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

• ClinicalTrials.gov Identifier: NCT05075408
• Recruitment Status: Completed
• First Posted: October 12, 2021
• Last Update Posted: April 9, 2024
• Sponsor: Galderma R&D
• Information provided by (Responsible Party): Galderma R&D

Tracking Information

• First Submitted Date: September 30, 2021
• First Posted Date: October 12, 2021
• Last Update Posted Date: April 9, 2024
• Actual Study Start Date: December 29, 2021
• Actual Primary Completion Date: January 3, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 5, 2024)

Proportion of Responders with an Improvement of Worst Itch Numeric Rating Scale (WI NRS) greater than and equal to (>=) 4 of from Baseline at Week 12 [ Time Frame: Baseline, Week 12 ]

Responder is defined as an improvement of >= 4 in WI NRS from baseline at Week 12 without use of rescue therapies and without treatment discontinuation due to lack of efficacy or AE/death related to study drug. The WI NRS is a scale that will be used by the responders to report the intensity of their worst pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores are provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicate worse outcome.

Original Primary Outcome Measures (submitted: September 30, 2021)

Percentage of Participants with an Improvement of >=4 from Baseline in Worst Itch Numeric Rating Scale (WI NRS) at Week 12 [ Time Frame: Baseline, Week 12 ]

The WI NRS is a scale that will be used by the participants to report the intensity of their worst pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores are provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicate worse outcome.

Current Secondary Outcome Measures (submitted: June 8, 2022)

• Proportion of Participants with an Improvement of >=3 from Baseline in Worst Itch Numeric Rating Scale (WI NRS) at Week 12 [ Time Frame: Baseline, Week 12 ]
  The WI NRS is a scale that will be used by the participants to report the intensity of their worst pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores are provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicate worse outcome.
• Proportion of Participants with an Improvement of >=4 from Baseline in Worst Itch Numeric Rating Scale (WI NRS) at Week 4 [ Time Frame: Baseline, Week 4 ]
  The WI NRS is a scale that will be used by the participants to report the intensity of their worst pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores are provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicate worse outcome.
• Proportion of Participants with an Improvement of >=4 from Baseline in Sleep Disturbance Numeric Rating Scale (SD NRS) at Week 12 [ Time Frame: Baseline, Week 12 ]
  The SD NRS is a scale that will be used by the participants to report the degree of their sleep loss related to chronic kidney disease with associated pruritus. Participants will be asked the following question: On a scale of 0 to 10, with 0 being 'no sleep loss related to the symptoms of pruritus' and 10 being 'I did not sleep at all due to the symptoms of pruritus, how would you rate your sleep last night?'. Higher scores indicate worse outcome.
• Proportion of Participants with an Improvement of >=3 from Baseline in Worst Itch Numeric Rating Scale (WI NRS) at Week 4 [ Time Frame: Baseline, Week 4 ]
  The WI NRS is a scale that will be used by the participants to report the intensity of their worst pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores are provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicate worse outcome.
• Proportion of Participants with an Improvement of >=4 from Baseline in Sleep Disturbance Numeric Rating Scale (SD NRS) at Week 4 [ Time Frame: Baseline, Week 4 ]
  The SD NRS is a scale that will be used by the participants to report the degree of their sleep loss related to chronic kidney disease with associated pruritus. Participants will be asked the following question: On a scale of 0 to 10, with 0 being 'no sleep loss related to the symptoms of pruritus' and 10 being 'I did not sleep at all due to the symptoms of pruritus, how would you rate your sleep last night?'. Higher scores indicate worse outcome.

Original Secondary Outcome Measures (submitted: September 30, 2021)

Percentage of Participants with an Improvement of >=3 from Baseline in Worst Itch Numeric Rating Scale (WI NRS) at Week 12 [ Time Frame: Baseline, Week 12 ]

The WI NRS is a scale that will be used by the participants to report the intensity of their worst pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores are provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicate worse outcome.

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: September 30, 2021)

• Percentage of Participants with an Improvement of >=4 from Baseline in Worst Itch Numeric Rating Scale (WI NRS) at Week 4 [ Time Frame: Baseline, Week 4 ]
  The WI NRS is a scale that will be used by the participants to report the intensity of their worst pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores are provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicate worse outcome.
• Percentage of Participants with an Improvement of >=4 from Baseline in Sleep Disturbance Numeric Rating Scale (SD NRS) at Week 12 [ Time Frame: Baseline, Week 12 ]
  The SD NRS is a scale that will be used by the participants to report the degree of their sleep loss related to chronic kidney disease with associated pruritus. Participants will be asked the following question: "On a scale of 0 to 10, with 0 being 'no sleep loss related to the symptoms of pruritus and 10 being 'I did not sleep at all due to the symptoms of pruritus, how would you rate your sleep last night?" Higher scores indicate worse outcome.
• Percentage of Participants with an Improvement of >=3 from Baseline in Worst Itch Numeric Rating Scale (WI NRS) at Week 4 [ Time Frame: Baseline, Week 4 ]
  The WI NRS is a scale that will be used by the participants to report the intensity of their worst pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores are provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicate worse outcome.
• Percentage of Participants with an Improvement of >=4 from Baseline in Sleep Disturbance Numeric Rating Scale (SD NRS) at Week 4 [ Time Frame: Baseline, Week 4 ]
  The SD NRS is a scale that will be used by the participants to report the degree of their sleep loss related to chronic kidney disease with associated pruritus. Participants will be asked the following question: "On a scale of 0 to 10, with 0 being 'no sleep loss related to the symptoms of pruritus and 10 being 'I did not sleep at all due to the symptoms of pruritus, how would you rate your sleep last night? Higher scores indicate worse outcome.

Descriptive Information

• Brief Title: To Evaluate the Efficacy and Safety of Nemolizumab for 12 Weeks in Participants With Chronic Kidney Disease With Associated Moderate to Severe Pruritus
• Official Title: A Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Efficacy and Safety of Nemolizumab in Subjects With Chronic Kidney Disease With Associated Moderate to Severe Pruritus
• Brief 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 moderate to severe pruritus.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Masking Description:

This is a double-blind study. The randomization code will remain blinded to all participants, study sites personnel and Sponsor/CRO study team members until completion of the study and after the study database has been locked.

Primary Purpose: Treatment

• Condition: Chronic Kidney Disease Associated Moderate to Severe Pruritus

Intervention

• Drug: Nemolizumab
  Participants will receive 2 subcutaneous injections for a total dose of 30 milligrams (mg) of nemolizumab every 4 weeks (Q4W), with a loading dose of 60 mg at baseline for a period of 12 weeks with an 8 week follow-up.
  Other Name: CD14152
• Drug: Nemolizumab
  Participants will receive 2 subcutaneous injections of 30 mg of nemolizumab Q4W starting at baseline for a period of 12 weeks with an 8 week follow-up.
  Other Name: CD14152
• Drug: Placebo
  Participants will receive 2 subcutaneous injections of 30 mg of placebo-matched to nemolizumab Q4W for a period of 12 weeks with an 8 week follow-up.

Study Arms

• Experimental: Nemolizumab 30 mg
  Intervention: Drug: Nemolizumab
• Experimental: Nemolizumab 60 mg
  Intervention: Drug: Nemolizumab
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 5, 2024): 258
• Original Estimated Enrollment (submitted: September 30, 2021): 252
• Actual Study Completion Date: January 3, 2024
• Actual Primary Completion Date: January 3, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Participants aged >= 18 years at the screening visit.
2. Has end-stage kidney disease (ESKD) and have been on hemodialysis three times per week for at least three months prior to the start of screening.

3. Hemodialysis participants meeting the Kidney Outcome Quality Initiative Guidelines of hemodialysis adequacy within 60 days of screening, two,

   •Single-poolsKt/V measurements of at least 1.2.

4. 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).
5. WI NRS score >= 5.0 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.

6. 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.

7. 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.
8. Participant willing and able to comply with all time commitments and procedural requirements of the clinical study protocol.
9. Understands and signs an informed consent form (ICF) before any investigational procedure(s) are performed.

Exclusion Criteria:

1. Body weight less than (<) 30 kg.
2. Pruritus caused by a concomitant condition unrelated to ESKD (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. History of or anticipated non-compliance with hemodialysis (i.e, such that it would adversely affect the conduct of the study or significantly change dialysis adequacy during the study) 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).
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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Hungary, Poland, Spain, United States

Administrative Information

• NCT Number: NCT05075408
• Other Study ID Numbers: RD.06.SPR.204358; 2021-004766-35 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Galderma R&D
• Original Responsible Party: Same as current
• Current Study Sponsor: Galderma R&D
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Galderma R&D
• Verification Date: February 2024