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

Phase 3RecruitingNCT05263206

Sanofi284 enrolled

Overview

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.

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

284

Conditions

Pruritus

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 90 Years

Medical Language ↔ Plain English

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.

Locations (85)

Kern Allergy and Medical Research- Site Number : 8400016

Bakersfield, California, United States

COMPLETED

Modena Allergy + Asthma- Site Number : 8400038

La Jolla, California, United States

RECRUITING

FoxHall Dermatology- Site Number : 8400042

Washington D.C., District of Columbia, United States

RECRUITING

Palm Harbor Dermatology- Site Number : 8400024

Belleair, Florida, United States

Outcomes

Primary Outcomes

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").

Time frame: 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").

Time frame: Baseline to Week 12

Secondary Outcomes

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").

Time frame: 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".

Time frame: 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").

Time frame: 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").

Time frame: 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").

Time frame: 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").

Time frame: Baseline to Week 24

Study A: Proportion of participants who scored "none" or "mild" in PGIS of pruritus at Week 12

Time frame: 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").

Time frame: 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").

Time frame: Baseline to Week 12

Study A: Absolute change from baseline in weekly average of daily sleep disturbance 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.

Time frame: Baseline to Week 24

Study A: Percent change from baseline in weekly average of daily sleep disturbance NRS at Week 24

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline to Week 24

Study A: Absolute change from baseline in weekly average of daily sleep disturbance NRS at Week 12

Time frame: Baseline to Week 12

Study A: Percent change from baseline in weekly average of daily sleep disturbance NRS at Week 12

Time frame: Baseline to Week 12

Study A: Change from baseline in DLQI score at Week 12

Time frame: 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.

Time frame: Baseline to Week 12

Study A: Change from baseline in HADS total score at Week 12

Time frame: 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

Time frame: Baseline to Week 36

Study A: Incidence of treatment-emergent antidrug antibodies (ADA) against dupilumab

Incidence of treatment-emergent ADA against dupilumab

Time frame: Baseline to Week 36

Study B: Proportion of participants who scored "none" or "mild" in PGIS of pruritus at Week 24

Time frame: Week 24

Study B: Proportion of participants who scored "none" or "mild" in PGIS of pruritus at Week 12

Time frame: 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").

Time frame: 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").

Time frame: Baseline to Week 12

Study B: 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").

Time frame: Baseline to Week 24

Study B: Percentage 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").

Time frame: Baseline to Week 24

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

WI-NRS is a PRO comprised of a single item rated on a scale from 0 ("No itch") to 10 ("Worst imaginable itch").

Time frame: Baseline to Week 19 through Week 24

Study B: Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by ≥5 from 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").

Time frame: 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 24

WI-NRS is a PRO comprised of a single item rated on a scale from 0 ("No itch") to 10 ("Worst imaginable itch").

Time frame: Baseline to Week 24

Study B: Proportion of participants with weekly average of daily WI-NRS <2 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").

Time frame: Week 24

Study B: 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").

Time frame: Baseline to Week 24

Study B: Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by ≥5 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").

Time frame: Baseline to Week 12

Study B: Proportion of participants with weekly average of daily WI-NRS <2 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").

Time frame: Week 12

Study B: Absolute change from baseline in weekly average of daily itch-related sleep disturbance NRS at Week 12 and Week 24

Time frame: Baseline to Week 12 and Week 24

Study B: Percent change from baseline in weekly average of daily itch-related sleep disturbance NRS at Week 12 and Week 24

Time frame: Baseline to Week 12 and Week 24

Study B: Change from baseline in DLQI score at Week 12 and Week 24

Time frame: Baseline to Week 12 and Week 24

Study B: Change from baseline in the ItchyQoL score at Week 12 and Week 24

Time frame: Baseline to Week 12 and Week 24

Study B: Change from baseline in HADS total score at Week 12 and Week 24

Time frame: Baseline to Week 12 and Week 24

Study B: Percentage of participants experiencing TEAEs or SAEs from baseline through EOS

Percentage of participants experiencing TEAEs or SAEs from baseline through EOS

Time frame: Baseline to Week 36

Study B: Incidence of treatment-emergent ADA against dupilumab

Incidence of treatment-emergent ADA against dupilumab

Time frame: Baseline to Week 36

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

Overview

Conditions

Interventions

Eligibility

Locations (85)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts