Evaluation of Dupilumab in Chinese Adult Patients With Moderate to Severe Atopic Dermatitis

Atopic Dermatitis Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Dupilumab in Chinese Adult Patients With Moderate-to-severe Atopic Dermatitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03912259
• Other study ID #: EFC15116
• Secondary ID: U1111-1190-7728
• Status: Completed
• Phase: Phase 3
• Start date: December 19, 2018
• Est. completion date: February 14, 2020

Study information

• Verified date: December 2023
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary Objective:

To evaluate the efficacy of dupilumab monotherapy compared to placebo treatment in adult participants with moderate-to-severe atopic dermatitis (AD).

Secondary Objectives:

• To evaluate the safety of dupilumab monotherapy compared to placebo treatment in adult participants with moderate-to-severe AD.

• To evaluate the effect of dupilumab on improving patient reported outcomes (PROs).

• To evaluate dupilumab immunogenicity.

Description:

The maximum study duration was 33 weeks per participants, including a screening period of up to 5 weeks, a 16-week randomized treatment period, and a 12-week follow-up period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 165
• Est. completion date: February 14, 2020
• Est. primary completion date: February 14, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Male or female, 18 years or older.

• AD (according to American Academy of Dermatology Consensus Criteria, 2014) that had been present for at least 3 years before the screening visit.

• Eczema Area and Severity Index (EASI) score greater than or equal to (>=) 16 at the screening and baseline visits.

• Investigator's Global Assessment (IGA) score >=3 (on the 0 to 4 IGA scale, in which 3 was moderate and 4 was severe) at the screening and baseline visits.

• Participants with >=10 percent (%) body surface area (BSA) of AD involvement at the screening and baseline visits.

• Baseline Pruritus Numerical Rating Scale (NRS) average score for maximum itch intensity >=4.

• Documented recent history (within 6 months before the screening visit) of inadequate response to treatment with topical medications or for whom topical treatments were otherwise medically inadvisable (e.g., because of important side effects or safety risks).

Exclusion criteria:

• Had used any of the following treatments within 4 weeks before the baseline visit, or any condition that, in the opinion of the investigator, was likely to require such treatment(s) during the first 4 weeks of study treatment:

• Immunosuppressive/immunomodulating drugs (e.g., systemic corticosteroids, cyclosporine, mycophenolate-mofetil, interferon-gamma [IFN-?], Janus kinase inhibitors, azathioprine, methotrexate);

• Phototherapy for AD.

• Treatment with topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI) within 1 week before the baseline visit.

• Treatment with systemic Traditional Chinese Medicine (TCM) within 4 weeks before the baseline visit or treatment with topical TCM within 1 week before the baseline visit.

• Treatment with biologics as follows:

• Any cell-depleting agents including but not limited to rituximab: within 6 months before the baseline visit, or until lymphocyte count returns to normal, whichever is longer;

• Other biologics: within 5 half-lives (if known) or 16 weeks prior to baseline visit, whichever was longer.

• Initiation of treatment of AD with prescription moisturizers or moisturizers containing additives such as ceramide, hyaluronic acid, urea, or filaggrin degradation products during the screening period (participants may continue using stable doses of such moisturizers if initiated before the screening visit).

• Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks of the baseline visit.

• Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit.

• Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before the baseline visit, or superficial skin infections within 1 week before the baseline visit. NOTE: participants may be rescreened after infection resolves.

• Known or suspected history of immunosuppression, including history of invasive opportunistic infections (e.g., tuberculosis [TB], histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution: or unusually frequent, recurrent, or prolonged infections, per investigator judgment.

• Active TB, latent untreated TB or a history of incompletely treated TB or non-tuberculous mycobacterial infection were excluded from the study unless that was well documented by a specialist that the participants had adequately treated and could then start treatment with a biologic agent, in the medical judgment of the Investigator and/or infectious disease specialist. TB testing would be performed according to local guidelines if required by regulatory authorities or ethics committees.

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

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Drug:
• Dupilumab
Pharmaceutical form: solution, Route of administration: SC
• Placebo
Pharmaceutical form: solution, Route of administration: SC
• Emollient (moisturizer)
Pharmaceutical form: cream, Route of administration: topical use

Locations

Country	Name	City	State
China	Investigational Site Number 1560001	Beijing
China	Investigational Site Number 1560003	Beijing
China	Investigational Site Number 1560004	Beijing
China	Investigational Site Number 1560010	Beijing
China	Investigational Site Number 1560019	Beijing
China	Investigational Site Number 1560021	Changchun
China	Investigational Site Number 1560006	Changsha
China	Investigational Site Number 1560017	Chongqing
China	Investigational Site Number 1560007	Hangzhou
China	Investigational Site Number 1560026	Hangzhou
China	Investigational Site Number 1560013	Jinan
China	Investigational Site Number 1560020	Kunming
China	Investigational Site Number 1560030	Lianyungang
China	Investigational Site Number 1560022	Nanjing
China	Investigational Site Number 1560029	Ningbo
China	Investigational Site Number 1560015	Shanghai
China	Investigational Site Number 1560016	Shanghai
China	Investigational Site Number 1560018	Shanghai
China	Investigational Site Number 1560023	Shanghai
China	Investigational Site Number 1560002	Shenyang
China	Investigational Site Number 1560005	Shenyang
China	Investigational Site Number 1560008	Shenyang
China	Investigational Site Number 1560024	Shenzhen
China	Investigational Site Number 1560027	Tianjin
China	Investigational Site Number 1560028	Wuxi
China	Investigational Site Number 1560012	Xi'An
China	Investigational Site Number 1560025	Yancheng

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Investigator's Global Assessment (IGA) Score of "0" or "1" and Reduction From Baseline of Greater Than or Equal to (>=) 2 Points at Week 16	The IGA is an assessment instrument used to rate the severity of AD globally based on a 5-point scale ranging from (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe), higher score indicated higher severity.	Baseline, Week 16
Secondary	Number of Participants With Eczema Area and Severity Index (EASI) - 75 Response (>= 75% Reduction in Score From Baseline) at Week 16	EASI: Measure to assess severity and extent of AD based on 4 AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation] and lichenification). Each characteristic was assessed for severity by Investigator/designee on scale of "0" (absent) through "3" (severe) and scored separately for each of 4 body regions (head, trunk, upper and lower extremities). Total score range from 0 (minimum) to 72 (maximum), higher scores indicated greater severity of AD.	Baseline, Week 16
Secondary	Number of Participants Who Achieved >=4 Points With Reduction From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score at Week 16	Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]), higher scores indicated greater severity.	Baseline, Week 16
Secondary	Number of Participants Who Achieved >=3 Points With Reduction From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale Score at Week 16	Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]), higher scores indicated greater severity.	Baseline, Week 16
Secondary	Percentage Change From Baseline at Week 16 in Weekly Average of Peak Daily Pruritus NRS	Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]), higher scores indicated greater severity.	Baseline, Week 16
Secondary	Change From Baseline at Week 16 in Weekly Average of Peak Daily Pruritus NRS	Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]), higher scores indicated greater severity.	Baseline, Week 16
Secondary	Percentage Change From Baseline to Week 16 in EASI Score	EASI: Measure to assess severity & extent of AD based on 4 AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation] & lichenification). Each characteristic was assessed for severity by Investigator/designee on scale of "0" (absent) through "3"(severe) & scored separately for each of 4 body regions (head, trunk, upper & lower extremities). Total score ranges from 0 (minimum) to 72 (maximum), higher scores indicated greater severity of AD.	Baseline to Week 16
Secondary	Change From Baseline to Week 16 in Percent Body Surface Area (BSA) of AD Involvement	BSA affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck [9%], anterior trunk [18%], back [18%], upper limbs [18%], lower limbs [36%], and genitals [1%]) and reported as a percentage of all major body sections combined. The reported percentage of BSA was combined percentage of all major body sections.	Baseline to Week 16
Secondary	Change From Baseline to Week 16 in Dermatology Life Quality Index (DLQI) Total Score	The DLQI was a validated questionnaire used to measure the impact of AD disease symptoms and treatment on health-related quality of life (QOL). DLQI consisting of a set of 10 questions which assess QOL over the past week. Responses to each questions were assessed on a scale of 0 to 3, where 0 is "not at all" and 3 is "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.	Baseline to Week 16
Secondary	Change From Baseline to Week 16 in Patient Oriented Eczema Measure (POEM)	The POEM is a 7-item self-assessment questionnaire that assesses disease symptoms on a scale ranging from 0 to 4 (0 = no days, 1 = 1 to 2 days, 2 = 3 to 4 days, 3 = 5 to 6 days, 4 = all days). The sum of the 7 items gives the total POEM score of 0 (absent disease) to 28 (severe disease). Higher scores indicated more severe disease and poor quality of life.	Baseline to Week 16
Secondary	Percentage Change From Baseline to Week 2 in Weekly Average of Peak Daily Pruritus NRS	Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]), higher scores indicated greater severity.	Baseline to Week 2
Secondary	Percentage Change From Baseline to Week 16 in EuroQoL Five Dimensions Questionnaire (EQ-5D) Index Scores	The EQ-5D is a standardized measure of health status which is consists of 2 parts; the descriptive system and the EQ visual analogue scale (EQVAS). The EQ-5D descriptive system includes 5 dimensions; mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension measured on 3 levels: "no problem" (level 1), "some problems" (level 2), "extreme problems" (level 3). The digits for 5 dimensions can be combined in a 5-digit number describing the respondent's health state. The 5 dimensional 3-level systems was converted into single index utility score between 0 to 1 that quantify health status, where 0 represents "death" and 1 represents "perfect health".	Baseline to Week 16
Secondary	Percentage Change From Baseline to Week 16 in EuroQoL Five Dimensions Questionnaire Visual Analog Scale Scores	The EQ-5D VAS records the respondent's self-rated health on a vertical, visual analogue scale ranged from 0-100 where 100 indicated "best imaginable health state" and 0 indicated "worst imaginable health state", higher scores indicated better outcome.	Baseline to Week 16
Secondary	Absolute Change From Baseline to Week 16 in EQ-5D Index Scores	The EQ-5D is a standardized measure of health status which consisted of 2 parts; the descriptive system and the EQVAS. The EQ-5D descriptive system includes 5 dimensions; mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension measured on 3 levels: "no problem" (level 1), "some problems" (level 2), "extreme problems" (level 3). The digits for 5 dimensions can be combined in a 5-digit number describing the respondent's health state. The 5 dimensional 3-level systems was converted into single index utility score between 0 to 1 that quantify health status, where 0 represents "death" and 1 represents "perfect health".	Baseline to Week 16
Secondary	Absolute Change From Baseline to Week 16 in EuroQoL Five Dimensions Questionnaire Visual Analog Scale Scores	The EQ-5D VAS records the respondent's self-rated health on a vertical, visual analogue scale ranged from 0-100 where 100 indicated "best imaginable health state" and 0 indicated "worst imaginable health state", higher scores indicated better outcome.	Baseline to Week 16
Secondary	Number of Participants Who Achieve Reduction of IGA Score by >=2 From Baseline to Week 16	The IGA is an assessment instrument used to rate the severity of AD globally, based on a 5-point scale ranging from (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe), higher score indicated higher severity. In this outcome measure, number of participants who achieved reduction from baseline of >=2 points in IGA score at Week 16 were reported.	Baseline to Week 16
Secondary	Number of Participants Achieving IGA 0 to 1 and a Reduction of >=2 Points From Baseline Through Week 16	The IGA is an assessment instrument used to rate the severity of AD globally based on a 5-point scale ranging from (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe), higher score indicated higher severity.	Baseline, Week 2, Week 4, Week 8, Week 12, Week 16
Secondary	Absolute Change in EASI Score From Baseline at Weeks 2, 4, 8, 12 and 16	EASI: Measure to assess severity & extent of AD based on 4 AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation] & lichenification). Each characteristic was assessed for severity by Investigator/designee on scale of "0" (absent) through "3" (severe) & scored separately for each of 4 body regions (head, trunk, upper & lower extremities). Total score range from 0 (minimum) to 72 (maximum), higher scores indicated greater severity of AD. Participants with missing EASI Score at each visit were imputed using MI (Multiple Imputation) method.	Baseline, Week 2, Week 4, Week 8, Week 12, Week 16
Secondary	Percentage Change in EASI Score From Baseline at Weeks 2, 4, 8, 12 and 16	EASI: Measure to assess severity & extent of AD based on 4 AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation] & lichenification). Each characteristic was assessed for severity by Investigator/designee on scale of "0" (absent) through "3" (severe) & scored separately for each of 4 body regions (head, trunk, upper & lower extremities). Total score range from 0 (minimum) to 72 (maximum), higher scores indicated greater severity of AD.	Baseline, Week 2, Week 4, Week 8, Week 12, Week 16
Secondary	Number of Participants With EASI-50 (>=50% Improvement From Baseline) at Week 16	EASI: Measure to assess severity & extent of AD based on 4 AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation] & lichenification). Each characteristic was assessed for severity by Investigator/designee on scale of "0" (absent) through "3" (severe) & scored separately for each of 4 body regions (head, trunk, upper & lower extremities). Total score range from 0 (minimum) to 72 (maximum), higher scores indicated greater severity of AD.	Baseline, Week 16
Secondary	Number of Participants With EASI-90 (>=90% Improvement From Baseline) at Week 16	EASI: Measure to assess severity & extent of AD based on 4 AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation] & lichenification). Each characteristic was assessed for severity by Investigator/designee on scale of "0" (absent) through "3" (severe) & scored separately for each of 4 body regions (head, trunk, upper & lower extremities). Total score range from 0 (minimum) to 72 (maximum), higher scores indicated greater severity of AD.	Baseline, Week 16
Secondary	Absolute Change in Weekly Average of Peak Daily Pruritus NRS Score From Baseline Through Week 16	Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]), higher scores indicated greater severity. Participants with missing Peak Daily Pruritus NRS Score at each visit were imputed using MI method.	From Baseline Through Week 16
Secondary	Percentage Change in Weekly Average of Peak Daily Pruritus NRS Score From Baseline Through Week 16	Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]), higher scores indicated greater severity. Participants with missing peak NRS scores at each visit were imputed using MI method.	From Baseline Through Week 16
Secondary	Number of Participants Who Responded "Absence of Pruritus" or "Mild Pruritus" in the Pruritus Categorical Scale at Week 16	The pruritus categorical scale was a 4-point scale used to assess symptoms of AD. The scale is rated as follows: 0: absence of pruritus; 1: mild pruritus (occasional slight itching/scratching); 2: moderate pruritus (constant or intermittent itching/scratching that does not disturb sleep) and 3: severe pruritus (bothersome itching/scratching that disturbs sleep), higher scores indicated worse outcome.	Week 16
Secondary	Number of Days of Sick Leave/Missed School Days	Participants who were employed or enrolled in school for full time were asked to report the number of sick leave/missed school days since the last study assessment. Participants were counted as Full time if the participant checked "Full time" at all visits through 16-week treatment period and participants were counted as Part time if the participant checked at least one "Part time" during 16-week treatment period.	Week 16
Secondary	Percentage of Participants With at Least One Day Sick Leave/Missed School Days	Participants who were employed or enrolled in school for full time were asked to report the number of sick leave/missed school days since the last study assessment. Participants were counted as Full time if the participant checked "Full time" at all visits through 16-week treatment period and participants were counted as Part time if the participant checked at least one "Part time" during 16-week treatment period.	Week 16