A Prospective, Multicenter, Long-Term Study to Assess the Safety and Efficacy of Nemolizumab (CD14152) in Subjects with Moderate-to-Severe Atopic Dermatitis.

See protocol page 11:
1. Adolescent subjects (aged 12-17) who have not participated in a previous
nemolizumab study (selected countries/selected sites - See Appendix 3) or
subjects who may benefit from study participation in the opinion of the
investigator and had participated in a prior nemolizumab study for AD including:
a. Subjects who completed the initial treatment period (Week 16 visit) in a
Phase 3 pivotal study (SPR.118161 or SPR.118169) and do not qualify for the
maintenance period;
OR
b. Subjects who completed the maintenance period (Week 48 visit) in a Phase 3
pivotal study (SPR.118161 or SPR.118169);
OR
c. Subjects who completed the treatment period (Week 16 visit) in the Phase 2
vaccination safety study (SPR.118380);
OR
d. Subjects who completed the treatment period (Week 16 visit) in the Phase 2
adolescent PK/safety study (SPR.116912);
OR
e. Subjects who completed the treatment period (Week 24 visit) in the Phase 2b
dose-ranging study (SPR.114322) and remain insufficiently controlled on topical
therapy alone;
OR
f. Subjects who discontinued study medication in a prior study and completed
required study visits prior to LTE participation (Week 16 visit for SPR.118161
and SPR.118169 initial treatment period, Week 32 visit for SPR.118161 and
SPR.118169 maintenance period; final study visits for SPR.118380 [Week 16],
SPR.116912 [Week 16], SPR.114322 [Week 24], SPR.201591 [Week 16], and
SPR.201593 [Week 13] , unless the subject experienced an AE that may present an
unreasonable risk if study medication is continued.
OR
g. Subjects who completed the treatment period (Week 16) in the Phase 3b study
(SPR.201591);
OR
h. Subjects who completed the treatment period (Week 13) in the Phase 2 DDI
study (SPR.201593).

Note(s): For ongoing studies, transfer into the LTE study should occur as soon
as possible to minimize gaps in study medication dosing. Subjects who satisfy
inclusion criteria 1a through 1c are permitted to enroll immediately into the
LTE study, provided other eligibility criteria are met.

Enrollment of subjects aged 12 to 17 years has been open after the IDMC has
assessed interim safety data from the phase 2 study (SPR.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
study sites confirming that the study is open for enrollment of adolescents.
Adolescents could not be enrolled in the study until such communication was
received.

2. Agree to apply a moisturizer at least once daily throughout the study and
agree to apply the authorized topical therapy, as determined appropriate by the
investigator.

3. Women of childbearing potential (ie, fertile, following menarche and until
becoming postmenopausal 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.

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). Note: *Double barrier methods* refers to
simultaneous use of a physical barrier by each partner. Use of a single barrier
method (e.g., 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
• Bilateral vasectomy of partner at least 3 months before the study

4. 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

5. Subject (and guardian, when applicable) willing and able to comply with all
of the time commitments and procedural requirements of the clinical study
protocol.

6. Understand and sign an informed consent form (and assent form, when
applicable), before any investigational procedure(s) being performed.

Additional Inclusion Criteria: For adolescent subjects (age 12-17) who have not
participated in a previous clinical study with nemolizumab only (selected
countries/selected sites - See Appendix 3):

7. 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.

8. EASI score >= 16 at both the screening and baseline visits.

9. 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.

10. AD involvement >= 10% of body surface area (BSA) at both the screening and
baseline visits.

11. SCORAD pruritus VAS score of at least 4.0 at the screening and baseline
visit. SCORAD pruritus VAS is completed by the subject as a single assessment
of their average pruritus symptoms over the past 3*days or nights on a scale
from 0 to 10.

12. 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:
a. Failure to achieve or maintain remission or low disease activity (equivalent
to IGA <= 2) despite treatment with a regimen of a medium or higher potency TCS
(with or without TCI), applied for at least 4 weeks or for the maximum duration
per prescribing information;
or
b. Requirement of a long-term treatment (> 4 weeks) with a high- or very
high-potency TCS (with or without TCI) to achieve or maintain remission or low
disease activity (equivalent to IGA <= 2);
or
c. 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.

See protocol page 12:
1. Subjects who, during their participation in a prior nemolizumab study,
experienced an AE which in the opinion of the investigator could indicate that
continued treatment with nemolizumab may present an unreasonable risk for the
subject.
2. Having received any of the following treatments in Table 3 within the
specified timeframe before the baseline visit.
3. Pregnant women (positive pregnancy test result at screening or baseline
visit), breastfeeding women, or women planning a pregnancy during the clinical
study.
4. Any medical or psychological condition at the screening visit 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).
5. Planning or expected to have a major surgical procedure during the clinical
study.
6. Subjects unwilling to refrain from using prohibited medications during the
clinical study (see Section 8.4.9.2).

Additional Exclusion Criteria: For new adolescent subjects or for subjects who
do not rollover from a prior nemolizumab study within 28 days of completing
final study assessments during the lead-in study:
7. Body weight < 30 kg.
8. Subjects meeting 1 or more of the following criteria at screening or
baseline:
8a. Had an asthma exacerbation requiring hospitalization in the preceding 12
months;
8b. Reporting asthma that has been not 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;
8c. Asthma Control Test (ACT) <= 19 (only for subjects with a history of asthma);
8d. Peak expiratory flow < 80% of the predicted value.
Note: In the event that PEF is * 80% of the predicted value at the screening
visit, PEF testing can be repeated once within 48 hours:
• For subjects without a history of asthma
• For subjects with a history of asthma but if the ACT score is >19 at
screening.
9. Subjects with a current medical history of chronic obstructive pulmonary
disease and/or chronic bronchitis.
10. 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 8.3.5.2.; Note: Subjects with chronic, stable
use of prophylactic treatment for recurrent herpes viral infection can be
included in this study.
11. Positive serology results (hepatitis B surface antigen [HBsAg] or hepatitis
B core antibody, [HBcAb], hepatitis C [HCV] antibody with positive HCV RNA, or
human immunodeficiency virus [HIV] antibody) at the screening visit.
Note: Subjects with a positive HBcAb and a negative HBsAg can be included if
hepatitis B surface antibody is positive (considered immune after a natural
infection). Subjects who are positive for HCV antibody and negative for HCV RNA
may be enrolled.
In the event of rescreening, the serology tests results (eg, HBV, HCV, HIV)
from the first screening can be used by the investigator to assess the
eligibility of rescreened subjects if those tests were performed within 6 weeks
prior to the baseline visit.
12. Subjects who, after a full treatment course of 16 weeks with dupilumab,
experience worsening of their AD or failed to achieve minimal improvement (eg,
<10% reduction in EASI or no reduction in IGA);
13. 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 carcinoma in situ of the
cervix that have been treated and have no evidence of recurrence in the last 12
weeks before the screening visit, or 2) actinic keratoses that have been
treated;
14. History of hypersensitivity (including anaphylaxis) to an immunoglobulin
product (plasma-derived or recombinant, eg, monoclonal antibody) or to any of
the study drug excipients.
15. History of intolerance to TCS or for whom TCS is not advisable (eg,
hypersensitivity to TCS, significant skin atrophy, etc), unless TCS was not
used as background therapy in the lead-in study, if applicable.
16. 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.
17. Known or suspected immunosuppression or unusually frequent, recurrent,
severe, or prolonged infections as per investigator judgment.
18. Presence of or current 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).
19. Any clinically relevant laboratory abnormalities, such as but not limited
to elevated ALT or AST (> 3 × upper limit of normal) in combination with
elevated bilirubin (> 2 × upper limit of normal), 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.
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, other than the nemolizumab for AD
studies (SPR.114322, SPR.116912, SPR.118380, SPR.118169, SPR.118161,
SPR.201591, and SPR.201593).
21. History of alcohol or substance abuse within 6 months of the screening
visit.