SAR231893-LPS15497- "Dupilumab Effect on Sleep in AD Patients"
- Registration Number
- NCT04033367
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
To evaluate the effect of dupilumab on sleep quality in adult participants with moderate to severe atopic dermatitis (AD).
Secondary Objectives:
To evaluate the effect of dupilumab on objective and subjective quantitative sleep parameters, AD related outcomes, and daytime consequences of sleep deprivation.
To continue to assess the safety and tolerability throughout the study.
- Detailed Description
Duration per participant was up to 28 weeks.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 188
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo/Dupilumab Placebo Participants received placebo matching to dupilumab injection SC on Day 1 then followed by placebo injection SC q2w up to Week 10 in the DB period of 12 weeks. After completion of DB period, participants entered in the OLE period (Week 12 to 24) and received dupilumab 600 mg (loading dose) at Week 12 followed by dupilumab 300 mg injection SC q2w up to Week 22. Dupilumab/Dupilumab Dupilumab Participants received dupilumab 600 milligrams (mg) (loading dose) injection subcutaneously (SC) on Day 1 followed by dupilumab 300 mg injection SC every 2 weeks (q2w) up to Week 10 in the double-blind (DB) period of 12 weeks. After completion of DB period, participants entered in the open-label extension (OLE) period (Week 12 to 24) and continued to receive dupilumab 300 mg injection SC q2w from Week 12 up to Week 22. Placebo/Dupilumab Dupilumab Participants received placebo matching to dupilumab injection SC on Day 1 then followed by placebo injection SC q2w up to Week 10 in the DB period of 12 weeks. After completion of DB period, participants entered in the OLE period (Week 12 to 24) and received dupilumab 600 mg (loading dose) at Week 12 followed by dupilumab 300 mg injection SC q2w up to Week 22.
- Primary Outcome Measures
Name Time Method DB Period: Percent Change From Baseline in Sleep Quality Numerical Rating Scale (NRS) at Week 12 Baseline, Week 12 Sleep quality NRS was used to assess the quality of the participant's previous night's sleep. It was collected on a 11-point scale ranged from 0 (worst possible sleep) to 10 (best possible sleep), where higher score indicated better outcome. Percent change from Baseline in sleep quality NRS at Week 12 was reported in this outcome measure.
- Secondary Outcome Measures
Name Time Method DB Period: Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Related Impairment Short Form 8a (SF8a) Total T-Score at Week 12 Baseline, Week 12 PROMIS is a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), Level 2, sleep disturbance measure. In this study, 8- item PROMIS Sleep Related Impairment SF8a that assesses the domain of sleep related impairment in the past 7 days in individuals aged 18 and older, was used. Each item asks the participant to rate the severity of the participant's sleep related impairment during the past 7 days (at each specified visit) on a 5-point scale (1 = not at all; 2 = a little bit; 3 = somewhat; 4 = quite a bit; and 5 = very much) with raw score ranging from 8 to 40; higher scores indicating greater severity of sleep impairment. PROMIS T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation of 10. Possible range for T-score is 30 to 80, with higher scores indicating greater severity of sleep impairment.
DB Period: Percent Change From Baseline in Peak Pruritus NRS at Week 12 Baseline, Week 12 Peak Pruritus NRS was an assessment tool that was used by participants to report the intensity of their pruritus (itch) during a 24-hour recall period. Participants were asked the following question: "On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable', how would you rate your itch at the worst moment during the previous 24 hours?". Participants answered the question at the specified time point (for the last 24 hours) on the scale of 0 (no itch) to 10 (worst itch imaginable), where higher scores indicated greater severity.
DB Period: Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Total Score at Week 12 Baseline, Week 12 SCORAD is a validated scoring index for AD, which consists of 3 components i.e., A =extent or affected body surface area (BSA) assessed as a percentage of each defined body area and reported as the sum of all areas, with a maximum score of 100%. B=severity of 6 specific symptoms of AD (redness, swelling, oozing/crusting, excoriation, skin thickening/lichenification, dryness) assessed using the following scale: none (0), mild (1), moderate (2), or severe (3) (for a maximum of 18 total points) and C=subjective symptoms scored by participants on VAS, where "0" is no itch (or no sleeplessness) and "10" is the worst imaginable itch (or sleeplessness) with a maximum score of 20. SCORAD total score was calculated using these 3 aspects: extent (A: 0-100), severity (B: 0-18), and subjective symptoms (C: 0-20) using the formula: A/5 + 7\*B/2+ C to give the SCORAD total score range of 0 to 103, where 0 = no disease to 103 = severe disease. Higher values of SCORAD represent worse outcome.
DB Period: Percentage of Participants With Eczema Area Severity Index-50 (EASI-50) (Greater Than or Equal to [>=] 50% Improvement From Baseline) at Week 12 Baseline, Week 12 EASI evaluates severity of participants with AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin\] and lower limbs \[including buttocks\]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in each body region: 0, 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), and 6 (90% to 100%). Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD. Percentage of participants with EASI-50 (\>=50% improvement from Baseline in EASI score) at Week 12 is reported in this outcome measure.
DB Period: Percentage of Participants With Eczema Area Severity Index-75 (EASI-75) (>= 75% Improvement From Baseline) at Week 12 Baseline, Week 12 EASI evaluates severity of participants with AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % BSA affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin\] and lower limbs \[including buttocks\]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in each body region: 0, 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), and 6 (90% to 100%). Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD. Percentage of participants with EASI-75 (\>=75% improvement from Baseline in EASI score) at Week 12 is reported in this outcome measure.
DB Period: Change From Baseline in Patient Oriented Eczema Measure (POEM) Total Score at Week 12 Baseline, Week 12 The POEM was a 7-item, validated questionnaire used in clinical practice and clinical trials to assess disease symptoms in children and adults with AD. The format is participant response to 7 items (dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping) based on symptom frequency during the past week (i.e., 0 = 'no days', 1 = '1 to 2 days', 2 = '3 to 4 days', 3 = '5 to 6' days, and 4 = 'every day'). 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.
DB Period: Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Week 12 Baseline, Week 12 DLQI was a 10-item questionnaire that measures the impact of skin disease. Each question was evaluated on a 4-point scale ranged from 0 to 3 where, 0 = not at all, 1= a little, 2= a lot, 3= very much, where higher scores indicated more impact on quality of life. Scores from all 10 questions were added up to give DLQI total score range from 0 (not at all) to 30 (very much). Higher scores indicated more impact on quality of life of participants.
DB Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Baseline up to 14 days after last IMP administration (i.e., up to Week 12) 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) were 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 TEAE period (from the first investigational medicinal product \[IMP\] administration to the last IMP administration + 14 days) in DB period.
Entire Study Duration: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Baseline up to 14 days after last IMP administration (i.e., up to Week 24) An 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. SAEs were 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 TEAE period (from the first IMP administration to the last IMP administration + 14 days).
DB Period: Change From Baseline in SCORAD Sleep Loss Visual Analog Scale (VAS) Score at Week 12 Baseline, Week 12 SCORAD is a validated scoring index for AD, which combines extent (A, 0-100), severity (B, 0-18), and subjective symptoms (C, 0-20) based on itch and sleeplessness, each scored (0-10). The SCORAD for an individual was calculated by the formula: A/5 + 7B/2 + C (can range from 0 to 103). Subjective symptoms (i.e., itch and sleeplessness/sleep loss) were each scored by the participant using a VAS ranging from 0 to 10, where "0" is no itch (or no sleep loss) and "10" is the worst imaginable itch (or sleeplessness). Change from Baseline in SCORAD sleeplessness/sleep loss VAS score is reported in this outcome measure.
DB Period: Change From Baseline in Weekly Average Sleep Efficiency (SE) at Week 12 Baseline, Week 12 A sleep diary was designed to gather information about participant's daily sleep pattern. It measured night-time sleep assessments. SE was calculated using the formula: (TST divided by \[Time of waking up for the day - Time of trying to fall sleep\]) multiplied by 100 percent (%). TST (in minutes) was calculated using the formula: Time of waking up for the day minus time of falling sleep minus Wake After Sleep Onset (WASO), where WASO = time awake after initial sleep onset but before the final awakening for the day. Baseline and Post-baseline weekly average data were calculated based on the mean of the data over the 7 days prior to and including the day at the Baseline or at the end of the corresponding week. In this outcome measure, change from Baseline in SE at Week 12 is reported.
DB Period: Change From Baseline in Weekly Average Wake After Sleep Onset (WASO) at Week 12 Baseline, Week 12 A sleep diary was designed to gather information about participant's daily sleep pattern. It measured night-time sleep assessments. WASO = time awake (in minutes) after initial sleep onset but before the final awakening for the day. Data for WASO was collected from Question 3 of the Sleep Diary: "Considering all the times you woke up last night, how much time were you awake in total?". Baseline and Post-baseline weekly average data were calculated based on the mean of the data over the 7 days prior to and including the day at the Baseline or at the end of the corresponding week. In this outcome measure, change from Baseline in WASO at Week 12 is reported.
DB Period: Change From Baseline in Weekly Average Total Sleep Time (TST) at Week 12 Baseline, Week 12 A sleep diary was designed to gather information about participant's daily sleep pattern. It measured night-time sleep assessments. TST (in minutes) was calculated using the formula: Time of waking up for the day minus time of falling sleep minus Wake After Sleep Onset (WASO), where WASO = time awake after initial sleep onset but before the final awakening for the day. Data for WASO was collected from Question 3 of the Sleep Diary: "Considering all the times you woke up last night, how much time were you awake in total?". Baseline and Post-baseline weekly average data were calculated based on the mean of the data over the 7 days prior to and including the day at the Baseline or at the end of the corresponding week. In this outcome measure, change from Baseline in TST at Week 12 is reported.
DB Period: Change From Baseline in Weekly Average Sleep Onset Latency (SOL) at Week 12 Baseline, Week 12 A sleep diary was designed to gather information about participant's daily sleep pattern. It measured night-time sleep assessments. SOL (in minutes) was calculated using the formula: Time of falling sleep - Time of trying to fall sleep. Baseline and Post-baseline weekly average data were calculated based on the mean of the data over the 7 days prior to and including the day at the Baseline or at the end of the corresponding week. In this outcome measure, change from Baseline in SOL at Week 12 is reported.
Trial Locations
- Locations (42)
Investigational Site Number :3800001
🇮🇹Pisa, Italy
Investigational Site Number :7240003
🇪🇸Manises, Valencia, Spain
Investigational Site Number :3800002
🇮🇹Roma, Italy
Investigational Site Number :7240004
🇪🇸Granada, Andalucia, Spain
Investigational Site Number :7240005
🇪🇸Sevilla, Spain
Investigational Site Number :3800003
🇮🇹Siena, Italy
Investigational Site Number :7240001
🇪🇸Barcelona / Sabadell, Castilla Y León, Spain
Investigational Site Number :3800006
🇮🇹Perugia, Italy
Investigational Site Number :8400012
🇺🇸North Little Rock, Arkansas, United States
Investigational Site Number :7240008
🇪🇸Madrid, Spain
Investigational Site Number :3800004
🇮🇹Reggio Calabria, Italy
Investigational Site Number :8260004
🇬🇧Edinburgh, Edinburgh, City Of, United Kingdom
Investigational Site Number :7240010
🇪🇸Madrid, Spain
Investigational Site Number :7240006
🇪🇸Córdoba, Spain
Investigational Site Number :7240002
🇪🇸Valencia, Spain
Investigational Site Number :7840001
🇦🇪Dubai, United Arab Emirates
Investigational Site Number :7560001
🇨🇭Bern, Switzerland
Investigational Site Number :8260002
🇬🇧Dudley, Birmingham, United Kingdom
Investigational Site Number :0360006
🇦🇺Phillip, Australian Capital Territory, Australia
Investigational Site Number :7840002
🇦🇪Abu Dhabi, United Arab Emirates
Investigational Site Number :8400002
🇺🇸Redwood City, California, United States
Investigational Site Number :8400005
🇺🇸Denver, Colorado, United States
Investigational Site Number :8400003
🇺🇸Sarasota, Florida, United States
Investigational Site Number :8400007
🇺🇸Medford, Oregon, United States
Investigational Site Number :8400001
🇺🇸Rolling Hills Estates, California, United States
Investigational Site Number :8400013
🇺🇸Colorado Springs, Colorado, United States
Investigational Site Number :0360001
🇦🇺Kogarah, New South Wales, Australia
Investigational Site Number :0360007
🇦🇺Woolloongabba, Queensland, Australia
Investigational Site Number :0360003
🇦🇺Carlton, Victoria, Australia
Investigational Site Number :2500001
🇫🇷Brest, France
Investigational Site Number :2760002
🇩🇪Frankfurt am Main, Germany
Investigational Site Number :2500006
🇫🇷Toulouse, France
Investigational Site Number :2500002
🇫🇷Paris, France
Investigational Site Number :2500003
🇫🇷Nantes, France
Investigational Site Number :2760006
🇩🇪Friedrichshafen, Germany
Investigational Site Number :3760005
🇮🇱Afula, Israel
Investigational Site Number :2760001
🇩🇪Göttingen, Germany
Investigational Site Number :2760004
🇩🇪Münster, Germany
Investigational Site Number :3800005
🇮🇹Rozzano, Milano, Italy
Investigational Site Number :3760003
🇮🇱Jerusalem, Israel
Investigational Site Number :2760005
🇩🇪Bad Bentheim, Germany
Investigational Site Number :8400008
🇺🇸Charleston, South Carolina, United States