A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Nemolizumab (CD14152) in Subjects with Prurigo Nodularis

1. Male or female and aged >=18 years at the time of screening;
2. Clinical diagnosis of PN for at least 6 months with:
a. Pruriginous nodular lesions on upper limbs, trunk, and/or lower limbs;
b. At least 20 nodules on the entire body with a bilateral distribution
c. 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;
3. Severe pruritus defined as follows on the PP NRS:
• At the screening visit (Visit 1): PP NRS score is >= 7.0 for the 24-hour
period immediately preceding the screening visit;
• At the baseline visit (Visit 2): Mean of the daily intensity of the PP NRS
score is >= 7.0 over the previous week;
4. Female subjects of childbearing potential (ie, fertile, following menarche
and until becoming post-menopausal unless permanently sterile) must agree to
use at least 1 adequate and approved method of contraception throughout the
study and for 12 weeks after the last study drug injection. Adequate and
approved methods of contraception applicable for the subject and/or her partner
are defined below:
• True abstinence, when in line with the preferred and usual lifestyle of the
subject. Periodic abstinence (eg, calendar, ovulation, symptothermal,
post-ovulation methods) and withdrawal are not acceptable methods of
contraception;
• Progestogen-only oral hormonal contraception;
• Combination of male condom with cap, diaphragm, or sponge with spermicide
(double barrier methods);
• 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;
• Vasectomy of male partner at least 3 months before the study
5. Female subjects of non-childbearing potential must meet 1 of the following
criteria:
• Absence of menstrual bleeding for 1 year prior to screening without any other
medical reason;
• Documented hysterectomy , bilateral salpingectomy, or bilateral oophorectomy
at least 3 months before the study;
6. Subject is 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.
7. Read, understood and signed an informed consent form (ICF) before any
investigational procedure(s) are performed.

1. Body weight < 30 kg;
2. Chronic pruritus resulting from another active condition other than PN, such
as but not limited to scabies, lichen simplex chronicus, psoriasis, atopic
dermatitis, contact dermatitis, acne, folliculitis, lichen planus, habitual
picking/excoriation disorder, sporotrichosis, bullous autoimmune disease,
end-stage renal disease, cholestatic liver disease (eg, primary biliary
cirrhosis) , or diabetes mellitus or thyroid disease that is not adequately
treated, as per standard of care;
3. Unilateral lesions of prurigo (eg, only one arm affected);
4. History of or current confounding skin condition (eg, Netherton syndrome,
cutaneous T-cell lymphoma [mycosis fungoides or Sezary syndrome], chronic
actinic dermatitis, dermatitis herpetiformis)
5. Subjects meeting 1 or more of the following criteria at screening or
baseline:
- Had an exacerbation of asthma requiring hospitalization in the preceding 12
months;
- 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;
- Asthma Control Test <= 19 (only for subjects with a history of asthma)
- Peak expiratory flow < 80% of the predicted value.
6. Subjects with a current medical history of chronic obstructive pulmonary
disease and/or chronic bronchitis;
7. 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 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 8.4.2.;
8. 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;
9. Requiring rescue therapy for PN during the screening period or expected to
require rescue therapy within 4 weeks following the baseline visit;
10. Subjects with active atopic dermatitis (signs and symptoms other than dry
skin) in the last 3 months;
11. Neuropathic and psychogenic pruritus such as but not limited to notalgia
paresthetica, brachioradial pruritus, small fiber neuropathy, skin picking
syndrome, or delusional parasitosis;
12. Having received any of the treatments in the table reported in the protocol
within the specified timeframe before the baseline visit;
13. Previous participation in a clinical study with nemolizumab;
14. 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;
15. History of lymphoproliferative disease or history of malignancy of any
organ system within the last 5 years, except for:
- 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 screening visit, or;
- Actinic keratoses that have been treated
16. History of hypersensitivity (including anaphylaxis) to an immunoglobulin
product (plasma-derived or recombinant, eg, monoclonal antibody) or to any of
the study drug excipients;
17. Known active or latent tuberculosis infection;
18. Known or suspected immunosuppression or unusually frequent, recurrent,
severe, or prolonged infections as per investigator judgment;
19. Any medical or psychological condition or any clinically relevant
laboratory abnormalities, such as but not limited to elevated alanine
aminotransferase (ALT) or aspartate aminotransferase (AST) (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);
20. History of alcohol or substance abuse within 6 months of the screening
visit;
21. Planned or expected major surgical procedure during the clinical study;
22. Subject is unwilling to refrain from using prohibited medications during
the clinical study;
23. Currently participating or participated in any other study of a drug or
device, within the past 8 weeks before the screening visit, or is in an
exclusion period (if verifiable) from a previous study.
For subjects accepting optional biopsy sampling (by signing an additional
consent), the following exclusion criteria also apply. If any of the below
criteria are met, biopsy samples must not be collected:
24. History of coagulation disorders
25. Known sensitivity to local anesthetics
26. Using platelet aggregation inhibitors, or anticoagulants (sporadic intake
or continuous low-dose intake of aspirin or other non-steroidal
anti-inflammatory drugs is allowed)
27. History or physical evidence of keloids or hypertrophic scarring resulting
from skin trauma. The clinical examination will include the observation of
scars.