Neurodermatitis
Conditions
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.
Interventions
Pharmaceutical form:Injection solution Route of administration: Subcutaneous
DRUGPlacebo
Pharmaceutical form:Injection solution Route of administration: Subcutaneous
DRUGMoisturizers
Pharmaceutical form: Route of administration: Topical
Pharmaceutical form: Route of administration: Topical
Pharmaceutical form: Route of administration: Topical
Sponsors
Regeneron Pharmaceuticals
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline, 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Investigator's Global Assessment For Prurigo Nodularis-Stage (IGA PN-S) Scores of 0 or 1 at Week 24 | 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 | Baseline, 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 | 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. |
| Change From Baseline in Sleep-NRS at Week 24 | Baseline, 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. |
| Percent Change From Baseline in WI-NRS Scores at Week 24 | Baseline, 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 | Baseline, 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 | Baseline, 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 Hospital Anxiety and Depression Scale (HADS) Total Score at Week 24 | Baseline, 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 | Baseline, 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 | Baseline, 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. |
| Percentage of Participants With >=4 Points Improvement (Reduction) From Baseline in WI-NRS Scores at Week 24 | Baseline, 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. |
| 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 | 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 | 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 | Baseline, 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 | 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 | 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 | Baseline, 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 | 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 | Baseline, 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 | 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 | Baseline, 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) | From the first IMP administration to the last IMP administration + 14 weeks (i.e., up to 36 weeks) | 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) | From the first IMP administration to the last IMP administration + 14 weeks (i.e., up to 36 weeks) | 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). |
| Percent Change From Baseline in WI-NRS Scores at Weeks 2, 4 and 12 | Baseline, 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. |
Countries
Canada, Chile, France, Hungary, Italy, Portugal, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
This study was conducted at 57 sites in 11 countries. A total of 221 participants were screened from 16 January 2020 to 24 February 2021, out of which 61 were screen failures. Screen failures were mainly due to not meeting eligibility criteria.
Pre-assignment details
A total of 160 participants were randomized in 1:1 ratio to receive study interventions (placebo or dupilumab) by interactive response technology (IRT).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy TCS/TCI at stable dose. | 82 |
| Dupilumab 300 mg Q2W 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. | 78 |
| Total | 160 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Poor compliance to protocol | 1 | 0 |
| Overall Study | Withdrawal by Subject | 23 | 6 |
Baseline characteristics
| Characteristic | Total | Dupilumab 300 mg Q2W | Placebo |
|---|---|---|---|
| Age, Continuous | 48.8 years STANDARD_DEVIATION 15.6 | 51.0 years STANDARD_DEVIATION 15.8 | 46.7 years STANDARD_DEVIATION 15.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 52 Participants | 25 Participants | 27 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 96 Participants | 48 Participants | 48 Participants |
| Sex: Female, Male Female | 103 Participants | 52 Participants | 51 Participants |
| Sex: Female, Male Male | 57 Participants | 26 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 82 | 0 / 77 |
| other Total, other adverse events | 10 / 82 | 11 / 77 |
| serious Total, serious adverse events | 4 / 82 | 2 / 77 |
Outcome results
Primary
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.
Time frame: Baseline, Week 12
Population: Analysis was performed on intent-to-treat (ITT) population which included all participants with a treatment kit number allocated and recorded in the IRT database analyzed according to the treatment group allocated by randomization regardless of if treatment kit was used or not.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | 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 | 22.0 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | 37.2 percentage of participants |
Comparison: A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the outcome measures were reported and continued when primary outcome measure was statistically significant at two-sided 0.05.p-value: 0.021695% CI: [1.08, 5]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Baseline, Week 24
Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Health-related Quality of Life (HRQoL) as Measured by Dermatology Life Quality Index (DLQI) at Week 24 | -6.77 score on a scale | Standard Error 1.18 |
| Dupilumab 300 mg Q2W | Change From Baseline in Health-related Quality of Life (HRQoL) as Measured by Dermatology Life Quality Index (DLQI) at Week 24 | -13.16 score on a scale | Standard Error 1.21 |
Comparison: A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the outcome measures were reported and continued when previous outcome measure was statistically significant at two-sided 0.05.p-value: <0.000195% CI: [-8.42, -4.36]ANCOVA
Secondary
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.
Time frame: Baseline, Week 24
Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Total Score at Week 24 | -2.59 score on a scale | Standard Error 1.03 |
| Dupilumab 300 mg Q2W | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Total Score at Week 24 | -5.55 score on a scale | Standard Error 1.06 |
Secondary
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.
Time frame: Baseline, Week 12
Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in HRQoL, as Measured by DLQI at Week 12 | -7.05 score on a scale | Standard Error 1.12 |
| Dupilumab 300 mg Q2W | Change From Baseline in HRQoL, as Measured by DLQI at Week 12 | -12.07 score on a scale | Standard Error 1.16 |
Secondary
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.
Time frame: Baseline, Weeks 4, 8, 12, and 24
Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in IGA PN-S Scores at Weeks 4, 8, 12, and 24 | Week 4 | -0.54 score on a scale | Standard Error 0.13 |
| Placebo | Change From Baseline in IGA PN-S Scores at Weeks 4, 8, 12, and 24 | Week 8 | -0.79 score on a scale | Standard Error 0.17 |
| Placebo | Change From Baseline in IGA PN-S Scores at Weeks 4, 8, 12, and 24 | Week 12 | -0.86 score on a scale | Standard Error 0.18 |
| Placebo | Change From Baseline in IGA PN-S Scores at Weeks 4, 8, 12, and 24 | Week 24 | -1.07 score on a scale | Standard Error 0.2 |
| Dupilumab 300 mg Q2W | Change From Baseline in IGA PN-S Scores at Weeks 4, 8, 12, and 24 | Week 24 | -2.03 score on a scale | Standard Error 0.2 |
| Dupilumab 300 mg Q2W | Change From Baseline in IGA PN-S Scores at Weeks 4, 8, 12, and 24 | Week 4 | -0.69 score on a scale | Standard Error 0.13 |
| Dupilumab 300 mg Q2W | Change From Baseline in IGA PN-S Scores at Weeks 4, 8, 12, and 24 | Week 12 | -1.47 score on a scale | Standard Error 0.18 |
| Dupilumab 300 mg Q2W | Change From Baseline in IGA PN-S Scores at Weeks 4, 8, 12, and 24 | Week 8 | -1.19 score on a scale | Standard Error 0.17 |
Secondary
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.
Time frame: Baseline, Week 24
Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Skin Pain-NRS at Week 24 | -2.74 score on a scale | Standard Error 0.51 |
| Dupilumab 300 mg Q2W | Change From Baseline in Skin Pain-NRS at Week 24 | -4.35 score on a scale | Standard Error 0.53 |
Comparison: A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the outcome measures were reported and continued when previous outcome measure was statistically significant at two-sided 0.05.p-value: 0.000395% CI: [-2.49, -0.73]ANCOVA
Secondary
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.
Time frame: Baseline, Week 24
Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Sleep-NRS at Week 24 | 0.76 score on a scale | Standard Error 0.45 |
| Dupilumab 300 mg Q2W | Change From Baseline in Sleep-NRS at Week 24 | 1.30 score on a scale | Standard Error 0.46 |
Comparison: A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the outcome measures were reported and continued when previous outcome measure was statistically significant at two-sided 0.05.p-value: 0.165895% CI: [-0.22, 1.3]ANCOVA
Secondary
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.
Time frame: Baseline, Weeks 12 and 24
Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in WI-NRS Scores at Weeks 12 and 24 | Week 12 | -3.04 score on a scale | Standard Error 0.46 |
| Placebo | Change From Baseline in WI-NRS Scores at Weeks 12 and 24 | Week 24 | -3.10 score on a scale | Standard Error 0.53 |
| Dupilumab 300 mg Q2W | Change From Baseline in WI-NRS Scores at Weeks 12 and 24 | Week 12 | -4.11 score on a scale | Standard Error 0.47 |
| Dupilumab 300 mg Q2W | Change From Baseline in WI-NRS Scores at Weeks 12 and 24 | Week 24 | -5.05 score on a scale | Standard Error 0.54 |
Secondary
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).
Time frame: From the first IMP administration to the last IMP administration + 14 weeks (i.e., up to 36 weeks)
Population: Analysis was performed on safety population which included all participants who received at least 1 dose of study intervention analyzed according to the intervention actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAEs | 47 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAEs | 4 Participants |
| Dupilumab 300 mg Q2W | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAEs | 47 Participants |
| Dupilumab 300 mg Q2W | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAEs | 2 Participants |
Secondary
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).
Time frame: From the first IMP administration to the last IMP administration + 14 weeks (i.e., up to 36 weeks)
Population: Analysis was performed on ADA population which included all participants who received at least one dose of the study drug and had at least one non-missing ADA result after first dose of study drug. Participants were analyzed according to the intervention actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-emergent and Treatment Boosted Antidrug Antibodies (ADA) | Treatment-emergent ADAs | 1 Participants |
| Placebo | Number of Participants With Treatment-emergent and Treatment Boosted Antidrug Antibodies (ADA) | Treatment-boosted ADAs | 0 Participants |
| Dupilumab 300 mg Q2W | Number of Participants With Treatment-emergent and Treatment Boosted Antidrug Antibodies (ADA) | Treatment-emergent ADAs | 7 Participants |
| Dupilumab 300 mg Q2W | Number of Participants With Treatment-emergent and Treatment Boosted Antidrug Antibodies (ADA) | Treatment-boosted ADAs | 0 Participants |
Secondary
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.
Time frame: Baseline, Week 4
Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Onset of Action Based on Change From Baseline in WI-NRS at Week 4 | -1.94 score on a scale | Standard Error 0.33 |
| Dupilumab 300 mg Q2W | Onset of Action Based on Change From Baseline in WI-NRS at Week 4 | -2.55 score on a scale | Standard Error 0.34 |
p-value: 0.03795% CI: [-1.18, -0.04]ANCOVA
Secondary
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.
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
Population: Analysis was performed on ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | 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 | Week 23 | 20.7 percentage of participants |
| Placebo | 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 | Week 7 | 15.9 percentage of participants |
| Placebo | 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 | Week 18 | 24.4 percentage of participants |
| Placebo | 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 | Week 8 | 14.6 percentage of participants |
| Placebo | 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 | Week 4 | 7.3 percentage of participants |
| Placebo | 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 | Week 9 | 24.4 percentage of participants |
| Placebo | 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 | Week 17 | 23.2 percentage of participants |
| Placebo | 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 | Week 10 | 18.3 percentage of participants |
| Placebo | 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 | Week 19 | 23.2 percentage of participants |
| Placebo | 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 | Week 11 | 17.1 percentage of participants |
| Placebo | 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 | Week 1 | 1.2 percentage of participants |
| Placebo | 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 | Week 12 | 22.0 percentage of participants |
| Placebo | 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 | Week 20 | 20.7 percentage of participants |
| Placebo | 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 | Week 13 | 19.5 percentage of participants |
| Placebo | 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 | Week 5 | 4.9 percentage of participants |
| Placebo | 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 | Week 14 | 22.0 percentage of participants |
| Placebo | 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 | Week 21 | 20.7 percentage of participants |
| Placebo | 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 | Week 15 | 20.7 percentage of participants |
| Placebo | 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 | Week 3 | 6.1 percentage of participants |
| Placebo | 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 | Week 16 | 19.5 percentage of participants |
| Placebo | 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 | Week 6 | 13.4 percentage of participants |
| Placebo | 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 | Week 22 | 22.0 percentage of participants |
| Placebo | 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 | Week 24 | 19.5 percentage of participants |
| Placebo | 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 | Week 2 | 1.2 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 9 | 32.1 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 1 | 1.3 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 2 | 5.1 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 3 | 12.8 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 4 | 16.7 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 5 | 17.9 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 17 | 47.4 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 18 | 48.7 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 19 | 51.3 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 20 | 51.3 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 21 | 48.7 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 6 | 23.1 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 22 | 50.0 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 7 | 24.4 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 8 | 28.2 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 10 | 32.1 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 11 | 33.3 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 12 | 37.2 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 13 | 39.7 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 14 | 39.7 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 15 | 44.9 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 16 | 44.9 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 23 | 55.1 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 24 | 57.7 percentage of participants |
Secondary
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.
Time frame: Baseline, Week 24
Population: Analysis was performed on ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With >=4 Points Improvement (Reduction) From Baseline in WI-NRS Scores at Week 24 | 19.5 percentage of participants |
| Dupilumab 300 mg Q2W | Percentage of Participants With >=4 Points Improvement (Reduction) From Baseline in WI-NRS Scores at Week 24 | 57.7 percentage of participants |
Comparison: A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the outcome measures were reported and continued when previous outcome measure was statistically significant at two-sided 0.05.p-value: <0.000195% CI: [3.56, 22.66]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Baseline, Week 24
Population: Analysis was performed on ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | 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 | 8.5 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | 32.1 percentage of participants |
Comparison: A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the outcome measures were reported and continued when previous outcome measure was statistically significant at two-sided 0.05p-value: 0.000195% CI: [2.03, 18.11]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: At Week 12
Population: Analysis was performed on ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With IGA PN-S Scores of 0 or 1 at Week 12 | 12.2 percentage of participants |
| Dupilumab 300 mg Q2W | Percentage of Participants With IGA PN-S Scores of 0 or 1 at Week 12 | 25.6 percentage of participants |
Comparison: A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the outcome measures were reported and continued when previous outcome measure was statistically significant at two-sided 0.05.p-value: 0.019495% CI: [1.13, 7.52]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Baseline, Week 4
Population: Analysis was performed on ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Improvement (Reduction) in WI-NRS >=4 Points From Baseline at Week 4 | 7.3 percentage of participants |
| Dupilumab 300 mg Q2W | Percentage of Participants With Improvement (Reduction) in WI-NRS >=4 Points From Baseline at Week 4 | 16.7 percentage of participants |
Secondary
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.
Time frame: At Weeks 4, 8, 12 and 24
Population: Analysis was performed on ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | 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 | Week 4 | 4.9 percentage of participants |
| Placebo | 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 | Week 8 | 15.9 percentage of participants |
| Placebo | 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 | Week 12 | 19.5 percentage of participants |
| Placebo | 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 | Week 24 | 18.3 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 24 | 51.3 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 4 | 14.1 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 12 | 42.3 percentage of participants |
| Dupilumab 300 mg Q2W | 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 | Week 8 | 23.1 percentage of participants |
Secondary
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.
Time frame: At Weeks 4 and 8
Population: Analysis was performed on ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Investigator's Global Assessment for PN-Stage (IGA PN-S) Score of 0 or 1 at Weeks 4 and 8 | Week 4 | 6.1 percentage of participants |
| Placebo | Percentage of Participants With Investigator's Global Assessment for PN-Stage (IGA PN-S) Score of 0 or 1 at Weeks 4 and 8 | Week 8 | 9.8 percentage of participants |
| Dupilumab 300 mg Q2W | Percentage of Participants With Investigator's Global Assessment for PN-Stage (IGA PN-S) Score of 0 or 1 at Weeks 4 and 8 | Week 4 | 7.7 percentage of participants |
| Dupilumab 300 mg Q2W | Percentage of Participants With Investigator's Global Assessment for PN-Stage (IGA PN-S) Score of 0 or 1 at Weeks 4 and 8 | Week 8 | 15.4 percentage of participants |
Secondary
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.
Time frame: At Week 24
Population: Analysis was performed on ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Investigator's Global Assessment For Prurigo Nodularis-Stage (IGA PN-S) Scores of 0 or 1 at Week 24 | 15.9 percentage of participants |
| Dupilumab 300 mg Q2W | Percentage of Participants With Investigator's Global Assessment For Prurigo Nodularis-Stage (IGA PN-S) Scores of 0 or 1 at Week 24 | 44.9 percentage of participants |
Comparison: A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the outcome measures were reported and continued when previous outcome measure was statistically significant at two-sided 0.05.p-value: <0.000195% CI: [2.02, 9.55]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Baseline, Week 24
Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in WI-NRS Scores at Week 24 | -36.18 percent change | Standard Error 6.21 |
| Dupilumab 300 mg Q2W | Percent Change From Baseline in WI-NRS Scores at Week 24 | -59.34 percent change | Standard Error 6.39 |
Comparison: A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the outcome measures were reported and continued when previous outcome measure was statistically significant at two-sided 0.05.p-value: <0.000195% CI: [-33.81, -12.51]ANCOVA
Secondary
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.
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
Population: Analysis was performed on ITT population. Here, 'number analyzed' = participants with available data for each specified category.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 | Week 7 | -28.99 percent change | Standard Error 4.69 |
| Placebo | 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 | Week 2 | -15.61 percent change | Standard Error 3.06 |
| Placebo | 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 | Week 3 | -20.44 percent change | Standard Error 3.66 |
| Placebo | 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 | Week 4 | -22.61 percent change | Standard Error 4 |
| Placebo | 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 | Week 5 | -25.21 percent change | Standard Error 4.21 |
| Placebo | 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 | Week 6 | -27.87 percent change | Standard Error 4.33 |
| Placebo | 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 | Week 1 | -9.49 percent change | Standard Error 2.12 |
| Placebo | 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 | Week 8 | -30.45 percent change | Standard Error 4.56 |
| Placebo | 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 | Week 9 | -34.86 percent change | Standard Error 4.89 |
| Placebo | 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 | Week 10 | -32.90 percent change | Standard Error 5.04 |
| Placebo | 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 | Week 11 | -34.64 percent change | Standard Error 5.25 |
| Placebo | 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 | Week 12 | -35.83 percent change | Standard Error 5.42 |
| Placebo | 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 | Week 13 | -34.49 percent change | Standard Error 5.69 |
| Placebo | 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 | Week 14 | -36.60 percent change | Standard Error 5.71 |
| Placebo | 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 | Week 15 | -35.96 percent change | Standard Error 5.74 |
| Placebo | 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 | Week 16 | -37.80 percent change | Standard Error 5.74 |
| Placebo | 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 | Week 17 | -39.15 percent change | Standard Error 5.98 |
| Placebo | 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 | Week 18 | -40.38 percent change | Standard Error 6.15 |
| Placebo | 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 | Week 19 | -40.03 percent change | Standard Error 6.05 |
| Placebo | 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 | Week 20 | -36.12 percent change | Standard Error 5.94 |
| Placebo | 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 | Week 21 | -36.43 percent change | Standard Error 6.16 |
| Placebo | 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 | Week 22 | -37.34 percent change | Standard Error 6.19 |
| Placebo | 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 | Week 23 | -36.87 percent change | Standard Error 6.19 |
| Placebo | 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 | Week 24 | -36.18 percent change | Standard Error 6.21 |
| Dupilumab 300 mg Q2W | 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 | Week 23 | -59.43 percent change | Standard Error 6.32 |
| Dupilumab 300 mg Q2W | 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 | Week 1 | -8.66 percent change | Standard Error 2.18 |
| Dupilumab 300 mg Q2W | 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 | Week 13 | -48.32 percent change | Standard Error 5.86 |
| Dupilumab 300 mg Q2W | 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 | Week 2 | -17.41 percent change | Standard Error 3.15 |
| Dupilumab 300 mg Q2W | 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 | Week 19 | -57.75 percent change | Standard Error 6.23 |
| Dupilumab 300 mg Q2W | 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 | Week 3 | -25.26 percent change | Standard Error 3.77 |
| Dupilumab 300 mg Q2W | 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 | Week 14 | -50.67 percent change | Standard Error 5.88 |
| Dupilumab 300 mg Q2W | 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 | Week 4 | -30.09 percent change | Standard Error 4.12 |
| Dupilumab 300 mg Q2W | 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 | Week 22 | -58.78 percent change | Standard Error 6.33 |
| Dupilumab 300 mg Q2W | 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 | Week 5 | -34.41 percent change | Standard Error 4.33 |
| Dupilumab 300 mg Q2W | 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 | Week 15 | -51.89 percent change | Standard Error 5.91 |
| Dupilumab 300 mg Q2W | 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 | Week 6 | -36.98 percent change | Standard Error 4.46 |
| Dupilumab 300 mg Q2W | 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 | Week 20 | -56.80 percent change | Standard Error 6.1 |
| Dupilumab 300 mg Q2W | 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 | Week 7 | -39.30 percent change | Standard Error 4.84 |
| Dupilumab 300 mg Q2W | 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 | Week 16 | -54.36 percent change | Standard Error 5.91 |
| Dupilumab 300 mg Q2W | 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 | Week 8 | -41.32 percent change | Standard Error 4.7 |
| Dupilumab 300 mg Q2W | 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 | Week 24 | -59.34 percent change | Standard Error 6.39 |
| Dupilumab 300 mg Q2W | 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 | Week 9 | -47.08 percent change | Standard Error 5.04 |
| Dupilumab 300 mg Q2W | 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 | Week 17 | -55.95 percent change | Standard Error 6.15 |
| Dupilumab 300 mg Q2W | 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 | Week 10 | -44.65 percent change | Standard Error 5.2 |
| Dupilumab 300 mg Q2W | 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 | Week 21 | -56.91 percent change | Standard Error 6.34 |
| Dupilumab 300 mg Q2W | 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 | Week 11 | -45.98 percent change | Standard Error 5.41 |
| Dupilumab 300 mg Q2W | 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 | Week 18 | -56.80 percent change | Standard Error 6.32 |
| Dupilumab 300 mg Q2W | 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 | Week 12 | -48.86 percent change | Standard Error 5.59 |
Secondary
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.
Time frame: Baseline, Weeks 2, 4 and 12
Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in WI-NRS Scores at Weeks 2, 4 and 12 | Week 2 | -15.61 percent change | Standard Error 3.06 |
| Placebo | Percent Change From Baseline in WI-NRS Scores at Weeks 2, 4 and 12 | Week 4 | -22.61 percent change | Standard Error 4 |
| Placebo | Percent Change From Baseline in WI-NRS Scores at Weeks 2, 4 and 12 | Week 12 | -35.83 percent change | Standard Error 5.42 |
| Dupilumab 300 mg Q2W | Percent Change From Baseline in WI-NRS Scores at Weeks 2, 4 and 12 | Week 2 | -17.41 percent change | Standard Error 3.15 |
| Dupilumab 300 mg Q2W | Percent Change From Baseline in WI-NRS Scores at Weeks 2, 4 and 12 | Week 4 | -30.09 percent change | Standard Error 4.12 |
| Dupilumab 300 mg Q2W | Percent Change From Baseline in WI-NRS Scores at Weeks 2, 4 and 12 | Week 12 | -48.86 percent change | Standard Error 5.59 |
Secondary
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.
Time frame: Baseline, Week 24
Population: Analysis was performed on ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Probability of Participants With an Improvement (Reduction) in WI-NRS by >=4 From Baseline at Week 24 | 0.353 probability of participants |
| Dupilumab 300 mg Q2W | Probability of Participants With an Improvement (Reduction) in WI-NRS by >=4 From Baseline at Week 24 | 0.670 probability of participants |