Clinical trial NCT04202679: Study of Dupilumab for the Treatment of Patients With Prurigo Nodularis, Inadequately Controlled on Topical Prescription Therapies or When Those Therapies Are Not Advisable (PRIME2)
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: 2019-12-17
Enrollment: 160
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 therapy 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 therapy 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) ranging from 0 to 10, participants must have an average worst itch score of \>=7 in the 7 days prior to Day1.
* Participants must have 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 topical corticosteroids (TCS) or when TCS are not medically advisable
* Have 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.

Must be willing and able to complete a daily symptom eDiary 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 that may interfere 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 atopic dermatitis 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 have ruled out active infection before randomization.
* Active chronic or acute infection (except HIV) requiring treatment with systemic antibiotics, antivirals, antiprotozoals, or antifungals within 2 weeks before the screening visit and 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 Greater Than or Equal to (>=) 4 Points Improvement (Reduction) From Baseline in Worst-Itch Numeric Rating Scale (WI-NRS) Scores at Week 12
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Percentage of Participants With >=4 Points Improvement (Reduction) From Baseline in WI-NRS Scores at Week 24
timeFrame: Baseline, Week 24
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 by >=4 Points and an IGA PN-S Score of 0 or 1 From Baseline at Week 24
timeFrame: Baseline, Week 24
measure: Percentage of Participants With IGA PN-S Scores of 0 or 1 at Week 12
timeFrame: At Week 12
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 Sleep-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 by >=4 From Baseline at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in WI-NRS Scores at Weeks 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 >=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 at Week 4
timeFrame: Baseline, Week 4
measure: Percentage of Participants With Investigator's Global Assessment for PN-Stage (IGA PN-S) Score of 0 or 1 at Weeks 4 and 8
timeFrame: At Weeks 4 and 8
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) Score of 0 or 1 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: Fort Smith
country: United States
facility: Investigational Site Number :8400054
state: Arkansas
city: Sacramento
country: United States
facility: Investigational Site Number :8400008
state: California
city: Pembroke Pines
country: United States
facility: Investigational Site Number :8400005
state: Florida
city: Plainfield
country: United States
facility: Investigational Site Number :8400002
state: Indiana
city: Baltimore
country: United States
facility: Investigational Site Number :8400003
state: Maryland
city: East Windsor
country: United States
facility: Investigational Site Number :8400006
state: New Jersey
city: Sugar Land
country: United States
facility: Investigational Site Number :8400001
state: Texas
city: Calgary
country: Canada
facility: Investigational Site Number :1240002
state: Alberta
city: Surrey
country: Canada
facility: Investigational Site Number :1240006
state: British Columbia
city: Markham
country: Canada
facility: Investigational Site Number :1240007
state: Ontario
city: Newmarket
country: Canada
facility: Investigational Site Number :1240008
state: Ontario
city: Toronto
country: Canada
facility: Investigational Site Number :1240001
state: Ontario
city: Saskatoon
country: Canada
facility: Investigational Site Number :1240009
state: Saskatchewan
city: Valdivia
country: Chile
facility: Investigational Site Number :1520005
state: Los Ríos
city: Osorno
country: Chile
facility: Investigational Site Number :1520006
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number :1520003
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number :1520001
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number :1520004
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number :1520002
city: Bordeaux
country: France
facility: Investigational Site Number :2500007
city: Brest
country: France
facility: Investigational Site Number :2500001
city: Le Mans
country: France
facility: Investigational Site Number :2500008
city: Lille
country: France
facility: Investigational Site Number :2500002
city: Lyon
country: France
facility: Investigational Site Number :2500006
city: Paris
country: France
facility: Investigational Site Number :2500004
city: Reims
country: France
facility: Investigational Site Number :2500005
city: Toulouse
country: France
facility: Investigational Site Number :2500003
city: Debrecen
country: Hungary
facility: Investigational Site Number :3480004
city: Orosháza
country: Hungary
facility: Investigational Site Number :3480002
city: Pécs
country: Hungary
facility: Investigational Site Number :3480005
city: Szeged
country: Hungary
facility: Investigational Site Number :3480003
city: Rozzano
country: Italy
facility: Investigational Site Number :3800001
state: Milano
city: Ancona
country: Italy
facility: Investigational Site Number :3800004
city: Catanzaro
country: Italy
facility: Investigational Site Number :3800003
city: Milano
country: Italy
facility: Investigational Site Number :3800002
city: Busan
country: Korea, Republic of
facility: Investigational Site Number :4100002
state: Busan-gwangyeoksi
city: Bucheon-si
country: Korea, Republic of
facility: Investigational Site Number :4100003
state: Gyeonggi-do
city: Incheon
country: Korea, Republic of
facility: Investigational Site Number :4100007
state: Incheon-gwangyeoksi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number :4100005
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number :4100001
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number :4100006
state: Seoul-teukbyeolsi
city: Coimbra
country: Portugal
facility: Investigational Site Number :6200001
city: Lisboa
country: Portugal
facility: Investigational Site Number :6200002
city: Porto
country: Portugal
facility: Investigational Site Number :6200003
city: Santullano
country: Spain
facility: Investigational Site Number :7240008
state: Asturias
city: Badalona
country: Spain
facility: Investigational Site Number :7240009
state: Barcelona [Barcelona]
city: Pontevedra
country: Spain
facility: Investigational Site Number :7240001
state: Galicia [Galicia]
city: Córdoba
country: Spain
facility: Investigational Site Number :7240004
city: Madrid
country: Spain
facility: Investigational Site Number :7240007
city: Valencia
country: Spain
facility: Investigational Site Number :7240003
city: Zaragoza
country: Spain
facility: Investigational Site Number :7240002
city: Hsinchu City
country: Taiwan
facility: Investigational Site Number :1580005
city: Kaohsiung
country: Taiwan
facility: Investigational Site Number :1580006
city: Taichung
country: Taiwan
facility: Investigational Site Number :1580008
city: Taipei
country: Taiwan
facility: Investigational Site Number :1580001
city: Taipei
country: Taiwan
facility: Investigational Site Number :1580002
city: Redhill
country: United Kingdom
facility: Investigational Site Number :8260001
state: Surrey
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: