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| Name | Class |
|---|---|
| Sanofi | INDUSTRY |
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The main objective of the trial is to evaluate the efficacy of 2 dose regimens of dupilumab compared to placebo, administered with concomitant topical corticosteroids (TCS), in adult patients with severe AD who are not adequately controlled with, or are intolerant to, oral Cyclosporine A (CSA), or when this treatment is currently not medically advisable.
The secondary objective is to assess the safety and tolerability of 2 dose regimens of dupilumab compared to placebo, administered with concomitant TCS, in adult patients with severe AD who are not adequately controlled with, or are intolerant to, oral CSA, or when this treatment is currently not medically advisable.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo QW + TCS | Experimental | Participants received one subcutaneous (SC) injection of dupilumab matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
|
| Dupilumab 300 mg Q2W + TCS | Experimental | Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
|
| Dupilumab 300 mg QW + TCS | Experimental | Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dupilumab | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Eczema Area and Severity Index (EASI) 75 (≥75% Improvement From Baseline) at Week 16 | The EASI score is used to measure the severity and extent of atopic dermatitis (AD) and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline to Week 16. The analysis population for efficacy analyses is the Full Analysis Set (FAS) which included all randomized participants. Efficacy analyses were based on the treatment allocated (as randomized). | Baseline, Week 16 |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 16 | The EASI score is used to measure the severity and extent of atopic dermatitis (AD) and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. The analysis population for efficacy analyses is the FAS which included all randomized participants. Efficacy analyses were based on the treatment allocated (as randomized). Here "number of participants analyzed" = participants who were evaluable for this endpoint. |
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Inclusion Criteria:
Male or female, 18 years or older
Severe, Chronic AD, (according to American Academy of Dermatology Consensus Criteria [Eichenfield 2014]) for whom treatment with potent TCS is indicated
EASI score ≥20 at the screening and baseline visits
IGA score ≥3 (on the 0 to 4 IGA scale) at the screening and baseline visits
≥10% body surface area (BSA) of AD involvement at the screening and baseline visits
Documented recent history (within 6 months before the screening visit) of inadequate response to treatment with TCS
Have applied a stable dose of topical emollient (moisturizer) twice daily for at least the 7 consecutive days immediately before the baseline visit
Documented history by a physician of either:
No prior CSA exposure and not currently a candidate for CSA treatment due to:
Previously exposed to CSA, and CSA treatment should not be continued or restarted due to:
Exclusion Criteria:
Participation in a prior dupilumab clinical study
Treatment with an investigational drug within 8 weeks or within 5 half-lives (if known), whichever is longer, before the screening visit
Hypersensitivity and/or intolerance to corticosteroids or to any other ingredients contained in the TCS product used in the study
Systemic CSA, systemic corticosteroids, or phototherapy within 4 weeks prior to screening, and azathioprine (AZA), methotrexate (MTX), mycophenolate mofetil (MMF), or Janus kinase (JAK) inhibitors within 8 weeks prior to screening
Treatment with TCI within 1 week before the screening visit
Treatment with biologics as follows:
Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks of the screening visit
Treatment with a live (attenuated) vaccine within 12 weeks before the screening
Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before the screening or superficial skin infections within 1 week before the screening visit. NOTE: patients may be rescreened no sooner than 2 weeks after infection resolves
Known or suspected history of immunosuppression, including history of invasive opportunistic infections (eg, tuberculosis [TB], histoplasmosis, Listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution; or unusually frequent, recurrent, or prolonged infections, per investigator judgment
Presence of any 1 of the following TB criteria:
NOTE: Any of these 3 TB tests will be performed on a country-by-country basis according to local guidelines only if required by regulatory authorities or ethics boards.
History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening
Positive hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBc Ab), or hepatitis C antibody (HCV Ab) at the screening visit
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trial Management | Regeneron Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Site 1 | Vienna | Austria | ||||
| Site 2 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36808602 | Derived | Silverberg JI, Lynde CW, Abuabara K, Patruno C, de Benedetto A, Zhang H, Thomas RB, Bego-Le-Bagousse G, Khokhar FA, Vakil J, Marco AR, Levit NA. Efficacy and Safety of Dupilumab Maintained in Adults >/= 60 Years of Age with Moderate-to-Severe Atopic Dermatitis: Analysis of Pooled Data from Four Randomized Clinical Trials. Am J Clin Dermatol. 2023 May;24(3):469-483. doi: 10.1007/s40257-022-00754-4. Epub 2023 Feb 20. | |
| 36723913 |
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After providing informed consent, participants were assessed for study eligibility. Screening assessments were performed between day -28 & day -15, prior to randomization. Participants who met eligibility criteria at baseline (day 1) were randomized in a 1:1:1 ratio to receive dupilumab (weekly [QW] or every 2 weeks [Q2W]) or placebo.
The study was conducted at 73 sites in Europe. A total of 390 participants were screened between 28 Jan 2016 and 14 Sep 2016. Of those, 325 participants were enrolled into the study and randomized. Sixty participants were considered screen failures, mostly due to unmet eligibility criteria.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo QW + TCS | Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Matching Placebo | Drug |
|
| Baseline, Week 16 |
| Percent Change From Baseline in Weekly Average of Peak Pruritus Numerical Rating Scale (NRS) at Week 16 | The Pruritus NRS is an assessment tool 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 you rate your 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]). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "Number of Participants Analyzed" = Participants who were evaluable for this endpoint. | Baseline, Week 16 |
| Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 16 | The SCORAD is a clinical tool for assessing the severity of AD. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "Number of Participants analyzed" = Participants who were evaluable for this endpoint. | Baseline, Week 16 |
| Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus NRS From Baseline to Week 16 | Pruritus NRS is an assessment tool 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]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "Number of participants analyzed" = participants who were evaluable for this endpoint. | Baseline to Week 16 |
| Change From Baseline in Percent Body Surface Area (BSA) Involvement With Atopic Dermatitis (AD) at Week 16 | 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%]). It was reported as a percentage of all major body sections combined. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "number of participants analyzed" = participants who were evaluable for this endpoint. | Baseline, Week 16 |
| Percentage of Participants With Investigator Global Assessment (IGA) 0 or 1 (on the 0 to 4 IGA Scale) and a Reduction From Baseline of ≥2 Points at Week 16 | IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5 point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). Participants with IGA score of "0" or "1" and a reduction from baseline of ≥2 points at Week 16 were reported. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). | Baseline, Week 16 |
| Change From Baseline in the Dermatology Life Quality Index (DLQI) at Week 16 | The DLQI is a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of AD disease symptoms and treatment on quality of life (QOL). The 10 questions assessed QOL over the past week, with an overall scoring of 0 (absent disease) to 30 (severe disease); a high score is indicative of a poor QOL. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "Number of Participants Analyzed" = Participants who were evaluable for this endpoint. | Baseline, Week 16 |
| Change From Baseline in the Patient Oriented Eczema Measure (POEM) at Week 16 | The POEM is a 7-item questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life [QOL]). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "Number of Participants Analyzed" = participants who were evaluable for this endpoint. | Baseline, Week 16 |
| Percentage of Participants With Eczema Area and Severity Index (EASI) Score (≥75% Improvement From Baseline) at Week 16 for Participants With Prior CSA Use | The EASI score is used to measure the severity and extent of atopic dermatitis (AD) and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline to Week 16. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "Number of Participants Analyzed" = Participants who were evaluable for this endpoint. | Baseline, Week 16 |
| Change From Baseline in Mean Weekly Dose of Topical Corticosteroid (TCS) Use During Treatment Period | The type, amount, frequency, and potency of topical products used during the study were recorded at home by participants in a medication diary. Participants returned TCS tubes at each clinic visit up until week 16, and these tubes were weighed by the site staff to determine the actual amount of TCS used. During the 16-week placebo-controlled study treatment period, medium-potency TCS dosing frequency was symptom-based (IGA score) adjusted every 4 weeks per the protocol-specified tapering algorithm. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "Number Analyzed" = Participants who were evaluable for this endpoint. | Baseline to week 16 |
| Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) Score at Week 16 | The HADS is a 14-item scale, with 7 items relating to anxiety and 7 relating to depression. Each item on the questionnaire is scored from 0-3, for possible scores ranging from 0 (no symptoms) to 21 (severe symptoms) for each of the anxiety and depression subscales. Recommended cut-off scores for both subscales to identify psychiatric distress are: 7 to 8 for possible presence, 10 to 11 for probable presence, and 14 to 15 for severe anxiety or depression. Scores less than 7 do not indicate psychiatric distress. Total score is the sum of the two sub-scores. | Baseline, Week 16 |
| Percentage of Participants Achieving SCORAD 50 (≥50% Improvement From Baseline) at Week 16 | The SCORAD is a clinical tool for assessing the severity of AD. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). | Baseline, Week 16 |
| Percent Change From Baseline in the Total Global Individual Signs Score (GISS) at Week 16 (Erythema, Infiltration/ Papulation, Excoriations, Lichenification) | Individual components of the AD lesions (erythema, infiltration/ papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0= none, 1= mild, 2= moderate and 3= severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Full Analysis Set (FAS) included all randomized. Here "Number of Participants Analyzed" = Participants who were evaluable for this endpoint. | Baseline, Week 16 |
| Percent Change From Baseline in Weekly Average of Peak Pruritus Numerical Rating Scale (NRS) Score at Week 2 | Pruritus NRS is an assessment tool 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 you rate your 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]). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "Number of Participants analyzed" = Participants who were evaluable for this endpoint. | Baseline, Week 2 |
| Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) From Baseline Through Treatment Period | Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug to the last study dose (Week 16). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. Safety analysis set (SAF) included all randomized participants who received any study drug; it was based on the treatment received (as treated). | Baseline to Week 16 |
| Percentage of Participants Having at Least One Serious Treatment Emergent Adverse Event (TEAE) Through Treatment Period | Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug to the last study dose (Week 16). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. SAF included all randomized participants who received any study drug; it was based on the treatment received (as treated). | Baseline to Week 16 |
| Percentage of Participants Having at Least One Treatment-Emergent Adverse Event (TEAE) Leading to Treatment Discontinuation Through Treatment Period | Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug to the last study dose (Week 16). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. SAF included all randomized participants who received any study drug; it was based on the treatment received (as treated). | Baseline to Week 16 |
| Percentage of Participants With Treatment-Emergent Adverse Events Through Treatment Period | Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug to the last study dose (Week 16). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. SAF included all randomized participants who received any study drug; it was based on the treatment received (as treated). | Baseline to Week 16 |
| Vienna |
| Austria |
| Brussels | Belgium |
| Leuven | Belgium |
| Loverval | Belgium |
| Site 1 | Berlin | Germany |
| Site 2 | Berlin | Germany |
| Site 3 | Berlin | Germany |
| Site 4 | Berlin | Germany |
| Site 5 | Berlin | Germany |
| Site 6 | Berlin | Germany |
| Site 7 | Berlin | Germany |
| Bochum | Germany |
| Site 1 | Dresden | Germany |
| Site 2 | Dresden | Germany |
| Site 3 | Dresden | Germany |
| Erlangen | Germany |
| Frankfurt am Main | Germany |
| Site 1 | Hamburg | Germany |
| Site 2 | Hamburg | Germany |
| Heidelberg | Germany |
| Kiel | Germany |
| Langenau | Germany |
| Leipzig | Germany |
| Lübeck | Germany |
| Magdeburg | Germany |
| Mahlow | Germany |
| Mainz | Germany |
| Site 1 | München | Germany |
| Site 2 | München | Germany |
| Münster | Germany |
| Osnabrück | Germany |
| Selters | Germany |
| Stuttgart | Germany |
| Tübingen | Germany |
| Dublin | Ireland |
| Amsterdam | Netherlands |
| Utrecht | Netherlands |
| Site 1 | Bialystok | Poland |
| Site 1 | Bydgoszcz | Poland |
| Site 2 | Bydgoszcz | Poland |
| Gdansk | Poland |
| Site 1 | Katowice | Poland |
| Site 2 | Katowice | Poland |
| Site 3 | Katowice | Poland |
| Kielce | Poland |
| Site 1 | Krakow | Poland |
| Site 2 | Krakow | Poland |
| Site 1 | Lodz | Poland |
| Site 2 | Lodz | Poland |
| Site 3 | Lodz | Poland |
| Lublin | Poland |
| Szczecin | Poland |
| Site 1 | Warsaw | Poland |
| Site 2 | Warsaw | Poland |
| Warsaw | Poland |
| Site 1 | Wroclaw | Poland |
| Site 2 | Wroclaw | Poland |
| Zgierz | Poland |
| Chelyabinsk | Russia |
| Kazan' | Russia |
| Moscow | Russia |
| Ryazan | Russia |
| Saint Petersburg | Russia |
| Košice | Slovakia |
| SvidnÃk | Slovakia |
| Site 1 | Barcelona | Spain |
| Site 2 | Barcelona | Spain |
| Site 1 | London | United Kingdom |
| Site 2 | London | United Kingdom |
| Oxford | United Kingdom |
| Portsmouth | United Kingdom |
| Sheffield | United Kingdom |
| Derived |
| Paller AS, Silverberg JI, Cork MJ, Guttman-Yassky E, Lockshin B, Irvine AD, Kim MB, Kabashima K, Chen Z, Lu Y, Bansal A, Rossi AB, Shabbir A. Efficacy and Safety of Dupilumab in Patients With Erythrodermic Atopic Dermatitis: A Post Hoc Analysis of 6 Randomized Clinical Trials. JAMA Dermatol. 2023 Mar 1;159(3):255-266. doi: 10.1001/jamadermatol.2022.6192. |
| 36525340 | Derived | Mickevicius T, Pink AE, Bhogal M, O'Brart D, Robbie SJ. Dupilumab-Induced, Tralokinumab-Induced, and Belantamab Mafodotin-Induced Adverse Ocular Events-Incidence, Etiology, and Management. Cornea. 2023 Apr 1;42(4):507-519. doi: 10.1097/ICO.0000000000003162. Epub 2022 Dec 15. |
| 34142350 | Derived | Griffiths C, de Bruin-Weller M, Deleuran M, Fargnoli MC, Staumont-Salle D, Hong CH, Sanchez-Carazo J, Foley P, Seo SJ, Msihid J, Chen Z, Cyr SL, Rossi AB. Dupilumab in Adults with Moderate-to-Severe Atopic Dermatitis and Prior Use of Systemic Non-Steroidal Immunosuppressants: Analysis of Four Phase 3 Trials. Dermatol Ther (Heidelb). 2021 Aug;11(4):1357-1372. doi: 10.1007/s13555-021-00558-0. Epub 2021 Jun 18. |
| 33453450 | Derived | Boguniewicz M, Beck LA, Sher L, Guttman-Yassky E, Thaci D, Blauvelt A, Worm M, Corren J, Soong W, Lio P, Rossi AB, Lu Y, Chao J, Eckert L, Gadkari A, Hultsch T, Ruddy M, Mannent LP, Graham NMH, Pirozzi G, Chen Z, Ardeleanu M. Dupilumab Improves Asthma and Sinonasal Outcomes in Adults with Moderate to Severe Atopic Dermatitis. J Allergy Clin Immunol Pract. 2021 Mar;9(3):1212-1223.e6. doi: 10.1016/j.jaip.2020.12.059. Epub 2021 Jan 13. |
| 33165005 | Derived | Silverberg JI, Simpson EL, Guttman-Yassky E, Cork MJ, de Bruin-Weller M, Yosipovitch G, Eckert L, Chen Z, Ardeleanu M, Shumel B, Hultsch T, Rossi AB, Hamilton JD, Orengo JM, Ruddy M, Graham NMH, Pirozzi G, Gadkari A. Dupilumab Significantly Modulates Pain and Discomfort in Patients With Atopic Dermatitis: A Post Hoc Analysis of 5 Randomized Clinical Trials. Dermatitis. 2021 Oct 1;32(1S):S81-S91. doi: 10.1097/DER.0000000000000698. |
| 31066001 | Derived | Eichenfield LF, Bieber T, Beck LA, Simpson EL, Thaci D, de Bruin-Weller M, Deleuran M, Silverberg JI, Ferrandiz C, Folster-Holst R, Chen Z, Graham NMH, Pirozzi G, Akinlade B, Yancopoulos GD, Ardeleanu M. Infections in Dupilumab Clinical Trials in Atopic Dermatitis: A Comprehensive Pooled Analysis. Am J Clin Dermatol. 2019 Jun;20(3):443-456. doi: 10.1007/s40257-019-00445-7. |
| 29336016 | Derived | de Bruin-Weller M, Graham NMH, Pirozzi G, Shumel B. Could conjunctivitis in patients with atopic dermatitis treated with dupilumab be caused by colonization with Demodex and increased interleukin-17 levels?: reply from the authors. Br J Dermatol. 2018 May;178(5):1220-1221. doi: 10.1111/bjd.16348. Epub 2018 Mar 2. No abstract available. |
| FG001 | Dupilumab 300 mg Q2W + TCS | Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
| FG002 | Dupilumab 300 mg QW + TCS | Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
| Completed Treatment (Week 16) |
|
| Completed Study (Week 28) |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo QW + TCS | Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
| BG001 | Dupilumab 300 mg Q2W + TCS | Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
| BG002 | Dupilumab 300 mg QW + TCS | Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| ||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Eczema Area and Severity Index (EASI) Score | The EASI score is used to measure the severity and extent of atopic dermatitis (AD) and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. | Mean | Standard Deviation | Score on a Scale |
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| Peak Weekly Averaged Pruritus Numerical Rating Scale (NRS) score | Pruritus NRS is an assessment tool used to report intensity of participant's pruritus (itch), both average & maximum intensity, during 24-hr recall period. Participants were asked two questions: 1) For average itch intensity: how would you rate your itch overall (on average) during the previous 24 hrs; & 2) For maximum itch intensity: How would you rate your itch at the worst moment during the previous 24 hrs? Both questions were rated on a scale: 0-10 with 0=no itch & 10=worst itch imaginable. | Here "Number of Participants Analyzed" = Participants who were evaluable for this baseline characteristic | Mean | Standard Deviation | Score on a Scale |
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| Body Surface Area (BSA) Involvement of Atopic Dermatitis | 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%]). It was reported as a percentage of all major body sections combined. | Mean | Standard Deviation | Score on a Scale |
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| Global Individual Signs Score (GISS) | Individual components of the AD lesions (erythema, infiltration/papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0 = none, 1 = mild, 2 = moderate and 3 = severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease). | Mean | Standard Deviation | Score on a Scale |
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| Dermatology Life Quality Index (DLQI) Total Score | The DLQI is a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of AD disease symptoms and treatment on quality of life (QOL). The 10 questions assessed QOL over the past week, with individual scoring per question of 0 (not at all) to 3 (very much) and an overall scoring of 0 (absent disease) to 30 (severe disease); a high score indicative of a poor QOL. | Mean | Standard Deviation | Score on a Scale |
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| Patient Oriented Eczema Measure (POEM) | The POEM is a 7-item questionnaire that assessed disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor QOL) | Here "Number of Participants Analyzed" = Participants who were evaluable for this baseline characteristic | Mean | Standard Deviation | Score on a Scale |
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| Total Hospital Anxiety and Depression Scale (HADS) | The HADS is a 14-item scale, with 7 items relating to anxiety and 7 relating to depression. Each item on the questionnaire is scored from 0-3, for possible scores ranging from 0 (no symptoms) to 21 (severe symptoms) for each of the anxiety and depression subscales. Recommended cut-off scores for both subscales to identify psychiatric distress are: 7 to 8 for possible presence, 10 to 11 for probable presence, and 14 to 15 for severe anxiety or depression. Scores less than 7 do not indicate psychiatric distress. Total score is the sum of the two sub-scores. | Mean | Standard Deviation | Score on a Scale |
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| SCORing Atopic Dermatitis (SCORAD) score | The SCORAD is a clinical tool for assessing the extent and severity of AD. Extent and intensity of eczema as well as subjective symptoms (insomnia, etc.) were assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). | Mean | Standard Deviation | Score on a Scale |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Investigator's Global Assessment (IGA) score | IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1= almost clear; 2= mild; 3= moderate; 4= severe) based on erythema and papulation/ infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Percentage of Participants With Eczema Area and Severity Index (EASI) 75 (≥75% Improvement From Baseline) at Week 16 | The EASI score is used to measure the severity and extent of atopic dermatitis (AD) and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline to Week 16. The analysis population for efficacy analyses is the Full Analysis Set (FAS) which included all randomized participants. Efficacy analyses were based on the treatment allocated (as randomized). | Posted | Number | Percentage of Participants | Baseline, Week 16 |
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| Secondary | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 16 | The EASI score is used to measure the severity and extent of atopic dermatitis (AD) and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. The analysis population for efficacy analyses is the FAS which included all randomized participants. Efficacy analyses were based on the treatment allocated (as randomized). Here "number of participants analyzed" = participants who were evaluable for this endpoint. | Posted | Least Squares Mean | Standard Error | Percent Change | Baseline, Week 16 |
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| Secondary | Percent Change From Baseline in Weekly Average of Peak Pruritus Numerical Rating Scale (NRS) at Week 16 | The Pruritus NRS is an assessment tool 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 you rate your 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]). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "Number of Participants Analyzed" = Participants who were evaluable for this endpoint. | Posted | Least Squares Mean | Standard Error | Percent Change | Baseline, Week 16 |
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| Secondary | Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 16 | The SCORAD is a clinical tool for assessing the severity of AD. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "Number of Participants analyzed" = Participants who were evaluable for this endpoint. | Posted | Least Squares Mean | Standard Error | Percent Change | Baseline, Week 16 |
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| Secondary | Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Peak Daily Pruritus NRS From Baseline to Week 16 | Pruritus NRS is an assessment tool 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]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "Number of participants analyzed" = participants who were evaluable for this endpoint. | Posted | Number | Percentage of participants | Baseline to Week 16 |
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| Secondary | Change From Baseline in Percent Body Surface Area (BSA) Involvement With Atopic Dermatitis (AD) at Week 16 | 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%]). It was reported as a percentage of all major body sections combined. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "number of participants analyzed" = participants who were evaluable for this endpoint. | Posted | Least Squares Mean | Standard Error | Percent BSA | Baseline, Week 16 |
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| Secondary | Percentage of Participants With Investigator Global Assessment (IGA) 0 or 1 (on the 0 to 4 IGA Scale) and a Reduction From Baseline of ≥2 Points at Week 16 | IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5 point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). Participants with IGA score of "0" or "1" and a reduction from baseline of ≥2 points at Week 16 were reported. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). | Posted | Number | Percentage of Participants | Baseline, Week 16 |
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| Secondary | Change From Baseline in the Dermatology Life Quality Index (DLQI) at Week 16 | The DLQI is a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of AD disease symptoms and treatment on quality of life (QOL). The 10 questions assessed QOL over the past week, with an overall scoring of 0 (absent disease) to 30 (severe disease); a high score is indicative of a poor QOL. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "Number of Participants Analyzed" = Participants who were evaluable for this endpoint. | Posted | Least Squares Mean | Standard Error | Score on a Scale | Baseline, Week 16 |
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| Secondary | Change From Baseline in the Patient Oriented Eczema Measure (POEM) at Week 16 | The POEM is a 7-item questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life [QOL]). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "Number of Participants Analyzed" = participants who were evaluable for this endpoint. | Posted | Least Squares Mean | Standard Error | Score on a Scale | Baseline, Week 16 |
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| Secondary | Percentage of Participants With Eczema Area and Severity Index (EASI) Score (≥75% Improvement From Baseline) at Week 16 for Participants With Prior CSA Use | The EASI score is used to measure the severity and extent of atopic dermatitis (AD) and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline to Week 16. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "Number of Participants Analyzed" = Participants who were evaluable for this endpoint. | Posted | Number | Percentage of Participants | Baseline, Week 16 |
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| Secondary | Change From Baseline in Mean Weekly Dose of Topical Corticosteroid (TCS) Use During Treatment Period | The type, amount, frequency, and potency of topical products used during the study were recorded at home by participants in a medication diary. Participants returned TCS tubes at each clinic visit up until week 16, and these tubes were weighed by the site staff to determine the actual amount of TCS used. During the 16-week placebo-controlled study treatment period, medium-potency TCS dosing frequency was symptom-based (IGA score) adjusted every 4 weeks per the protocol-specified tapering algorithm. The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "Number Analyzed" = Participants who were evaluable for this endpoint. | Posted | Least Squares Mean | Standard Error | Grams | Baseline to week 16 |
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| Secondary | Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) Score at Week 16 | The HADS is a 14-item scale, with 7 items relating to anxiety and 7 relating to depression. Each item on the questionnaire is scored from 0-3, for possible scores ranging from 0 (no symptoms) to 21 (severe symptoms) for each of the anxiety and depression subscales. Recommended cut-off scores for both subscales to identify psychiatric distress are: 7 to 8 for possible presence, 10 to 11 for probable presence, and 14 to 15 for severe anxiety or depression. Scores less than 7 do not indicate psychiatric distress. Total score is the sum of the two sub-scores. | Analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "Number of Participants Analyzed" = Participants who were evaluable for this endpoint. | Posted | Least Squares Mean | Standard Error | Score on a Scale | Baseline, Week 16 |
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| Secondary | Percentage of Participants Achieving SCORAD 50 (≥50% Improvement From Baseline) at Week 16 | The SCORAD is a clinical tool for assessing the severity of AD. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). | Posted | Number | Percentage of Participants | Baseline, Week 16 |
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| Secondary | Percent Change From Baseline in the Total Global Individual Signs Score (GISS) at Week 16 (Erythema, Infiltration/ Papulation, Excoriations, Lichenification) | Individual components of the AD lesions (erythema, infiltration/ papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0= none, 1= mild, 2= moderate and 3= severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Full Analysis Set (FAS) included all randomized. Here "Number of Participants Analyzed" = Participants who were evaluable for this endpoint. | Posted | Least Squares Mean | Standard Error | Percent Change | Baseline, Week 16 |
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| Secondary | Percent Change From Baseline in Weekly Average of Peak Pruritus Numerical Rating Scale (NRS) Score at Week 2 | Pruritus NRS is an assessment tool 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 you rate your 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]). The analysis population for efficacy analyses is the FAS. Efficacy analyses were based on the treatment allocated (as randomized). Here "Number of Participants analyzed" = Participants who were evaluable for this endpoint. | Posted | Least Squares Mean | Standard Error | Percent Change | Baseline, Week 2 |
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| Secondary | Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) From Baseline Through Treatment Period | Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug to the last study dose (Week 16). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. Safety analysis set (SAF) included all randomized participants who received any study drug; it was based on the treatment received (as treated). | Posted | Number | Percentage of Participants | Baseline to Week 16 |
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| Secondary | Percentage of Participants Having at Least One Serious Treatment Emergent Adverse Event (TEAE) Through Treatment Period | Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug to the last study dose (Week 16). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. SAF included all randomized participants who received any study drug; it was based on the treatment received (as treated). | Posted | Number | Percentage of Participants | Baseline to Week 16 |
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| Secondary | Percentage of Participants Having at Least One Treatment-Emergent Adverse Event (TEAE) Leading to Treatment Discontinuation Through Treatment Period | Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug to the last study dose (Week 16). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. SAF included all randomized participants who received any study drug; it was based on the treatment received (as treated). | Posted | Number | Percentage of participants | Baseline to Week 16 |
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| Secondary | Percentage of Participants With Treatment-Emergent Adverse Events Through Treatment Period | Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug to the last study dose (Week 16). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. SAF included all randomized participants who received any study drug; it was based on the treatment received (as treated). | Posted | Number | Percentage of participants | Baseline to Week 16 |
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All Adverse Events (AEs) were collected from signature of informed consent form up to end of study (EOS), Week 28, regardless of seriousness or relationship to investigational product.
Pre-treatment AEs were AEs that developed/worsened in severity during pre-treatment period (from informed consent to first dose of study drug); All AEs collected during treatment and follow-up period were considered treatment emergent AEs (TEAEs). TEAEs were AEs that developed or worsened in severity compared to baseline during treatment and follow-up period.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo QW + TCS | Participants received one subcutaneous (SC) injection of matching placebo once per week (QW) (following two SC injections on day 1) from Week 1 to Week 15. All participants required to undergo treatment with topical corticosteroids (TCS) using standardized regimen that continued through the end of treatment period (Week 16). At week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). | 0 | 108 | 2 | 108 | 45 | 108 |
| EG001 | Dupilumab 300 mg Q2W + TCS | Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). | 0 | 107 | 2 | 107 | 54 | 107 |
| EG002 | Dupilumab 300 mg QW + TCS | Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). | 0 | 110 | 3 | 110 | 51 | 110 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pancreatitis acute | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
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| Hepatotoxicity | Hepatobiliary disorders | MedDRA 19.1 | Systematic Assessment |
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| Uterine leiomyoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.1 | Systematic Assessment |
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| Hemiparesis | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
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| Ureterolithiasis | Renal and urinary disorders | MedDRA 19.1 | Systematic Assessment |
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| Emphysema | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
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| Dermatitis atopic | Skin and subcutaneous tissue disorders | MedDRA 19.1 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Conjunctivitis allergic | Eye disorders | MedDRA 19.1 | Systematic Assessment |
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| Conjunctivitis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
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| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
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| Dermatitis atopic | Skin and subcutaneous tissue disorders | MedDRA 19.1 | Systematic Assessment |
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The investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trial Administrator | Regeneron Pharmaceuticals, Inc. | 844-734-6643 | clinicaltrials@regeneron.com |
| ID | Term |
|---|---|
| D003876 | Dermatitis, Atopic |
| ID | Term |
|---|---|
| D012873 | Skin Diseases, Genetic |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D003872 | Dermatitis |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D017443 | Skin Diseases, Eczematous |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C582203 | dupilumab |
Not provided
Not provided
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| A hierarchical testing approach was used to control Type-1 error at 0.05 across 2 dose regimens. Difference is Dupilumab minus placebo. Confidence Interval (CI) calculated using normal approximation. Participants with missing values at Week 16 were categorized as non-responders at Week 16. Participants who used rescue treatment were categorized as non-responders from time rescue treatment was initiated. | Cochran-Mantel-Haenszel | < 0.0001 | Threshold for significance at 0.05 level. P-values were derived by Cochran-Mantel-Haenszel (CMH) test stratified by disease severity (IGA 3 vs IGA 4) and prior Cyclosporine A (CSA) use (Yes, No). | difference in percentages | 33 | 2-Sided | 95 | 20.41 | 45.57 | Superiority |
| OG002 | Dupilumab 300 mg QW + TCS | Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
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| OG002 | Dupilumab 300 mg QW + TCS | Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
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| OG002 | Dupilumab 300 mg QW + TCS | Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
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Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
| OG002 | Dupilumab 300 mg QW + TCS | Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
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| OG002 | Dupilumab 300 mg QW + TCS | Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
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| OG002 | Dupilumab 300 mg QW + TCS | Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
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| OG002 | Dupilumab 300 mg QW + TCS | Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
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| OG002 | Dupilumab 300 mg QW + TCS | Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
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Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
| OG002 | Dupilumab 300 mg QW + TCS | Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
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Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]).
| OG002 | Dupilumab 300 mg QW + TCS | Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
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| Dupilumab 300 mg Q2W + TCS |
Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
| OG002 | Dupilumab 300 mg QW + TCS | Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
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| OG002 | Dupilumab 300 mg QW + TCS | Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
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Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]).
| OG002 | Dupilumab 300 mg QW + TCS | Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
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| OG002 | Dupilumab 300 mg QW + TCS | Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
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| Dupilumab 300 mg Q2W + TCS |
Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
| OG002 | Dupilumab 300 mg QW + TCS | Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
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Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
| OG002 | Dupilumab 300 mg QW + TCS | Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
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Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
| OG002 | Dupilumab 300 mg QW + TCS | Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
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Participants received one subcutaneous (SC) injection of dupilumab 300 mg every 2 weeks (Q2W) from Week 1 to Week 15 (following a SC loading dose of 600 mg on day 1). During weeks in which dupilumab was not administered, participants received matching placebo. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]).
| OG002 | Dupilumab 300 mg QW + TCS | Participants received one subcutaneous (SC) injection of dupilumab 300 mg once per week (QW) (following an SC loading dose of 600 mg on day 1) from Week 1 to Week 15. All participants were required to undergo treatment with topical corticosteroids (TCS) using a standardized regimen that continued through the end of the treatment period (Week 16). Starting at week 16, participants could roll over into an open-label extension (OLE) study (R668-AD-1225), if they were considered eligible. Participants who did not enter the OLE study were followed for up to an additional 12 weeks for safety ([Week 28, end of study (EOS) period]). |
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