Vitiligo
Conditions
Keywords
Vitiligo, depigmenting disorder, topical JAK inhibitor
Brief summary
The purpose of the study is to evaluate the Mechanism Of Action (MOA) of ruxolitinib cream in vitiligo by assessing the change in biomarkers.
Interventions
DRUGRuxolitinib cream
Ruxolitinib cream is a topical formulation applied as a thin film to affected areas.
DRUGVehicle Cream
Vehicle cream is matching in appearance to ruxolitinib cream and is to be applied in the same manner as ruxolitinib cream.
Sponsors
Incyte Corporation
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Double-blind
Intervention model description
Randomized, double-blind, vehicle-controlled, with an open-label treatment extension.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A clinical diagnosis of nonsegmental vitiligo with depigmented areas including ≥ 0.5% BSA on the face, ≥ 0.5 F-VASI, ≥ 3% BSA on nonfacial areas, and ≥ 3 T-VASI; total body vitiligo area (facial and nonfacial) should not exceed 50% BSA. * At least 1 active vitiligo lesion (eg, such as confetti lesion, trichrome appearance, pinkish rim, or other evidence of inflammatory activity) at the site for skin biopsy. * Agree to discontinue all agents used to treat vitiligo from screening through the final safety follow-up visit. Over-the-counter preparations deemed acceptable by the investigator and camouflage makeups are permitted.
Exclusion criteria
* No pigmented hair within any of the vitiligo areas on the face. * Other forms of vitiligo (eg, segmental) or other differential diagnosis of vitiligo or other skin depigmentation disorders (eg, piebaldism, pityriasis alba, leprosy, postinflammatory hypopigmentation, progressive macule hypomelanosis, nevus anemicus, chemical leukoderma, and tinea versicolor). * Used depigmentation treatments (eg, monobenzone) for past treatment of vitiligo or other pigmented areas except hydroquinone. * Any other skin disease that, in the opinion of the investigator, would interfere with the study medication application or study assessments. * Conditions at baseline that would interfere with evaluation of vitiligo. * Use of any protocol-defined treatments within the indicated washout period before baseline.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in Chemokine (C-X-C Motif) Ligand 10 (CXCL10), an Immune Biomarker, at Week 4, Week 12, and Week 24 | Baseline; Week 4, Week 12, and Week 24 | Baseline was defined as the last non-missing measurement obtained on or before the first application of study drug. Percentage change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] / Baseline value)\*100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation of Key Skin Inflammatory Biomarkers of Vitiligo in Target Lesions to Efficacy Readouts | Baseline, Week 12, and Week 24 | Clinical scores (facial Vitiligo Area Scoring Index \[F-VASI\] and total body Vitiligo Area Scoring Index \[T-VASI\]) were evaluated for correlation with skin CXCL10 levels. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Double-Blind Period | from the time of Informed Consent Form signing until the start of the Treatment-Extension Period or 30 days after the last application of study drug during the Double-Blind Period (up to Week 24 + 30 days) | An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE could have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. A TEAE was defined as any AE reported for the first time or the worsening of a pre-existing event after the first application of study drug. |
| Number of Participants With TEAEs During the Treatment-Extension Period | from the completion of the Week 24 assessments until at least 30 days after the last application of study drug at Week 52 + 30 days | An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE could have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. A TEAE was defined as any AE reported for the first time or the worsening of a pre-existing event after the first application of study drug. |
| Number of Participants With a Grade 3 or Higher TEAE During the Double-Blind Period | from the time of Informed Consent Form signing until the start of the Treatment-Extension Period or 30 days after the last application of study drug during the Double-Blind Period (up to Week 24 + 30 days) | An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. A TEAE was defined as any AE reported for the first time or the worsening of a pre-existing event after the first application of study drug. AE severity was assessed per the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0: Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated; Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living; Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living; Grade 4: life-threatening consequences; urgent treatment indicated; Grade 5: fatal. |
| Number of Participants With a Grade 3 or Higher TEAE During the Treatment-Extension Period | from the completion of the Week 24 assessments until at least 30 days after the last application of study drug at Week 52 + 30 days | An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. A TEAE was defined as any AE reported for the first time or the worsening of a pre-existing event after the first application of study drug. AE severity was assessed per the CTCAE, version 5.0: Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated; Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living; Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living; Grade 4: life-threatening consequences; urgent treatment indicated; Grade 5: fatal. |
Countries
Canada, France, United States
Participant flow
Pre-assignment details
This study was conducted at a total of 11 sites in Canada, France, and the United States.
Participants by arm
| Arm | Count |
|---|---|
| Double-Blind Period: Ruxolitinib Cream 1.5% BID Participants applied ruxolitinib 1.5% cream twice daily (BID) for 24 weeks. | 41 |
| Double-Blind Period: Vehicle Cream BID Participants applied matching vehicle cream BID for 24 weeks. | 19 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| 24-Week Double-Blind Period | Lost to Follow-up | 2 | 3 | 0 | 0 |
| 24-Week Double-Blind Period | Withdrawal by Subject | 2 | 2 | 0 | 0 |
| 28-Week Treatment-Extension Period | Lost to Follow-up | 0 | 0 | 5 | 2 |
| 28-Week Treatment-Extension Period | Participant Refused Safety Follow-up | 0 | 0 | 3 | 2 |
| 28-Week Treatment-Extension Period | Pregnancy | 0 | 0 | 1 | 0 |
| 28-Week Treatment-Extension Period | Withdrawal by Subject | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Double-Blind Period: Ruxolitinib Cream 1.5% BID | Total | Double-Blind Period: Vehicle Cream BID |
|---|---|---|---|
| Age, Continuous | 45.1 years STANDARD_DEVIATION 12.73 | 44.7 years STANDARD_DEVIATION 12.77 | 43.7 years STANDARD_DEVIATION 13.16 |
| Chemokine (C-X-C Motif) Ligand 10 (CXCL10), an immune biomarker | 600.066 nanograms per Liter (ng/L) STANDARD_DEVIATION 959.3097 | 542.778 nanograms per Liter (ng/L) STANDARD_DEVIATION 804.0389 | 415.471 nanograms per Liter (ng/L) STANDARD_DEVIATION 177.4902 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 12 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants | 44 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 8 Participants | 3 Participants |
| Race/Ethnicity, Customized Black/African-American | 4 Participants | 6 Participants | 2 Participants |
| Race/Ethnicity, Customized Middle Eastern | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian/Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Reported | 5 Participants | 5 Participants | 0 Participants |
| Race/Ethnicity, Customized South Asian | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White/Caucasian | 25 Participants | 38 Participants | 13 Participants |
| Sex: Female, Male Female | 18 Participants | 26 Participants | 8 Participants |
| Sex: Female, Male Male | 23 Participants | 34 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 19 |
| other Total, other adverse events | 10 / 55 | 7 / 19 |
| serious Total, serious adverse events | 1 / 55 | 0 / 19 |
Outcome results
Primary
Percentage Change From Baseline in Chemokine (C-X-C Motif) Ligand 10 (CXCL10), an Immune Biomarker, at Week 4, Week 12, and Week 24
Baseline was defined as the last non-missing measurement obtained on or before the first application of study drug. Percentage change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] / Baseline value)\*100.
Time frame: Baseline; Week 4, Week 12, and Week 24
Population: Safety Population: all participants who applied at least 1 dose of study drug. Treatment groups for this population were to be determined according to the actual treatment the participant received on Day 1. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Period: Ruxolitinib Cream 1.5% BID | Percentage Change From Baseline in Chemokine (C-X-C Motif) Ligand 10 (CXCL10), an Immune Biomarker, at Week 4, Week 12, and Week 24 | Week 4 | -20.93 percent change | Standard Deviation 36.216 |
| Double-Blind Period: Ruxolitinib Cream 1.5% BID | Percentage Change From Baseline in Chemokine (C-X-C Motif) Ligand 10 (CXCL10), an Immune Biomarker, at Week 4, Week 12, and Week 24 | Week 12 | -18.33 percent change | Standard Deviation 40.035 |
| Double-Blind Period: Ruxolitinib Cream 1.5% BID | Percentage Change From Baseline in Chemokine (C-X-C Motif) Ligand 10 (CXCL10), an Immune Biomarker, at Week 4, Week 12, and Week 24 | Week 24 | -12.92 percent change | Standard Deviation 46.146 |
| Double-Blind Period: Vehicle Cream BID | Percentage Change From Baseline in Chemokine (C-X-C Motif) Ligand 10 (CXCL10), an Immune Biomarker, at Week 4, Week 12, and Week 24 | Week 4 | 8.13 percent change | Standard Deviation 52.491 |
| Double-Blind Period: Vehicle Cream BID | Percentage Change From Baseline in Chemokine (C-X-C Motif) Ligand 10 (CXCL10), an Immune Biomarker, at Week 4, Week 12, and Week 24 | Week 12 | 21.13 percent change | Standard Deviation 70.69 |
| Double-Blind Period: Vehicle Cream BID | Percentage Change From Baseline in Chemokine (C-X-C Motif) Ligand 10 (CXCL10), an Immune Biomarker, at Week 4, Week 12, and Week 24 | Week 24 | 22.17 percent change | Standard Deviation 68.893 |
Secondary
Correlation of Key Skin Inflammatory Biomarkers of Vitiligo in Target Lesions to Efficacy Readouts
Clinical scores (facial Vitiligo Area Scoring Index \[F-VASI\] and total body Vitiligo Area Scoring Index \[T-VASI\]) were evaluated for correlation with skin CXCL10 levels.
Time frame: Baseline, Week 12, and Week 24
Population: Safety Population. Repeated measures correlation (Crm) takes into account that measures were taken from the same individual across multiple timepoints. Included in the analysis were only those participants with values at each of 3 timepoints: Baseline, Week 12, and Week 24.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Period: Ruxolitinib Cream 1.5% BID | Correlation of Key Skin Inflammatory Biomarkers of Vitiligo in Target Lesions to Efficacy Readouts | F-VASI | -0.34 correlation coefficient |
| Double-Blind Period: Ruxolitinib Cream 1.5% BID | Correlation of Key Skin Inflammatory Biomarkers of Vitiligo in Target Lesions to Efficacy Readouts | T-VASI | -0.43 correlation coefficient |
| Double-Blind Period: Vehicle Cream BID | Correlation of Key Skin Inflammatory Biomarkers of Vitiligo in Target Lesions to Efficacy Readouts | F-VASI | 0.15 correlation coefficient |
| Double-Blind Period: Vehicle Cream BID | Correlation of Key Skin Inflammatory Biomarkers of Vitiligo in Target Lesions to Efficacy Readouts | T-VASI | 0.02 correlation coefficient |
Comparison: F-VASIp-value: 0.004repeated measures correlation
Comparison: F-VASIp-value: 0.41repeated measures correlation
Comparison: T-VASIp-value: 0.0002repeated measures correlation
Comparison: T-VASIp-value: 0.91repeated measures correlation
Secondary
Number of Participants With a Grade 3 or Higher TEAE During the Double-Blind Period
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. A TEAE was defined as any AE reported for the first time or the worsening of a pre-existing event after the first application of study drug. AE severity was assessed per the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0: Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated; Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living; Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living; Grade 4: life-threatening consequences; urgent treatment indicated; Grade 5: fatal.
Time frame: from the time of Informed Consent Form signing until the start of the Treatment-Extension Period or 30 days after the last application of study drug during the Double-Blind Period (up to Week 24 + 30 days)
Population: Double-Blind Safety Population. Treatment groups for this population were determined according to the actual treatment the participant applied on Day 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-Blind Period: Ruxolitinib Cream 1.5% BID | Number of Participants With a Grade 3 or Higher TEAE During the Double-Blind Period | 1 Participants |
| Double-Blind Period: Vehicle Cream BID | Number of Participants With a Grade 3 or Higher TEAE During the Double-Blind Period | 0 Participants |
Secondary
Number of Participants With a Grade 3 or Higher TEAE During the Treatment-Extension Period
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. A TEAE was defined as any AE reported for the first time or the worsening of a pre-existing event after the first application of study drug. AE severity was assessed per the CTCAE, version 5.0: Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated; Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living; Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living; Grade 4: life-threatening consequences; urgent treatment indicated; Grade 5: fatal.
Time frame: from the completion of the Week 24 assessments until at least 30 days after the last application of study drug at Week 52 + 30 days
Population: Treatment-Extension Evaluable Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-Blind Period: Ruxolitinib Cream 1.5% BID | Number of Participants With a Grade 3 or Higher TEAE During the Treatment-Extension Period | 0 Participants |
| Double-Blind Period: Vehicle Cream BID | Number of Participants With a Grade 3 or Higher TEAE During the Treatment-Extension Period | 1 Participants |
Secondary
Number of Participants With TEAEs During the Treatment-Extension Period
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE could have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. A TEAE was defined as any AE reported for the first time or the worsening of a pre-existing event after the first application of study drug.
Time frame: from the completion of the Week 24 assessments until at least 30 days after the last application of study drug at Week 52 + 30 days
Population: Treatment-Extension Evaluable Population: all participants who applied ruxolitinib cream at least once during the Treatment-Extension Period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-Blind Period: Ruxolitinib Cream 1.5% BID | Number of Participants With TEAEs During the Treatment-Extension Period | 12 Participants |
| Double-Blind Period: Vehicle Cream BID | Number of Participants With TEAEs During the Treatment-Extension Period | 3 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Double-Blind Period
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE could have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. A TEAE was defined as any AE reported for the first time or the worsening of a pre-existing event after the first application of study drug.
Time frame: from the time of Informed Consent Form signing until the start of the Treatment-Extension Period or 30 days after the last application of study drug during the Double-Blind Period (up to Week 24 + 30 days)
Population: Double-Blind Safety Population: all participants who applied ruxolitinib cream or vehicle cream at least once during the Double-Blind Period. Treatment groups for this population were determined according to the actual treatment the participant applied on Day 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-Blind Period: Ruxolitinib Cream 1.5% BID | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Double-Blind Period | 19 Participants |
| Double-Blind Period: Vehicle Cream BID | Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Double-Blind Period | 7 Participants |