Non-Segmental Vitiligo
Conditions
Keywords
Vitiligo, Non-segmental vitiligo (NSV), Upadacitinib, ABT-494, RINVOQ
Brief summary
Vitiligo is a common chronic autoimmune disease that causes the body's immune system to attack its own pigment producing skin cells. This study is to evaluate how safe and effective upadacitinib is in participants with non-segmental vitiligo. Adverse effects and change in disease activity will be assessed. Upadacitinib is being evaluated for the treatment of non-segmental vitiligo. The study will enroll approximately 160 participants aged 18-65 with non-segmental vitiligo in 5 treatment arms across 35 sites worldwide. Participants will either receive study drug vs placebo oral tablets once daily (QD) for 24 weeks (Period A). In Period B (up to 52 weeks), participants who received placebo during the first 24 weeks will switch to study drug. Participants who received study drug during the first 24 weeks, will continue to receive study drug. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
Interventions
DRUGUpadacitinib
Oral tablets
DRUGPlacebo
Oral tablets
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of non-segmental vitiligo (NSV) and no segmental or localized vitiligo. * Participants with all of the following at Screening and Baseline. * Visits: ≥ 0.5 F-VASI and ≥ 5 total vitiligo area scoring index (T-VASI). * Participants who have had prior exposure to immunomodulatory biologic therapy, for any indications, but discontinued the biologic therapy prior to the first dose of study drug. Recommended washout periods for biologic therapies include ≥ 4 weeks for etanercept; ≥ 8 weeks for adalimumab, infliximab, certolizumab, golimumab, abatacept, tocilizumab, and ixekizumab; ≥ 16 weeks for secukinumab; and ≥ 12 weeks for ustekinumab. For biologic therapies not specified, therapies must be discontinued at least 5 times the mean terminal elimination half-life of a drug or 3 months prior to Baseline, whichever is longer.
Exclusion criteria
* Participants with segmental or localized vitiligo. * Participants with other skin conditions that would interfere with evaluation of vitiligo, participants with uncontrolled thyroid disease, and participants with \> 33% leukotrichia on the face or \> 33% leukotrichia on the body (including face). * Participants previously treated with any topical or systemic janus kinase (JAK) inhibitor or permanent skin bleaching agents. * Participants treated with any systemic vitiligo therapy (e.g., methotrexate, mycophenolate mofetil, corticosteroids), supplemental vitiligo therapy (antioxidants/vitamins/herbal medicine/traditional Chinese medicine), and/or topical vitiligo therapy including permanent or temporary tattoos within a minimum of 30 days prior to the first dose of study drug (Note: Camouflage and makeup may be used). * Participants treated with any phototherapy, including excimer (or other forms of laser therapy), within a minimum of 12 weeks prior to the first dose of study drug. * Participants have history of malignancy other than successfully treated non-melanoma skin cancer (NMSC) or localized carcinoma in situ of the cervix. * Recent (within past 6 months) cerebrovascular accident, myocardial infarction, coronary stenting, and aorto-coronary bypass surgery; * History of an organ transplant which requires continued immunosuppression; * History of gastrointestinal (GI) perforation (other than due to appendicitis or mechanical injury), diverticulitis, or significantly increased risk for GI perforation per investigator judgment; * Conditions that could interfere with drug absorption including but not limited to short bowel syndrome or gastric bypass surgery; subjects with a history of gastric banding/segmentation are not excluded; * Uncontrolled thyroid disease;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Facial-Vitiligo Area Scoring Index (F-VASI) at Week 24 | Baseline, Week 24 | The vitiligo area scoring index (VASI) is a validated scoring method used to assess the areas of depigmentation due to vitiligo. The F-VASI includes contributions from the face, with a possible range from 0 to 3, with higher scores indicating more severe disease. Negative changes from baseline indicate improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving F-VASI 75 (≥ 75% Improvement in F-VASI From Baseline) at Week 24 | Baseline, Week 24 | The vitiligo area scoring index (VASI) is a validated scoring method used to assess the areas of depigmentation due to vitiligo. The F-VASI includes contributions from the face, with a possible range from 0 to 3, with higher scores indicating more severe disease. |
| Percentage of Participants Achieving F-VASI 50 (≥ 50% Improvement in F-VASI From Baseline) at Week 24 | Baseline, Week 24 | The vitiligo area scoring index (VASI) is a validated scoring method used to assess the areas of depigmentation due to vitiligo. The F-VASI includes contributions from the face, with a possible range from 0 to 3, with higher scores indicating more severe disease. |
| Percentage of Participants Achieving Total Vitiligo Area Scoring Index (T-VASI) 50 (≥ 50% Improvement in T-VASI From Baseline) at Week 24 | Baseline, Week 24 | The vitiligo area scoring index (VASI) is a validated scoring method used to assess the areas of depigmentation due to vitiligo. It is based on a composite estimate of the overall area of vitiligo patches, measured by the number of hand units (palm plus 5 digits = 1% body surface area \[BSA\]) multiplied by the degree of depigmentation within each affected area (0%, 10%, 25%, 50%, 75%, 90%, or 100%). The T-VASI is calculated using a formula that includes contributions from all body regions, with a possible range from 0 to 100, with higher scores indicating more severe disease. |
| Percent Change From Baseline in T-VASI at Week 24 | Baseline, Week 24 | The vitiligo area scoring index (VASI) is a validated scoring method used to assess the areas of depigmentation due to vitiligo. It is based on a composite estimate of the overall area of vitiligo patches, measured by the number of hand units (palm plus 5 digits = 1% body surface area \[BSA\]) multiplied by the degree of depigmentation within each affected area (0%, 10%, 25%, 50%, 75%, 90%, or 100%). The T-VASI is calculated using a formula that includes contributions from all body regions, with a possible range from 0 to 100, with higher scores indicating more severe disease. Negative changes from baseline indicate improvement. |
| Change From Baseline in the Vitiligo Quality-of-Life (VitiQoL) Instrument Total Score at Week 24 | Baseline, Week 24 | The VitiQoL is a validated questionnaire used in clinical trials to assess stigma-related vitiligo impacts. The VitiQoL uses subject-elicited social, affective, and behavior items, asking the subject's appraisal of the vitiligo-related impacts over the last month. Fifteen items are scored on a 7-point scale ranging from 0 (Not at all) to 6 (All of the time). Item scores (0 to 6) are summed to provide a total score range of 0 to 90; higher scores indicate greater impairment of quality of life (QoL). Negative changes from baseline indicate improvement. |
Countries
Canada, France, Japan, United States
Participant flow
Pre-assignment details
ITT Population in Period 1 (ITT\_1): all randomized participants in Period 1, analyzed according to the treatment groups that they were randomized to. Per protocol, participants who were randomized to Placebo at Baseline were analyzed as one group in Period 1. ITT Population in Period 2 (ITT\_2): all participants who entered Period 2, analyzed according to the treatment groups that they were randomized to at Baseline.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Period 1 Participants received Placebo for upadacitinib administered orally once a day (QD) as tablets for 24 weeks during Period 1. | 46 |
| Upa 6 mg Period 1, Then Upa 6 mg Period 2 Participants received upadacitinib 6 mg administered orally once a day (QD) as tablets for 24 weeks during Period 1. Participants then received upadacitinib 6 mg administered orally once a day (QD) as tablets for 28 weeks during Period 2. | 49 |
| Upa 11 mg Period 1, Then Upa 11 mg Period 2 Participants received upadacitinib 11 mg administered orally once a day (QD) as tablets for 24 weeks during Period 1. Participants then received upadacitinib 11 mg administered orally once a day (QD) as tablets for 28 weeks during Period 2. | 47 |
| Upa 22 mg Period 1, Then Upa 22 mg Period 2 Participants received upadacitinib 22 mg administered orally once a day (QD) as tablets for 24 weeks during Period 1. Participants then received upadacitinib 22 mg administered orally once a day (QD) as tablets for 28 weeks during Period 2. | 43 |
| Total | 185 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Period 1 (Baseline-Week 24) | Death | 0 | 0 | 0 | 0 | 0 | 1 |
| Period 1 (Baseline-Week 24) | Lost to Follow-up | 0 | 0 | 0 | 2 | 1 | 0 |
| Period 1 (Baseline-Week 24) | Withdrawal by Subject | 2 | 0 | 0 | 1 | 1 | 4 |
| Period 2 (Week 24-52) | Lost to Follow-up | 0 | 1 | 0 | 2 | 6 | 2 |
| Period 2 (Week 24-52) | Withdrawal by Subject | 0 | 1 | 1 | 4 | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo Period 1 | Upa 6 mg Period 1, Then Upa 6 mg Period 2 | Upa 11 mg Period 1, Then Upa 11 mg Period 2 | Upa 22 mg Period 1, Then Upa 22 mg Period 2 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 46.8 years STANDARD_DEVIATION 10.48 | 45.1 years STANDARD_DEVIATION 11.68 | 45.5 years STANDARD_DEVIATION 11.9 | 48.2 years STANDARD_DEVIATION 11.13 | 46.3 years STANDARD_DEVIATION 11.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 6 Participants | 4 Participants | 5 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 41 Participants | 43 Participants | 43 Participants | 38 Participants | 165 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Facial Vitiligo Area Scoring Index (F-VASI) | 1.043 units on a scale STANDARD_DEVIATION 0.6094 | 1.154 units on a scale STANDARD_DEVIATION 0.7655 | 1.021 units on a scale STANDARD_DEVIATION 0.5781 | 1.159 units on a scale STANDARD_DEVIATION 0.6585 | 1.094 units on a scale STANDARD_DEVIATION 0.6559 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 6 Participants | 7 Participants | 6 Participants | 25 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 3 Participants | 3 Participants | 1 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) White | 34 Participants | 35 Participants | 36 Participants | 33 Participants | 138 Participants |
| Sex: Female, Male Female | 29 Participants | 26 Participants | 34 Participants | 26 Participants | 115 Participants |
| Sex: Female, Male Male | 17 Participants | 23 Participants | 13 Participants | 17 Participants | 70 Participants |
| Total Vitiligo Area Scoring Index (T-VASI) | 21.014 units on a scale STANDARD_DEVIATION 16.9516 | 20.993 units on a scale STANDARD_DEVIATION 15.9672 | 22.322 units on a scale STANDARD_DEVIATION 18.1784 | 21.843 units on a scale STANDARD_DEVIATION 15.9324 | 21.534 units on a scale STANDARD_DEVIATION 16.6634 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 46 | 0 / 49 | 0 / 47 | 1 / 43 | 0 / 21 | 0 / 22 | 0 / 45 | 0 / 45 | 0 / 33 |
| other Total, other adverse events | 26 / 46 | 19 / 49 | 28 / 47 | 23 / 43 | 9 / 21 | 11 / 22 | 12 / 45 | 22 / 45 | 17 / 33 |
| serious Total, serious adverse events | 1 / 46 | 1 / 49 | 0 / 47 | 3 / 43 | 1 / 21 | 0 / 22 | 0 / 45 | 2 / 45 | 0 / 33 |
Outcome results
Primary
Percent Change From Baseline in Facial-Vitiligo Area Scoring Index (F-VASI) at Week 24
The vitiligo area scoring index (VASI) is a validated scoring method used to assess the areas of depigmentation due to vitiligo. The F-VASI includes contributions from the face, with a possible range from 0 to 3, with higher scores indicating more severe disease. Negative changes from baseline indicate improvement.
Time frame: Baseline, Week 24
Population: ITT\_1: all randomized participants in Period 1, analyzed according to the treatment groups that they were randomized to; mixed model repeated measures analysis (MMRM) including observed measurements at all visits
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo Period 1 | Percent Change From Baseline in Facial-Vitiligo Area Scoring Index (F-VASI) at Week 24 | -14.36 Percent change from baseline |
| Upa 6 mg Period 1, Then Upa 6 mg Period 2 | Percent Change From Baseline in Facial-Vitiligo Area Scoring Index (F-VASI) at Week 24 | -21.96 Percent change from baseline |
| Upa 11 mg Period 1, Then Upa 11 mg Period 2 | Percent Change From Baseline in Facial-Vitiligo Area Scoring Index (F-VASI) at Week 24 | -35.63 Percent change from baseline |
| Upa 22 mg Period 1, Then Upa 22 mg Period 2 | Percent Change From Baseline in Facial-Vitiligo Area Scoring Index (F-VASI) at Week 24 | -33.96 Percent change from baseline |
Comparison: Upa 6 mg Period 1 versus Placebo Period 1p-value: 0.30495% CI: [-22.18, 6.97]Mixed-Effect Model Repeat Measurement
Comparison: Upa 11 mg Period 1 versus Placebo Period 1p-value: 0.00595% CI: [-36.02, -6.52]Mixed-Effect Model Repeat Measurement
Comparison: Upa 22 mg Period 1 versus Placebo Period 1p-value: 0.01395% CI: [-35.04, -4.16]Mixed-Effect Model Repeat Measurement
Secondary
Change From Baseline in the Vitiligo Quality-of-Life (VitiQoL) Instrument Total Score at Week 24
The VitiQoL is a validated questionnaire used in clinical trials to assess stigma-related vitiligo impacts. The VitiQoL uses subject-elicited social, affective, and behavior items, asking the subject's appraisal of the vitiligo-related impacts over the last month. Fifteen items are scored on a 7-point scale ranging from 0 (Not at all) to 6 (All of the time). Item scores (0 to 6) are summed to provide a total score range of 0 to 90; higher scores indicate greater impairment of quality of life (QoL). Negative changes from baseline indicate improvement.
Time frame: Baseline, Week 24
Population: ITT\_1: all randomized participants in Period 1, analyzed according to the treatment groups that they were randomized to; mixed model repeated measures analysis (MMRM) including observed measurements at all visits.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo Period 1 | Change From Baseline in the Vitiligo Quality-of-Life (VitiQoL) Instrument Total Score at Week 24 | -5.5 units on a scale |
| Upa 6 mg Period 1, Then Upa 6 mg Period 2 | Change From Baseline in the Vitiligo Quality-of-Life (VitiQoL) Instrument Total Score at Week 24 | -7.5 units on a scale |
| Upa 11 mg Period 1, Then Upa 11 mg Period 2 | Change From Baseline in the Vitiligo Quality-of-Life (VitiQoL) Instrument Total Score at Week 24 | -3.7 units on a scale |
| Upa 22 mg Period 1, Then Upa 22 mg Period 2 | Change From Baseline in the Vitiligo Quality-of-Life (VitiQoL) Instrument Total Score at Week 24 | -6.6 units on a scale |
Comparison: Upa 6 mg Period 1 versus Placebo Period 1p-value: 0.54595% CI: [-8.3, 4.4]Mixed-Effect Model Repeat Measurement
Comparison: Upa 11 mg Period 1 versus Placebo Period 1p-value: 0.56595% CI: [-4.5, 8.3]Mixed-Effect Model Repeat Measurement
Comparison: Upa 22 mg Period 1 versus Placebo Period 1p-value: 0.75495% CI: [-7.8, 5.6]Mixed-Effect Model Repeat Measurement
Secondary
Percentage of Participants Achieving F-VASI 50 (≥ 50% Improvement in F-VASI From Baseline) at Week 24
The vitiligo area scoring index (VASI) is a validated scoring method used to assess the areas of depigmentation due to vitiligo. The F-VASI includes contributions from the face, with a possible range from 0 to 3, with higher scores indicating more severe disease.
Time frame: Baseline, Week 24
Population: ITT\_1: all randomized participants in Period 1, analyzed according to the treatment groups that they were randomized to; NRI-MI (non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 or any other missing data that can be reasonably assumed to be Missing at Random)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Period 1 | Percentage of Participants Achieving F-VASI 50 (≥ 50% Improvement in F-VASI From Baseline) at Week 24 | 10.9 percentage of participants |
| Upa 6 mg Period 1, Then Upa 6 mg Period 2 | Percentage of Participants Achieving F-VASI 50 (≥ 50% Improvement in F-VASI From Baseline) at Week 24 | 16.3 percentage of participants |
| Upa 11 mg Period 1, Then Upa 11 mg Period 2 | Percentage of Participants Achieving F-VASI 50 (≥ 50% Improvement in F-VASI From Baseline) at Week 24 | 38.3 percentage of participants |
| Upa 22 mg Period 1, Then Upa 22 mg Period 2 | Percentage of Participants Achieving F-VASI 50 (≥ 50% Improvement in F-VASI From Baseline) at Week 24 | 39.5 percentage of participants |
Comparison: Upa 6 mg Period 1 versus Placebo Period 1p-value: 0.32795% CI: [-6.6, 19.7]Cochran-Mantel-Haenszel
Comparison: Upa 11 mg Period 1 versus Placebo Period 1p-value: <0.00195% CI: [13.8, 44.9]Cochran-Mantel-Haenszel
Comparison: Upa 22 mg Period 1 versus Placebo Period 1p-value: <0.00195% CI: [12.6, 44.7]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving F-VASI 75 (≥ 75% Improvement in F-VASI From Baseline) at Week 24
The vitiligo area scoring index (VASI) is a validated scoring method used to assess the areas of depigmentation due to vitiligo. The F-VASI includes contributions from the face, with a possible range from 0 to 3, with higher scores indicating more severe disease.
Time frame: Baseline, Week 24
Population: ITT\_1: all randomized participants in Period 1, analyzed according to the treatment groups that they were randomized to; NRI-MI (non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 or any other missing data that can be reasonably assumed to be Missing at Random)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Period 1 | Percentage of Participants Achieving F-VASI 75 (≥ 75% Improvement in F-VASI From Baseline) at Week 24 | 2.2 percentage of participants |
| Upa 6 mg Period 1, Then Upa 6 mg Period 2 | Percentage of Participants Achieving F-VASI 75 (≥ 75% Improvement in F-VASI From Baseline) at Week 24 | 8.2 percentage of participants |
| Upa 11 mg Period 1, Then Upa 11 mg Period 2 | Percentage of Participants Achieving F-VASI 75 (≥ 75% Improvement in F-VASI From Baseline) at Week 24 | 19.1 percentage of participants |
| Upa 22 mg Period 1, Then Upa 22 mg Period 2 | Percentage of Participants Achieving F-VASI 75 (≥ 75% Improvement in F-VASI From Baseline) at Week 24 | 14.0 percentage of participants |
Comparison: Upa 6 mg Period 1 versus Placebo Period 1p-value: 0.195% CI: [-1.3, 15.2]Cochran-Mantel-Haenszel
Comparison: Upa 11 mg Period 1 versus Placebo Period 1p-value: 0.00295% CI: [6.5, 29]Cochran-Mantel-Haenszel
Comparison: Upa 22 mg Period 1 versus Placebo Period 1p-value: 0.02695% CI: [1.4, 21.9]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving Total Vitiligo Area Scoring Index (T-VASI) 50 (≥ 50% Improvement in T-VASI From Baseline) at Week 24
The vitiligo area scoring index (VASI) is a validated scoring method used to assess the areas of depigmentation due to vitiligo. It is based on a composite estimate of the overall area of vitiligo patches, measured by the number of hand units (palm plus 5 digits = 1% body surface area \[BSA\]) multiplied by the degree of depigmentation within each affected area (0%, 10%, 25%, 50%, 75%, 90%, or 100%). The T-VASI is calculated using a formula that includes contributions from all body regions, with a possible range from 0 to 100, with higher scores indicating more severe disease.
Time frame: Baseline, Week 24
Population: ITT\_1: all randomized participants in Period 1, analyzed according to the treatment groups that they were randomized to; NRI-MI (non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 or any other missing data that can be reasonably assumed to be Missing at Random)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Period 1 | Percentage of Participants Achieving Total Vitiligo Area Scoring Index (T-VASI) 50 (≥ 50% Improvement in T-VASI From Baseline) at Week 24 | 2.2 percentage of participants |
| Upa 6 mg Period 1, Then Upa 6 mg Period 2 | Percentage of Participants Achieving Total Vitiligo Area Scoring Index (T-VASI) 50 (≥ 50% Improvement in T-VASI From Baseline) at Week 24 | 6.1 percentage of participants |
| Upa 11 mg Period 1, Then Upa 11 mg Period 2 | Percentage of Participants Achieving Total Vitiligo Area Scoring Index (T-VASI) 50 (≥ 50% Improvement in T-VASI From Baseline) at Week 24 | 6.4 percentage of participants |
| Upa 22 mg Period 1, Then Upa 22 mg Period 2 | Percentage of Participants Achieving Total Vitiligo Area Scoring Index (T-VASI) 50 (≥ 50% Improvement in T-VASI From Baseline) at Week 24 | 11.6 percentage of participants |
Comparison: Upa 6 mg Period 1 versus Placebo Period 1p-value: 0.3495% CI: [-3.9, 11.2]Cochran-Mantel-Haenszel
Comparison: Upa 11 mg Period 1 versus Placebo Period 1p-value: 0.35895% CI: [-4.3, 11.8]Cochran-Mantel-Haenszel
Comparison: Upa 22 mg Period 1 versus Placebo Period 1p-value: 0.02795% CI: [1, 17.2]Cochran-Mantel-Haenszel
Secondary
Percent Change From Baseline in T-VASI at Week 24
The vitiligo area scoring index (VASI) is a validated scoring method used to assess the areas of depigmentation due to vitiligo. It is based on a composite estimate of the overall area of vitiligo patches, measured by the number of hand units (palm plus 5 digits = 1% body surface area \[BSA\]) multiplied by the degree of depigmentation within each affected area (0%, 10%, 25%, 50%, 75%, 90%, or 100%). The T-VASI is calculated using a formula that includes contributions from all body regions, with a possible range from 0 to 100, with higher scores indicating more severe disease. Negative changes from baseline indicate improvement.
Time frame: Baseline, Week 24
Population: ITT\_1: all randomized participants in Period 1, analyzed according to the treatment groups that they were randomized to; mixed model repeated measures analysis (MMRM) including observed measurements at all visits.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo Period 1 | Percent Change From Baseline in T-VASI at Week 24 | -6.42 Percent change from baseline |
| Upa 6 mg Period 1, Then Upa 6 mg Period 2 | Percent Change From Baseline in T-VASI at Week 24 | -13.87 Percent change from baseline |
| Upa 11 mg Period 1, Then Upa 11 mg Period 2 | Percent Change From Baseline in T-VASI at Week 24 | -17.26 Percent change from baseline |
| Upa 22 mg Period 1, Then Upa 22 mg Period 2 | Percent Change From Baseline in T-VASI at Week 24 | -20.69 Percent change from baseline |
Comparison: Upa 6 mg Period 1 versus Placebo Period 1p-value: 0.1295% CI: [-16.86, 1.96]Mixed-Effect Model Repeat Measurement
Comparison: Upa 11 mg Period 1 versus Placebo Period 1p-value: 0.02695% CI: [-20.37, -1.32]Mixed-Effect Model Repeat Measurement
Comparison: Upa 22 mg Period 1 versus Placebo Period 1p-value: 0.00595% CI: [-24.24, -4.3]Mixed-Effect Model Repeat Measurement