYP 2B6
-
CYP2C8
Paclitaxel
CYP2C9
Warfarin, Phenytoin
CYP2C19
S-mephenytoin
CYP3A
Alfentanil, Astemizole, Cisapride, Cyclosporine, 
Dihydroergotamine, Ergotamine, Fentanyl, Pimozide, 
Quinidine, Sirolimus, Tacrolimus, Terfenadine
CYP2D6
Thioridazine, Pimozide
(1) CYP substrates with a narrow therapeutic index refers to drugs whose exposure-
response relationship indicates that small increases in their exposure levels by the 
concomitant use of CYP inhibitors may lead to serious safety concerns (eg, Torsades de 
Pointes). This is not an exhaustive list.
Source: Center for Drug Evaluation and Research (CDER), Food and Drug Administration, U.S. Department of Health 
and Human Services. Guidance for Industry: Drug Interaction Studies—Study Design, Data Analysis, Implications for 
Dosing, and Labeling Recommendations (Draft Guidance). February 2012.
 
              
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Appendix 4: Investigator’s Global Assessment (IGA)
Status
Score Definition
Clear
0
Minor, residual hypopigmentation/hyperpigmentation, no erythema 
or induration/papulation, no oozing/crusting.
Almost 
clear
1
Trace faint pink erythema, with barely perceptible 
induration/papulation and no oozing/crusting.
Mild
2
Faint pink erythema with mild induration/papulation and no 
oozing/crusting.
Moderate
3
Pink-red erythema with moderate induration/papulation with or 
without oozing/crusting.
Severe
4
Deep or bright red erythema with severe induration/papulation with 
oozing/crusting.
Source: Paller AS, Tom WL, Lebwohl MG, et al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal 
phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. J Am 
Acad Dermatol. 2016;75(3):494-503.e6.
 
              
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Appendix 5: Eczema Area and Severity Index (EASI)
Body region
EASI score
Head/Neck (H)
(E + I + Ex + L) x Area x 0.1
Upper limbs (UL)
(E + I + Ex + L) x Area x 0.2
Trunk (T)
(E + I + Ex + L) x Area x 0.3
Lower limbs (LL)
(E + I + Ex + L) x Area x 0.4
EASI = Sum of the above 4 body region scores
The degree of severity of each sign (E=erythema, I=induration/papulation, 
Ex=excoriation, L=lichenification) in each of the 4 body regions is evaluated based on a 
scale ranging from 0 to 3 (0: none; 1: mild; 2: moderate; 3: severe), with half points 
allowed.
Area (the affected body area) is defined as follows: 0=0%; 1=1-9%; 2=10-29%; 3=30-
49%; 4=50-69%; 5=70-89%; 6=90-100%. Among the four zones, trunk includes the 
genital area, and lower limbs include the buttocks. 
Source: Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M. The Eczema Area and Severity Index 
(EASI): assessment of reliability in atopic dermatitis. EASI Evaluator Group. Exp Dermatol. 2001;10(1):11-8.
 
              
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Appendix 6: Pruritus (Peak and Average) Numeric Rating Scale (PP NRS and AP 
NRS)
For average itch intensity: “On a scale of 0 to 10, with 0 being ‘no itch’ and 10 being the
‘worst itch imaginable’, how would you rate your itch overall during the previous 24 
hours?”
  No                                           
Worst 
  itch 
itch 
imaginable
For maximum itch intensity: “On a scale of 0 to 10, with 0 being ‘no itch’ and 10 being 
the ‘worst itch imaginable’, how would you rate your itch at the worst moment during the 
previous 24 hours?”
  No                                           
Worst 
  itch 
itch 
imaginable
0
1
2
3
4
5
6
7
8
9
10
0
1
2
3
4
5
6
7
8
9
10
 
              
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Appendix 7: Sleep Disturbance Numeric Rating Scale (SD NRS)
“On a scale of 0 to 10, with 0 being ‘no sleep loss related to the symptoms of atopic 
dermatitis’ and 10 being ‘I did not sleep at all due to the symptoms of atopic 
dermatitis’, how would you rate your sleep last night?”
  No                                           
    
I did 
  sleep 
    not sleep 
  loss
    
at all
0
1
2
3
4
5
6
7
8
9
10
 
              
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Appendix 13: Patient Global Assessment of Disease (PGAD)
Overall, how would you describe your atopic dermatitis right now?
Clear
Almost clear
Mild
Moderate
Severe
 
              
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Appendix 14: Patient Global Assessment of Treatment (PGAT)
How would you rate the way your atopic dermatitis responded to the study 
medication?
Poor
Fair 
Good
Very Good
Excellent
 
              
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Appendix 15: Pruritus Categorical Scale (PCS)
Please rate your overall itch during the previous 24 hours:
Score Definition
0
Absence of itch
1
Mild itch
2
Moderate itch
3
Severe itch
 
              
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Instructions for POEM scoring:
 
              
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Appendix 27: Subject Information and Interview Guide
 
              
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EVM-25004 Patient Interview Guide
Instructions and Questions
Note: Below is a semi-structured script. It is to be used as a guide only. The actual areas of 
conversation are fluid and may be discussed at moments different from the order appearing 
below. The interview will be approximately 60-90 minutes with breaks as needed. The interviewer 
may adapt the guide in order to cover the topics in the amount of time allotted for the session or 
in order to best elicit concepts from the participants.
Interviewer is responsible for pre-populating dates throughout interview guide and the scores in the 
PRO Data section.
Prior to the start of the discussion, please check that:
Patient has been deemed eligible.
Yes
No 
Patient has consented prior to the discussion.
Yes
No 
Introduction
Thank you for agreeing to take part in this interview. Before we get started: 
When did you first enroll in the trial? ___________________ (enter date)
[Interviewer: have date available for confirmation if patient cannot come up with exact date]
Are you still in the study, or did you withdraw early? 
If the patient stopped the study prematurely, please STOP the interview.
Number of visits completed: _______ (enter number of visits)
If the patient has not completed the week 16 visit, please STOP the interview.
As you read in the consent form at the beginning of the clinical trial, this session will be audio-
recorded. However, your name will not be linked with the recording, transcription, or your 
responses during the interview. Is it okay for me to record the conversation today?
 
              
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If yes, continue to “Background for All Interviews.” 
If no (interview to restate information that is present on the consent form):
Unfortunately, since you do not agree to the recording of this interview, you won’t be able to 
participate in the study. Thank you for your willingness to participate in the study.
Notes for the Reviewer
Objective of the Interview: The purpose of this interview is to assess the experience of AD and 
treatment benefit among adults and adolescents with AD in the US, the UK, Canada and Australia 
who have participated in the Galderma clinical Study RD.06.SPR.118161: a Phase III, multi-center, 
randomized, double-blind, placebo-controlled trial that assesses the efficacy and safety of 
nemolizumab (CD141152) in adults and adolescents with moderate-to-severe AD.
Interviews will be conducted within a two-week time window after completion of Week 16.
Written informed consent will be obtained by the clinical site personnel prior to the interviews. 
Results from these interviews will be documented in a study report and will not be part of the 
clinical study report (CSR). 
Exit Interviews: The specific aims of the exit interviews are to:
●
The perceived treatment effects and changes in a patient’s daily life since receiving the 
study treatment (placebo or Nemolizumab)
●
The meaning and importance of changes in different atopic dermatitis (AD) elements, 
including associated symptoms
●
The relevance and importance of pruritus and sleep disturbance (SD) concepts
●
To document treatment satisfaction and subjects’ experience with clinical trial 
participation
The interviews will last approximately 60 minutes and will be conducted in English by moderators 
trained by Evidera. 
 
              
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Overview of Interview Guide: 
The guide is divided into three parts: Part 1. Past and Current Experience of Atopic Dermatitis 
(AD) and Expectations of the Trial; Part 2. Changes During the Clinical Trial related to AD 
Symptoms and Sleep Disturbance; Part 3: Overall Perception of Treatment/Clinical Trial 
This is a semi-structured interview guide:

The discussions during the interview will be largely driven by how much the study 
participant is willing to share about their experience. Probes are included to encourage 
the participant when necessary.

The script in the interview guide is meant to help focus the content of the discussion. 

The actual areas of conversation are fluid and may be discussed at moments different from 
what appears below. 
Depending on the information emerging from the interview and timing, some questions may be 
modified or not asked by the interviewer. Detailed interviewer training will be provided prior to 
the first interview to ensure interviewers clearly understand the content of the guide and priority 
questions. Additional instruction may be added for interviewer training as the interviews 
progress.
In addition to this interview guide, interviewers will be provided with tables on AD symptoms and 
impact to complete during the interview. 
Interview Guide
Note: The following section includes key points or concepts that will be covered during the interview. 
This is not a script and the language and wording of the questions can be adjusted to the patient’s 
level of understanding and adapted where appropriate to keep the conversation fluid. If the 
participant does not understand a question, an example can be provided to facilate understanding. 
The definition of a meaningful change/ meaningful improvement is also provided.
In each section of the interview there are probes (or follow-up questions) to elicit additional 
information from patients. Some of these probes may not be asked depending on the flow or the 
timing of the interview.
The interview guide includes instructions for interviews in red. Questions in green are optional and 
will be asked if time permits. 
 
              
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Background for All Interviews [5 min]
Great, thanks again for taking the time to speak with me today. As explained in the form that you 
signed, we are talking to people who have atopic dermatitis (AD) with itching and are 
experiencing sleep disturbance (SD) who are involved in Galderma’s Phase III clinical trial. We are 
particularly interested in your experiences with your condition, your experiences in the trial, and 
your impressions of any changes you experienced throughout the study to date. 
All of your responses will be anonymous, meaning your name will not be linked with any of your 
responses. I want to hear about your experience so please share as much information as you feel 
comfortable with telling me. There are no right or wrong answers. 
Your participation is voluntary which means that you do not have to do this. You can skip any 
question you do not want to answer, and you can choose to stop the interview at any time. 
[U.S. PATIENTS ONLY] Although your participation is voluntary, please remember that you will be 
compensated for your time when you complete the interview. 
As a reminder, this interview may take up to 90 min to complete.
I want to remind you that the interview is being recorded. I will try not to use your name from the 
point I turn the recorder on, and I will ask you to try and not to use your name, the names of your 
friends, family members or medical doctors, name of the places you live, location of the hospital/ 
clinic etc. This will help to keep the interview anonymous.
Before we begin, let me suggest some things that will make our discussion more productive.

Your name and any other personally identifiable information will be kept as confidential 
and you won’t be able to be individually identified in any of the reports that result from 
the interviews. The information collected during the interview study will be used to help 
make important decisions about research on this medication in the future.

My role here is to ask questions and to listen. I’ll also be summarizing information at 
times. I’ll ask questions about issues related to your experience and I’ll move the 
discussion from one question to the next, to try to keep us on track so that we can finish 
within the scheduled time. 

I am not a medical doctor, so I am not qualified to give medical advice. I encourage you to 
follow-up with your regular doctor if you have any questions about your medication or 
condition after this interview.
 
              
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
[U.S. PATIENTS ONLY] When we are done with the interview, I will have the honorarium 
of $100. 

Please feel free to let me know if you need a break. You can ask me questions at any 
time.
What to Expect from the Interview:
This interview will occur in two parts. In Part 1, we will explore your experience of the disease 
(symptoms and impacts) prior to the clinical trial, along with treatments you’ve tried. In Part 2, 
we will explore your experiences with the study treatment that you received between baseline 
[date] and Week 16 [date], and any perceived effects or changes you’ve experienced as a result of 
treatment. We will explore what aspects are most meaningful to you and ask you to rate the 
significance of any change.
Any questions before we begin? 
I will now start audio-recording.
Begin Recorder: This is participant ID [insert ID number from Clinical Trial here] for Study EVM-
25004 on [Date]. Do I have your permission to record this interview? Affirmative verbal response 
required. And can you please confirm that you completed the informed consent form? Affirmative
verbal response required.
 
              
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Part 1. Past and Current Experience of Atopic Dermatitis (AD) 
and Expectations of the Trial
First, I would like to ask you questions about your past and current experiences with AD and related 
symptoms and impacts. We’ll then discuss the perceived changes as a result of the clinical trial in 
Part 2 of this interview.
1.1 Past symptoms of AD [15 min]
Before you started the current study, what are the symptoms you experienced that you think may 
be related to your AD? 
[Interviewer]: Please make sure patient is describing symptoms BEFORE study entry, 
within the 2 weeks prior to starting the study. Please provide the patient with the date 
of the baseline visit and ask them to recall experience BEFORE baseline. Please ask 
them to recall any significant personal, work or other event happened at this period to 
help them to recall back and anchoring their answer.
We are only interested in the 2 weeks prior to the start of the study and do not need 
to assess a lifetime of symptoms.
Let the patient spontaneously report symptoms first, and then probe. Obtain the list of 
symptoms first, then go into more detail (i.e. frequency, duration, etc.) for each 
symptom individually. Please enter symptoms the patient indicated that they had 
PRIOR to the current study in Table 1.
For each symptom reported by the patient, please ask if the symptom severity changed since the 
patient started the clinical trial? [Optional]
For each symptom endorsed by the patient:

Frequency: How often did you experience this [symptom] before the trial?

Location: Where on your body did you experience this [symptom]?

Duration: Did the [symptom] come and go or was it present all the time?
o
If the [symptom] comes and goes: How long did the [symptom] last for?

Symptom severity:
 
              
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o
On a scale of 0 to 10, where 0=not severe at all and 10= extremely severe, how 
bad or severe was this [symptom] when you began the study?
o
Using the same scale, how severe was this symptom for you at Week 16?
[Interviewer]: Please be ready to remind the patient of their Week 16 visit date. During 
this interview we are only interested in the patients experience before the trial and 
between Baseline and Week 16.
Of these symptoms you have mentioned (such as…list 3-4 symptoms mentioned – see Table 1), 
which of the symptoms that you experienced would you call the worst one? 
[Interviewer]: Let the patient spontaneously report what they feel is the worst 
symptom, and then probe if needed. 
 
              
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1.2 Past impact of AD Symptoms on Daily Lives [10 min]
1.
Before you started the current study, how did the ADs symptoms affect your daily life? 
Probes: sleep disturbance, daily activities, leisure activities, rrelationships affected, 
emotions, other?
[Interviewer]: Please make sure patient is describing impacts BEFORE study entry, 
within 2-weeks of starting the study. Please provide the patient with the date of the 
baseline visit and ask them to recall experience BEFORE baseline. Please ask them to 
recall any significant personal, work or other event happened at this period to help 
them to recall back and anchoring their answer.
We are only interested in the 2 weeks prior to the start of the study and do not need 
to assess a lifetime of impacts.
Let the patient spontaneously report impacts first, and then probe based on table. 
Obtain the list of impacts first, then go into more detail (i.e. changed, resolved, etc.) 
for each impact individually. Please enter impacts the patient indicated that they had 
PRIOR to the current study in Table 2.
If subject states multiple categories under the main impact concept, no need to ask 
follow-up for each sub-category if more than 5 different impacts are reported. Only 
focus on the main category. If not many impacts are reported, you may have time to 
go through each sub-category. 
2.
For each impact reported by the patient, please ask if the impact changed/solved since 
the patient started the clinical trial? Yes/ no 
[Interviewer]: Please make sure patient is describing change between Baseline and 
Week 16 only. 
3.
For each impact reported by the patient, please ask if that impact was related to itch or 
other symptom? if other, which one?
4.
Of all the impact you have been talking about (such as…list 3-4 impacts mentioned – see 
Table 2), which one would you say is the worst one? Why?
[Interviewer]: Let the patient spontaneously report what they feel is the worst impact, 
and then probe if needed. 
 
              
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1.3 Experience of AD Treatment [5 min] [Optional]
Now I would like to ask you some questions about previous treatments you have had for AD PRIOR 
to enrollment in the trial.
[Interviewer]: Only probe on most recent treatments. We do not need a 
comprehensive list of all treatments ever used. 
1.
Prior to your involvement in the clinical trial did you use any treatments specifically for 
your AD?
o
If so, what were they? How much did they help to manage your itch? How much 
did they help to manage your sleep disturbance?
o
What would you look for in an ideal treatment?
o
What factors do you consider when selecting a course of treatment? What type 
of things do you take into considerations when you are deciding how successful a 
treatment is or could be?
1.4 Decision and Expectations of the Trial [5 min]
I would now like to ask you some questions about your decision to enroll in this trial.
1.
What made you decide to enroll in Galderma’s clinical trial?
2.
Did you have any expectations when entering the clinical trial? If so, what were they?
3.
Did you have any concerns when entering the clinical trial? If so, what were they?
4.
What were you hoping for in terms of a change in your itch from the study treatment?
5.
What were you hoping for in terms of change in your sleep disturbance from the study 
treatment?
 
              
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Part 2. Changes During the Clinical Trial related to AD Symptoms 
and Sleep Disturbance
2.1 Exploration of NEW Symptoms [5 min]
So far, we have been talking about symptoms you had before the study. Now, I would like to know 
about any NEW SYMPTOMS you had since the being in this study that were new for you (i.e. had 
not experienced before the study). Can you describe the new symptoms? 
[Interviewer]: Please make sure you clarify with the patient that we are only interested 
in new symptoms from Baseline to Week 16. Please remind the baseline and week 16 
dates if necessary.
Let the patient spontaneously report new symptoms and then probe. Obtain the list of 
new symptoms first, then go into more detail (i.e. frequency, duration, etc.) for each 
symptom individually. Enter NEW symptoms the patient indicated that they had during 
the study up to Week 16 in Table 3.
For each new symptom (Table 3)
1.
For each symptom endorsed:
a.
When this [new symptom] was first noticed in the trial?
b.
Frequency: How often did you experience [symptom] during the trial?
c.
Location: Where on your body did you experience [symptom]?
d.
Duration: Did the [symptom] come and go or was it present all the time?
e.
If [symptom] comes and goes: How long did the [symptom] last for?
f.
Severity: 
i.
On a scale of 0 to 10, where 0=not severe at all and 10= extremely severe, how 
bad, severe was this symptom when it was at its worst during the study (Baseline 
to Week 16).
ii.
Using the same scale, how severe is this symptom for you at Week 16?
 
              
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a.
What specifically did you notice? Probe for the nature of the change 
b.
When during the trial did you first notice the change? Probe weeks into the trial (up 
to Week 16)
i.
Please give us some examples of how you noticed the change? What made you 
realize there was a change? 
c.
Has the change stayed consistent during the trial? 
i.
If no: Did it come and go? If so, how long did it stay? Did it disappear or 
increase/decrease?)
d.
Rating of the change (between Baseline to Week 16) using a Global Assessment of 
Change (GAC) scale: “much worse,” “a little worse,” “the same,” “a little better,” , or 
“much better”
i.
Those who reported worsening on GAC, ask: Is this increase in [symptom] a 
meaningful or important change for you?’ (Yes/No)
[Interviewer]: If the patient has difficulties understanding what a meaningful change 
means, please tell them that this is a change, positive or negative, that results in a 
change in their life, in the way they feel, function and their capacity to do things.
o
In what ways? Can you provide some examples? Probe for 
examples/participant rationale 
[Interviewer]: Please probe for the following examples. If yes, was the change good or 
bad? How big was that change? Was the amount of change important for you? How 
did it affect your life? 
ii.
Those who reported improvement on GAC, ask: Is this decrease in [symptom] a 
meaningful change for you? (Yes/No)
o
In what ways? Can you provide some examples? 
 
              
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[Interviewer]: Please report the impacts the patient indicated that they had changed 
since they started the clinical trial or during the trial (up to Week 16) in the Table 6.
[Interviewer]: for each impact change endorsed, please probe for improvement and 
worsening when appropriate
For each impact endorsed: 
a.
What specifically did you notice? Probe for the nature of the change
b.
When during the trial did you first notice the change? Probe weeks into the trial
i.
What are some examples of how you noticed the change? What made you realize 
there was a change? 
c.
Has the change stayed consistent during the trial? 
i.
If no: Did it come and go? If so, how long did it stay? Did it disappear or 
increase/decrease?)
d.
Rating of the change using a GAC scale: “much worse”, “a little worse”, “the same”, “a 
little better”, or “much better”
i.
Those who reported worsening on GAC then ask: Is this increase in [impact] a 
meaningful change you?’ (Yes/No)
[Interviewer]: If the patient has difficulties understanding what a meaningful 
change means, please tell them that this is a change, positive or negative, that 
results in a change in their life, in the way they feel, function and their capacity to 
do things.
o
In what ways? Can you provide some examples? Probe for examples/participant 
rationale 
 
              
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[Interviewer]: Please probe for the following examples. If yes, was the change good 
or bad? How big was that change? Was the amount of change important for you? 
How did it affect your life?
ii.
Those who reported improvement on GAC were then asked: Is this decrease in 
[impact] a meaningful change for you? (Yes/No)
o
In what ways? Can you provide some examples? Probe for examples/participant 
rationale 
 
              
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2.5 PRO Data [10 min]
At the beginning of the trial and throughout the trial you completed a few sleep questionnaires, 
including the Sleep Diary. For the next phase of the interview, I would like to explore with you 
which changes on the sleep diary questions would matter to you.
Thank you. For the next phase of the interview, I would like to explore with you which changes in 
the sleep diary questions would matter to you.
Sleep Diary
Item 3: 
The item 3 of the sleep diary asks about the time it takes you to fall asleep.
Before entering in the clinical trial, how long did it take you to fall asleep during a typical 
nighttime sleep? 
a.
Were these difficulties usually related to AD symptoms or other things?
iii.
What would be the smallest improvement (in time gained of sleep) that would be 
meaningful or important to you? Why?
[Interviewer]: If the patient has difficulties understanding what a meaningful 
improvement means, please tell them that this is an improvement that results in a 
positive change in their life (emotions or capacity to do things).
b.
What would that change or improvement of [XXX improvement reported by the 
patient] in your sleep mean for you in terms of quality of sleep?
Item 4: 
The item 4 of the sleep diary asks about the number of times you wake up during the night, due 
to the symptoms of atopic dermatitis (for example itching, burning). 
Before entering in the clinical trial, how many times did you usually woke up due to AD symptoms 
during a typical nighttime sleep? 
iv.
What would be the smallest improvement (in number of awakenings due to AD) that 
would be meaningful or important to you? Why?
 
              
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[Interviewer]: If the patient has difficulties understanding what a meaningful 
improvement means, please tell them that this is an improvement that results in a 
positive change in their life (emotions or capacity to do things).
c.
What would that change or improvement of [XXX improvement reported by the 
patient] in your sleep mean for you in terms of quality of sleep?
Item 5
The item 5 of the diary asks about the total time your nighttime awakenings due to AD symptoms 
last.
d.
Before entering in the clinical trial, how long did your awakenings related to AD 
symptoms usually last during a typical nighttime sleep? 
e.
What would be the smallest improvement (in time gained of sleep) that would be 
meaningful or important to you? Why? 
[Interviewer]: If the patient has difficulties understanding what a meaningful 
improvement means, please tell them that this is an improvement that results in a 
positive change in their life (emotions or capacity to do things).
f.
What would that change or improvement of [XXX improvement reported by the 
patient] in your sleep mean for you in terms of quality of sleep?
Items 6/7:
The sleep diary also asks about the awakenings related to other things (for example to drink 
water, to go to the bathroom). 
g.
Based on your experience, can you please describe the differences between 
awakenings related to AD symptoms and awakenings related other things?
h.
Does the experience of a nighttime awakening related to AD and the experience a 
nighttime awakening related to other things mean the same for you? Why or why 
not?
 
              
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[Interviewer]: If the patient has difficulties understanding this question, ask them 
when they wake up during the night because of their AD, if the duration and 
discomfort of this awakening is the same as when they wake up during the night to 
drink, go to the bathroom or for other things not related to their AD.
Part 3: Overall Perception of Treatment/Clinical Trial
3.1 Treatment Perception [5 min]
Now, switching gears to your general impressions of the treatment between Baseline and Week 16.
1.
Overall, what did you like and what did you not like about the treatment?
2.
Overall, would you say the treatment you received helped you in the management of 
your condition?
a.
If yes, why?
b.
If no, why?
3.
Overall, was the treatment able to meet your expectations? 
4.
Overall, how satisfied were you with your treatment? 
a.
On a scale of 0 to 10, please rate how satisfied you currently are with the study 
treatment. A zero would mean you are not satisfied at all and a 10 mean you are 
extremely satisfied. 
5.
What would need to change to consider the treatment successful? 
6.
How does the treatment you received in the clinical trial compare to the treatment(s) 
you took previously? Probe on differences in efficacy and preferences for mode of 
administration
7.
Did you experience any effects/changes from the treatment that you did not expect?
8.
Based on your experience, would you recommend this treatment to others with itch and 
sleep disturbance?
a.
If yes, why?
 
              
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b.
If no, why?
3.2 Trial Perception [Optional] [5 min]
And finally, I would like to ask about your general thoughts on the clinical trial overall.
1.
Overall, what did you think about the clinical trial? Probe on experience with study visits, 
study procedures, study assessments (frequency and length of patient questionnaires)
2.
Did being a part of the trial impact your day-to-day life? Probe for examples; Probe about 
the nature, extent, frequency, and duration of impacts 
3.
Anything else you would like to share that I did not ask about related to your experience 
with AD, itch, sleep disturbance, or the clinical trial? 
Thank you for your time and for all the insightful information and experiences you have shared 
with us today. Answer any questions or provide information, as needed about the payment card.
 
              
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INVESTIGATOR SIGNATURE PAGE
Protocol Title:
A Randomized, Double-Blind, Placebo-Controlled Study to Assess the 
Efficacy and Safety of Nemolizumab (CD14152) in Subjects with 
Moderate-to-Severe Atopic Dermatitis 
Protocol Number:
RD.06.SPR.118161
Confidentiality and Current GCP Compliance Statement
I, the undersigned, have reviewed this protocol (and amendments), including appendices,
and I will conduct the study as described in compliance with this protocol (and 
amendments), GCP, and relevant ICH guidelines.
Once the protocol has been approved by the IEC/IRB, I will not modify this protocol 
without obtaining prior approval of Galderma S.A./Galderma R&D, LLC and of the 
IEC/IRB. I will submit the protocol amendments and/or any ICF modifications to 
Galderma S.A./Galderma R&D, LLC and the IEC/IRB, and approval will be obtained 
before any amendments are implemented.
I understand that all information obtained during the conduct of the study with regard to 
the subjects’ state of health will be regarded as confidential. No subjects’ names will be 
disclosed. All subjects will be identified by assigned numbers on all CRFs, laboratory 
samples, or source documents forwarded to the sponsor. Clinical information may be 
reviewed by the sponsor or its agents or regulatory agencies. Agreement must be obtained 
from the subject before disclosure of subject information to a third party.
Information developed in this clinical study may be disclosed by Galderma 
S.A./Galderma R&D, LLC to other clinical investigators, regulatory agencies, or other 
health authority or government agencies as required.
Investigator Signature
Date
Printed Name
Title
Institution
Study Center Number
 
              
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SAP_001.pdf: 
 
 
 
This document is confidential 
SAP Version: Final Version 1.0, 09-Nov-2022 
Controlled Document ID: 3903A.01, Effective Date 31-Aug-2020 
Filing requirements: TMF 
Page 1 of 124 
Statistical Analysis Plan for Interventional Studies 
 
 
SAP Text Version Number: Final Version 1.0 
SAP Text Date: (DD-Mmm-YYYY): 09-Nov-2022 
 
Sponsor Name: Galderma Research & Development, LLC 
 
Protocol Number: RD.06.SPR.118161 
 
Protocol Title: A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and 
Safety of Nemolizumab (CD14152) in Subjects with Moderate-to-Severe Atopic Dermatitis 
 
Protocol Version and Date (DD-Mmm-YYYY): Version 8.0 (4-Nov-2021) 
 
Syneos Health Project Code 1008782 
 
Authors: 
 
 
 
 
 
 
Notice of Confidential and Proprietary Information: 
The information contained in this document is confidential belonging to Galderma Research & 
Development, LLC. Acceptance of this document constitutes agreement by the recipient that no 
information contained herein will be published or disclosed without prior written authorization from an 
official of Galderma Research & Development, LLC. However, this document may be disclosed to 
appropriate Institutional Review Board and Ethics Committees or duly authorized representatives of a 
national regulatory authority under the condition that they are requested to keep it confidential. In the 
event of an actual or suspected breach of this obligation, Syneos Health should be notified promptly. 
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Statistical Analysis Plan for Interventional Studies
Sponsor: Galderma Research & Development, LLC; Protocol No.: RD.06.SPR.118161 
 
This document is confidential. 
SAP Version: Final Version 1.0, 09-Nov-2022 
Controlled Document ID: 3903A.01, Effective Date 31-Aug-2020 
Filing requirements: TMF 
Page 13 of 124 
 
All placebo-treated subjects (i.e., subjects in group 2 from the Initial Period) who responded to placebo 
during the Initial Period will continue to receive placebo Q4W in the Maintenance Period. Beginning at 
Week 16, subjects in group 1A will receive active (i.e., nemolizumab [CD14152]) study drug injections 
Q4W up to Week 44. Subjects in group 1B will receive active (i.e., nemolizumab [CD14152]) study drug 
injections Q8W, with placebo at alternating visits to maintain the blind. Group 1B subjects will receive the 
last active study drug injection at Week 40 (final injection at Week 44 will be placebo). Group 1C subjects 
will receive placebo Q4W (i.e., through Week 44). 
Clinical assessments will occur according to the schedule of assessments through the Week 48 visit. 
Subjects should continue the same background topical therapy used in the Initial Period leading up to the 
Week 16 visit, including tapering or complete cessation (no use), if applicable. Throughout the 
Maintenance Period, adjustments to background topical therapy, as determined by the investigator, are 
 Subjects who complete the Week 48 visit may be 
eligible to enroll into the LTE study (Protocol 118163). The Follow-up visit is not required for subjects who 
participate in the LTE study. Subjects who discontinue the Maintenance period prematurely should 
complete an Early termination (ET) visit and a Follow-up visit 12 weeks after the last study drug injection. 
Follow-up 
The Follow-up visit will be conducted 12 weeks after the last study drug injection for subjects who decline 
or are not eligible to enter the LTE study. The Follow-up visit is not required for subjects who participate in 
the LTE study. (Twelve weeks corresponds to approximately 5 half-lives when nemolizumab 30 mg is 
dosed subcutaneously Q4W.) 
Figure 4-1: Study Visit Schema 
 
Abbreviations: BL=Baseline; q4wk=every 4 weeks; q8wk=every 8 weeks; W=week. 
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Statistical Analysis Plan for Interventional Studies
Sponsor: Galderma Research & Development, LLC; Protocol No.: RD.06.SPR.118161 
This document is confidential. 
SAP Version: Final Version 1.0, 09-Nov-2022 
Controlled Document ID: 3903A.02, Effective Date 31-Aug-2020 
Filing requirements: TMF 
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Statistical Analysis Plan for Interventional Studies
Sponsor: Galderma Research & Development, LLC; Protocol No.: RD.06.SPR.118161 
This document is confidential. 
SAP Version: Final Version 1.0, 09-Nov-2022 
Controlled Document ID: 3903A.02, Effective Date 31-Aug-2020 
Filing requirements: TMF 
Page 37 of 124 
Week 48
337
>=323
NA
>=281 except for PIQs
* PIQs assessment is available during Initial period only. Visit window after Week 16 will not be applicable for PIQs. 
Analysis visit of diary (ePRO) data will be defined depending on the data collection as below. 
For the diary data at post-baseline visit, only the diary data assessed within the timeframe below (+1 hour 
to end time in spec) will be considered for analysis. If >1 diary recorded on a day (within window), only 
one of them to take for analysis (i.e. latest one for evening diary, earliest one for morning diary). 
 
Evening assessment (PP/AP NRS, Topical medication, PCS) recorded from 17:00:00 to 00:59:59 
 
Morning assessment (SD NRS, morning sleep diary) recorded from 5:00:00 to 17:59:59 
Consecutive daily assessment: 
For the evening assessments (PP NRS, AP NRS) during Initial Period, the daily data collected up to 
Week 16 will be classified into analysis visits considering the data during the 7 days immediately 
preceding the target study day of analysis visit. Similarly, for the morning assessment (SD NRS, morning 
sleep diary) during Initial Period, the 7 days data up to the target study day will be classified into analysis 
visit. Details of the analysis visit window are in the table below. Only the data belongs to Initial Period will 
be considered for classifying the analysis visit in Initial Period. 
Table 8-2: Analysis Visit Window for Evening and Morning Assessments during Initial Period 
Analysis Visit 
Target Study Day 
of Analysis Visit 
Visit Window for evening 
assessment (PP NRS, AP 
NRS, Topical Medication) 
Visit Window for morning 
assessment (SD NRS, 
morning sleep diary) 
Baseline* 
1 
-7 to -1 
-6 to 1 
Week 1 
8 
1 to 7 
2 to 8 
Week 2 
15 
8 to 14 
9 to 15 
Week 3 
22 
15 to 21 
16 to 22 
Week 4 
29 
22 to 28 
23 to 29 
Week 5 
36 
29 to 35 
30 to 36 
Week 6 
43 
36 to 42 
37 to 43 
Week 7 
50 
43 to 49 
44 to 50 
Week 8 
57 
50 to 56 
51 to 57 
Week 9 
64 
57 to 63 
58 to 64 
Week 10 
71 
64 to 70 
65 to 71 
Week 11 
78 
71 to 77 
72 to 78 
Week 12 
85 
78 to 84 
79 to 85 
Week 13 
92 
85 to 91 
86 to 92 
Week 14 
99 
92 to 98 
93 to 99 
Week 15 
106 
99 to 105 
100 to 106 
Week 16** 
113 
106 to 112 before dosing 
107 to 113 
* if there are less than 4 days non-missing data available within window, the lower bound of interval will be extended 
up to 7 additional days to obtain 4 days non-missing data for Baseline weekly score calculation. The timeframe 
window will not be considered. 
** if <4 days non-missing data within Week 16 window, the upper bound will be extended first up to +5 days to obtain 
4 non-missing data. If still <4 non-missing data after extending the upper bound, the lower bound will be extended 
again up to +5 days to obtain 4 days non-missing data. For evening assessment, only the data before Week 16 
dosing (or re-randomization if missing Week 16 dosing) will be considered for Initial Treatment Period analysis. 
10-Nov-2022 00:00:00
CD14152.SPR118161.SAP.V01
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Statistical Analysis Plan for Interventional Studies
Sponsor: Galderma Research & Development, LLC; Protocol No.: RD.06.SPR.118161 
This document is confidential. 
SAP Version: Final Version 1.0, 09-Nov-2022 
Controlled Document ID: 3903A.02, Effective Date 31-Aug-2020 
Filing requirements: TMF 
Page 38 of 124 
In case topical medication used (daily evening assessment throughout the study), 7 days immediately 
preceding the target study day will be considered to define analysis visit during the study. The same 
window with evening assessment (PP NRS, AP NRS) in Table 8-2 will be used for Initial Period. For 
Maintenance Period, the target study day of Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, 
Week 44 and Week 48 will be Day 141, Day 169, Day 197, Day 225, Day 253, Day 281, Day 309, and 
Day 337. 
initial period. The extended timeframe (+1 hour to end time) to be considered. 
Intermittent daily assessment before the visit: 
For the evening assessments (PP NRS and AP NRS during Maintenance Period, and PCS assessment), 
the 7 days immediately preceding the actual subject visit date will be classified into the analysis visit. i.e., 
from 
bject visit date  7 
 
Similarly, for the morning 
assessments (SD NRS, morning sleep dairy), the 7 days data from 
 
 will be classified into the analysis visit. In maintenance period, the diary data will 
analysis visit window/timeframe and before dosing. 
 
In case of missing/skipped visit, unscheduled or early termination visit, the diary data will be windowed 
based on the study day (see Tables 8-3 and 8-4). If a subject missed/skipped a visit due to any reason 
(e.g., skipped a visit due to COVID-19), the diary data which have been reported during that time will be 
mapped to the analysis visit based on the study day and 7 days consecutive data will be classified into 
the analysis visit as in the tables below. For the unscheduled or early termination visit data, the same 
approach will be applied to window the data into analysis visit. 
 
In case of evening diary (e.g., PP/AP NRS), the data within analysis visit window but after dosing on the 
clinic visit date will not be used for weekly score calculation at the corresponding analysis visit. 
Table 8-3: Analysis Visit Window for Missing/Skipped Visit, Unscheduled or Early termination Visit for 
PP/AP/SD NRS and Sleep Diary 
Analysis Visit 
Target Study Day of 
Analysis Visit 
Visit Window for 
evening assessment 
(PP NRS, AP NRS)* 
Visit Window for morning 
assessment (SD NRS, 
morning sleep diary) 
Week 24 
169 
162 to168 
163 to 169 
Week 32 
225 
218 to 224 
219 to 225 
Week 40 
281 
274 to 280 
275 to 281 
Week 48 
337 
330 to 336 
331 to 337 
* for evening diary, only the data before dosing on the clinic visit date will be considered for analysis. 
Table 8-4: Analysis Visit Window for Missing/Skipped Visit, Unscheduled or Early Termination Visit for 
PCS Assessments 
Analysis Visit 
Target Study Day of 
Analysis Visit 
Visit Window for PCS 
Baseline 
1 
-7 to -1 
Week 8 
57 
50 to 56 
Week 15 
106 
99 to 105 
Week 16* 
113 
106 to 112 before dosing 
10-Nov-2022 00:00:00
CD14152.SPR118161.SAP.V01
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Approved






















Statistical Analysis Plan for Interventional Studies
Sponsor: Galderma Research & Development, LLC; Protocol No.: RD.06.SPR.118161 
This document is confidential. 
SAP Version: Final Version 1.0, 09-Nov-2022 
Controlled Document ID: 3903A.02, Effective Date 31-Aug-2020 
Filing requirements: TMF 
Page 49 of 124 
10-Nov-2022 00:00:00
CD14152.SPR118161.SAP.V01
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Approved
CCI




Statistical Analysis Plan for Interventional Studies
Sponsor: Galderma Research & Development, LLC; Protocol No.: RD.06.SPR.118161 
This document is confidential. 
SAP Version: Final Version 1.0, 09-Nov-2022 
Controlled Document ID: 3903A.02, Effective Date 31-Aug-2020 
Filing requirements: TMF 
Page 51 of 124 
10-Nov-2022 00:00:00
CD14152.SPR118161.SAP.V01
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Approved
CCI








Statistical Analysis Plan for Interventional Studies
Sponsor: Galderma Research & Development, LLC; Protocol No.: RD.06.SPR.118161 
This document is confidential. 
SAP Version: Final Version 1.0, 09-Nov-2022 
Controlled Document ID: 3903A.02, Effective Date 31-Aug-2020 
Filing requirements: TMF 
Page 55 of 124 
10-Nov-2022 00:00:00
CD14152.SPR118161.SAP.V01
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Approved
CCI


























Statistical Analysis Plan for Interventional Studies
Sponsor: Galderma Research & Development, LLC; Protocol No.: RD.06.SPR.118161 
This document is confidential. 
SAP Version: Final Version 1.0, 09-Nov-2022 
Controlled Document ID: 3903A.02, Effective Date 31-Aug-2020 
Filing requirements: TMF 
Page 68 of 124 
study drug, TEAE leading to permanent discontinuation of study drug, TEAE leading to 
permanent discontinuation from study, TEAE of special interest, TEAE leading to death, TEAE 
related to study drug leading to death. For the summary of Follow-up period, the summaries of 
provided. 
 
TEAEs by System Organ Class and Preferred Term 
 
Serious TEAEs by System Organ Class and Preferred Term 
 
TEAEs by System Organ Class, Preferred Term and Maximum Severity 
 
Severe TEAEs by System Organ Class and Preferred Term 
 
TEAEs Leading to Permanent Discontinuation of Study Drug by System Organ Class and 
Preferred Term, which is only for Treatment period. No summary of Follow-up period. 
 
TEAEs occurred in >=5% of subjects by System Organ Class and Preferred Term 
 
TEAEs occurred in >=5% of subjects by Preferred Term 
For overall study period which includes all periods (initial, maintenance and follow-up), the following 
summary tables will also be presented and repeated for all TEAEs (all causalities) and study drug related 
TEAEs. 
 
Overall Summary of TEAEs 
 
TEAEs by System Organ Class and Preferred Term 
The overall study period summary will be presented by 4 treatment groups (Nemolizumab 30mg Q4W, 
Nemolizumab 30mg Q4W to Q8W, Nemolizumab 30mg Q4W to Placebo, and Placebo). Nemolizumab 
30mg Q4W includes all subjects in the population who received Nemolizumab 30mg in Initial Period or 
who received Nemolizumab 30mg Q4W continuously during Initial and Maintenance Periods. Similarly, 
Placebo includes all subjects in the population who received Placebo in Initial Period or who received 
Placebo continuously during Initial and Maintenance Periods. 
For the subset of subjects with COVID-19 infection, the following summary tables will be provided 
additionally and it will be repeated for all TEAEs and Study drug related TEAEs, separately. 
 
Overall summary of TEAEs 
 
TEAEs by System Organ Class and Preferred Term 
 
Serious TEAEs by System Organ Class and Preferred Term 
 
TEAEs of Special Interest by Category, System Organ Class and Preferred Term 
A separate summary below for TEAEs of Special Interest will be provided by periods (initial, maintenance) 
and repeated for all TEAEs (all causalities) and Study drug related TEAEs.  
 
Overall Summary of TEAEs of Special Interest 
 
TEAEs of Special Interest by Category, System Organ Class and Preferred Term 
 
TEAEs of Special Interest by Category, System Organ Class, Preferred Term and Maximum 
Severity 
Adjudicated events will also be summarized as below by periods (initial, maintenance) and repeated for 
all TEAEs (all causalities) and Study drug related TEAEs. 
10-Nov-2022 00:00:00
CD14152.SPR118161.SAP.V01
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Approved




Statistical Analysis Plan for Interventional Studies
Sponsor: Galderma Research & Development, LLC; Protocol No.: RD.06.SPR.118161 
This document is confidential. 
SAP Version: Final Version 1.0, 09-Nov-2022 
Controlled Document ID: 3903A.02, Effective Date 31-Aug-2020 
Filing requirements: TMF 
Page 70 of 124 
elevated to > 2.5 × ULN), albumin, total protein, uric acid, sodium, potassium, calcium, chloride, 
glucose, urea, total cholesterol, triglycerides, low-density lipoprotein (LDL), and high-density 
lipoprotein (HDL). Follicle-stimulating hormone (FSH) will be collected for postmenopausal subjects. 
 
Urinalysis: pH, glucose, ketones, blood, protein, leukocytes, nitrites, bilirubin, urobilinogen, and 
specific gravity. 
Laboratory assessments are performed at Screening, Baseline, Week 8, Week 16, Early Termination and 
Follow-up during the Initial Period. 
Laboratory assessments are performed at Week 32, Week 48, Early Termination and Follow-Up during 
the Maintenance Period. 
Hematology and chemistry laboratory data (absolute values and change from Baseline; and change from 
Week 16 for Maintenance Period) will be summarized as continuous variables (scheduled visits only) for 
the Initial Period and the Maintenance Period. Urinalysis laboratory data will be summarized by visit 
(scheduled visit only). Last post-baseline, worst post-baseline and maximum post-baseline results will 
also be included and will include unscheduled visits in the derivation. And worst post-baseline value will 
be defined as the highest or lowest value relative to the reference range during the respective treatment 
Period. 
Shift tables will be generated using the reference ranges (Low, Normal, High and Missing) for hematology 
and chemistry laboratory data. The number and percentage of subjects shifting from reference ranges 
between Baseline and each visit (scheduled visits only) will be summarized for the Initial Period and the 
Maintenance Period. In addition, shift table from Week 16 will be provided for the Maintenance Period. 
Last, worst and maximum post baseline values will also be included in the shift tables and will include 
unscheduled visits in the derivation. Worst post baseline value will be defined as the highest or lowest 
value relative to the reference range. 
Summary of the number and percentage of subjects who met criteria of potential clinically significant (CS) 
value will be summarized (scheduled visits only) for hematology and chemistry laboratory data. Last, 
worst and maximum post-baseline results will also be included in the summary. Potentially CS ranges for 
adult and adolescent are listed in sections 22.3 and 22.4. 
For statistical and graphical summaries of the laboratory tests, values below or above the limit of 
 detection minus 1% for values below 
the lower limit and are substituted with the upper limit of detection plus 1% for values above the upper 
 
shown including the < or > sign. 
Distribution of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase 
(ALP), Total bilirubin and Creatinine Phospokinease (CPK) will be displayed graphically as boxplot by 
treatment group for each scheduled visit and the maximum post-Baseline (including unscheduled visits in 
the derivation) values for the Initial Period and the Maintenance Period. 
By-subject listing will be presented for all laboratory data. By-subject listing for subjects with at least one 
abnormal result (out of reference range) will be provided for hematology and clinical chemistry. By-subject 
listing for subjects with at least one potentially CS result will be provided for hematology and clinical 
chemistry. 
10-Nov-2022 00:00:00
CD14152.SPR118161.SAP.V01
1.0
Approved


















Statistical Analysis Plan for Interventional Studies
Sponsor: Galderma Research & Development, LLC; Protocol No.: RD.06.SPR.118161 
This document is confidential. 
SAP Version: Final Version 1.0, 09-Nov-2022 
Controlled Document ID: 3903A.02, Effective Date 31-Aug-2020 
Filing requirements: TMF 
Page 79 of 124 
If the categories are not ordered (e.g., Medical History, Reasons for Discontinuation from the 
Study, etc.), then only those categories for which there is at least 1 subject represented are 
included. 
 
An Unknown or Missing category are added to each parameter for which information is not 
available for 1 or more subjects. 
 
Unless otherwise specified, the estimated mean, median, Q1 and Q3 for a set of values are printed 
out to 1 more significant digit than the original values, and standard deviations are printed out to 2 
more significant digits than the original values. The minimum and maximum should report the same 
significant digits as the original values. Missing descriptive statistics or p-values which cannot be 
estimated are 
-  
 
Percentage values are printed to one decimal place, in parentheses with no spaces, one space 
after the count (e.g., 7 (12.8%), 13 (5.4%)). Pre-determine how to display values that round down 
to 0.0. A common convention is to display as '<0.1', or as appropriate with additional decimal 
places. Unless otherwise noted, for all percentages, the number of subjects in the analysis 
population for the treatment group who have an observation will be the denominator. Percentages 
after zero counts should not be displayed and percentages equating to 100% are presented as 
100%, without decimal places. 
 
Tabular display of data for medical history, prior/concomitant medications, and all tabular displays of 
adverse event data are presented by the body system, treatment class, or SOC. The body system, 
drug class and SOC are displayed in alphabetically order. Within body system, drug class and SOC, 
preferred term will be display in descending frequency. If incidence for more than 1 preferred term is 
identical, they should then be sorted alphabetically. 
 
P-values are presented with 4 decimal places. If the p-value is less than 0.0001, it will be 
presented as <0.0001. If the p-value is returned as >0.9999, it is presented as >0.9999. 
 
The percentage of subjects is normally calculated as a proportion of the number of subjects 
assessed in the relevant treatment group (or overall) for the analysis population presented. 
However, careful consideration is required in many instances due to the complicated nature of 
selecting the denominator, usually the appropriate number of subjects exposed. Describe details 
of this in footnotes or programming notes. 
 
For categorical summaries (number and percentage of subjects) where a subject can be included 
in more than one category, describe in a footnote or programming note as needed if the subject 
are included in the summary statistics for all relevant categories or just 1 category and the criteria 
for selecting the criteria. 
 
Where a category with a subheading (such as system organ class) has to be split over more than 
of each subsequent page. The 
overall summary statistics for the subheading should only be output on the first relevant page. 
17.2.5.3. 
Listing Conventions 
 
Listings will be sorted for presentation in order of subject number, visit/collection day, and 
visit/collection time. 
 
-
- 
whichever is appropriate. 
 
Dates are printed in SAS DATE9
are represented on subject listings as dashes (--JUL2000). Dates that are missing because they 
 
10-Nov-2022 00:00:00
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1.0
Approved


















































































Statistical Analysis Plan for Interventional Studies
Sponsor: Galderma Research & Development, LLC; Protocol No.: RD.06.SPR.118161 
This document is confidential. 
SAP Version: Final Version 1.0, 09-Nov-2022 
Controlled Document ID: 3903A.02, Effective Date 31-Aug-2020 
Filing requirements: TMF 
Page 120 of 124 
For IGA,  
 
Proc mi data = analysis_data seed=118161  minimum=0 maximum=xx nimpute=number_of_imputations 
out=out_data; 
  class trtp stratum; 
  monotone logistic (/details);  
  var base stratum y4 y8 y12 y16; 
run; 
 
 
10-Nov-2022 00:00:00
CD14152.SPR118161.SAP.V01
1.0
Approved


Statistical Analysis Plan for Interventional Studies
Sponsor: Galderma Research & Development, LLC; Protocol No.: RD.06.SPR.118161 
This document is confidential. 
SAP Version: Final Version 1.0, 09-Nov-2022 
Controlled Document ID: 3903A.02, Effective Date 31-Aug-2020 
Filing requirements: TMF 
Page 121 of 124 
5. The example SAS code for pooling phase for ANCOVA model by PROC MIANALYZE: 
proc sort data=diff; by avisitn trtp; run; 
proc sort data=lsm; by avisitn trtp; run; 
proc mianalyze data=diff; by avisitn trtp; 
modeleffects estimate; 
stderr stderr; 
ods output ParameterEstimates=estdiff; run; 
 
proc mianalyze data=lsm; by avisitn trtp; 
modeleffects estimate; 
stderr stderr; 
ods output ParameterEstimates=estlsm; run; 
 
 
10-Nov-2022 00:00:00
CD14152.SPR118161.SAP.V01
1.0
Approved