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)

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.

Detailed description

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

Interventions

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

Primary outcome measures

• 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]
• 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]

Secondary outcome measures (12)

• 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]
• 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]
• 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]
• Study A: Time to first response of WI-NRS ≥4 points reduction from baseline by Week 24 [Time frame: Baseline to Week 24]
• Study A: Absolute change from baseline in weekly average of daily WI-NRS at Week 24 [Time frame: Baseline to Week 24]
• Study A: Percent change from baseline in weekly average of daily WI-NRS at Week 24 [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 [Time frame: Baseline to Week 12]
• Study A: Percent change from baseline in weekly average of daily WI-NRS at Week 12 [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 [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 [Time frame: Baseline to Week 24]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 18 centers

• Kern Allergy and Medical Research- Site Number : 8400016 — Bakersfield
• Modena Allergy + Asthma- Site Number : 8400038 — La Jolla
• FoxHall Dermatology- Site Number : 8400042 — Washington D.C.
• Palm Harbor Dermatology- Site Number : 8400024 — Belleair
• University of Miami Hospital- Site Number : 8400011 — Miami
• Skin Care Physicians of Georgia - Macon- Site Number : 8400030 — Macon
• Aeroallergy Research Laboratory- Site Number : 8400036 — Savannah
• Dawes Fretzin Clinical Research- Site Number : 8400007 — Indianapolis
• … and 10 more centers

China · 9 centers

• Investigational Site Number : 1560003 — Beijing
• Investigational Site Number : 1560004 — Chengdu
• Investigational Site Number : 1560009 — Chongqing
• Investigational Site Number : 1560006 — Guangzhou
• Investigational Site Number : 1560005 — Guangzhou
• Investigational Site Number : 1560002 — Hangzhou
• Investigational Site Number : 1560001 — Shanghai
• Investigational Site Number : 1560011 — Suzhou
• … and 1 more center

Argentina · 8 centers

• Investigational Site Number : 0320004 — Rosario
• Investigational Site Number : 0320008 — Rosario
• Investigational Site Number : 0320005 — Buenos Aires
• Investigational Site Number : 0320001 — Buenos Aires
• Investigational Site Number : 0320006 — Buenos Aires
• Investigational Site Number : 0320007 — Buenos Aires
• Investigational Site Number : 0320002 — Buenos Aires
• Investigational Site Number : 0320003 — Buenos Aires

Canada · 7 centers

• Investigational Site Number : 1240001 — Calgary
• Investigational Site Number : 1240008 — Edmonton
• Investigational Site Number : 1240002 — London
• Investigational Site Number : 1240003 — Markham
• Investigational Site Number : 1240006 — Toronto
• Investigational Site Number : 1240005 — Montreal
• Investigational Site Number : 1240004 — Verdun

Hungary · 7 centers

• Investigational Site Number : 3480001 — Budapest
• Investigational Site Number : 3480009 — Budapest
• Investigational Site Number : 3480005 — Debrecen
• Investigational Site Number : 3480010 — Gyula
• Investigational Site Number : 3480003 — Szeged
• Investigational Site Number : 3480011 — Székesfehérvár
• Investigational Site Number : 3480002 — Zalaegerszeg

Italy · 7 centers

• Azienda Ospedaliero-Universitaria di Ferrara-Site Number : 3800007 — Cona
• AUSL Toscana Centro - Presidio Ospedaliero "Piero Palagi-"Site Number : 3800005 — Florence
• Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico-Site Number : 3800003 — Milan
• Investigational Site Number : 3800002 — Rozzano
• Investigational Site Number : 3800006 — Naples
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Site Number : 3800001 — Rome
• Azienda Ospedaliero Universitaria delle Marche-Site Number : 3800004 — Ancona

Japan · 7 centers

• Investigational Site Number : 3920007 — Urayasu
• Investigational Site Number : 3920003 — Obihiro
• Investigational Site Number : 3920006 — Sapporo
• Investigational Site Number : 3920004 — Habikino
• Investigational Site Number : 3920002 — Sakai
• Investigational Site Number : 3920005 — Izumo
• Investigational Site Number : 3920001 — Tachikawa

South Korea · 7 centers

• Investigational Site Number : 4100003 — Busan
• Investigational Site Number : 4100004 — Ansan-si
• Investigational Site Number : 4100005 — Seoul
• … and 4 more centers

Poland · 6 centers

• Investigational Site Number : 6160001 — Krakow
• Investigational Site Number : 6160007 — Wroclaw
• Investigational Site Number : 6160003 — Wroclaw
• Investigational Site Number : 6160003 — Wroclaw
• Investigational Site Number : 6160008 — Warsaw
• Investigational Site Number : 6160005 — Warsaw

Germany · 5 centers

• Investigational Site Number : 2760005 — Bad Bentheim
• Investigational Site Number : 2760002 — Berlin
• Investigational Site Number : 2760004 — Frankfurt
• Investigational Site Number : 2760003 — Mainz
• Investigational Site Number : 2760001 — Münster

Spain · 5 centers

Center list to be confirmed — check the primary protocol.

Taiwan · 4 centers

Center list to be confirmed — check the primary protocol.

France · 3 centers

• Investigational Site Number : 2500001 — Brest
• Investigational Site Number : 2500003 — Nice
• Investigational Site Number : 2500004 — Reims

Identifiers

NCT: NCT05263206 · EFC16973 · U1111-1253-9888 · 2023-508879-36-00 · 2023-508879-36 · 2021-004315-76

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗