A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Nemolizumab (CD14152) in Subjects with Moderate-to-Severe Atopic Dermatitis

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 atopic dermatitis (AD) for at least 2 years before the screening
visit, and confirmed according to American Academy of Dermatology Consensus
Criteria 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.
7. Documented recent history (within 6 months before the screening visit) of
inadequate response to topical medications (TCS with or without TCI).
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 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. *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;
- 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 or bilateral salpingectomy 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.

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 atopic dermatitis (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.
7. Having received any of the treatments specified in Table 6 reported in the
protocol within the specified timeframe before the baseline visit.
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)
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 Tcell 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.
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.