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

Pruritus Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05263206
• Other study ID #: EFC16973
• Secondary ID: U1111-1253-98882
• Status: Recruiting
• Phase: Phase 3
• Start date: February 15, 2022
• Est. completion date: October 3, 2025

Study information

• Verified date: May 2024
• Source: Sanofi
• Contact: Trial Transparency email recommended (Toll free number for US &
• Phone: 800-633-1610
• Email: Contact-US[@]sanofi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 208
• Est. completion date: October 3, 2025
• Est. primary completion date: March 21, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Pruritus

Intervention

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

Locations

Country	Name	City	State
Argentina	Investigational Site Number : 0320001	Caba	Buenos Aires
Argentina	Investigational Site Number : 0320005	Caba	Buenos Aires
Argentina	Investigational Site Number : 0320006	Caba	Buenos Aires
Argentina	Investigational Site Number : 0320002	Ciudad Autonoma Bs As
Argentina	Investigational Site Number : 0320003	Ciudad Autonoma Buenos Aires
Argentina	Investigational Site Number : 0320004	Rosario	Santa Fe
Canada	Investigational Site Number : 1240001	Calgary	Alberta
Canada	Investigational Site Number : 1240008	Edmonton	Alberta
Canada	Investigational Site Number : 1240002	London	Ontario
Canada	Investigational Site Number : 1240003	Markham	Ontario
Canada	Investigational Site Number : 1240005	Montreal	Quebec
Canada	Investigational Site Number : 1240006	Toronto	Ontario
Canada	Investigational Site Number : 1240004	Verdun	Quebec
China	Investigational Site Number : 1560003	Beijing
China	Investigational Site Number : 1560004	Chengdu
China	Investigational Site Number : 1560005	Guangzhou
China	Investigational Site Number : 1560002	Hangzhou
China	Investigational Site Number : 1560001	Shanghai
France	Investigational Site Number : 2500002	Lille
Germany	Investigational Site Number : 2760002	Berlin
Hungary	Investigational Site Number : 3480001	Budapest
Hungary	Investigational Site Number : 3480005	Debrecen
Hungary	Investigational Site Number : 3480003	Szeged
Hungary	Investigational Site Number : 3480002	Zalaegerszeg
Italy	Investigational Site Number : 3800004	Ancona
Italy	Investigational Site Number : 3800005	Firenze
Italy	Investigational Site Number : 3800003	Milano	Lombardia
Italy	Investigational Site Number : 3800001	Roma
Italy	Investigational Site Number : 3800002	Rozzano	Lombardia
Japan	Investigational Site Number : 3920002	Sakai-shi	Osaka
Japan	Investigational Site Number : 3920001	Tachikawa-shi	Tokyo
Korea, Republic of	Investigational Site Number : 4100004	Ansan-si	Gyeonggi-do
Korea, Republic of	Investigational Site Number : 4100003	Busan
Korea, Republic of	Investigational Site Number : 4100001	Seoul
Korea, Republic of	Investigational Site Number : 4100002	Seoul
Korea, Republic of	Investigational Site Number : 4100005	Seoul	Seoul-teukbyeolsi
Poland	Investigational Site Number : 6160001	Krakow
Poland	Investigational Site Number : 6160005	Warszawa	Mazowieckie
Poland	Investigational Site Number : 6160003	Wroclaw	Dolnoslaskie
Spain	Investigational Site Number : 7240005	Alicante
Spain	Investigational Site Number : 7240003	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240006	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240004	Córdoba
Spain	Investigational Site Number : 7240001	Pontevedra	Galicia [Galicia]
United States	Kern Research, Inc Site Number : 8400016	Bakersfield	California
United States	Johns Hopkins University Site Number : 8400020	Baltimore	Maryland
United States	Palm Harbor Dermatology Site Number : 8400024	Bellair	Florida
United States	Nebraska Medical Research Institute, Inc. Site Number : 8400014	Bellevue	Nebraska
United States	Dawes Fretzin Clinical Research Group, LLC Site Number : 8400007	Indianapolis	Indiana
United States	DS Research Site Number : 8400031	Louisville	Kentucky
United States	Skin Care Physicians of Georgia Site Number : 8400030	Macon	Georgia
United States	University of Miami Site Number : 8400011	Miami	Florida
United States	Icahn School of Medicine at Mount Sinai Site Number : 8400034	New York	New York
United States	National Allergy, Asthma & Urticaria Centers of Charleston, PA Site Number : 8400032	North Charleston	South Carolina
United States	Aeroallergy Research Laboratories Of Savannah Inc Site Number : 8400036	Savannah	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  China,  France,  Germany,  Hungary,  Italy,  Japan,  Korea, Republic of,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Study A: Incidence of treatment-emergent antidrug antibodies (ADA) against dupilumab	Incidence of treatment-emergent ADA against dupilumab	Baseline to Week 36
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Study B: Incidence of treatment-emergent ADA against dupilumab	Incidence of treatment-emergent ADA against dupilumab	Baseline to Week 24

External Links

•   EFC16973 Chronic Pruritus of Unknown Origin Website