To Evaluate the Efficacy and Safety of Nemolizumab for 12 Weeks in Participants With Chronic Kidney Disease With Associated Severe Pruritus

• Status: Not yet recruiting
• Trial end date: 2024-01-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to evaluate the efficacy of nemolizumab compared to placebo at reducing the intensity of pruritus after a 12-week treatment period in adult hemodialysis participants with severe pruritus.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Galderma R&D

Criteria

Inclusion Criteria:

1. Has end-stage renal disease (ESRD) and has been on hemodialysis at least three times per week for at least three months prior to the start of screening.

2. Hemodialysis participants meeting the Kidney Outcome Quality Initiative Guidelines of hemodialysis adequacy within 45 days of screening, two single-pools of: -Kt/V at least 1.2.

3. Pruritus for >= three months (documented pruritus with no etiology identified other than CKD by medical record, previous physician's letter/statement, or a written conversation of site investigators).

4. WI NRS score >= 7.0 at the screening and baseline visit. Screening WI NRS score will be determined by a single WI NRS assessment (score ranging from 0 to 10) for the 24-hour period immediately preceding the screening visit. Baseline WI NRS score will be determined based on the weekly average of daily WI NRS scores (score ranging from 0 to 10) during the seven days immediately preceding baseline (rounding is not permitted). A minimum of four daily scores out of the seven days immediately preceding baseline is required for this calculation.

5. Women of childbearing potential (WOCBP) (i.e., 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 participant, or to use an adequate and approved method of contraception throughout the study and for 12 weeks after the last study injection.

Adequate and approved methods of contraception applicable for the participant 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).

• 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 three months before the study.

• Bilateral vasectomy of partner at least three months before the study.

6. Women are considered to be of non-childbearing potential if they meet one of the following criteria:

• Absence of menstrual bleeding for one 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 three months before screening.

Exclusion Criteria:

1. Body weight less than (<) 30 kg.

2. Pruritus caused by a concomitant condition (e.g., dermatologic or systemic disorders such as, but not limited to atopic dermatitis (AD), psoriasis, prurigo nodularis (PN), Chronic T- cell Lymphoma, Leukemia or cholestatic liver disease).

3. Localized itch of only the palms of the hands.

4. Pruritus present only during hemodialysis session.

5. Non-compliance with hemodialysis in the opinion of the investigator.

6. New York Heart Association Class IV symptoms or myocardial infarction within three months prior to screening.

7. History of stroke or transient ischemic attack within six months prior to screening.

8. Participants meeting one 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 (i.e. symptoms occurring on greater than (>) two days per week, nighttime awakenings two or more times per week, or some interference with normal activities) during the preceding three months.

• Asthma Control Test (ACT) <= 19 (only for participants with a history of asthma).

• Peak expiratory flow (PEF) < 80% of the predicted value.

Note: PEF test should be performed post hemodialysis. 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 participants without a history of asthma.

• For participants with a history of asthma but if the ACT score is >19 at screening.

9. Cutaneous infection within one week before the baseline visit, any infection requiring treatment with oral or parenteral antibiotics, antivirals, antiparasitics or antifungals within two weeks before the baseline visit.

10. Any confirmed or suspected coronavirus disease (COVID-19) infection within two weeks before the screening or baseline visit. Participants may be rescreened after the infection has resolved. Resolution of COVID-19 infection can be confirmed by recovery assessment methods, as described in the protocol.

11. • Positive serology results (hepatitis B surface antigen [HbsAg] or hepatitis B core antibody [HbcAb], hepatitis C [HCV] antibody with positive confirmatory test for hepatitis C virus [HCV] (e.g., HCV polymerase chain reaction [PRC]), or human immunodeficiency virus [HIV] antibody) at the screening visit.

12. Known active or untreated latent tuberculosis (TB) infection or history of either untreated or inadequately treated active or latent TB according to the local applicable guidelines.

13. Known or suspected immunosuppression beyond that expected due to end-stage kidney disease and its comorbidities or unusually frequent, recurrent, severe, or prolonged infections as per investigator judgment.

14. History of lymphoproliferative disease or history of malignancy of any organ system within the last five 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.

15. Pregnant women (positive serum pregnancy test result at any visits), breastfeeding women, or women planning a pregnancy during the clinical study.

16. In the opinion of the investigator the participant has any medical or psychological condition that could pose undue risk to the participant, prevent study completion, or adversely affect the validity or interpretability of the study measurements or interfered with study assessments.

17. Any clinically relevant laboratory abnormalities, such as but not limited to elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) (> 3* upper limit of normal [ULN]) in combination with elevated bilirubin (> 2 * ULN), during the screening period that may put the participant at significant risk according to the investigator's judgment, if he/she participates in the clinical study.

18. Planned or expected major surgical procedure during the clinical study, including a scheduled kidney transplant during the study.

19. Has not adhered to the restrictions in the selected medications prior to screening or is not expected to be compliant with restrictions during the study.

20. Requiring rescue therapy for pruritus during the screening period or expected to require rescue therapy within 4 weeks following the Baseline visit.

21. Previous treatment with nemolizumab.

22. History of hypersensitivity (including anaphylaxis) to an immunoglobulin product (plasma-derived or recombinant, e.g. monoclonal antibody) or to any of the study drug excipients.

23. Currently participating or participated in any other study of an investigational drug or device, within the past four weeks (or five half-lives of the investigational medication, whichever is longer) before the screening visit.

24. History of alcohol or substance abuse within six months of the screening visit.