Back to resultsStudy of Dupilumab for the Treatment of Patients With Prurigo Nodularis, Inadequately Controlled on Topical Prescription Therapies or When Those Therapies Are Not Advisable (PRIME2)
Primary Purpose
Neurodermatitis
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Dupilumab SAR231893
Placebo
Moisturizers
Low to medium potent topical corticosteroids
Topical calcineurin inhibitors
Sponsored by
About this trial
This is an interventional treatment trial for Neurodermatitis
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.
Sites / Locations
- Investigational Site Number :8400054
- Investigational Site Number :8400008
- Investigational Site Number :8400005
- Investigational Site Number :8400002
- Investigational Site Number :8400003
- Investigational Site Number :8400006
- Investigational Site Number :8400001
- Investigational Site Number :1240002
- Investigational Site Number :1240006
- Investigational Site Number :1240007
- Investigational Site Number :1240008
- Investigational Site Number :1240001
- Investigational Site Number :1240009
- Investigational Site Number :1520005
- Investigational Site Number :1520006
- Investigational Site Number :1520003
- Investigational Site Number :1520001
- Investigational Site Number :1520004
- Investigational Site Number :1520002
- Investigational Site Number :2500007
- Investigational Site Number :2500001
- Investigational Site Number :2500008
- Investigational Site Number :2500002
- Investigational Site Number :2500006
- Investigational Site Number :2500004
- Investigational Site Number :2500005
- Investigational Site Number :2500003
- Investigational Site Number :3480004
- Investigational Site Number :3480002
- Investigational Site Number :3480005
- Investigational Site Number :3480003
- Investigational Site Number :3800001
- Investigational Site Number :3800004
- Investigational Site Number :3800003
- Investigational Site Number :3800002
- Investigational Site Number :4100002
- Investigational Site Number :4100003
- Investigational Site Number :4100007
- Investigational Site Number :4100005
- Investigational Site Number :4100001
- Investigational Site Number :4100006
- Investigational Site Number :6200001
- Investigational Site Number :6200002
- Investigational Site Number :6200003
- Investigational Site Number :7240008
- Investigational Site Number :7240009
- Investigational Site Number :7240001
- Investigational Site Number :7240004
- Investigational Site Number :7240007
- Investigational Site Number :7240003
- Investigational Site Number :7240002
- Investigational Site Number :1580005
- Investigational Site Number :1580006
- Investigational Site Number :1580008
- Investigational Site Number :1580001
- Investigational Site Number :1580002
- Investigational Site Number :8260001
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo
Dupilumab 300 mg Q2W
Arm Description
Participants received placebo matched to dupilumab 600 milligrams (mg) (loading dose), subcutaneously (SC) on Day 1 followed by placebo matched to dupilumab 300 mg once every 2 weeks (q2w) for 24 weeks added to background therapy of topical corticosteroids/topical calcineurin inhibitors (TCS/TCI) at stable dose.
Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose.
Outcomes
Primary Outcome Measures
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
WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. Percentage of participants with >=4 points improvement (reduction) from baseline in WI-NRS scores at Week 12 is reported in this outcome measure.
Secondary Outcome Measures
Percentage of Participants With >=4 Points Improvement (Reduction) From Baseline in WI-NRS Scores at Week 24
WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. Percentage of participants with >=4 points improvement (reduction) from baseline in WI-NRS scores at Week 24 is reported in this outcome measure.
Percentage of Participants With Investigator's Global Assessment For Prurigo Nodularis-Stage (IGA PN-S) Scores of 0 or 1 at Week 24
IGA PN-S is an instrument used to assess the overall number and thickness of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 to 4 where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Higher scores indicate severe prurigo nodularis. In this outcome measure, percentage of participants with IGA PN-S score of either 0 (clear) or 1 (almost clear) has been reported.
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
WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch), higher scores indicated more severity. IGA PN-S assess the overall number and thickness of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 to 4 where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Higher scores indicated greater severity. Percentage of participants with both an improvement (reduction) in WI-NRS by >=4 Points (from Baseline) and an IGA PN-S score of 0 or 1 were reported in this outcome measure.
Percentage of Participants With IGA PN-S Scores of 0 or 1 at Week 12
IGA PN-S is an instrument used to assess the overall number and thickness of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 to 4 where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Higher scores indicate severe prurigo nodularis. In this outcome measure, percentage of participants with IGA PN-S score of either 0 (clear) or 1 (almost clear) has been reported.
Percent Change From Baseline in WI-NRS Scores at Week 24
WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. Least squares (LS) means and standard error (SE) were obtained from Analysis of covariance (ANCOVA) model.
Change From Baseline in Health-related Quality of Life (HRQoL) as Measured by Dermatology Life Quality Index (DLQI) at Week 24
DLQI is developed to measure dermatology specific HRQoL in adult participants. It comprises of set of 10 questions assessing the impact of skin disease on participants' HRQoL over the previous week. Responses to each question were assessed on a 4-point Likert scale ranged from 0 (not at all) to 3 (very much). Scores from all 10 questions added up to give total DLQI scores ranged from 0 (not at all) to 30 (very much), higher scores indicated more impact on quality of life. LS means and SE were obtained from ANCOVA model.
Change From Baseline in Skin Pain-NRS at Week 24
Skin Pain-NRS was used to measure skin pain intensity. Participants were asked daily to rate the intensity of their worst skin pain over the past 24 hours, using a 11-point scale ranging from 0 ("No pain") to 10 ("Worst possible pain"). Higher scores indicated more severity. LS means and SE were obtained from ANCOVA model.
Change From Baseline in Sleep-NRS at Week 24
Sleep-NRS was used to measure sleep intensity. Participants were asked to rate their sleep quality on their past night upon awakening, using a 11-point NRS ranging from 0 to 10, where 0 = worst possible sleep and 10 = best possible sleep. Higher scores indicated less severity. LS means and SE were obtained from ANCOVA model.
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Total Score at Week 24
HADS is a 14-item self-administered questionnaire that consists of 2 scales, one measuring anxiety (HADS-A), and the other measuring depression (HADS-D). Each subscale comprised of 7 items with a scoring range from 0 (less severity of anxiety and depression) to 21 (greater severity of anxiety and depression symptoms) for each subscale. The total HADS score ranges from 0 (less severity) to 42 (more severity), with a high score indicative of a severe anxiety and/or depression level. LS means and SE were obtained from ANCOVA model.
Probability of Participants With an Improvement (Reduction) in WI-NRS by >=4 From Baseline at Week 24
WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. Probability of participants with an improvement (reduction) in WI-NRS at Week 24 was based on Kaplan-Meier estimates and was reported in this outcome measure.
Change From Baseline in WI-NRS Scores at Weeks 12 and 24
WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. LS means and SE were obtained from ANCOVA model.
Percent Change From Baseline in WI-NRS Scores at Weeks 2, 4 and 12
WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. LS means and SE were obtained from ANCOVA model.
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
WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. LS means and SE were obtained from ANCOVA model.
Percentage of Participants With Improvement (Reduction) in WI-NRS >=4 Points From Baseline at Week 4
WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. Percentage of participants with improvement (Reduction) in WI-NRS scale by >=4 Points at Week 4 is reported in this outcome 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
WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. 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 is reported in this outcome measure.
Onset of Action Based on Change From Baseline in WI-NRS at Week 4
Onset of action was defined as the first p<0.05 difference from placebo in the weekly average WI-NRS that remained significant at subsequent measurements. WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated greater severity.
Percentage of Participants With Investigator's Global Assessment for PN-Stage (IGA PN-S) Score of 0 or 1 at Weeks 4 and 8
IGA PN-S is an instrument used to assess the overall number and thickness of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 to 4: where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Higher scores indicate severe prurigo nodularis. In this outcome measure, percentage of participants with IGA PN-S score of either 0 (clear) or 1 (almost clear) has been reported.
Change From Baseline in IGA PN-S Scores at Weeks 4, 8, 12, and 24
IGA PN-S is an instrument used to assess the overall number and thickness of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 to 4: where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Higher scores indicate severe prurigo nodularis. LS means and SE were obtained from ANCOVA model.
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
The IGA PN-A is an instrument used to assess the overall activity of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 to 4: where 0 = clear (0% nodules showing excoriations/crusts), 1 = almost clear (up to 10% nodules showing excoriations/crusts), 2 = mild (11-25% nodules showing excoriations/crusts), 3 = moderate (26-75% nodules showing excoriations/crusts) and 4 = severe (76-100% of nodules showing excoriations/crusts). Higher scores indicate severe prurigo nodularis. In this outcome measure, percentage of participants with IGA PN-A score of either 0 (clear) or 1 (almost clear) has been reported.
Change From Baseline in HRQoL, as Measured by DLQI at Week 12
DLQI is developed to measure dermatology specific HRQoL in adult participants. It comprises of set of 10 questions assessing the impact of skin disease on participants' HRQoL over the previous week. Responses to each question were assessed on a 4-point Likert scale ranged from 0 (not at all) to 3 (very much). Scores from all 10 questions added up to give total DLQI scores ranged from 0 (not at all) to 30 (very much), higher scores indicated more impact on quality of life. LS means and SE were obtained from ANCOVA model.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. Serious adverse events (SAEs) was defined as any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as AEs that developed, worsened or became serious during the treatment-emergent (TE) period (time from the first investigational medicinal product [IMP] administration to the last IMP administration + 14 weeks).
Number of Participants With Treatment-emergent and Treatment Boosted Antidrug Antibodies (ADA)
ADA response was categorized as: Treatment emergent and Treatment-boosted. Treatment emergent ADAs were defined as a participant with no positive assay response at baseline but with a positive assay response during the entire TEAE period. Treatment boosted ADAs: defined as participants with a positive ADA assay response at baseline and with at least a 4-fold increase in titer compared to baseline during the TE period (time from the first IMP administration to the last IMP administration + 14 weeks). Titer values were defined as low titer (< 1,000); moderate (1,000 <= titer <= 10,000) and high titer (> 10,000).
Full Information
NCT ID
NCT04202679
First Posted
December 16, 2019
Last Updated
November 21, 2022
Sponsor
Sanofi
Collaborators
Regeneron Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT04202679
Brief Title
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
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
January 16, 2020 (Actual)
Primary Completion Date
August 30, 2021 (Actual)
Study Completion Date
November 22, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
Collaborators
Regeneron Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neurodermatitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
160 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received placebo matched to dupilumab 600 milligrams (mg) (loading dose), subcutaneously (SC) on Day 1 followed by placebo matched to dupilumab 300 mg once every 2 weeks (q2w) for 24 weeks added to background therapy of topical corticosteroids/topical calcineurin inhibitors (TCS/TCI) at stable dose.
Arm Title
Dupilumab 300 mg Q2W
Arm Type
Experimental
Arm Description
Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose.
Intervention Type
Drug
Intervention Name(s)
Dupilumab SAR231893
Intervention Description
Pharmaceutical form:Injection solution Route of administration: Subcutaneous
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Pharmaceutical form:Injection solution Route of administration: Subcutaneous
Intervention Type
Drug
Intervention Name(s)
Moisturizers
Intervention Description
Pharmaceutical form:
Route of administration: Topical
Intervention Type
Drug
Intervention Name(s)
Low to medium potent topical corticosteroids
Intervention Description
Pharmaceutical form:
Route of administration: Topical
Intervention Type
Drug
Intervention Name(s)
Topical calcineurin inhibitors
Intervention Description
Pharmaceutical form:
Route of administration: Topical
Primary Outcome Measure Information:
Title
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
Description
WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. Percentage of participants with >=4 points improvement (reduction) from baseline in WI-NRS scores at Week 12 is reported in this outcome measure.
Time Frame
Baseline, Week 12
Secondary Outcome Measure Information:
Title
Percentage of Participants With >=4 Points Improvement (Reduction) From Baseline in WI-NRS Scores at Week 24
Description
WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. Percentage of participants with >=4 points improvement (reduction) from baseline in WI-NRS scores at Week 24 is reported in this outcome measure.
Time Frame
Baseline, Week 24
Title
Percentage of Participants With Investigator's Global Assessment For Prurigo Nodularis-Stage (IGA PN-S) Scores of 0 or 1 at Week 24
Description
IGA PN-S is an instrument used to assess the overall number and thickness of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 to 4 where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Higher scores indicate severe prurigo nodularis. In this outcome measure, percentage of participants with IGA PN-S score of either 0 (clear) or 1 (almost clear) has been reported.
Time Frame
At Week 24
Title
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
Description
WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch), higher scores indicated more severity. IGA PN-S assess the overall number and thickness of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 to 4 where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Higher scores indicated greater severity. Percentage of participants with both an improvement (reduction) in WI-NRS by >=4 Points (from Baseline) and an IGA PN-S score of 0 or 1 were reported in this outcome measure.
Time Frame
Baseline, Week 24
Title
Percentage of Participants With IGA PN-S Scores of 0 or 1 at Week 12
Description
IGA PN-S is an instrument used to assess the overall number and thickness of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 to 4 where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Higher scores indicate severe prurigo nodularis. In this outcome measure, percentage of participants with IGA PN-S score of either 0 (clear) or 1 (almost clear) has been reported.
Time Frame
At Week 12
Title
Percent Change From Baseline in WI-NRS Scores at Week 24
Description
WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. Least squares (LS) means and standard error (SE) were obtained from Analysis of covariance (ANCOVA) model.
Time Frame
Baseline, Week 24
Title
Change From Baseline in Health-related Quality of Life (HRQoL) as Measured by Dermatology Life Quality Index (DLQI) at Week 24
Description
DLQI is developed to measure dermatology specific HRQoL in adult participants. It comprises of set of 10 questions assessing the impact of skin disease on participants' HRQoL over the previous week. Responses to each question were assessed on a 4-point Likert scale ranged from 0 (not at all) to 3 (very much). Scores from all 10 questions added up to give total DLQI scores ranged from 0 (not at all) to 30 (very much), higher scores indicated more impact on quality of life. LS means and SE were obtained from ANCOVA model.
Time Frame
Baseline, Week 24
Title
Change From Baseline in Skin Pain-NRS at Week 24
Description
Skin Pain-NRS was used to measure skin pain intensity. Participants were asked daily to rate the intensity of their worst skin pain over the past 24 hours, using a 11-point scale ranging from 0 ("No pain") to 10 ("Worst possible pain"). Higher scores indicated more severity. LS means and SE were obtained from ANCOVA model.
Time Frame
Baseline, Week 24
Title
Change From Baseline in Sleep-NRS at Week 24
Description
Sleep-NRS was used to measure sleep intensity. Participants were asked to rate their sleep quality on their past night upon awakening, using a 11-point NRS ranging from 0 to 10, where 0 = worst possible sleep and 10 = best possible sleep. Higher scores indicated less severity. LS means and SE were obtained from ANCOVA model.
Time Frame
Baseline, Week 24
Title
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Total Score at Week 24
Description
HADS is a 14-item self-administered questionnaire that consists of 2 scales, one measuring anxiety (HADS-A), and the other measuring depression (HADS-D). Each subscale comprised of 7 items with a scoring range from 0 (less severity of anxiety and depression) to 21 (greater severity of anxiety and depression symptoms) for each subscale. The total HADS score ranges from 0 (less severity) to 42 (more severity), with a high score indicative of a severe anxiety and/or depression level. LS means and SE were obtained from ANCOVA model.
Time Frame
Baseline, Week 24
Title
Probability of Participants With an Improvement (Reduction) in WI-NRS by >=4 From Baseline at Week 24
Description
WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. Probability of participants with an improvement (reduction) in WI-NRS at Week 24 was based on Kaplan-Meier estimates and was reported in this outcome measure.
Time Frame
Baseline, Week 24
Title
Change From Baseline in WI-NRS Scores at Weeks 12 and 24
Description
WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. LS means and SE were obtained from ANCOVA model.
Time Frame
Baseline, Weeks 12 and 24
Title
Percent Change From Baseline in WI-NRS Scores at Weeks 2, 4 and 12
Description
WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. LS means and SE were obtained from ANCOVA model.
Time Frame
Baseline, Weeks 2, 4 and 12
Title
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
Description
WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. LS means and SE were obtained from ANCOVA model.
Time Frame
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
Title
Percentage of Participants With Improvement (Reduction) in WI-NRS >=4 Points From Baseline at Week 4
Description
WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. Percentage of participants with improvement (Reduction) in WI-NRS scale by >=4 Points at Week 4 is reported in this outcome measure.
Time Frame
Baseline, Week 4
Title
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
Description
WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. 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 is reported in this outcome measure.
Time Frame
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
Title
Onset of Action Based on Change From Baseline in WI-NRS at Week 4
Description
Onset of action was defined as the first p<0.05 difference from placebo in the weekly average WI-NRS that remained significant at subsequent measurements. WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated greater severity.
Time Frame
Baseline, Week 4
Title
Percentage of Participants With Investigator's Global Assessment for PN-Stage (IGA PN-S) Score of 0 or 1 at Weeks 4 and 8
Description
IGA PN-S is an instrument used to assess the overall number and thickness of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 to 4: where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Higher scores indicate severe prurigo nodularis. In this outcome measure, percentage of participants with IGA PN-S score of either 0 (clear) or 1 (almost clear) has been reported.
Time Frame
At Weeks 4 and 8
Title
Change From Baseline in IGA PN-S Scores at Weeks 4, 8, 12, and 24
Description
IGA PN-S is an instrument used to assess the overall number and thickness of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 to 4: where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Higher scores indicate severe prurigo nodularis. LS means and SE were obtained from ANCOVA model.
Time Frame
Baseline, Weeks 4, 8, 12, and 24
Title
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
Description
The IGA PN-A is an instrument used to assess the overall activity of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 to 4: where 0 = clear (0% nodules showing excoriations/crusts), 1 = almost clear (up to 10% nodules showing excoriations/crusts), 2 = mild (11-25% nodules showing excoriations/crusts), 3 = moderate (26-75% nodules showing excoriations/crusts) and 4 = severe (76-100% of nodules showing excoriations/crusts). Higher scores indicate severe prurigo nodularis. In this outcome measure, percentage of participants with IGA PN-A score of either 0 (clear) or 1 (almost clear) has been reported.
Time Frame
At Weeks 4, 8, 12 and 24
Title
Change From Baseline in HRQoL, as Measured by DLQI at Week 12
Description
DLQI is developed to measure dermatology specific HRQoL in adult participants. It comprises of set of 10 questions assessing the impact of skin disease on participants' HRQoL over the previous week. Responses to each question were assessed on a 4-point Likert scale ranged from 0 (not at all) to 3 (very much). Scores from all 10 questions added up to give total DLQI scores ranged from 0 (not at all) to 30 (very much), higher scores indicated more impact on quality of life. LS means and SE were obtained from ANCOVA model.
Time Frame
Baseline, Week 12
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Description
An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. Serious adverse events (SAEs) was defined as any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as AEs that developed, worsened or became serious during the treatment-emergent (TE) period (time from the first investigational medicinal product [IMP] administration to the last IMP administration + 14 weeks).
Time Frame
From the first IMP administration to the last IMP administration + 14 weeks (i.e., up to 36 weeks)
Title
Number of Participants With Treatment-emergent and Treatment Boosted Antidrug Antibodies (ADA)
Description
ADA response was categorized as: Treatment emergent and Treatment-boosted. Treatment emergent ADAs were defined as a participant with no positive assay response at baseline but with a positive assay response during the entire TEAE period. Treatment boosted ADAs: defined as participants with a positive ADA assay response at baseline and with at least a 4-fold increase in titer compared to baseline during the TE period (time from the first IMP administration to the last IMP administration + 14 weeks). Titer values were defined as low titer (< 1,000); moderate (1,000 <= titer <= 10,000) and high titer (> 10,000).
Time Frame
From the first IMP administration to the last IMP administration + 14 weeks (i.e., up to 36 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number :8400054
City
Fort Smith
State/Province
Arkansas
ZIP/Postal Code
72916
Country
United States
Facility Name
Investigational Site Number :8400008
City
Sacramento
State/Province
California
ZIP/Postal Code
95816
Country
United States
Facility Name
Investigational Site Number :8400005
City
Pembroke Pines
State/Province
Florida
ZIP/Postal Code
33028
Country
United States
Facility Name
Investigational Site Number :8400002
City
Plainfield
State/Province
Indiana
ZIP/Postal Code
46168
Country
United States
Facility Name
Investigational Site Number :8400003
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Investigational Site Number :8400006
City
East Windsor
State/Province
New Jersey
ZIP/Postal Code
08520
Country
United States
Facility Name
Investigational Site Number :8400001
City
Sugar Land
State/Province
Texas
ZIP/Postal Code
77479
Country
United States
Facility Name
Investigational Site Number :1240002
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2G 1B1
Country
Canada
Facility Name
Investigational Site Number :1240006
City
Surrey
State/Province
British Columbia
ZIP/Postal Code
V3R 6A7
Country
Canada
Facility Name
Investigational Site Number :1240007
City
Markham
State/Province
Ontario
ZIP/Postal Code
L3P 1X3
Country
Canada
Facility Name
Investigational Site Number :1240008
City
Newmarket
State/Province
Ontario
ZIP/Postal Code
L3Y 5G8
Country
Canada
Facility Name
Investigational Site Number :1240001
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5A 3R6
Country
Canada
Facility Name
Investigational Site Number :1240009
City
Saskatoon
State/Province
Saskatchewan
ZIP/Postal Code
S7K 0H6
Country
Canada
Facility Name
Investigational Site Number :1520005
City
Valdivia
State/Province
Los RÃos
ZIP/Postal Code
5110683
Country
Chile
Facility Name
Investigational Site Number :1520006
City
Osorno
State/Province
Reg Metropolitana De Santiago
ZIP/Postal Code
5311523
Country
Chile
Facility Name
Investigational Site Number :1520003
City
Santiago
State/Province
Reg Metropolitana De Santiago
ZIP/Postal Code
7580206
Country
Chile
Facility Name
Investigational Site Number :1520001
City
Santiago
State/Province
Reg Metropolitana De Santiago
ZIP/Postal Code
7640881
Country
Chile
Facility Name
Investigational Site Number :1520004
City
Santiago
State/Province
Reg Metropolitana De Santiago
ZIP/Postal Code
80004005
Country
Chile
Facility Name
Investigational Site Number :1520002
City
Santiago
Country
Chile
Facility Name
Investigational Site Number :2500007
City
Bordeaux
ZIP/Postal Code
33075
Country
France
Facility Name
Investigational Site Number :2500001
City
Brest
ZIP/Postal Code
29200
Country
France
Facility Name
Investigational Site Number :2500008
City
Le Mans
ZIP/Postal Code
72037
Country
France
Facility Name
Investigational Site Number :2500002
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Investigational Site Number :2500006
City
Lyon
ZIP/Postal Code
69003
Country
France
Facility Name
Investigational Site Number :2500004
City
Paris
ZIP/Postal Code
75010
Country
France
Facility Name
Investigational Site Number :2500005
City
Reims
ZIP/Postal Code
51100
Country
France
Facility Name
Investigational Site Number :2500003
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Investigational Site Number :3480004
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
Facility Name
Investigational Site Number :3480002
City
Orosháza
ZIP/Postal Code
5900
Country
Hungary
Facility Name
Investigational Site Number :3480005
City
Pécs
ZIP/Postal Code
7632
Country
Hungary
Facility Name
Investigational Site Number :3480003
City
Szeged
ZIP/Postal Code
6720
Country
Hungary
Facility Name
Investigational Site Number :3800001
City
Rozzano
State/Province
Milano
ZIP/Postal Code
20089
Country
Italy
Facility Name
Investigational Site Number :3800004
City
Ancona
ZIP/Postal Code
60032
Country
Italy
Facility Name
Investigational Site Number :3800003
City
Catanzaro
ZIP/Postal Code
88100
Country
Italy
Facility Name
Investigational Site Number :3800002
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
Investigational Site Number :4100002
City
Busan
State/Province
Busan-gwangyeoksi
ZIP/Postal Code
49241
Country
Korea, Republic of
Facility Name
Investigational Site Number :4100003
City
Bucheon-si
State/Province
Gyeonggi-do
ZIP/Postal Code
14584
Country
Korea, Republic of
Facility Name
Investigational Site Number :4100007
City
Incheon
State/Province
Incheon-gwangyeoksi
ZIP/Postal Code
21431
Country
Korea, Republic of
Facility Name
Investigational Site Number :4100005
City
Seoul
State/Province
Seoul-teukbyeolsi
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Investigational Site Number :4100001
City
Seoul
State/Province
Seoul-teukbyeolsi
ZIP/Postal Code
06973
Country
Korea, Republic of
Facility Name
Investigational Site Number :4100006
City
Seoul
State/Province
Seoul-teukbyeolsi
ZIP/Postal Code
07441
Country
Korea, Republic of
Facility Name
Investigational Site Number :6200001
City
Coimbra
ZIP/Postal Code
3000-075
Country
Portugal
Facility Name
Investigational Site Number :6200002
City
Lisboa
ZIP/Postal Code
1998-018
Country
Portugal
Facility Name
Investigational Site Number :6200003
City
Porto
ZIP/Postal Code
4099-001
Country
Portugal
Facility Name
Investigational Site Number :7240008
City
Santullano
State/Province
Asturias
ZIP/Postal Code
33619
Country
Spain
Facility Name
Investigational Site Number :7240009
City
Badalona
State/Province
Barcelona [Barcelona]
ZIP/Postal Code
08916
Country
Spain
Facility Name
Investigational Site Number :7240001
City
Pontevedra
State/Province
Galicia [Galicia]
ZIP/Postal Code
36071
Country
Spain
Facility Name
Investigational Site Number :7240004
City
Córdoba
ZIP/Postal Code
14004
Country
Spain
Facility Name
Investigational Site Number :7240007
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Investigational Site Number :7240003
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Investigational Site Number :7240002
City
Zaragoza
ZIP/Postal Code
50009
Country
Spain
Facility Name
Investigational Site Number :1580005
City
Hsinchu City
ZIP/Postal Code
30059
Country
Taiwan
Facility Name
Investigational Site Number :1580006
City
Kaohsiung
ZIP/Postal Code
833
Country
Taiwan
Facility Name
Investigational Site Number :1580008
City
Taichung
Country
Taiwan
Facility Name
Investigational Site Number :1580001
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Investigational Site Number :1580002
City
Taipei
ZIP/Postal Code
10449
Country
Taiwan
Facility Name
Investigational Site Number :8260001
City
Redhill
State/Province
Surrey
ZIP/Postal Code
RH1 5RH
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Learn more about this trial
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)
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