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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease Associated Moderate to Severe Pruritus
• Intervention / Treatment: Drug: Nemolizumab; Drug: Nemolizumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 258
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Galderma Research & Development; Phone Number: 817-961-5000; Email: clinical.studies@galderma.com

Study Locations

• Hungary
  • Budapest, Hungary, 1076
    • Galderma Investigational Site 6301
  • Kecskemét, Hungary, 6000
    • Galderma Investigational Site 6304
  • Miskolc, Hungary, 3526
    • Galderma Investigational Site 6305
  • Szentes, Hungary, 6600
    • Galderma Investigational Site 6310
  • Szombathely, Hungary, 9700
    • Galderma Investigational Site 6298
• Poland
  • Brodnica, Poland, 87-300
    • Galderma Investigational Site 6294
  • Olkusz, Poland, 32-300
    • Galderma Investigational Site 6293
  • Wrocław, Poland, 50-556
    • Galderma Investigational Site 6297
  • Łódź, Poland, 90-153
    • Galderma Investigational Site 6296
• Spain
  • Alcobendas, Spain, 28108
    • Galderma Investigational Site 6309
  • Córdoba, Spain, 14004
    • Galderma Investigational Site 6292
  • L'Hospitalet De Llobregat, Spain, 08097
    • Galderma Investigational Site 5580
  • Madrid, Spain, 28046
    • Galderma Investigational Site 6190
  • Madrid, Spain, 28040
    • Galderma Investigational Site 5171
  • Manises, Spain, 46940
    • Galderma Investigational Site 6278
  • Sevilla, Spain, 41009
    • Galderma Investigational Site 6295
  • Valencia, Spain, 46017
    • Galderma Investigational Site 6311
• United States
  • California
    • Bakersfield, California, United States, 93309
      • Galderma Investigational Site 9989
    • Glendale, California, United States, 91205
      • Galderma Investigational Site 9991
    • Glendale, California, United States, 91206
      • Galderma Investigational Site 7018
    • La Palma, California, United States, 90623
      • Galderma Investigational Site 7015
    • Los Angeles, California, United States, 90048
      • Galderma Investigational Site 9996
    • Lynwood, California, United States, 90262
      • Galderma Investigational Site 9978
    • Riverside, California, United States, 92505
      • Galderma Investigational Site 7017
    • Tarzana, California, United States, 91356
      • Galderma Investigational Site 9973
    • Victorville, California, United States, 92392
      • Galderma Investigational Site 7028
    • Victorville, California, United States, 92394-1868
      • Galderma Investigational Site 9964
    • Whittier, California, United States, 90603
      • Galderma Investigational Site 7003
  • Colorado
    • Denver, Colorado, United States, 80230
      • Galderma Investigational Site 9971
  • Connecticut
    • Bloomfield, Connecticut, United States, 06002
      • Galderma Investigational Site 9988
    • Middlebury, Connecticut, United States, 06762
      • Galderma Investigational Site 9980
  • Florida
    • Boca Raton, Florida, United States, 33421
      • Galderma Investigational Site 9970
    • Coral Gables, Florida, United States, 33134
      • Galderma Investigational Site 7037
    • Hollywood, Florida, United States, 33021
      • Galderma Investigational Site 7026
    • Miami, Florida, United States, 33125
      • Galderma Investigational Site 9965
    • Miami, Florida, United States, 33155
      • Galderma Investigational Site7016
    • Sanford, Florida, United States, 32771
      • Galderma Investigational Site 7032
    • Tampa, Florida, United States, 33603
      • Galderma Investigational Site 7004
    • Tampa, Florida, United States, 33603
      • Galderma Investigational Site 7025
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Galderma Investigational Site 7027
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • Galderma Investigational Site 9983
    • Wichita, Kansas, United States, 67214
      • Galderma Investigational Site 9972
  • Michigan
    • Roseville, Michigan, United States, 48066
      • Galderma Investigational Site 9963
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Galderma Investigational Site 7020
    • Minneapolis, Minnesota, United States, 55404
      • Galderma Investigational Site 9982
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Galderma Investigational Site 7035
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Galderma Investigational Site 9962
  • New York
    • Bronx, New York, United States, 10461
      • Galderma Investigational Site 9995
    • Fresh Meadows, New York, United States, 11365
      • Galderma Investigational Site 7038
    • Great Neck, New York, United States, 11021
      • Galderma Investigational Site 9998
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Galderma Investigational Site 7007
  • Oregon
    • Roseburg, Oregon, United States, 97471
      • Galderma Investigational Site 9992
  • South Carolina
    • Spartanburg, South Carolina, United States, 29306
      • Galderma Investigational Site 9999
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Galderma Investigational Site 9967
  • Texas
    • Arlington, Texas, United States, 76015
      • Galderma Investigational Site 7039
    • Dallas, Texas, United States, 75231
      • Galderma Investigational Site 7040
    • El Paso, Texas, United States, 79925
      • Galderma Investigational Site 9966
    • Greenville, Texas, United States, 75402
      • Galderma Investigational Site 9977
    • Houston, Texas, United States, 77054
      • Galderma Investigational Site 7011
    • McKinney, Texas, United States, 75069
      • Galderma Investigational Site 7022
    • San Antonio, Texas, United States, 78258
      • Galderma Investigational Site 7010
    • The Woodlands, Texas, United States, 77384
      • Galderma Investigational Site 7019
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Galderma Investigational Site 9968
  • Wisconsin
    • Wauwatosa, Wisconsin, United States, 53226
      • Galderma Investigational Site 9969

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	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.
Experimental: Nemolizumab 30 mg	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 Names: 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 Names: CD14152
Experimental: Nemolizumab 60 mg	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 Names: 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 Names: CD14152

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants with an Improvement of >=3 from Baseline in Worst Itch Numeric Rating Scale (WI NRS) at 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.	Baseline, Week 12
Proportion of Participants with an Improvement of >=4 from Baseline in Worst Itch Numeric Rating Scale (WI NRS) at 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.	Baseline, Week 4
Proportion of Participants with an Improvement of >=4 from Baseline in Sleep Disturbance Numeric Rating Scale (SD NRS) at 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.	Baseline, Week 12
Proportion of Participants with an Improvement of >=3 from Baseline in Worst Itch Numeric Rating Scale (WI NRS) at 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.	Baseline, Week 4
Proportion of Participants with an Improvement of >=4 from Baseline in Sleep Disturbance Numeric Rating Scale (SD NRS) at 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.	Baseline, Week 4

Collaborators and Investigators

• Sponsor: Galderma R&D

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2021
• Primary Completion (Actual): January 3, 2024
• Study Completion (Actual): January 3, 2024

Study Registration Dates

• First Submitted: September 30, 2021
• First Submitted That Met QC Criteria: September 30, 2021
• First Posted (Actual): October 12, 2021

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Chronic Kidney Disease; Moderate to Severe Pruritus; Nemolizumab; CD14152
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Skin Manifestations; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Pruritus
• Other Study ID Numbers: RD.06.SPR.204358; 2021-004766-35 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No