A Phase 3b, Double-Blind, Multicenter, Randomized, Vehicle-Controlled, Efficacy, and Safety Study of Ruxolitinib Cream in Adults With Moderate Atopic Dermatitis
Overview
- Phase
- Phase 3
- Intervention
- Ruxolitinib Cream
- Conditions
- Atopic Dermatitis
- Sponsor
- Incyte Corporation
- Enrollment
- 241
- Locations
- 94
- Primary Endpoint
- VC Period: Proportion of participants who achieved Investigator's Global Assessment Treatment Success (IGA-TS)
- Status
- Completed
- Last Updated
- 6 months ago
Overview
Brief Summary
This study is being conducted to establish the efficacy of ruxolitinib cream in participants with moderate AD who had an inadequate response to, or are intolerant to, or contraindicated to topical corticosteroid (TCS)s and topical calcineurin inhibitor (TCI)s.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Adults aged ≥ 18 years at screening (Note: Legal adult age for Korea is ≥ 19 years).
- •Diagnosis of AD as defined by the Hanifin and Rajka (1980) criteria.
- •AD duration of at least 2 years.
- •IGA score of 3 at screening and Day
- •EASI score \> 7 at screening and Day
- •Itch NRS score ≥ 4 at Day 1, defined as the average of the 7 days directly before Day 1, with Itch NRS values available for at least 4 of the 7 days.
- •%BSA (excluding the scalp) with AD involvement of at least 10% and up to 20% at screening and Day
- •DLQI score \> 10 at screening and Day
- •Documented recent history (within 12 months before the screening visit) of inadequate response, intolerance, or contraindication to TCSs and TCIs.
- •Agree to discontinue all agents used to treat AD from screening through the final follow up visit, except as outlined in the protocol.
Exclusion Criteria
- •Unstable course of AD (spontaneously improving or rapidly deteriorating) as determined by the investigator in the 4 weeks prior to Day
- •Concurrent conditions and history of other diseases as follows:
- •Immunocompromised (eg, lymphoma, acquired immunodeficiency syndrome, Wiskott-Aldrich syndrome).
- •Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before Day
- •Active acute bacterial, fungal, or viral skin infection (eg, herpes simplex, herpes zoster, chickenpox) within 1 week before Day
- •Any other concomitant skin disorder (eg, generalized erythroderma, such as Netherton syndrome), pigmentation, or extensive scarring that, in the opinion of the investigator, may interfere with the evaluation of AD lesions or compromise participant safety.
- •Presence of AD lesions only on the hands or feet without prior history of involvement of other classic areas of involvement such as the face or the flexural folds.
- •Other types of eczema within the 6 months prior to screening. Note: Seborrheic dermatitis on the scalp is allowed, as the scalp will not be treated with study cream.
- •Current or history of hepatitis B or C virus infection.
- •Any serious illness or medical, physical, or psychiatric condition(s) that, in the investigator's opinion, would interfere with full participation in the study, including administration of study cream and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
Arms & Interventions
VC Period: Ruxolitinib 1.5% Cream BID
Participants received ruxolitinib 1.5% cream, applied topically to the affected areas as a thin film twice daily (BID) from Day 1 to Week 8 during the Vehicle Control (VC) Period. Participants applied cream BID to areas identified at Baseline even if the areas improved.
Intervention: Ruxolitinib Cream
VC Period: Vehicle Cream BID
Participants received vehicle cream, applied topically to the affected areas as a thin film twice daily (BID) from Day 1 to Week 8 during the VC Period. Participants applied cream BID to areas identified at Baseline even if the areas improved.
Intervention: Vehicle Cream
VC Extension Period/Escape Arm: Ruxolitinib 1.5% Cream BID
Participants who applied ruxolitinib 1.5% cream during VC Period, continued applying ruxolitinib 1.5% cream topically to the affected areas as a thin film BID from Week 8 to 24 during the Vehicle Control Extension (VCE) Period. Participants stopped treatment 3 days after lesions disappeared and restarted at the first sign of recurrence.
Intervention: Ruxolitinib Cream
VC Extension Period/Escape Arm: Vehicle Cream BID
Participants who applied vehicle cream during the VC Period, continued applying vehicle cream as a thin film twice daily (BID) from Weeks 8 to 24 during the VCE Period. Participants applied cream BID to areas identified at Baseline even if the areas improved. Participants will be eligible to enter the ruxolitinib 1.5% cream open-label escape arm as defined in the protocol.
Intervention: Vehicle Cream
VC Extension Period: Ruxolitinib 1.5% cream open-label escape arm
Participants received ruxolitinib 1.5% cream, applied topically to the affected areas as a thin film twice daily (BID) during the VCE Period. Participants applied cream BID to areas identified at Baseline even if the areas improved.
Intervention: Ruxolitinib Cream
Outcomes
Primary Outcomes
VC Period: Proportion of participants who achieved Investigator's Global Assessment Treatment Success (IGA-TS)
Time Frame: Baseline to Week 8
Defined as Investigator's Global Assessment (IGA) score of 0 or 1 with ≥ 2 grade improvement from baseline.
VC Period: Proportion of participants who achieved Eczema Area and Severity Index 75 (EASI75)
Time Frame: Baseline to Week 8
Defined as ≥ 75% improvement in Eczema Area and Severity Index (EASI) score.
Secondary Outcomes
- VC Period: Proportion of participants achieving at least a 4-point decrease from baseline in current Itch NRS score at 5, 15, 30, 45, and 60 minutes and 2, 4, and 6 hours post-initial dose on Day 1.(Baseline to Day 1)
- VC Period: Time to achieve a ≥ 4-point improvement in Itch Numeric Rating Scale (NRS) score (ITCH4)(Baseline to Week 8)
- VC and VCE Periods: Change from baseline in SCORAD score(Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24)
- VC and VCE Periods: Time to concurrently meeting all of the following criteria: IGA score ≥ 3, EASI score ≥ 16, Itch NRS score ≥ 4, BSA ≥ 10%, and DLQI score > 10(Baseline to Week 24)
- VC Period: Proportion of participants who experience a relapse after study treatment discontinuation(Week 24 to Follow-up (30 days))
- VC Period: Proportion of participants who achieved Investigator's Global Assessment - Treatment Success (IGA-TS)(Baseline to Weeks 2 and 4)
- VC Period: Change from baseline (pre-study cream application) in current Itch NRS score at 5, 15, 30, 45, and 60 minutes and 2, 4, and 6 hours post-initial dose on Day 1.(Baseline to Day 1)
- VC and VCE Periods: Proportion of participants achieving both EASI75 and IGA-TS(Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24)
- VCE Period: Time to open-label escape arm(Baseline to Week 24)
- VC Period: Proportion of participants with a ≥ 4-point improvement in Itch Numeric Rating Scale (NRS) score (ITCH4)(Baseline to Weeks 2 and 4)
- VC Period: Proportion of participants who achieved Eczema Area and Severity Index 75 (EASI75)(Baseline to Weeks 2 and 4)
- VC Period: Time to achieve ≥ 2-point improvement from in Itch Numeric Rating Scale (NRS) score (ITCH2)(Baseline to Week 8)
- VC Period: Proportion of participants achieving at least a 2-point decrease from baseline in current Itch NRS score at 5, 15, 30, 45, and 60 minutes and 2, 4, and 6 hours post-initial dose on Day 1.(Baseline to Day 1)
- VC and VCE Periods: Change from baseline in EASI score(Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24)
- VC and VCE Periods: Change from baseline in Skin Pain NRS score(Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24)
- VC and VCE Periods: Change From Baseline in Patient-Oriented Eczema Measure (POEM) Score(Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24)
- VC and VCE Period: Change From Baseline in PROMIS Short Form - Sleep Disturbance (8b) 7-Day Recall Score(Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24)
- VC Period: Number of Treatment Emergent Adverse Events (TEAEs)(Up to Week 24, followed by 30 days follow-up)
- VC and VCE Periods: Proportion of participants who achieved EASI90(Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24)
- VC and VCE Periods: Change from Baseline in Atopic Dermatitis Afflicted Percentage of Body Surface Area (%BSA)(Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24)
- VC and VCE Periods: Change from baseline in Itch NRS score(Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24)
- VC and VCE Periods: Proportion of participants concurrently meeting all of the following criteria: IGA score ≥ 3, EASI score ≥ 16, Itch NRS score ≥ 4, BSA ≥ 10%, and DLQI score > 10(Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24)
- VC and VCE Periods: Proportion of participants who achieve ≥ 4-point improvement in DLQI from baseline(Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24)
- VC and VCE Periods: Change From Baseline in EuroQuality of Life Five Dimensions (EQ-5D-5L) Visual Analogue Scale (VAS) Score(Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24)
- VC and VCE Periods: Proportion of participants who achieved EASI50(Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24)
- VCE period: Time to first re-treatment(Week 8 to Week 24)
- VC and VCE Periods: Change from baseline in the HADS scores(Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24)
- VCE Period: Proportion of time off study treatment due to lesion clearance(Week 8 to Week 24)
- VCE period: Proportion of time on study treatment(Week 8 to Week 24)
- VC and VCE Periods: Change From Baseline in Dermatology Life Quality Index (DLQI) Score(Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24)
- VC and VCE Periods: Change from baseline in PROMIS Short Form - Sleep-Related Impairment (8a) 24-Hour Recall Score(Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24)
- VC and VCE Periods: Change from baseline score in Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD)(Baseline to Week 8 and Week 24)