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

• ClinicalTrials.gov Identifier: NCT05263206
• Recruitment Status: Recruiting
• First Posted: March 2, 2022
• Last Update Posted: March 18, 2024
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pruritus	Drug: Dupilumab; Drug: Placebo; Drug: Fexofenadine (loratadine if not available); Drug: Moisturizer	Phase 3

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 208 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: February 15, 2022
• Estimated Primary Completion Date: March 21, 2025
• Estimated Study Completion Date: October 3, 2025

Arms and Interventions

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: Placebo; Injection solution SC; Drug: Fexofenadine (loratadine if not available); Tablet or capsule Oral; Drug: Moisturizer; Topical

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: 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").
2. Study B: Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by ≥4 from baseline to Week 12 [ Time Frame: 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").

Secondary Outcome Measures :

1. Study A; Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by ≥4 from baseline to Week 12 [ Time Frame: 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").
2. Study A: Proportion of participants who scored "none" or "mild" in Patient Global Impression of Severity (PGIS) of pruritus at Week 24 [ Time Frame: 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".
3. Study A: Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by ≥4 from baseline over time until Week 24 [ Time Frame: Baseline to 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").
4. Study A: Time to first response of WI-NRS ≥4 points reduction from baseline by Week 24 [ Time Frame: Baseline to 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").
5. Study A: Absolute change from baseline in weekly average of daily WI-NRS at Week 24 [ Time Frame: Baseline to 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").
6. Study A: Percent change from baseline in weekly average of daily WI-NRS at Week 24 [ Time Frame: Baseline to 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").
7. Study A: Proportion of participants who scored "none" or "mild" in PGIS of pruritus at Week 12 [ Time Frame: 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".
8. Study A: Absolute change from baseline in weekly average of daily WI-NRS at Week 12 [ Time Frame: 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").
9. Study A: Percent change from baseline in weekly average of daily WI-NRS at Week 12 [ Time Frame: 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").
10. Study A: Absolute change from baseline in weekly average of daily sleep disturbances numerical rating scale (NRS) at Week 24 [ Time Frame: Baseline to 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.
11. Study A: Percent change from baseline in weekly average of daily sleep disturbances NRS at Week 24 [ Time Frame: Baseline to 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.
12. Study A: Change from baseline in Dermatology Life Quality Index (DLQI) score at Week 24 [ Time Frame: Baseline to 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.
13. Study A: Change from baseline in the Itchy quality of life (ItchyQoL) score at Week 24 [ Time Frame: Baseline to Week 24 ]
    ItchyQoL is a pruritus-specific QoL instrument that measures specifically disease burden in pruritus patients.
14. Study A: Change from baseline in Hospital Anxiety and Depression Scale (HADS) total score at Week 24 [ Time Frame: Baseline to 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.
15. Study A: Absolute change from baseline in weekly average of daily sleep disturbances NRS at Week 12 [ Time Frame: Baseline to 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.
16. Study A: Percent change from baseline in weekly average of daily sleep disturbances NRS at Week 12 [ Time Frame: Baseline to 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.
17. Study A: Change from baseline in DLQI score at Week 12 [ Time Frame: Baseline to 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.
18. Study A: Change from baseline in the ItchyQoL score at Week 12 [ Time Frame: Baseline to 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.
19. Study A: Change from baseline in HADS total score at Week 12 [ Time Frame: Baseline to 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.
20. Study A: Percentage of participants experiencing treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs) from baseline through end of study (EOS) [ Time Frame: Baseline to Week 36 ]
    Percentage of participants experiencing TEAEs or SAEs from baseline through EOS
21. Study A: Incidence of treatment-emergent antidrug antibodies (ADA) against dupilumab [ Time Frame: Baseline to Week 36 ]
    Incidence of treatment-emergent ADA against dupilumab
22. Study B: Proportion of participants who scored "none" or "mild" in PGIS of pruritus at Week 12 [ Time Frame: 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".
23. Study B: Absolute change from baseline in weekly average of daily WI-NRS at Week 12 [ Time Frame: 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").
24. Study B: Percent change from baseline in weekly average of daily WI-NRS at Week 12 [ Time Frame: 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").
25. Study B: Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by ≥4 from baseline over time until Week 12 [ Time Frame: 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").
26. Study B: Time to first response of WI-NRS ≥4 points reduction from baseline by Week 12 [ Time Frame: 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").
27. Study B: Absolute change from baseline in weekly average of daily sleep disturbances NRS at Week 12 [ Time Frame: Baseline to 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.
28. Study B: Percent change from baseline in weekly average of daily sleep disturbances NRS at Week 12 [ Time Frame: Baseline to 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.
29. Study B: Change from baseline in DLQI score at Week 12 [ Time Frame: Baseline to 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.
30. Study B: Change from baseline in the ItchyQoL score at Week 12 [ Time Frame: Baseline to 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.
31. Study B: Change from baseline in HADS total score at Week 12 [ Time Frame: Baseline to 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.
32. Study B: Percentage of participants experiencing TEAEs or SAEs from baseline through EOS [ Time Frame: Baseline to Week 24 ]
    Percentage of participants experiencing TEAEs or SAEs from baseline through EOS
33. Study B: Incidence of treatment-emergent ADA against dupilumab [ Time Frame: Baseline to Week 24 ]
    Incidence of treatment-emergent ADA against dupilumab

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Trial Transparency email recommended (Toll free number for US & Canada); 800-633-1610 ext option 6; Contact-US@sanofi.com

Locations

United States, California

Kern Research, Inc Site Number : 8400016; Recruiting

Bakersfield, California, United States, 93301

United States, Florida

Palm Harbor Dermatology Site Number : 8400024; Recruiting

Bellair, Florida, United States, 32756

University of Miami Site Number : 8400011; Recruiting

Miami, Florida, United States, 33136

United States, Georgia

Skin Care Physicians of Georgia Site Number : 8400030; Recruiting

Macon, Georgia, United States, 31217

Aeroallergy Research Laboratories Of Savannah Inc Site Number : 8400036; Recruiting

Savannah, Georgia, United States, 31406

United States, Indiana

Dawes Fretzin Clinical Research Group, LLC Site Number : 8400007; Recruiting

Indianapolis, Indiana, United States, 46250

United States, Kentucky

DS Research Site Number : 8400031; Recruiting

Louisville, Kentucky, United States, 40241

United States, Maryland

Johns Hopkins University Site Number : 8400020; Recruiting

Baltimore, Maryland, United States, 21205

United States, Nebraska

Nebraska Medical Research Institute, Inc. Site Number : 8400014; Recruiting

Bellevue, Nebraska, United States, 68123

United States, New York

Icahn School of Medicine at Mount Sinai Site Number : 8400034; Recruiting

New York, New York, United States, 10029

United States, South Carolina

National Allergy, Asthma & Urticaria Centers of Charleston, PA Site Number : 8400032; Recruiting

North Charleston, South Carolina, United States, 29420

Argentina

Investigational Site Number : 0320005; Recruiting

Caba, Buenos Aires, Argentina, 1015

Investigational Site Number : 0320001; Recruiting

Caba, Buenos Aires, Argentina, C1023AAB

Investigational Site Number : 0320006; Recruiting

Caba, Buenos Aires, Argentina, C1055AAO

Investigational Site Number : 0320004; Recruiting

Rosario, Santa Fe, Argentina, S2000DEJ

Investigational Site Number : 0320002; Recruiting

Buenos Aires, Argentina, C1121ABE

Investigational Site Number : 0320003; Recruiting

Ciudad Autonoma Buenos Aires, Argentina, C1414AIF

Canada, Alberta

Investigational Site Number : 1240001; Completed

Calgary, Alberta, Canada, T2G 1B1

Investigational Site Number : 1240008; Completed

Edmonton, Alberta, Canada, T6G 1C3

Canada, Ontario

Investigational Site Number : 1240002; Recruiting

London, Ontario, Canada, N6A2C2

Investigational Site Number : 1240003; Recruiting

Markham, Ontario, Canada, L3P 1X3

Investigational Site Number : 1240006; Recruiting

Toronto, Ontario, Canada, M4C 1L1

Canada, Quebec

Investigational Site Number : 1240005; Recruiting

Montreal, Quebec, Canada, H4A 3T2

Investigational Site Number : 1240004; Recruiting

Verdun, Quebec, Canada, H4G 3E7

China

Investigational Site Number : 1560003; Recruiting

Beijing, China, 100191

Investigational Site Number : 1560004; Recruiting

Chengdu, China, 610041

Investigational Site Number : 1560005; Recruiting

Guangzhou, China, 510080

Investigational Site Number : 1560002; Recruiting

Hangzhou, China, 310006

Investigational Site Number : 1560001; Recruiting

Shanghai, China, 200040

France

Investigational Site Number : 2500002; Active, not recruiting

Lille, France, 59037

Germany

Investigational Site Number : 2760002; Recruiting

Berlin, Germany, 12200

Hungary

Investigational Site Number : 3480001; Recruiting

Budapest, Hungary, 1036

Investigational Site Number : 3480005; Recruiting

Debrecen, Hungary, 4031

Investigational Site Number : 3480003; Recruiting

Szeged, Hungary, 6720

Investigational Site Number : 3480002; Recruiting

Zalaegerszeg, Hungary, 8900

Italy

Investigational Site Number : 3800003; Recruiting

Milano, Lombardia, Italy, 20122

Investigational Site Number : 3800002; Recruiting

Rozzano, Lombardia, Italy, 20089

Investigational Site Number : 3800004; Recruiting

Ancona, Italy, 60126

Investigational Site Number : 3800005; Recruiting

Firenze, Italy, 50125

Investigational Site Number : 3800001; Recruiting

Roma, Italy, 00168

Japan

Investigational Site Number : 3920002; Recruiting

Sakai-shi, Osaka, Japan, 593-8324

Investigational Site Number : 3920001; Recruiting

Tachikawa-shi, Tokyo, Japan, 190-0023

Korea, Republic of

Investigational Site Number : 4100004; Completed

Ansan-si, Gyeonggi-do, Korea, Republic of, 15355

Investigational Site Number : 4100005; Recruiting

Seoul, Seoul-teukbyeolsi, Korea, Republic of, 03080

Investigational Site Number : 4100003; Recruiting

Busan, Korea, Republic of, 602-739

Investigational Site Number : 4100001; Completed

Seoul, Korea, Republic of, 07441

Investigational Site Number : 4100002; Recruiting

Seoul, Korea, Republic of, 5278

Poland

Investigational Site Number : 6160003; Recruiting

Wroclaw, Dolnoslaskie, Poland, 51-503

Investigational Site Number : 6160005; Recruiting

Warszawa, Mazowieckie, Poland, 02-172

Investigational Site Number : 6160001; Recruiting

Krakow, Poland, 30-033

Spain

Investigational Site Number : 7240003; Recruiting

Barcelona, Barcelona [Barcelona], Spain, 08003

Investigational Site Number : 7240006; Recruiting

Barcelona, Barcelona [Barcelona], Spain, 08041

Investigational Site Number : 7240001; Recruiting

Pontevedra, Galicia [Galicia], Spain, 36002

Investigational Site Number : 7240005; Recruiting

Alicante, Spain, 03010

Investigational Site Number : 7240004; Recruiting

Córdoba, Spain, 14004

Sponsors and Collaborators

Sanofi

More Information

Additional Information:

EFC16973 Chronic Pruritus of Unknown Origin Website 

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT05263206
• Other Study ID Numbers: EFC16973; U1111-1253-9888 ( Registry Identifier: ICTRP ); 2023-508879-36-00 ( Registry Identifier: CTIS ); 2023-508879-36 ( Registry Identifier: CTIS ); 2021-004315-76 ( EudraCT Number )
• First Posted: March 2, 2022
• Last Update Posted: March 18, 2024
• Last Verified: March 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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

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

Additional relevant MeSH terms:

Pruritus; Skin Diseases; Skin Manifestations; Loratadine; Fexofenadine; Antipruritics; Dermatologic Agents; Anti-Allergic Agents; Histamine H1 Antagonists, Non-Sedating; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs