The primary objective of this study is to assess the PK/PD relationship of nemolizumab in adult participants aged 18 years or above with chronic pruritus of unknown origin (CPUO) during a 16-week treatment period.

This study is to assess the PK/PD relationship of nemolizumab in adult participants with CPUO. The study will consist of a 2 to 4-week screening period, a 16-week treatment period, and an 8-week follow up period (12 weeks after last study drug injection). Participants will be randomized 4:1 to nemolizumab or placebo. Dosing will be adjusted according to participants body weight ( less than [<] 90 kilograms [kg] versus >= 90 kg). Participation in the study will last up to 28 weeks.

Inclusion Criteria:

• Participants are eligible to be included in the study only if all of the following criteria apply:

  1. Participant must be 18 years of age or older.

  2. Participants with chronic pruritus on normal-appearing skin (except for dry skin or excoriations) for at least 6 months before the screening visit.

  3. Chronic pruritus considered of unknown origin (i.e., without a clear association to another condition or medication) as assessed by the investigator at baseline.

  4. The pruritus must affect at least 4 of the following body areas: left lower limb, right lower limb, left upper limb, right upper limb, anterior trunk, posterior trunk.

  5. History of insufficient control of the chronic pruritus with prior treatment.

  6. Peak Pruritus Numeric Rating Scale (PP NRS) score greater than and equal to (>=) 7 in the 24-hour period prior to the Screening visit.

  7. Weekly average Peak Pruritus Numeric Rating Scale (PP NRS) score >= 7 in the week (7 days) immediately prior to randomization, as recorded in the patient diary.

  8. Female of childbearing potential must agree to use at least 1 adequate and approved method of contraception throughout the study and for 12 weeks after the last study intervention injection.

     Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

  9. Females 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, confirmed with follicle stimulating hormone (FSH) level in the postmenopausal range

• Documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy at least 3 months before screening 10. Signed informed consent. 11. Participant is willing and able to comply with all of the time commitments and procedural requirements of the clinical study protocol.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply :

Medical Conditions

1. Known dermatologic, systemic, neurologic or psychiatric condition(s), other than dry skin, that considered by the investigator to be the primary cause of current pruritus.
2. Documented parasitic infection, including skin parasites such as scabies, within 12 weeks prior randomization.
3. 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.
4. Diagnosis of chronic pruritus of neuropathic origin including but not limited to scalp dysesthesia, brachioradial pruritus, generalized neuropathic pruritus or chronic pruritus of psychogenic origin (pruritus associated with psychological disorders such as delusional parasitosis or Morgellons disease).
5. Any medical or psychological condition or any clinically relevant laboratory abnormalities that put the participant at significant risk.
6. History of bullous pemphigoid or positive bullous pemphigoid autoantibodies at screening.
7. History of mastocytosis or serum total tryptase greater than (>) 20 nanograms per milliliter (ng/ml) at screening.
8. Active tuberculosis (TB) or non-tuberculosis mycobacterial infection, or a history of incompletely treated TB.
9. Positive serology results Hepatitis B surface antigen or (HBsAg) or Antibody to Hepatitis B core antigen (HBcAb), Hepatitis C virus (HCV) antibody with positive confirmatory test for HCV (e.g., polymerase chain reaction [PCR]), or Human Immunodeficiency Virus [HIV] antibody) at the screening visit.
10. Known or suspected immunodeficiency.
11. Lymphoproliferative disease or malignancy within the last 5 years.
12. Presence of major psychiatric diagnosis, clinically significant dementia, intellectual impairment, or any medical condition or disability which, in the investigator's opinion, may confound the assessment of nemolizumab's safety or efficacy or interfere with the participant's ability to comply with protocol mandated activities.
13. Receipt of prohibited medications within the specified timeframe before the baseline visit
14. Previous participation in a clinical study with nemolizumab
15. Currently participating or participated in any other study of an investigational drug or device, within the past 8 weeks (or 5 half-lives of the investigational drug, whichever is longer) before the screening visit, or is in an exclusion period (if verifiable) from a previous study.
16. Body weight < 30 kg.
17. Prior treatment with commercially available nemolizmab
18. Hypersensitivity to the active substance (nemolizumab) or to any of the excipients of the study intervention.
19. Requiring rescue therapy for pruritus during the screening period.
20. Alcohol or substance abuse within 6 months of the screening visit.
21. Planned or anticipated major surgical procedure or other activity that would interfere with the participant's ability to comply with protocol-mandated assessments.
22. Pregnant or breastfeeding female, or female planning a pregnancy during the study.
23. Vulnerable participant as defined by International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP).

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.