A Study to Evaluate Upadacitinib in Combination With Topical Corticosteroids in Adolescent and Adult Participants With Moderate to Severe Atopic Dermatitis (AD Up)

• ClinicalTrials.gov Identifier: NCT03568318
• Recruitment Status: Enrolling by invitation
• First Posted: June 26, 2018
• Results First Posted: March 31, 2022
• Last Update Posted: April 12, 2024
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: June 14, 2018
• First Posted Date: June 26, 2018
• Results First Submitted Date: February 7, 2022
• Results First Posted Date: March 31, 2022
• Last Update Posted Date: April 12, 2024
• Actual Study Start Date: August 9, 2018
• Actual Primary Completion Date: February 16, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 7, 2022)

• Main Study: Percentage of Participants Achieving at Least a 75% Reduction in Eczema Area and Severity Index Score (EASI 75) From Baseline at Week 16 [ Time Frame: Baseline and Week 16 ]
  EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1], moderate [2], or severe [3]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease.
• Main Study: Percentage of Participants Achieving Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) of 0 or 1 With a Reduction From Baseline of ≥ 2 Points at Week 16 [ Time Frame: Baseline and Week 16 ]
  The vIGA-AD is a validated assessment instrument to rate the severity of atopic dermatitis globally, based on the following scale:

  • 0 - Clear: No inflammatory signs of AD;
  • 1 - Almost clear: Barely perceptible erythema, induration/papulation and/or lichenification;
  • 2 - Mild: Slight but definite erythema, induration/papulation and/or minimal lichenification. No oozing or crusting;
  • 3 - Moderate: Clearly perceptible erythema, induration/papulation and/or lichenification, oozing or crusting may be present;
  • 4 - Severe: Marked erythema, induration/papulation and/or lichenification; Oozing or crusting may be present.

Original Primary Outcome Measures (submitted: June 14, 2018)

• Proportion of participants achieving at least a 75% reduction in Eczema Area and Severity Index (EASI 75) [ Time Frame: At Week 16 ]
  The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of atopic dermatitis (AD).
• Proportion of participants achieving validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) of 0 or 1 with at least two grades of reduction [ Time Frame: At Week 16 ]
  The vIGA-AD is a validated assessment instrument used in clinical studies to rate the severity of AD globally.

Current Secondary Outcome Measures (submitted: February 7, 2022)

• Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus Numerical Rating Scale (NRS) at Week 16 [ Time Frame: Baseline (last available rolling average before the first dose of study drug) and Week 16 ]
  Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Pruritus NRS was analyzed based on weekly rolling averages of daily scores.
• Main Study: Percentage of Participants Achieving a 90% Reduction From Baseline in EASI Score (EASI 90) at Week 16 [ Time Frame: Baseline and Week 16 ]
  EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/ neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1], moderate [2], or severe [3]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease.
• Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 4 [ Time Frame: Baseline (last available rolling average before the first dose of study drug) and Week 4 ]
  Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Pruritus NRS was analyzed based on weekly rolling averages of daily scores.
• Main Study: Percentage of Participants Achieving an EASI 75 Response at Week 4 [ Time Frame: Baseline and Week 4 ]
  EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1], moderate [2], or severe [3]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease. An EASI 75 response is defined as at least a 75% reduction (improvement) from Baseline in EASI score.
• Main Study: Percentage of Participants Achieving an EASI 75 Response at Week 2 [ Time Frame: Baseline and Week 2 ]
  EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1], moderate [2], or severe [3]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease. An EASI 75 response is defined as at least a 75% reduction (improvement) from Baseline in EASI score.
• Main Study: Percentage of Participants Achieving an EASI 90 Response at Week 4 [ Time Frame: Baseline and Week 4 ]
  EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/ neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1], moderate [2], or severe [3]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease.
• Main Study: Percentage of Participants Achieving a 100% Reduction From Baseline in EASI Score (EASI 100) at Week 16 [ Time Frame: Baseline and Week 16 ]
  EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored from 0 [none], to 3 [severe]) for redness, thickness, scratching, and lichenification. The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease. The percentage of participants with an EASI 100 response at Week 16 was pre-specified as a ranked secondary endpoint for participants in the Upadacitinib 30 mg + Topical Corticosteroids group versus Placebo + Topical Corticosteroids group only.
• Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 1 [ Time Frame: Baseline (last available rolling average before the first dose of study drug) and Week 1 ]
  Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Pruritus NRS was analyzed based on weekly rolling averages of daily scores.
• Main Study: Percent Change From Baseline in Worst Pruritus NRS at Week 16 [ Time Frame: Baseline (last available rolling average before the first dose of study drug) and Week 16 ]
  Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Pruritus NRS was analyzed based on weekly rolling averages of daily scores. A negative change from Baseline indicates improvement.
• Main Study: Percent Change From Baseline in EASI Score at Week 16 [ Time Frame: Baseline and Week 16 ]
  EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1)] moderate [2], or severe [3]) for Redness (erythema, inflammation), Thickness (induration, papulation, swelling - acute eczema), Scratching (excoriation), and Lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease; a negative change from Baseline indicates improvement.
• Adolescents: Percentage of Participants Achieving an EASI 75 Response at Week 16 [ Time Frame: Baseline and Week 16 ]
  EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1], moderate [2], or severe [3]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease. An EASI 75 response is defined as at least a 75% reduction (improvement) from Baseline in EASI score.
• Adolescents: Percentage of Participants Achieving a vIGA-AD of 0 or 1 With a Reduction From Baseline of ≥ 2 Points at Week 16 [ Time Frame: Baseline and Week 16 ]
  The vIGA-AD is a validated assessment instrument to rate the severity of atopic dermatitis globally, based on the following scale:

  • 0 - Clear: No signs of AD;
  • 1 - Almost clear: Barely perceptible erythema, induration/papulation and/or lichenification;
  • 2 - Mild: Slight but definite erythema, induration/papulation and/or minimal lichenification. No oozing or crusting;
  • 3 - Moderate: Clearly perceptible erythema, induration/papulation and/or lichenification, possible oozing or crusting;
  • 4 - Severe: Marked erythema, induration/papulation and/or lichenification; possible oozing or crusting.
• Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 16 [ Time Frame: Baseline (last available rolling average before the first dose of study drug) and Week 16 ]
  Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst pruritus NRS was analyzed based on weekly rolling averages of daily scores.
• Adolescents: Percentage of Participants Achieving an EASI 90 Response at Week 16 [ Time Frame: Baseline and Week 16 ]
  EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1], moderate [2], or severe [3]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease. An EASI 90 response is defined as at least a 90% reduction (improvement) from Baseline in EASI score.
• Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 4 [ Time Frame: Baseline (last available rolling average before the first dose of study drug) and Week 4 ]
  Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst pruritus NRS was analyzed based on weekly rolling averages of daily scores.
• Adolescents: Percentage of Participants Achieving an EASI 75 Response at Week 4 [ Time Frame: Baseline and Week 4 ]
  EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1], moderate [2], or severe [3]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease. An EASI 75 response is defined as at least a 75% reduction (improvement) from Baseline in EASI score.
• Adolescents: Percentage of Participants Achieving an EASI 75 Response at Week 2 [ Time Frame: Baseline and Week 2 ]
  EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1], moderate [2], or severe [3]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease. An EASI 75 response is defined as at least a 75% reduction (improvement) from Baseline in EASI score.
• Adolescents: Percentage of Participants Achieving an EASI 90 Response at Week 4 [ Time Frame: Baseline and Week 4 ]
  EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1], moderate [2], or severe [3]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease. An EASI 90 response is defined as at least a 90% reduction (improvement) from Baseline in EASI score.
• Adolescents: Percentage of Participants Achieving an EASI 100 Response at Week 16 [ Time Frame: Baseline and Week 16 ]
  EASI is used to measure the extent and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. and the severity score is calculated as the sum of the intensity scores (scored from 0 [none], to 3 [severe]) for redness, thickness, scratching, and lichenification. The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease. An EASI 100 response is defined as a 100% reduction (improvement) from Baseline in EASI score. The percentage of participants with an EASI 100 response at Week 16 was pre-specified as a secondary endpoint for participants in the Upadacitinib 30 mg + TCS group versus Placebo + TCS group only.
• Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 1 [ Time Frame: Baseline (last available rolling average before the first dose of study drug) and Week 1 ]
  Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst pruritus NRS was analyzed based on weekly rolling averages of daily scores.
• Adolescents: Percent Change From Baseline in Worst Pruritus NRS at Week 16 [ Time Frame: Baseline (last available rolling average before the first dose of study drug) and Week 16 ]
  Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Pruritus NRS was analyzed based on weekly rolling averages of daily scores. A negative change from Baseline indicates improvement.
• Adolescents: Percent Change From Baseline in EASI Score at Week 16 [ Time Frame: Baseline and Week 16 ]
  EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1)] moderate [2], or severe [3]) for Redness (erythema, inflammation), Thickness (induration, papulation, swelling - acute eczema), Scratching (excoriation), and Lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease; a negative change from Baseline indicates improvement.

Original Secondary Outcome Measures (submitted: June 14, 2018)

• Proportion of participants achieving an improvement (reduction) in worst pruritus Numerical Rating Scale (NRS) ≥ 4 [ Time Frame: At Week 16 ]
  The Worst Pruritus NRS is an assessment tool that participants used to report the intensity of their pruritus during a 24-hour recall period.
• Proportion of participants achieving EASI 90 [ Time Frame: At Week 16 ]
  The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate Upadacitinib in Combination With Topical Corticosteroids in Adolescent and Adult Participants With Moderate to Severe Atopic Dermatitis
• Official Title: A Phase 3 Randomized, Placebo-Controlled, Double-Blind Study to Evaluate Upadacitinib in Combination With Topical Corticosteroids in Adolescent and Adult Subjects With Moderate to Severe Atopic Dermatitis
• Brief Summary: The objective of this study is to assess the efficacy and safety of upadacitinib combined with topical corticosteroids (TCS) for the treatment of adolescent and adult participants with moderate to severe atopic dermatitis (AD) who are candidates for systemic therapy.

Detailed Description

This study includes a 35-day screening period, a 16-week double-blind period, a blinded extension period up to Week 260, a blinded Long-term Extension (LTE) Period after Week 260 to Week 524, and a 30-day follow-up visit. Participants who meet eligibility criteria in the Main Study will be randomly assigned in a 1:1:1 ratio to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily, in combination with topical corticosteroids.

Upon completion of enrollment of 810 participants in the Main Study, a supplemental study will continue to enroll adolescent participants (Adolescent Sub-study) until a total of 180 adolescent participants are enrolled in the overall study (Main Study + Adolescent Sub-study).

Approximately 1000 participants from M16-045 or M18-891 and approximately 500 participants from M16-047 will have the opportunity to enroll into the blinded Long-Term Extension (LTE) period (Week 260 - Week 524) after reaching Week 260 in their respective studies.

Randomization for the Main Study will be stratified by Baseline disease severity (validated Investigator Global Assessment Scale for Atopic Dermatitis [vIGA-AD] score of moderate [3] versus severe [4]), by geographic region (US/Puerto Rico/Canada, Japan, China, and Other), and by age (adolescent [ages 12 to 17] versus adult [ages 18 to 75]). The separate randomization for the Adolescent Sub-study will be stratified by Baseline disease severity (moderate [vIGA-AD 3] versus severe [vIGA-AD 4]) and by geographic region (US/Puerto Rico/Canada and Other).

At Week 16 of both the Main Study and the Adolescent Sub-study, participants in the placebo group will be re-randomized in a 1:1 ratio to receive daily oral doses of upadacitinib 30 mg or upadacitinib 15 mg in the blinded extension period, and participants originally randomized to upadacitinib will continue upadacitinib in the extension period at the same dose. For the Main Study, the re-randomization will be stratified by Eczema Area and Severity Index (EASI) 50 responder status (Yes/No), by geographic region (US/Puerto Rico/Canada, Japan, China, and Other) and by age (adolescent [ages 12 to 17] versus adult [ages 18 to 75]). For the Adolescent Sub-study, the re-randomization will be stratified by EASI 50 responder (Yes/No) and by geographic region (US/Puerto Rico/Canada and Other).

Starting at Week 4, rescue treatment for AD may be provided at the discretion of the investigator if medically necessary The Primary Analysis for the Main Study will be conducted after all ongoing participants have completed Week 16. In addition, a Primary Analysis for the adolescent population (including the adolescent participants from the Main Study and the Adolescent Sub-study) will be conducted after all ongoing adolescent participants have completed Week 16.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Atopic Dermatitis

Intervention

• Drug: Placebo
  Tablets taken orally once a day
• Drug: Upadacitinib
  Tablets taken orally once a day
  Other Names:

  • ABT-494
  • RINVOQ™
• Drug: Topical corticosteroids (TCS)

  Topical corticosteroids will be applied in a stepdown regimen, starting with medium potency once daily to areas with active lesions until lesions are clear or almost clear, or for 3 consecutive weeks, whichever is shorter; then low potency topical corticosteroids once daily. If lesions return or persist, this step-down approach will be repeated until lesion resolution or evidence of local or systemic topical corticosteroids toxicity.

  Recommended TCS include triamcinolone acetonide 0.1% cream or fluocinolone acetonide 0.025% ointment as medium potency topical corticosteroids and hydrocortisone 1% cream as low potency topical corticosteroid.

Study Arms

• Placebo Comparator: Placebo / Upadacitinib + Topical Corticosteroids
  Participants will receive placebo orally once a day (QD) for 16 weeks in the double-blind treatment period. At Week 16 participants will be re-randomized to receive either upadacitinib 15 mg or upadacitinib 30 mg QD up to Week 260. Participants will also receive concomitant topical corticosteroids following a step-down regimen through Week 52.
  Interventions:

  • Drug: Placebo
  • Drug: Upadacitinib
  • Drug: Topical corticosteroids (TCS)
• Experimental: Upadacitinib 15 mg QD + Topical Corticosteroids
  Participants will receive upadacitinib 15 mg orally once a day for up to 260 weeks. Participants will also receive concomitant topical corticosteroids following a step-down regimen through Week 52.
  Interventions:

  • Drug: Upadacitinib
  • Drug: Topical corticosteroids (TCS)
• Experimental: Upadacitinib 30 mg QD + Topical Corticosteroids
  Participants will receive upadacitinib 30 mg orally once a day for up to 260 weeks. Participants will also receive concomitant topical corticosteroids following a step-down regimen through Week 52.
  Interventions:

  • Drug: Upadacitinib
  • Drug: Topical corticosteroids (TCS)
• Experimental: Long-Term Extension
  Participants who reach Week 260 in Studies M16-045, M18-891, and M16-047 will have the opportunity to roll over into the blinded LTE period of M16-047 to continue receiving the same daily dose of upadacitinib for up to Week 524.
  Interventions:

  • Drug: Upadacitinib
  • Drug: Topical corticosteroids (TCS)

Publications *

• Silverberg JI, Simpson EL, Calimlim BM, Litcher-Kelly L, Li X, Sun X, Leshem YA. Determining Severity Strata for Three Atopic Dermatitis Patient-Reported Outcome Questionnaires: Defining Severity Score Ranges for the Worst Pruritus Numerical Rating Scale and the Atopic Dermatitis Symptom and Impact Scales (ADerm-SS and ADerm-IS). Dermatol Ther (Heidelb). 2022 Dec;12(12):2817-2827. doi: 10.1007/s13555-022-00836-5. Epub 2022 Nov 4.
• Mendes-Bastos P, Ladizinski B, Guttman-Yassky E, Jiang P, Liu J, Prajapati VH, Simpson EL, Vigna N, Teixeira HD, Barbarot S. Characterization of acne associated with upadacitinib treatment in patients with moderate-to-severe atopic dermatitis: A post hoc integrated analysis of 3 phase 3 randomized, double-blind, placebo-controlled trials. J Am Acad Dermatol. 2022 Oct;87(4):784-791. doi: 10.1016/j.jaad.2022.06.012. Epub 2022 Jun 15.
• Reich K, Teixeira HD, de Bruin-Weller M, Bieber T, Soong W, Kabashima K, Werfel T, Zeng J, Huang X, Hu X, Hendrickson BA, Ladizinski B, Chu AD, Silverberg JI. Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up): results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2021 Jun 5;397(10290):2169-2181. doi: 10.1016/S0140-6736(21)00589-4. Epub 2021 May 21. Erratum In: Lancet. 2021 Jun 19;397(10292):2336. Lancet. 2021 Aug 28;398(10302):746.

Recruitment Information

• Recruitment Status: Enrolling by invitation
• Estimated Enrollment (submitted: April 11, 2024): 1500
• Original Estimated Enrollment (submitted: June 14, 2018): 810
• Estimated Study Completion Date: November 16, 2030
• Actual Primary Completion Date: February 16, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Body weight of ≥ 40 kg at Baseline Visit for participants ≥ 12 and < 18 years of age
• Chronic atopic dermatitis (AD) with onset of symptoms at least 3 years prior to Baseline Visit and subject meets Hanifin and Rajka criteria.
• Active moderate to severe atopic dermatitis defined by Eczema Area and Severity Index (EASI) ≥ 16, validated Investigator's Global Assessment (vIGA) ≥ 3, ≥ 10% of body surface area (BSA) with AD involvement, and weekly average of daily Worst Pruritus numerical rating scale (NRS) ≥ 4.
• Subject has applied a topical emollient (moisturizer) twice daily for at least 7 days before the Baseline Visit.
• Documented history of inadequate response to topical corticosteroids or topical calcineurin inhibitor OR documented systemic treatment for AD within 6 months prior to Baseline Visit

Exclusion Criteria:

• Prior exposure to any Janus kinase (JAK) inhibitor
• Unable or unwilling to discontinue current atopic dermatitis (AD) treatments prior to the study
• Requirement of prohibited medications during the study
• Other active skin diseases or skin infections requiring systemic treatment or would interfere with appropriate assessment of atopic dermatitis lesions
• Female subject who is pregnant, breastfeeding, or considering pregnancy during the study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years to 75 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Canada, China, Czechia, France, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Netherlands, New Zealand, Norway, Puerto Rico, Slovakia, Spain, Sweden, United Kingdom, United States

Administrative Information

• NCT Number: NCT03568318
• Other Study ID Numbers: M16-047; 2017-005126-37 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
• URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html

• Current Responsible Party: AbbVie
• Original Responsible Party: Same as current
• Current Study Sponsor: AbbVie
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: ABBVIE INC.; AbbVie

• PRS Account: AbbVie
• Verification Date: October 2023