Cutaneous Lichen Planus
Conditions
Keywords
Lichen Planus, Skin Diseases, 18424, Ruxolitinib, topical cream
Brief summary
The purpose of this study will be to evaluate efficacy and safety of Ruxolitinib cream in participants With Cutaneous Lichen Planus. This is randomized, double-blind, vehicle-controlled (DBVC) study with a DBVC period of 16 weeks followed by an open label period (OLE) period of 16 weeks.
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
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Study will include a 16 week double-blind period followed by a 16 week open-label period.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of LP with predominant cutaneous involvement. * IGA score of 3 or 4 at screening and baseline. * Baseline LP-related Itch NRS score ≥ 4. * Willingness to avoid pregnancy or fathering children.
Exclusion criteria
* Concurrent conditions and history of other diseases: 1. Variants of LP deemed by the investigators to be inappropriate for topical treatment, including but not limited to predominant mucosal (such as oral or vaginal) LP. 2. Active ongoing inflammatory diseases of the skin other than LP that might confound the evaluation of LP lesions or compromise participant safety. 3. Any other concomitant skin disorder (eg, generalized erythroderma such as Netherton's syndrome), pigmentation, or extensive scarring that in the opinion of the investigator may interfere with the evaluation of LP lesions or compromise participant safety. 4. Immunocompromised (eg, lymphoma, acquired immunodeficiency syndrome, or Wiskott-Aldrich syndrome). 5. Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before baseline. 6. Active acute bacterial, fungal, or viral skin infection (eg, herpes simplex, herpes zoster, chickenpox, clinically infected AD, or impetigo) within 1 week before baseline. * Laboratory values outside of the protocol-defined criteria. * Pregnant or lactating participants, or those considering pregnancy during the period of their study participation. * Other exclusive criteria may apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Investigator's Global Assessment-Treatment Success (IGA-TS) at Week 16 | Baseline; Week 16 | The Investigator's Global Assessment (IGA) is a modified global assessment tool to assess the severity of lesions. Grading was based on 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), and 4 (severe). IGA-TS response was defined as an IGA score of 0 or 1 with a ≥2-grade improvement from Baseline at Week 16. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving IGA-TS at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Baseline; Weeks 18, 20, 24, 28, and 32 | The IGA is a global assessment tool to assess the severity of lesions. The IGA includes items such as depigmentation/hypopigmentation, lichenification (fine wrinkling/cigarette paper skin), excoriations, petechiae/ecchymosis, telangiectasias, erosions, fissures, or ulcers. Grading was based on 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), and 4 (severe). IGA-TS response was defined as an IGA score of 0 or 1 with a ≥2-grade improvement from Baseline at each scheduled post-Baseline visit. Participants with a score of 0 have a morphology of: no inflammatory signs (no erythema, no induration/papulation). Postinflammatory hyperpigmentation and/or hypopigmentation may be present. Participants with a score of 1 have a morphology of: barely perceptible erythema, barely perceptible induration/papulation/elevation, and/or minimal scale. Features include palpable, slightly erythematous papules. |
| Percentage of Participants With ITCH4 at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Baseline; Weeks 2, 4, 8, 12, and 16 | ITCH4 response was defined as a ≥4-point improvement in the Itch Numeric Rating Scale (NRS) score from Baseline at each scheduled post-Baseline visit, up to and including Week 32. The Itch NRS is a daily participant-reported measure (24-hour recall) of the worst level of itch intensity. Participants were instructed to complete and record their Itch NRS in a diary each evening beginning on the day of screening through Week 32 or treatment discontinuation. Participants rated itch severity of their lichen planus by selecting a number from 0 (no itch) to 10 (worst imaginable itch) that best described the worst level of itch they experienced in the past 24 hours. |
| Percentage of Participants With ITCH4 at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Baseline; Weeks 18, 20, 24, 28, and 32 | ITCH4 response was defined as a ≥4-point improvement in the Itch Numeric Rating Scale (NRS) score from Baseline at each scheduled post-Baseline visit, up to and including Week 32. The Itch NRS is a daily participant-reported measure (24-hour recall) of the worst level of itch intensity. Participants were instructed to complete and record their Itch NRS in a diary each evening beginning on the day of screening through Week 32 or treatment discontinuation. Participants rated itch severity of their lichen planus by selecting a number from 0 (no itch) to 10 (worst imaginable itch) that best described the worst level of itch they experienced in the past 24 hours. |
| Time to Achieve ITCH4 in the Double-blind, Vehicle-controlled Period | up to Week 16 | ITCH4 response was defined as a ≥4-point improvement in the Itch Numeric Rating Scale (NRS) score from Baseline at each scheduled post-Baseline visit, up to and including Week 32. The Itch NRS is a daily participant-reported measure (24-hour recall) of the worst level of itch intensity. Participants were instructed to complete and record their Itch NRS in a diary each evening beginning on the day of screening through Week 32 or treatment discontinuation. Participants rated itch severity of their lichen planus by selecting a number from 0 (no itch) to 10 (worst imaginable itch) that best described the worst level of itch they experienced in the past 24 hours. |
| Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Baseline; Weeks 2, 4, 8, 12, and 16 | Participants were instructed to complete and record the Skin Pain NRS in a diary each evening beginning on the day of screening through Week 32 or treatment discontinuation. Participants rated their pain, which included all types of pain (e.g., burning, tearing, pulling, stabbing, etc.) severity of lichen planus by selecting a number from 0 (no pain) to 10 (worst imaginable pain) that best described the worst level of pain they experienced in the past 24 hours. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Percentage of Participants Achieving IGA-TS at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Baseline; Weeks 2, 4, 8, 12, and 16 | The IGA is a global assessment tool to assess the severity of lesions. The IGA includes items such as depigmentation/hypopigmentation, lichenification (fine wrinkling/cigarette paper skin), excoriations, petechiae/ecchymosis, telangiectasias, erosions, fissures, or ulcers. Grading was based on 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), and 4 (severe). IGA-TS response was defined as an IGA score of 0 or 1 with a ≥2-grade improvement from Baseline at each scheduled post-Baseline visit. Participants with a score of 0 have a morphology of: no inflammatory signs (no erythema, no induration/papulation). Postinflammatory hyperpigmentation and/or hypopigmentation may be present. Participants with a score of 1 have a morphology of: barely perceptible erythema, barely perceptible induration/papulation/elevation, and/or minimal scale. Features include palpable, slightly erythematous papules. |
| Number of Participants With Any Treatment-emergent Adverse Event (TEAE) During the Double-blind, Vehicle-controlled Period | from Baseline to Week 16 plus 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 it is considered drug related. An AE could therefore 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 an AE either reported for the first time or the worsening of a pre-existing event after the first application of study drug. |
| Number of Participants With Any ≥Grade 3 TEAE During the Double-blind, Vehicle-controlled Period | from Baseline to Week 16 plus 30 days | A TEAE was defined as an AE either reported for the first time or the worsening of a pre-existing event after the first application of study drug. The severity of AEs was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (v5.0) Grades 1 through 5. The investigator made an assessment of intensity for each AE and SAE reported during the study and assigned it to 1 of the following categories: 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 Any TEAE During the Open-label Extension Period | from Week 17 to Week 32 plus 30 days | An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug related. An AE could therefore 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 an AE either reported for the first time or the worsening of a pre-existing event after the first application of study drug. |
| Number of Participants With Any ≥Grade 3 TEAE During the Open-label Extension Period | from Week 17 to Week 32 plus 30 days | A TEAE was defined as an AE either reported for the first time or the worsening of a pre-existing event after the first application of study drug. The severity of AEs was assessed using the CTCAE v5.0 Grades 1 through 5. The investigator made an assessment of intensity for each AE and SAE reported during the study and assigned it to 1 of the following categories: 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. |
| Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Baseline; Weeks 18, 20, 24, 28, and 32 | Participants were instructed to complete and record the Skin Pain NRS in a diary each evening beginning on the day of screening through Week 32 or treatment discontinuation. Participants rated their pain, which included all types of pain (e.g., burning, tearing, pulling, stabbing, etc.) severity of lichen planus by selecting a number from 0 (no pain) to 10 (worst imaginable pain) that best described the worst level of pain they experienced in the past 24 hours. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
Countries
Canada, United States
Participant flow
Pre-assignment details
This study was conducted at 19 study centers in Canada and the United States.
Participants by arm
| Arm | Count |
|---|---|
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID Participants applied ruxolitinib 1.5% cream twice daily (BID) for 16 weeks. | 32 |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID Participants applied matching vehicle cream BID for 16 weeks. | 32 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| 16-Week DBVC Period | Withdrawal by Subject | 2 | 3 | 0 | 0 |
| 16-Week OLE Period | Lack of Efficacy | 0 | 0 | 0 | 1 |
| 16-Week OLE Period | Lost to Follow-up | 0 | 0 | 1 | 2 |
| 16-Week OLE Period | Withdrawal by Subject | 0 | 0 | 0 | 3 |
Baseline characteristics
| Characteristic | Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Total |
|---|---|---|---|
| Age, Continuous | 56.3 years STANDARD_DEVIATION 14.35 | 58.2 years STANDARD_DEVIATION 10.86 | 57.3 years STANDARD_DEVIATION 12.66 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants | 31 Participants | 62 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Biracial | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black/African-American | 9 Participants | 9 Participants | 18 Participants |
| Race/Ethnicity, Customized Mixed Race | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White/Caucasian | 21 Participants | 19 Participants | 40 Participants |
| Sex: Female, Male Female | 22 Participants | 24 Participants | 46 Participants |
| Sex: Female, Male Male | 10 Participants | 8 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 60 |
| other Total, other adverse events | 6 / 32 | 14 / 60 |
| serious Total, serious adverse events | 0 / 32 | 0 / 60 |
Outcome results
Primary
Percentage of Participants Achieving Investigator's Global Assessment-Treatment Success (IGA-TS) at Week 16
The Investigator's Global Assessment (IGA) is a modified global assessment tool to assess the severity of lesions. Grading was based on 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), and 4 (severe). IGA-TS response was defined as an IGA score of 0 or 1 with a ≥2-grade improvement from Baseline at Week 16.
Time frame: Baseline; Week 16
Population: Intent-to-Treat (ITT) Population: all randomized participants. Treatment groups were defined according to the treatment assignment at the time of randomization regardless of the actual study drug the participant might have taken during their participation in the Double-blind; vehicle-controlled (DBVC) period. Missing post-Baseline values were imputed as nonresponders. Only participants with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Percentage of Participants Achieving Investigator's Global Assessment-Treatment Success (IGA-TS) at Week 16 | 50.0 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Percentage of Participants Achieving Investigator's Global Assessment-Treatment Success (IGA-TS) at Week 16 | 21.9 percentage of participants |
p-value: 0.012995% CI: [7.55, 51.33]Cochran-Mantel-Haenszel
95% CI: [1.32, 12.38]
Secondary
Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period
Participants were instructed to complete and record the Skin Pain NRS in a diary each evening beginning on the day of screening through Week 32 or treatment discontinuation. Participants rated their pain, which included all types of pain (e.g., burning, tearing, pulling, stabbing, etc.) severity of lichen planus by selecting a number from 0 (no pain) to 10 (worst imaginable pain) that best described the worst level of pain they experienced in the past 24 hours. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline; Weeks 2, 4, 8, 12, and 16
Population: ITT Population. No imputation was performed for missing values. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Baseline | 4.86 scores on a scale | Standard Deviation 2.303 |
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 2 | -1.69 scores on a scale | Standard Deviation 2.047 |
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 4 | -2.64 scores on a scale | Standard Deviation 2.307 |
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 8 | -2.96 scores on a scale | Standard Deviation 2.622 |
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 12 | -3.01 scores on a scale | Standard Deviation 2.823 |
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 16 | -3.02 scores on a scale | Standard Deviation 2.656 |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 12 | -0.84 scores on a scale | Standard Deviation 1.613 |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Baseline | 4.51 scores on a scale | Standard Deviation 2.618 |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 8 | -0.95 scores on a scale | Standard Deviation 1.385 |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 2 | -0.55 scores on a scale | Standard Deviation 0.975 |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 16 | -1.25 scores on a scale | Standard Deviation 2.263 |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 4 | -0.69 scores on a scale | Standard Deviation 1.261 |
Secondary
Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Open-label Extension Period
Participants were instructed to complete and record the Skin Pain NRS in a diary each evening beginning on the day of screening through Week 32 or treatment discontinuation. Participants rated their pain, which included all types of pain (e.g., burning, tearing, pulling, stabbing, etc.) severity of lichen planus by selecting a number from 0 (no pain) to 10 (worst imaginable pain) that best described the worst level of pain they experienced in the past 24 hours. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline; Weeks 18, 20, 24, 28, and 32
Population: ITT Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Baseline | 4.86 scores on a scale | Standard Deviation 2.303 |
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 18 | -3.65 scores on a scale | Standard Deviation 2.086 |
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 20 | -3.81 scores on a scale | Standard Deviation 2.079 |
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 24 | -3.82 scores on a scale | Standard Deviation 2.385 |
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 28 | -3.99 scores on a scale | Standard Deviation 2.272 |
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 32 | -4.25 scores on a scale | Standard Deviation 2.276 |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 28 | -3.54 scores on a scale | Standard Deviation 3.145 |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Baseline | 4.51 scores on a scale | Standard Deviation 2.618 |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 24 | -3.13 scores on a scale | Standard Deviation 2.868 |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 18 | -2.46 scores on a scale | Standard Deviation 2.253 |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 32 | -3.51 scores on a scale | Standard Deviation 3.47 |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Change From Baseline in the Skin Pain NRS Score at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 20 | -2.96 scores on a scale | Standard Deviation 2.584 |
Secondary
Number of Participants With Any ≥Grade 3 TEAE During the Double-blind, Vehicle-controlled Period
A TEAE was defined as an AE either reported for the first time or the worsening of a pre-existing event after the first application of study drug. The severity of AEs was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (v5.0) Grades 1 through 5. The investigator made an assessment of intensity for each AE and SAE reported during the study and assigned it to 1 of the following categories: 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 Baseline to Week 16 plus 30 days
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Number of Participants With Any ≥Grade 3 TEAE During the Double-blind, Vehicle-controlled Period | 0 Participants |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Number of Participants With Any ≥Grade 3 TEAE During the Double-blind, Vehicle-controlled Period | 0 Participants |
Secondary
Number of Participants With Any ≥Grade 3 TEAE During the Open-label Extension Period
A TEAE was defined as an AE either reported for the first time or the worsening of a pre-existing event after the first application of study drug. The severity of AEs was assessed using the CTCAE v5.0 Grades 1 through 5. The investigator made an assessment of intensity for each AE and SAE reported during the study and assigned it to 1 of the following categories: 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 Week 17 to Week 32 plus 30 days
Population: Open-label Extension Evaluable Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Number of Participants With Any ≥Grade 3 TEAE During the Open-label Extension Period | 0 Participants |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Number of Participants With Any ≥Grade 3 TEAE During the Open-label Extension Period | 1 Participants |
Secondary
Number of Participants With Any TEAE During the Open-label Extension Period
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug related. An AE could therefore 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 an AE either reported for the first time or the worsening of a pre-existing event after the first application of study drug.
Time frame: from Week 17 to Week 32 plus 30 days
Population: Open-label Extension Evaluable Population: all participants who applied ruxolitinib 1.5% cream at least once during the Open-label Extension Period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Number of Participants With Any TEAE During the Open-label Extension Period | 8 Participants |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Number of Participants With Any TEAE During the Open-label Extension Period | 11 Participants |
Secondary
Number of Participants With Any Treatment-emergent Adverse Event (TEAE) During the Double-blind, Vehicle-controlled Period
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug related. An AE could therefore 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 an AE either reported for the first time or the worsening of a pre-existing event after the first application of study drug.
Time frame: from Baseline to Week 16 plus 30 days
Population: Safety Population: all participants who applied ruxolitinib 1.5% cream BID or vehicle cream BID at least once. Treatment groups for this population were determined according to the actual treatment the participant applied on Day 1 regardless of assigned study drug treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) During the Double-blind, Vehicle-controlled Period | 15 Participants |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) During the Double-blind, Vehicle-controlled Period | 9 Participants |
Secondary
Percentage of Participants Achieving IGA-TS at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period
The IGA is a global assessment tool to assess the severity of lesions. The IGA includes items such as depigmentation/hypopigmentation, lichenification (fine wrinkling/cigarette paper skin), excoriations, petechiae/ecchymosis, telangiectasias, erosions, fissures, or ulcers. Grading was based on 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), and 4 (severe). IGA-TS response was defined as an IGA score of 0 or 1 with a ≥2-grade improvement from Baseline at each scheduled post-Baseline visit. Participants with a score of 0 have a morphology of: no inflammatory signs (no erythema, no induration/papulation). Postinflammatory hyperpigmentation and/or hypopigmentation may be present. Participants with a score of 1 have a morphology of: barely perceptible erythema, barely perceptible induration/papulation/elevation, and/or minimal scale. Features include palpable, slightly erythematous papules.
Time frame: Baseline; Weeks 2, 4, 8, 12, and 16
Population: ITT Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Percentage of Participants Achieving IGA-TS at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 4 | 25.8 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Percentage of Participants Achieving IGA-TS at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 12 | 53.3 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Percentage of Participants Achieving IGA-TS at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 8 | 51.6 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Percentage of Participants Achieving IGA-TS at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 16 | 53.3 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Percentage of Participants Achieving IGA-TS at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 2 | 9.7 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Percentage of Participants Achieving IGA-TS at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 16 | 24.1 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Percentage of Participants Achieving IGA-TS at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 2 | 6.5 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Percentage of Participants Achieving IGA-TS at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 4 | 13.3 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Percentage of Participants Achieving IGA-TS at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 8 | 12.9 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Percentage of Participants Achieving IGA-TS at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 12 | 24.1 percentage of participants |
p-value: 0.014195% CI: [7.71, 53.51]Cochran-Mantel-Haenszel
95% CI: [1.31, 13.17]
Secondary
Percentage of Participants Achieving IGA-TS at Each Scheduled Post-Baseline Visit in the Open-label Extension Period
The IGA is a global assessment tool to assess the severity of lesions. The IGA includes items such as depigmentation/hypopigmentation, lichenification (fine wrinkling/cigarette paper skin), excoriations, petechiae/ecchymosis, telangiectasias, erosions, fissures, or ulcers. Grading was based on 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), and 4 (severe). IGA-TS response was defined as an IGA score of 0 or 1 with a ≥2-grade improvement from Baseline at each scheduled post-Baseline visit. Participants with a score of 0 have a morphology of: no inflammatory signs (no erythema, no induration/papulation). Postinflammatory hyperpigmentation and/or hypopigmentation may be present. Participants with a score of 1 have a morphology of: barely perceptible erythema, barely perceptible induration/papulation/elevation, and/or minimal scale. Features include palpable, slightly erythematous papules.
Time frame: Baseline; Weeks 18, 20, 24, 28, and 32
Population: ITT Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Percentage of Participants Achieving IGA-TS at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 20 | 62.1 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Percentage of Participants Achieving IGA-TS at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 28 | 58.6 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Percentage of Participants Achieving IGA-TS at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 24 | 58.6 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Percentage of Participants Achieving IGA-TS at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 32 | 60.0 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Percentage of Participants Achieving IGA-TS at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 18 | 58.6 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Percentage of Participants Achieving IGA-TS at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 32 | 60.9 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Percentage of Participants Achieving IGA-TS at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 18 | 25.0 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Percentage of Participants Achieving IGA-TS at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 20 | 33.3 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Percentage of Participants Achieving IGA-TS at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 24 | 44.0 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Percentage of Participants Achieving IGA-TS at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 28 | 45.8 percentage of participants |
Secondary
Percentage of Participants With ITCH4 at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period
ITCH4 response was defined as a ≥4-point improvement in the Itch Numeric Rating Scale (NRS) score from Baseline at each scheduled post-Baseline visit, up to and including Week 32. The Itch NRS is a daily participant-reported measure (24-hour recall) of the worst level of itch intensity. Participants were instructed to complete and record their Itch NRS in a diary each evening beginning on the day of screening through Week 32 or treatment discontinuation. Participants rated itch severity of their lichen planus by selecting a number from 0 (no itch) to 10 (worst imaginable itch) that best described the worst level of itch they experienced in the past 24 hours.
Time frame: Baseline; Weeks 2, 4, 8, 12, and 16
Population: ITT Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Percentage of Participants With ITCH4 at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 4 | 44.8 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Percentage of Participants With ITCH4 at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 12 | 52.0 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Percentage of Participants With ITCH4 at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 8 | 53.8 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Percentage of Participants With ITCH4 at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 16 | 57.7 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Percentage of Participants With ITCH4 at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 2 | 21.4 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Percentage of Participants With ITCH4 at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 16 | 19.2 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Percentage of Participants With ITCH4 at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 2 | 3.3 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Percentage of Participants With ITCH4 at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 4 | 7.1 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Percentage of Participants With ITCH4 at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 8 | 7.4 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Percentage of Participants With ITCH4 at Each Scheduled Post-Baseline Visit in the Double-Blind, Vehicle-Controlled Period | Week 12 | 12.0 percentage of participants |
p-value: 0.002795% CI: [16.61, 64]Cochran-Mantel-Haenszel
95% CI: [1.85, 24.02]
Secondary
Percentage of Participants With ITCH4 at Each Scheduled Post-Baseline Visit in the Open-label Extension Period
ITCH4 response was defined as a ≥4-point improvement in the Itch Numeric Rating Scale (NRS) score from Baseline at each scheduled post-Baseline visit, up to and including Week 32. The Itch NRS is a daily participant-reported measure (24-hour recall) of the worst level of itch intensity. Participants were instructed to complete and record their Itch NRS in a diary each evening beginning on the day of screening through Week 32 or treatment discontinuation. Participants rated itch severity of their lichen planus by selecting a number from 0 (no itch) to 10 (worst imaginable itch) that best described the worst level of itch they experienced in the past 24 hours.
Time frame: Baseline; Weeks 18, 20, 24, 28, and 32
Population: ITT Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Percentage of Participants With ITCH4 at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 20 | 73.9 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Percentage of Participants With ITCH4 at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 28 | 86.4 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Percentage of Participants With ITCH4 at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 24 | 79.2 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Percentage of Participants With ITCH4 at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 32 | 84.2 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Percentage of Participants With ITCH4 at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 18 | 72.7 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Percentage of Participants With ITCH4 at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 32 | 73.3 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Percentage of Participants With ITCH4 at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 18 | 48.0 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Percentage of Participants With ITCH4 at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 20 | 63.6 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Percentage of Participants With ITCH4 at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 24 | 76.2 percentage of participants |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Percentage of Participants With ITCH4 at Each Scheduled Post-Baseline Visit in the Open-label Extension Period | Week 28 | 76.5 percentage of participants |
Secondary
Time to Achieve ITCH4 in the Double-blind, Vehicle-controlled Period
ITCH4 response was defined as a ≥4-point improvement in the Itch Numeric Rating Scale (NRS) score from Baseline at each scheduled post-Baseline visit, up to and including Week 32. The Itch NRS is a daily participant-reported measure (24-hour recall) of the worst level of itch intensity. Participants were instructed to complete and record their Itch NRS in a diary each evening beginning on the day of screening through Week 32 or treatment discontinuation. Participants rated itch severity of their lichen planus by selecting a number from 0 (no itch) to 10 (worst imaginable itch) that best described the worst level of itch they experienced in the past 24 hours.
Time frame: up to Week 16
Population: ITT Population. Only those participants achieving a ≥4-point improvement in daily Itch NRS score from Baseline were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Double-Blind, Vehicle-Controlled Period: Ruxolitinib Cream 1.5% BID | Time to Achieve ITCH4 in the Double-blind, Vehicle-controlled Period | 17.0 days |
| Double-Blind, Vehicle-Controlled Period: Vehicle Cream BID | Time to Achieve ITCH4 in the Double-blind, Vehicle-controlled Period | 97.0 days |
p-value: 0.000895% CI: [1.51, 5.381]Log Rank