Efficacy and Safety of Subcutaneous Dupilumab for the Treatment of Adult Participants With Chronic Pruritus of Unknown Origin (CPUO) (LIBERTY-CPUO-CHIC)

Master Protocol of Two Randomized, Double Blind, Placebo-controlled, Multi-center, Parallel Group Studies to Evaluate the Efficacy and Safety of Dupilumab in Adult Patients With Chronic Pruritus of Unknown Origin (CPUO)

The main objective of the study is to assess efficacy and safety of dupilumab given up to 24 weeks in adults with CPUO.

This is a master protocol which includes 2 parallel-treatment, double-blind, 2- arm Phase 3 staggered studies of similar design (Study A and Study B) in male and female participants aged 18 to 90 years with CPUO. Study B design may be adapted based on the results of Study A.

For both Study A and B, after an up-to-4-week screening period, participants with severe pruritus (worst-itch numerical rating scale [WI-NRS ≥7) will enter a 4-week run-in period during with a non-sedative antihistamine and an emollient (moisturizer). Participants with severe pruritus (WI-NRS ≥7) at baseline will be randomized (1:1) to be treated for 24 weeks (Study A) or 12 weeks (Study B) with either dupilumab or matching placebo in addition to their antihistamine and emollient regimen. The treatment period for both study A and B will be followed by a 12-week follow-up period.

Study Overview

• Status: Recruiting
• Conditions: Pruritus
• Intervention / Treatment: Drug: Dupilumab; Drug: Fexofenadine (loratadine if not available); Drug: Moisturizer; Drug: Placebo

Detailed Description

Study duration per participant will be up to 44 weeks (Study A) and 32 weeks (Study B).

• Study Type: Interventional
• Enrollment (Estimated): 208
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free number for US & Canada); Phone Number: option 6 800-633-1610; Email: Contact-US@sanofi.com

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1121ABE
    • Recruiting
    • Investigational Site Number : 0320002
  • Ciudad Autonoma Buenos Aires, Argentina, C1414AIF
    • Recruiting
    • Investigational Site Number : 0320003
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, 1015
      • Recruiting
      • Investigational Site Number : 0320005
    • Caba, Buenos Aires, Argentina, C1023AAB
      • Recruiting
      • Investigational Site Number : 0320001
    • Caba, Buenos Aires, Argentina, C1055AAO
      • Recruiting
      • Investigational Site Number : 0320006
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000DEJ
      • Recruiting
      • Investigational Site Number : 0320004
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2G 1B1
      • Completed
      • Investigational Site Number : 1240001
    • Edmonton, Alberta, Canada, T6G 1C3
      • Completed
      • Investigational Site Number : 1240008
  • Ontario
    • London, Ontario, Canada, N6A2C2
      • Recruiting
      • Investigational Site Number : 1240002
    • Markham, Ontario, Canada, L3P 1X3
      • Recruiting
      • Investigational Site Number : 1240003
    • Toronto, Ontario, Canada, M4C 1L1
      • Recruiting
      • Investigational Site Number : 1240006
  • Quebec
    • Montreal, Quebec, Canada, H4A 3T2
      • Recruiting
      • Investigational Site Number : 1240005
    • Verdun, Quebec, Canada, H4G 3E7
      • Recruiting
      • Investigational Site Number : 1240004
• China
  • Beijing, China, 100191
    • Recruiting
    • Investigational Site Number : 1560003
  • Chengdu, China, 610041
    • Recruiting
    • Investigational Site Number : 1560004
  • Guangzhou, China, 510080
    • Recruiting
    • Investigational Site Number : 1560005
  • Hangzhou, China, 310006
    • Recruiting
    • Investigational Site Number : 1560002
  • Shanghai, China, 200040
    • Recruiting
    • Investigational Site Number : 1560001
• France
  • Lille, France, 59037
    • Active, not recruiting
    • Investigational Site Number : 2500002
• Germany
  • Berlin, Germany, 12200
    • Recruiting
    • Investigational Site Number : 2760002
• Hungary
  • Budapest, Hungary, 1036
    • Recruiting
    • Investigational Site Number : 3480001
  • Debrecen, Hungary, 4031
    • Recruiting
    • Investigational Site Number : 3480005
  • Szeged, Hungary, 6720
    • Recruiting
    • Investigational Site Number : 3480003
  • Zalaegerszeg, Hungary, 8900
    • Recruiting
    • Investigational Site Number : 3480002
• Italy
  • Ancona, Italy, 60126
    • Recruiting
    • Investigational Site Number : 3800004
  • Firenze, Italy, 50125
    • Recruiting
    • Investigational Site Number : 3800005
  • Roma, Italy, 00168
    • Recruiting
    • Investigational Site Number : 3800001
  • Lombardia
    • Milano, Lombardia, Italy, 20122
      • Recruiting
      • Investigational Site Number : 3800003
    • Rozzano, Lombardia, Italy, 20089
      • Recruiting
      • Investigational Site Number : 3800002
• Japan
  • Osaka
    • Sakai-shi, Osaka, Japan, 593-8324
      • Recruiting
      • Investigational Site Number : 3920002
  • Tokyo
    • Tachikawa-shi, Tokyo, Japan, 190-0023
      • Recruiting
      • Investigational Site Number : 3920001
• Korea, Republic of
  • Busan, Korea, Republic of, 602-739
    • Recruiting
    • Investigational Site Number : 4100003
  • Seoul, Korea, Republic of, 07441
    • Completed
    • Investigational Site Number : 4100001
  • Seoul, Korea, Republic of, 5278
    • Recruiting
    • Investigational Site Number : 4100002
  • Gyeonggi-do
    • Ansan-si, Gyeonggi-do, Korea, Republic of, 15355
      • Completed
      • Investigational Site Number : 4100004
  • Seoul-teukbyeolsi
    • Seoul, Seoul-teukbyeolsi, Korea, Republic of, 03080
      • Recruiting
      • Investigational Site Number : 4100005
• Poland
  • Krakow, Poland, 30-033
    • Recruiting
    • Investigational Site Number : 6160001
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 51-503
      • Recruiting
      • Investigational Site Number : 6160003
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 02-172
      • Recruiting
      • Investigational Site Number : 6160005
• Spain
  • Alicante, Spain, 03010
    • Recruiting
    • Investigational Site Number : 7240005
  • Córdoba, Spain, 14004
    • Recruiting
    • Investigational Site Number : 7240004
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08003
      • Recruiting
      • Investigational Site Number : 7240003
    • Barcelona, Barcelona [Barcelona], Spain, 08041
      • Recruiting
      • Investigational Site Number : 7240006
  • Galicia [Galicia]
    • Pontevedra, Galicia [Galicia], Spain, 36002
      • Recruiting
      • Investigational Site Number : 7240001
• United States
  • California
    • Bakersfield, California, United States, 93301
      • Recruiting
      • Kern Research, Inc Site Number : 8400016
  • Florida
    • Bellair, Florida, United States, 32756
      • Recruiting
      • Palm Harbor Dermatology Site Number : 8400024
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami Site Number : 8400011
  • Georgia
    • Macon, Georgia, United States, 31217
      • Recruiting
      • Skin Care Physicians of Georgia Site Number : 8400030
    • Savannah, Georgia, United States, 31406
      • Recruiting
      • Aeroallergy Research Laboratories Of Savannah Inc Site Number : 8400036
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Recruiting
      • Dawes Fretzin Clinical Research Group, LLC Site Number : 8400007
  • Kentucky
    • Louisville, Kentucky, United States, 40241
      • Recruiting
      • DS Research Site Number : 8400031
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Recruiting
      • Johns Hopkins University Site Number : 8400020
  • Nebraska
    • Bellevue, Nebraska, United States, 68123
      • Recruiting
      • Nebraska Medical Research Institute, Inc. Site Number : 8400014
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai Site Number : 8400034
  • South Carolina
    • North Charleston, South Carolina, United States, 29420
      • Recruiting
      • National Allergy, Asthma & Urticaria Centers of Charleston, PA Site Number : 8400032

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant must be 18 (or the legal age of consent in the jurisdiction in which the study is taking place) to 90 years of age inclusive, at the time of signing the informed consent.
• Participants with chronic pruritus for at least 6 months before the screening visit.
• Chronic pruritus considered of unknown origin as assessed by the investigator at baseline (excluding chronic pruritus secondary to dermatological or systemic conditions, of neuropathic or psychogenic origin or secondary to drugs).
• Chronic pruritus must affect at least 2 of the following body areas: legs, arms, or trunk.
• History of insufficient control of the chronic pruritus with prior treatment.
• Participants should receive optimal treatment for concomitant conditions that could impact pruritus (eg, diabetes, iron deficiency).
• Participants must have a history of severe itch and a worst itch score of ≥7 at screening on the WI-NRS (score scale ranges from 0 to 10; higher score indicates worse itch) and Patient global impression of severity (PGIS) of pruritus scored "severe" at screening.
• Participants must have an average worst itch score of ≥7 in the 7 days prior to run-in visit and in the 7 days prior to Day 1 on the WI-NRS.
• Participants scored "severe" in the PGIS of pruritus on Day 1.

Exclusion Criteria:

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

• Severe concomitant illness(es) that, in the Investigator's judgment, would adversely affect the patient's participation in the study.
• Patients with active tuberculosis or non-tuberculous mycobacterial infection, or a history of incompletely treated tuberculosis, unless it is well documented by a specialist that the participant has been adequately treated and can now start treatment with a biologic agent.
• Diagnosed with, suspected of, or at high risk of endoparasitic infection, and/or use of antiparasitic drug within 2 weeks before the screening visit.
• HIV infection.
• Severe renal failure (dialysis).
• Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 2 weeks before the run-in visit.
• Known or suspected immunodeficiency.
• Active malignancy or history of malignancy within 5 years before the baseline visit, except completely treated in situ carcinoma of the cervix and completely treated and resolved non metastatic squamous or basal cell carcinoma of the skin.
• History of hypersensitivity or intolerance to non-sedative antihistamines.
• Participation in prior dupilumab clinical study or have been treated with commercially available dupilumab.

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dupilumab; Loading dose administered subcutaneous (SC), followed by SC once every 2 weeks (Q2W) on top of non-sedative antihistamine and moisturizer	Drug: Dupilumab; Injection solution subcutaneous; Drug: Fexofenadine (loratadine if not available); Tablet or capsule Oral; Drug: Moisturizer; Topical
Placebo Comparator: Placebo; Loading dose administered SC, followed by SC Q2W on top of non-sedative antihistamine and moisturizer	Drug: Fexofenadine (loratadine if not available); Tablet or capsule Oral; Drug: Moisturizer; Topical; Drug: Placebo; Injection solution SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study A: Proportion of participants with improvement (reduction) in weekly average of daily worst-itch numerical rating scale (WI-NRS) by ≥4 from baseline to Week 24	WI-NRS is a patient reported outcome (PRO) comprised of a single item rated on a scale from 0 ("No itch") to 10 ("Worst imaginable itch").	Baseline to Week 24
Study B: Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by ≥4 from baseline to Week 12	WI-NRS is a PRO comprised of a single item rated on a scale from 0 ("No itch") to 10 ("Worst imaginable itch").	Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study A; Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by ≥4 from baseline to Week 12	WI-NRS is a PRO comprised of a single item rated on a scale from 0 ("No itch") to 10 ("Worst imaginable itch").	Baseline to Week 12
Study A: Proportion of participants who scored "none" or "mild" in Patient Global Impression of Severity (PGIS) of pruritus at Week 24	The PGIS of pruritus is a one-item categorical scale that asks participants to provide the overall self-assessment of their pruritus severity on a 4-point scale for the past week. Response choices are: "None", "Mild", "Moderate", "Severe".	Week 24
Study A: Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by ≥4 from baseline over time until Week 24	WI-NRS is a PRO comprised of a single item rated on a scale from 0 ("No itch") to 10 ("Worst imaginable itch").	Baseline to Week 24
Study A: Time to first response of WI-NRS ≥4 points reduction from baseline by Week 24	WI-NRS is a PRO comprised of a single item rated on a scale from 0 ("No itch") to 10 ("Worst imaginable itch").	Baseline to Week 24
Study A: Absolute change from baseline in weekly average of daily WI-NRS at Week 24	WI-NRS is a PRO comprised of a single item rated on a scale from 0 ("No itch") to 10 ("Worst imaginable itch").	Baseline to Week 24
Study A: Percent change from baseline in weekly average of daily WI-NRS at Week 24	WI-NRS is a PRO comprised of a single item rated on a scale from 0 ("No itch") to 10 ("Worst imaginable itch").	Baseline to Week 24
Study A: Proportion of participants who scored "none" or "mild" in PGIS of pruritus at Week 12	The PGIS of pruritus is a one-item categorical scale that asks participants to provide the overall self-assessment of their pruritus severity on a 4-point scale for the past week. Response choices are: "None", "Mild", "Moderate", "Severe".	Week 12
Study A: Absolute change from baseline in weekly average of daily WI-NRS at Week 12	WI-NRS is a PRO comprised of a single item rated on a scale from 0 ("No itch") to 10 ("Worst imaginable itch").	Baseline to Week 12
Study A: Percent change from baseline in weekly average of daily WI-NRS at Week 12	WI-NRS is a PRO comprised of a single item rated on a scale from 0 ("No itch") to 10 ("Worst imaginable itch").	Baseline to Week 12
Study A: Absolute change from baseline in weekly average of daily sleep disturbances numerical rating scale (NRS) at Week 24	The sleep disturbance NRS is to be used by the participants to report the degree of their sleep loss related to itch over the past 24 hours. Participants will rate their sleep disturbance from 0 ('no sleep loss related to itch') to 10 ('I cannot sleep at all due to itch') once daily in the morning.	Baseline to Week 24
Study A: Percent change from baseline in weekly average of daily sleep disturbances NRS at Week 24	The sleep disturbance NRS is to be used by the participants to report the degree of their sleep loss related to itch over the past 24 hours. Participants will rate their sleep disturbance from 0 ('no sleep loss related to itch') to 10 ('I cannot sleep at all due to itch') once daily in the morning.	Baseline to Week 24
Study A: Change from baseline in Dermatology Life Quality Index (DLQI) score at Week 24	The DLQI is a validated 10-item questionnaire to measure dermatology-specific quality of life (QoL) in adult patients. Overall scoring ranges from 0 to 30, with a higher score indicating a poorer QoL.	Baseline to Week 24
Study A: Change from baseline in the Itchy quality of life (ItchyQoL) score at Week 24	ItchyQoL is a pruritus-specific QoL instrument that measures specifically disease burden in pruritus patients.	Baseline to Week 24
Study A: Change from baseline in Hospital Anxiety and Depression Scale (HADS) total score at Week 24	The HADS is a validated questionnaire for screening anxiety and depression in non-psychiatric populations. The total score ranges from 0 to 42. 0 to 7= normal; 8 to 10= borderline abnormal; 11 to 21= abnormal.	Baseline to Week 24
Study A: Absolute change from baseline in weekly average of daily sleep disturbances NRS at Week 12	The sleep disturbance NRS is to be used by the participants to report the degree of their sleep loss related to itch over the past 24 hours. Participants will rate their sleep disturbance from 0 ('no sleep loss related to itch') to 10 ('I cannot sleep at all due to itch') once daily in the morning.	Baseline to Week 12
Study A: Percent change from baseline in weekly average of daily sleep disturbances NRS at Week 12	The sleep disturbance NRS is to be used by the participants to report the degree of their sleep loss related to itch over the past 24 hours. Participants will rate their sleep disturbance from 0 ('no sleep loss related to itch') to 10 ('I cannot sleep at all due to itch') once daily in the morning.	Baseline to Week 12
Study A: Change from baseline in DLQI score at Week 12	The DLQI is a validated 10-item questionnaire to measure dermatology-specific quality of life (QoL) in adult patients. Overall scoring ranges from 0 to 30, with a higher score indicating a poorer QoL.	Baseline to Week 12
Study A: Change from baseline in the ItchyQoL score at Week 12	ItchyQoL is a pruritus-specific QoL instrument that measures specifically disease burden in pruritus patients. It is a 22-item instrument that measures the degree to which pruritus affects quality-of-life for the past week. The overall score is the average of the 22 items ranging from 1 to 5. A higher score corresponds to a more adverse impact on QoL.	Baseline to Week 12
Study A: Change from baseline in HADS total score at Week 12	The HADS is a validated questionnaire for screening anxiety and depression in non-psychiatric populations. The total score ranges from 0 to 42. 0 to 7= normal; 8 to 10= borderline abnormal; 11 to 21= abnormal.	Baseline to Week 12
Study A: Percentage of participants experiencing treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs) from baseline through end of study (EOS)	Percentage of participants experiencing TEAEs or SAEs from baseline through EOS	Baseline to Week 36
Study A: Incidence of treatment-emergent antidrug antibodies (ADA) against dupilumab	Incidence of treatment-emergent ADA against dupilumab	Baseline to Week 36
Study B: Proportion of participants who scored "none" or "mild" in PGIS of pruritus at Week 12	The PGIS of pruritus is a one-item categorical scale that asks participants to provide the overall self-assessment of their pruritus severity on a 4-point scale for the past week. Response choices are: "None", "Mild", "Moderate", "Severe".	Week 12
Study B: Absolute change from baseline in weekly average of daily WI-NRS at Week 12	WI-NRS is a PRO comprised of a single item rated on a scale from 0 ("No itch") to 10 ("Worst imaginable itch").	Baseline to Week 12
Study B: Percent change from baseline in weekly average of daily WI-NRS at Week 12	WI-NRS is a PRO comprised of a single item rated on a scale from 0 ("No itch") to 10 ("Worst imaginable itch").	Baseline to Week 12
Study B: Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by ≥4 from baseline over time until Week 12	WI-NRS is a PRO comprised of a single item rated on a scale from 0 ("No itch") to 10 ("Worst imaginable itch").	Baseline to Week 12
Study B: Time to first response of WI-NRS ≥4 points reduction from baseline by Week 12	WI-NRS is a PRO comprised of a single item rated on a scale from 0 ("No itch") to 10 ("Worst imaginable itch").	Baseline to Week 12
Study B: Absolute change from baseline in weekly average of daily sleep disturbances NRS at Week 12	The sleep disturbance NRS is to be used by the participants to report the degree of their sleep loss related to itch over the past 24 hours. Participants will rate their sleep disturbance from 0 ('no sleep loss related to itch') to 10 ('I cannot sleep at all due to itch') once daily in the morning.	Baseline to Week 12
Study B: Percent change from baseline in weekly average of daily sleep disturbances NRS at Week 12	The sleep disturbance NRS is to be used by the participants to report the degree of their sleep loss related to itch over the past 24 hours. Participants will rate their sleep disturbance from 0 ('no sleep loss related to itch') to 10 ('I cannot sleep at all due to itch') once daily in the morning.	Baseline to Week 12
Study B: Change from baseline in DLQI score at Week 12	The DLQI is a validated 10-item questionnaire to measure dermatology-specific quality of life (QoL) in adult patients. Overall scoring ranges from 0 to 30, with a higher score indicating a poorer QoL.	Baseline to Week 12
Study B: Change from baseline in the ItchyQoL score at Week 12	ItchyQoL is a pruritus-specific QoL instrument that measures specifically disease burden in pruritus patients. It is a 22-item instrument that measures the degree to which pruritus affects quality-of-life for the past week. The overall score is the average of the 22 items ranging from 1 to 5. A higher score corresponds to a more adverse impact on QoL.	Baseline to Week 12
Study B: Change from baseline in HADS total score at Week 12	The HADS is a validated questionnaire for screening anxiety and depression in non-psychiatric populations. The total score ranges from 0 to 42. 0 to 7= normal; 8 to 10= borderline abnormal; 11 to 21= abnormal.	Baseline to Week 12
Study B: Percentage of participants experiencing TEAEs or SAEs from baseline through EOS	Percentage of participants experiencing TEAEs or SAEs from baseline through EOS	Baseline to Week 24
Study B: Incidence of treatment-emergent ADA against dupilumab	Incidence of treatment-emergent ADA against dupilumab	Baseline to Week 24

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

Helpful Links

• EFC16973 Chronic Pruritus of Unknown Origin Website

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2022
• Primary Completion (Estimated): March 21, 2025
• Study Completion (Estimated): October 3, 2025

Study Registration Dates

• First Submitted: February 22, 2022
• First Submitted That Met QC Criteria: February 22, 2022
• First Posted (Actual): March 2, 2022

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Manifestations; Pruritus; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dermatologic Agents; Anti-Allergic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Histamine H1 Antagonists, Non-Sedating; Loratadine; Fexofenadine
• Other Study ID Numbers: EFC16973; U1111-1253-9888 (Registry Identifier: ICTRP); 2021-004315-76 (EudraCT Number); 2023-508879-36-00 (Registry Identifier: CTIS); 2023-508879-36 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

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