Clinical trial NCT05263206: Efficacy and Safety of Subcutaneous Dupilumab for the Treatment of Adult Participants With Chronic Pruritus of Unknown Origin (CPUO) (LIBERTY-CPUO-CHIC)
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Pruritus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2022-03-02
Enrollment: 284
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 was to 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 and will be treated 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 with either dupilumab or matching placebo in addition to their non-sedative antihistamine and emollient regimen. The treatment period for both study A and B will be followed by a 12-week follow-up period.

Detailed description: Study duration per participant will be up to 44 weeks for both Study A and Study B.

Eligibility 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.

Primary outcomes:
measure: 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
timeFrame: Baseline to Week 24
measure: Study B: Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by ≥4 from baseline to Week 12
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Study A; Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by ≥4 from baseline to Week 12
timeFrame: Baseline to Week 12
measure: Study A: Proportion of participants who scored "none" or "mild" in Patient Global Impression of Severity (PGIS) of pruritus at Week 24
timeFrame: Week 24
measure: Study A: Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by ≥4 from baseline over time until Week 24
timeFrame: Baseline to Week 24
measure: Study A: Time to first response of WI-NRS ≥4 points reduction from baseline by Week 24
timeFrame: Baseline to Week 24
measure: Study A: Absolute change from baseline in weekly average of daily WI-NRS at Week 24
timeFrame: Baseline to Week 24
measure: Study A: Percent change from baseline in weekly average of daily WI-NRS at Week 24
timeFrame: Baseline to Week 24
measure: Study A: Proportion of participants who scored "none" or "mild" in PGIS of pruritus at Week 12
timeFrame: Week 12
measure: Study A: Absolute change from baseline in weekly average of daily WI-NRS at Week 12
timeFrame: Baseline to Week 12
measure: Study A: Percent change from baseline in weekly average of daily WI-NRS at Week 12
timeFrame: Baseline to Week 12
measure: Study A: Absolute change from baseline in weekly average of daily sleep disturbance numerical rating scale (NRS) at Week 24
timeFrame: Baseline to Week 24
measure: Study A: Percent change from baseline in weekly average of daily sleep disturbance NRS at Week 24
timeFrame: Baseline to Week 24
measure: Study A: Change from baseline in Dermatology Life Quality Index (DLQI) score at Week 24
timeFrame: Baseline to Week 24
measure: Study A: Change from baseline in the Itchy quality of life (ItchyQoL) score at Week 24
timeFrame: Baseline to Week 24
measure: Study A: Change from baseline in Hospital Anxiety and Depression Scale (HADS) total score at Week 24
timeFrame: Baseline to Week 24
measure: Study A: Absolute change from baseline in weekly average of daily sleep disturbance NRS at Week 12
timeFrame: Baseline to Week 12
measure: Study A: Percent change from baseline in weekly average of daily sleep disturbance NRS at Week 12
timeFrame: Baseline to Week 12
measure: Study A: Change from baseline in DLQI score at Week 12
timeFrame: Baseline to Week 12
measure: Study A: Change from baseline in the ItchyQoL score at Week 12
timeFrame: Baseline to Week 12
measure: Study A: Change from baseline in HADS total score at Week 12
timeFrame: Baseline to Week 12
measure: Study A: Percentage of participants experiencing treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs) from baseline through end of study (EOS)
timeFrame: Baseline to Week 36
measure: Study A: Incidence of treatment-emergent antidrug antibodies (ADA) against dupilumab
timeFrame: Baseline to Week 36
measure: Study B: Proportion of participants who scored "none" or "mild" in PGIS of pruritus at Week 24
timeFrame: Week 24
measure: Study B: Proportion of participants who scored "none" or "mild" in PGIS of pruritus at Week 12
timeFrame: Week 12
measure: Study B: Absolute change from baseline in weekly average of daily WI-NRS at Week 12
timeFrame: Baseline to Week 12
measure: Study B: Percent change from baseline in weekly average of daily WI-NRS at Week 12
timeFrame: Baseline to Week 12
measure: Study B: Absolute change from baseline in weekly average of daily WI-NRS at Week 24
timeFrame: Baseline to Week 24
measure: Study B: Percentage change from baseline in weekly average of daily WI-NRS at Week 24
timeFrame: Baseline to Week 24
measure: Study B: Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by ≥4 from baseline, sustained from Week 19 through Week 24
timeFrame: Baseline to Week 19 through Week 24
measure: Study B: Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by ≥5 from baseline to Week 24
timeFrame: Baseline to Week 24
measure: Study B: Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by ≥4 from baseline to Week 24
timeFrame: Baseline to Week 24
measure: Study B: Proportion of participants with weekly average of daily WI-NRS <2 at Week 24
timeFrame: Week 24
measure: Study B: Time to first response of WI-NRS ≥4 points reduction from baseline by Week 24
timeFrame: Baseline to Week 24
measure: Study B: Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by ≥5 from baseline to Week 12
timeFrame: Baseline to Week 12
measure: Study B: Proportion of participants with weekly average of daily WI-NRS <2 at Week 12
timeFrame: Week 12
measure: Study B: Absolute change from baseline in weekly average of daily itch-related sleep disturbance NRS at Week 12 and Week 24
timeFrame: Baseline to Week 12 and Week 24
measure: Study B: Percent change from baseline in weekly average of daily itch-related sleep disturbance NRS at Week 12 and Week 24
timeFrame: Baseline to Week 12 and Week 24
measure: Study B: Change from baseline in DLQI score at Week 12 and Week 24
timeFrame: Baseline to Week 12 and Week 24
measure: Study B: Change from baseline in the ItchyQoL score at Week 12 and Week 24
timeFrame: Baseline to Week 12 and Week 24
measure: Study B: Change from baseline in HADS total score at Week 12 and Week 24
timeFrame: Baseline to Week 12 and Week 24
measure: Study B: Percentage of participants experiencing TEAEs or SAEs from baseline through EOS
timeFrame: Baseline to Week 36
measure: Study B: Incidence of treatment-emergent ADA against dupilumab
timeFrame: Baseline to Week 36
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: Kern Allergy and Medical Research- Site Number : 8400016
state: California
city: La Jolla
country: United States
facility: Modena Allergy + Asthma- Site Number : 8400038
state: California
city: Washington
country: United States
facility: FoxHall Dermatology- Site Number : 8400042
state: District of Columbia
city: Belleair
country: United States
facility: Palm Harbor Dermatology- Site Number : 8400024
state: Florida
city: Miami
country: United States
facility: University of Miami Hospital- Site Number : 8400011
state: Florida
city: Macon
country: United States
facility: Skin Care Physicians of Georgia - Macon- Site Number : 8400030
state: Georgia
city: Savannah
country: United States
facility: Aeroallergy Research Laboratory- Site Number : 8400036
state: Georgia
city: Indianapolis
country: United States
facility: Dawes Fretzin Clinical Research- Site Number : 8400007
state: Indiana
city: Louisville
country: United States
facility: Dermatology Specialists Research (DS Research) - Kentucky- Site Number : 8400031
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Hospital- Site Number : 8400020
state: Maryland
city: Bellevue
country: United States
facility: The Asthma and Allergy Center- Site Number : 8400014
state: Nebraska
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai- Site Number : 8400034
state: New York
city: Fargo
country: United States
facility: AXIS Clinicals - Fargo- Site Number : 8400037
state: North Dakota
city: Boardman
country: United States
facility: Optima Research - Boardman- Site Number : 8400039
state: Ohio
city: Columbia
country: United States
facility: Columbia Dermatology & Aesthetics- Site Number : 8400047
state: South Carolina
city: North Charleston
country: United States
facility: National Allergy and Asthma - North Charleston - Northside Drive- Site Number : 8400032
state: South Carolina
city: Sugar Land
country: United States
facility: Complete Dermatology - Sugar Land- Site Number : 8400046
state: Texas
city: Rosario
country: Argentina
facility: Investigational Site Number : 0320004
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320005
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320001
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320006
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320002
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320003
city: Calgary
country: Canada
facility: Investigational Site Number : 1240001
state: Alberta
city: Edmonton
country: Canada
facility: Investigational Site Number : 1240008
state: Alberta
city: London
country: Canada
facility: Investigational Site Number : 1240002
state: Ontario
city: Markham
country: Canada
facility: Investigational Site Number : 1240003
state: Ontario
city: Toronto
country: Canada
facility: Investigational Site Number : 1240006
state: Ontario
city: Montreal
country: Canada
facility: Investigational Site Number : 1240005
state: Quebec
city: Verdun
country: Canada
facility: Investigational Site Number : 1240004
state: Quebec
city: Beijing
country: China
facility: Investigational Site Number : 1560003
city: Chengdu
country: China
facility: Investigational Site Number : 1560004
city: Guangzhou
country: China
facility: Investigational Site Number : 1560005
city: Hangzhou
country: China
facility: Investigational Site Number : 1560002
city: Shanghai
country: China
facility: Investigational Site Number : 1560001
city: Lille
country: France
facility: Investigational Site Number : 2500002
city: Berlin
country: Germany
facility: Investigational Site Number : 2760002
city: Mainz
country: Germany
facility: Investigational Site Number : 2760003
city: Budapest
country: Hungary
facility: Investigational Site Number : 3480001
city: Debrecen
country: Hungary
facility: Investigational Site Number : 3480005
city: Szeged
country: Hungary
facility: Investigational Site Number : 3480003
city: Zalaegerszeg
country: Hungary
facility: Investigational Site Number : 3480002
city: Torette
country: Italy
facility: Investigational Site Number : 3800004
state: Ancona
city: Florence
country: Italy
facility: Investigational Site Number : 3800005
state: Firenze
city: Milan
country: Italy
facility: Investigational Site Number : 3800003
state: Milano
city: Rozzano
country: Italy
facility: Investigational Site Number : 3800002
state: Milano
city: Rome
country: Italy
facility: Investigational Site Number : 3800001
state: Roma
city: Urayasu-shi
country: Japan
facility: Investigational Site Number : 3920007
state: Chiba
city: Obihiro
country: Japan
facility: Investigational Site Number : 3920003
state: Hokkaido
city: Sapporo
country: Japan
facility: Investigational Site Number : 3920006
state: Hokkaido
city: Habikino
country: Japan
facility: Investigational Site Number : 3920004
state: Osaka
city: Sakai
country: Japan
facility: Investigational Site Number : 3920002
state: Osaka
city: Izumo
country: Japan
facility: Investigational Site Number : 3920005
state: Shimane
city: Tachikawa
country: Japan
facility: Investigational Site Number : 3920001
state: Tokyo
city: Busan
country: Korea, Republic of
facility: Investigational Site Number : 4100003
state: Busan-gwangyeoksi
city: Ansan-si
country: Korea, Republic of
facility: Investigational Site Number : 4100004
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100005
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100002
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100001
state: Seoul-teukbyeolsi
city: Wroclaw
country: Poland
facility: Investigational Site Number : 6160007
state: Dolnoslaskie
city: Wroclaw
country: Poland
facility: Investigational Site Number : 6160003
state: Dolnoslaskie
city: Wroclaw
country: Poland
facility: Investigational Site Number : 6160003
state: Dolnoslaskie
city: Krakow
country: Poland
facility: Investigational Site Number : 6160001
state: Malopolskie
city: Warsaw
country: Poland
facility: Investigational Site Number : 6160008
state: Mazowieckie
city: Warsaw
country: Poland
facility: Investigational Site Number : 6160005
state: Mazowieckie
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240003
state: Barcelona [Barcelona]
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240006
state: Catalunya [Cataluña]
city: Pontevedra
country: Spain
facility: Investigational Site Number : 7240001
state: Pontevedra [Pontevedra]
city: Alicante
country: Spain
facility: Investigational Site Number : 7240005
city: Córdoba
country: Spain
facility: Investigational Site Number : 7240004
city: Kaohsiung
country: Taiwan
facility: Investigational Site Number : 1580003
city: New Taipei City
country: Taiwan
facility: Investigational Site Number : 1580004
city: Taipei City
country: Taiwan
facility: Investigational Site Number : 1580001
city: Taoyuan City
country: Taiwan
facility: Investigational Site Number : 1580002
Study officials:
References: