Clinical trial NCT04183335: Study of Dupilumab for the Treatment of Patients With Prurigo Nodularis, Inadequately Controlled on Topical Prescription Therapies or When Those Therapies Are Not Advisable (LIBERTY-PN PRIME)
Official title: A Randomized, Double Blind, Placebo-controlled, Multi-center, Parallel Group Study to Evaluate the Efficacy and Safety of Dupilumab in Patients With Prurigo Nodularis Who Are Inadequately Controlled on Topical Prescription Therapies or When Those Therapies Are Not Advisable
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Neurodermatitis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2019-12-03
Enrollment: 151
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To demonstrate the efficacy of dupilumab on itch response in participants with prurigo nodularis (PN), inadequately controlled on topical prescription therapies or when those therapies are not advisable.

Secondary Objectives:

To demonstrate the efficacy of dupilumab on additional itch endpoints in participants with PN, inadequately controlled on topical prescription therapies or when those therapies are not advisable.

To demonstrate efficacy of dupilumab on skin lesions of PN. To demonstrate the improvement in health-related quality of life. To evaluate safety outcome measures. To evaluate immunogenicity of dupilumab.

Detailed description: The duration of study for each participant included 2-4 weeks of screening period, 24 weeks of treatment period and 12 weeks of post treatment period.

Eligibility criteria: Inclusion Criteria:

Must be 18 to 80 years of age, at the time of signing the informed consent.

With a clinical diagnosis of PN defined by all of the following:

* Diagnosed by a dermatologist for at least 3 months before the screening visit.
* On the worst-Itch Numeric Rating Scale (WI-NRS) ranged from 0 to 10, participants who had an average worst itch score of greater than or equal to (\>=) 7 in the 7 days prior to Day 1.
* Participants who had a minimum of 20 PN lesions in total on both legs, and/or both arms and/or trunk, at screening visit and Day 1.
* History of failing a 2-week course of medium-to-superpotent TCS or when TCS were not medically advisable.
* Had applied a stable dose of topical emollient (moisturizer) once or twice daily for at least 5 out of the 7 consecutive days immediately before Day 1.
* Was willing and abled to complete a daily symptom electronic-diary for the duration of the study.

Exclusion Criteria:

Participants were excluded from the study if any of the following criteria apply:

* Presence of skin morbidities other than PN and mild atopic dermatitis (AD) that interfered with the assessment of the study outcomes.
* PN secondary to medications.
* PN secondary to medical conditions such as neuropathy or psychiatric disease.
* Within 6 months before the screening visit, or documented diagnosis of moderate to severe AD from screening visit to randomization visit.
* Severe concomitant illness(es) under poor control that, in the investigator's judgment, would adversely affect the participant's participation in the study.
* Severe renal conditions (eg, participants with uremia and/or on dialysis).
* Participants with uncontrolled thyroid disease.
* Active tuberculosis or non-tuberculous mycobacterial infection, or a history of incompletely treated tuberculosis unless documented adequately treated.
* Diagnosed active endoparasitic infections; suspected or high risk of endoparasitic infection, unless clinical and (if necessary) laboratory assessment had ruled out active infection before randomization.
* Active chronic or acute infection (except human immunodeficiency virus infection) required treatment with systemic antibiotics, antivirals, antiprotozoals, or antifungals within 2 weeks before the screening visit or during the screening period.
* 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, completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Primary outcomes:
measure: Percentage of Participants With Improvement (Reduction) in Worst Itch Numeric Rating Scale (WI-NRS) Scores by Greater Than or Equal to (>=) 4 Points From Baseline to Week 24
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Percentage of Participants With Investigator's Global Assessment For Prurigo Nodularis-Stage (IGA PN-S) Scores of 0 or 1 at Week 24
timeFrame: At Week 24
measure: Percentage of Participants With Both an Improvement (Reduction) in WI-NRS Scores by >=4 Points and an IGA PN-S Scores of 0 or 1 From Baseline at Week 24
timeFrame: Baseline, Week 24
measure: Percent Change From Baseline in WI-NRS Scores at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by Dermatology Life Quality Index (DLQI) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Skin Pain-NRS at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Total Score at Week 24
timeFrame: Baseline, Week 24
measure: Probability of Participants With an Improvement (Reduction) in WI-NRS Scores by >=4 Points From Baseline at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in WI-NRS Scores at Week 12 and 24
timeFrame: Baseline, Weeks 12 and 24
measure: Percent Change From Baseline in WI-NRS Scores at Weeks 2, 4 and 12
timeFrame: Baseline, Weeks 2, 4 and 12
measure: Percent Change From Baseline in WI-NRS Scores at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24
timeFrame: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24
measure: Percentage of Participants With Improvement (Reduction) in WI-NRS Scores by >=4 Points From Baseline at Week 12
timeFrame: Baseline, Week 12
measure: Percentage of Participants With Improvement (Reduction) in WI-NRS Scores by >=4 Points From Baseline at Week 4
timeFrame: Baseline, Week 4
measure: Percentage of Participants Achieving >=4 Points Improvement (Reduction) From Baseline in WI-NRS Scores at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24
timeFrame: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24
measure: Onset of Action Based on Change From Baseline in WI-NRS Scores at Week 3
timeFrame: Baseline, Week 3
measure: Percentage of Participants With Investigator's Global Assessment for PN-Stage (IGA PN-S) 0 or 1 Score at Weeks 4, 8, and 12
timeFrame: At Weeks 4, 8 and 12
measure: Change From Baseline in IGA PN-S Scores at Weeks 4, 8, 12, and 24
timeFrame: Baseline, Weeks 4, 8, 12, and 24
measure: Percentage of Participants With Investigator's Global Assessment for PN-Activity (IGA PN-A) 0 or 1 Score at Weeks 4, 8, 12 and 24
timeFrame: At Weeks 4, 8, 12 and 24
measure: Change From Baseline in HRQoL as Measured by DLQI at Week 12
timeFrame: Baseline, Week 12
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: From the first IMP administration to the last IMP administration + 14 weeks (i.e., up to 36 weeks)
measure: Number of Participants With Treatment-emergent and Treatment Boosted Antidrug Antibodies (ADA)
timeFrame: From the first IMP administration to the last IMP administration + 14 weeks (i.e., up to 36 weeks)
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Investigational Site Number :8400011
state: Arizona
city: Fort Smith
country: United States
facility: Investigational Site Number :8400022
state: Arkansas
city: Sacramento
country: United States
facility: Investigational Site Number :8400026
state: California
city: Miami
country: United States
facility: Investigational Site Number :8400014
state: Florida
city: Columbus
country: United States
facility: Investigational Site Number :8400004
state: Georgia
city: Newnan
country: United States
facility: Investigational Site Number :8400003
state: Georgia
city: Sandy Springs
country: United States
facility: Investigational Site Number :8400017
state: Georgia
city: Indianapolis
country: United States
facility: Investigational Site Number :8400016
state: Indiana
city: Clarkston
country: United States
facility: Investigational Site Number :8400018
state: Michigan
city: Saint Louis
country: United States
facility: Investigational Site Number :8400013
state: Missouri
city: East Windsor
country: United States
facility: Investigational Site Number :8400024
state: New Jersey
city: Athens
country: United States
facility: Investigational Site Number :8400009
state: Ohio
city: Dublin
country: United States
facility: Investigational Site Number :8400001
state: Ohio
city: Tulsa
country: United States
facility: Investigational Site Number :8400007
state: Oklahoma
city: Philadelphia
country: United States
facility: Investigational Site Number :8400010
state: Pennsylvania
city: Charleston
country: United States
facility: Investigational Site Number :8400015
state: South Carolina
city: Bellaire
country: United States
facility: Investigational Site Number :8400006
state: Texas
city: Houston
country: United States
facility: Investigational Site Number :8400025
state: Texas
city: Pflugerville
country: United States
facility: Investigational Site Number :8400002
state: Texas
city: San Antonio
country: United States
facility: Investigational Site Number :8400019
state: Texas
city: Norfolk
country: United States
facility: Investigational Site Number :8400005
state: Virginia
city: Caba
country: Argentina
facility: Investigational Site Number :0320008
state: Buenos Aires
city: Caba
country: Argentina
facility: Investigational Site Number :0320005
state: Buenos Aires
city: Caba
country: Argentina
facility: Investigational Site Number :0320002
state: Buenos Aires
city: Caba
country: Argentina
facility: Investigational Site Number :0320004
state: Ciudad De Buenos Aires
city: Caba
country: Argentina
facility: Investigational Site Number :0320007
state: Ciudad De Buenos Aires
city: San Miguel de Tucuman
country: Argentina
facility: Investigational Site Number :0320003
state: Tucumán
city: Buenos Aires
country: Argentina
facility: Investigational Site Number :0320001
city: Caba
country: Argentina
facility: Investigational Site Number :0320006
city: Mendoza
country: Argentina
facility: Investigational Site Number :0320009
city: Beijing
country: China
facility: Investigational Site Number :1560004
city: Chengdu
country: China
facility: Investigational Site Number :1560001
city: Hangzhou
country: China
facility: Investigational Site Number :1560002
city: Wuxi
country: China
facility: Investigational Site Number :1560003
city: Reims
country: France
facility: Investigational Site Number :2500005
city: Yokohama-shi
country: Japan
facility: Investigational Site Number :3920009
state: Kanagawa
city: Kyoto-shi
country: Japan
facility: Investigational Site Number :3920005
state: Kyoto
city: Nagasaki-shi
country: Japan
facility: Investigational Site Number :3920007
state: Nagasaki
city: Tokorozawa-shi
country: Japan
facility: Investigational Site Number :3920003
state: Saitama
city: Izumo-shi
country: Japan
facility: Investigational Site Number :3920010
state: Shimane
city: Bunkyo-ku
country: Japan
facility: Investigational Site Number :3920004
state: Tokyo
city: Itabashi-ku
country: Japan
facility: Investigational Site Number :3920006
state: Tokyo
city: Shinagawa-Ku
country: Japan
facility: Investigational Site Number :3920001
state: Tokyo
city: Nagoya-shi
country: Japan
facility: Investigational Site Number :3920002
city: Seongnam-si
country: Korea, Republic of
facility: Investigational Site Number :4100007
state: Gyeonggi-do
city: Incheon
country: Korea, Republic of
facility: Investigational Site Number :4100005
state: Incheon-gwangyeoksi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number :4100002
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number :4100003
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number :4100004
state: Seoul-teukbyeolsi
city: Incheon
country: Korea, Republic of
facility: Investigational Site Number :4100001
city: Guadalajara
country: Mexico
facility: Investigational Site Number :4840002
state: Jalisco
city: Monterrey
country: Mexico
facility: Investigational Site Number :4840001
state: Nuevo León
city: Monterrey
country: Mexico
facility: Investigational Site Number :4840005
state: Nuevo León
city: Guadalajara
country: Mexico
facility: Investigational Site Number :4840006
city: Veracruz
country: Mexico
facility: Investigational Site Number :4840003
city: Chelyabinsk
country: Russian Federation
facility: Investigational Site Number :6430008
city: Krasnodar
country: Russian Federation
facility: Investigational Site Number :6430007
city: Moscow
country: Russian Federation
facility: Investigational Site Number :6430005
city: Moscow
country: Russian Federation
facility: Investigational Site Number :6430010
city: Moscow
country: Russian Federation
facility: Investigational Site Number :6430006
city: Saratov
country: Russian Federation
facility: Investigational Site Number :6430009
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number :6430002
city: Stavropol
country: Russian Federation
facility: Investigational Site Number :6430001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: