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)

Neurodermatitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04202679
• Other study ID #: EFC16460
• Secondary ID: 2019-003801-90U1
• Status: Completed
• Phase: Phase 3
• Start date: January 16, 2020
• Est. completion date: November 22, 2021

Study information

• Verified date: November 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: November 22, 2021
• Est. primary completion date: August 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Neurodermatitis
• Prurigo

Intervention

Drug:
• Dupilumab SAR231893
Pharmaceutical form:Injection solution Route of administration: Subcutaneous
• Placebo
Pharmaceutical form:Injection solution Route of administration: Subcutaneous
• Moisturizers
Pharmaceutical form: Route of administration: Topical
• Low to medium potent topical corticosteroids
Pharmaceutical form: Route of administration: Topical
• Topical calcineurin inhibitors
Pharmaceutical form: Route of administration: Topical

Locations

Country	Name	City	State
Canada	Investigational Site Number :1240002	Calgary	Alberta
Canada	Investigational Site Number :1240007	Markham	Ontario
Canada	Investigational Site Number :1240008	Newmarket	Ontario
Canada	Investigational Site Number :1240009	Saskatoon	Saskatchewan
Canada	Investigational Site Number :1240006	Surrey	British Columbia
Canada	Investigational Site Number :1240001	Toronto	Ontario
Chile	Investigational Site Number :1520006	Osorno	Reg Metropolitana De Santiago
Chile	Investigational Site Number :1520001	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number :1520002	Santiago
Chile	Investigational Site Number :1520003	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number :1520004	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number :1520005	Valdivia	Los Ríos
France	Investigational Site Number :2500007	Bordeaux
France	Investigational Site Number :2500001	Brest
France	Investigational Site Number :2500008	Le Mans
France	Investigational Site Number :2500002	Lille
France	Investigational Site Number :2500006	Lyon
France	Investigational Site Number :2500004	Paris
France	Investigational Site Number :2500005	Reims
France	Investigational Site Number :2500003	Toulouse
Hungary	Investigational Site Number :3480004	Debrecen
Hungary	Investigational Site Number :3480002	Orosháza
Hungary	Investigational Site Number :3480005	Pécs
Hungary	Investigational Site Number :3480003	Szeged
Italy	Investigational Site Number :3800004	Ancona
Italy	Investigational Site Number :3800003	Catanzaro
Italy	Investigational Site Number :3800002	Milano
Italy	Investigational Site Number :3800001	Rozzano	Milano
Korea, Republic of	Investigational Site Number :4100003	Bucheon-si	Gyeonggi-do
Korea, Republic of	Investigational Site Number :4100002	Busan	Busan-gwangyeoksi
Korea, Republic of	Investigational Site Number :4100007	Incheon	Incheon-gwangyeoksi
Korea, Republic of	Investigational Site Number :4100001	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number :4100005	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number :4100006	Seoul	Seoul-teukbyeolsi
Portugal	Investigational Site Number :6200001	Coimbra
Portugal	Investigational Site Number :6200002	Lisboa
Portugal	Investigational Site Number :6200003	Porto
Spain	Investigational Site Number :7240009	Badalona	Barcelona [Barcelona]
Spain	Investigational Site Number :7240004	Córdoba
Spain	Investigational Site Number :7240007	Madrid
Spain	Investigational Site Number :7240001	Pontevedra	Galicia [Galicia]
Spain	Investigational Site Number :7240008	Santullano	Asturias
Spain	Investigational Site Number :7240003	Valencia
Spain	Investigational Site Number :7240002	Zaragoza
Taiwan	Investigational Site Number :1580005	Hsinchu City
Taiwan	Investigational Site Number :1580006	Kaohsiung
Taiwan	Investigational Site Number :1580008	Taichung
Taiwan	Investigational Site Number :1580001	Taipei
Taiwan	Investigational Site Number :1580002	Taipei
United Kingdom	Investigational Site Number :8260001	Redhill	Surrey
United States	Investigational Site Number :8400003	Baltimore	Maryland
United States	Investigational Site Number :8400006	East Windsor	New Jersey
United States	Investigational Site Number :8400054	Fort Smith	Arkansas
United States	Investigational Site Number :8400005	Pembroke Pines	Florida
United States	Investigational Site Number :8400002	Plainfield	Indiana
United States	Investigational Site Number :8400008	Sacramento	California
United States	Investigational Site Number :8400001	Sugar Land	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  Chile,  France,  Hungary,  Italy,  Korea, Republic of,  Portugal,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline, Week 12
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.	Baseline, Week 24
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.	At Week 24
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.	Baseline, Week 24
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.	At Week 12
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.	Baseline, Week 24
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.	Baseline, Week 24
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.	Baseline, Week 24
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.	Baseline, Week 24
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.	Baseline, Week 24
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.	Baseline, Week 24
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.	Baseline, Weeks 12 and 24
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.	Baseline, Weeks 2, 4 and 12
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.	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
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.	Baseline, Week 4
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.	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
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.	Baseline, Week 4
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.	At Weeks 4 and 8
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.	Baseline, Weeks 4, 8, 12, and 24
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.	At Weeks 4, 8, 12 and 24
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.	Baseline, Week 12
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).	From the first IMP administration to the last IMP administration + 14 weeks (i.e., up to 36 weeks)
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).	From the first IMP administration to the last IMP administration + 14 weeks (i.e., up to 36 weeks)