A 52-Week Study of Ritlecitinib Oral Capsules in Adults and Adolescents With Vitiligo (Active and Stable)

Study Overview
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Brief Summary
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A 52-Week Study of Ritlecitinib Oral Capsules in Adults and Adolescents with Vitiligo (Active and Stable)

Detailed Description
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Study B7981040 is a Phase 3 randomized, double-blind, 52-week placebo-controlled, multi center study investigating the efficacy, safety, and tolerability of ritlecitinib in adult and adolescent participants with non segmental vitiligo (both active and stable vitiligo).

Official Title
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A PHASE 3 RANDOMIZED, DOUBLE-BLIND, 52-WEEK PLACEBO-CONTROLLED, MULTI-CENTER STUDY INVESTIGATING THE EFFICACY, SAFETY, AND TOLERABILITY OF RITLECITINIB IN ADULT AND ADOLESCENT PARTICIPANTS WITH NON SEGMENTAL VITILIGO

Conditions
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Non-segmental Vitiligo (Both Active and Stable Vitiligo)

Intervention / Treatment
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* Drug: Ritlecitinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants ≥18 years of age, inclusive. Adolescents (12 to <18 years of age) are also eligible for this study, but only if approved by the local IRB/EC and regulatory health authority. Where these approvals have not been granted, only participants ≥18 years of age will be enrolled. Adolescent participants will not be enrolled in the United States. Disease Characteristics: Eligible participants must have at both Screening and Baseline: A clinical diagnosis of non segmental vitiligo for at least 3 months; and BSA involvement 4%-60% inclusive, excluding involvements at palms of the hands, dorsal aspect of fingers and thumbs including metacarpophalangeal joints, soles of the feet, or dorsal aspect of the feet; and BSA ≥0.5% involvement on the face (face is defined as including the area on the forehead to the original hairline, on the check to the jawline vertically to the jawline, and laterally from the corner of the mouth to the tragus. The face will not include scalp, ears, neck, or surface area of the lips, but will include the nose and the eyelids; and F-VASI ≥0.5 & T-VASI ≥3; and Either active or stable disease non segmental vitiligo at both Screening and Baseline visits. All participants who do not have the features of active vitiligo (defined below) are required to have stable disease. Active vitiligo is defined as: Participants will be classified as having active vitiligo based on the presence of at least one active lesion at baseline defined as one of the following: New/extending lesion(s) in the 3 months prior to Screening visit (confirmed by photographs or medical record): Confetti-like lesion(s); Trichrome lesion(s); Koebner phenomenon/phenomena (excluding Type 1 [history based on isomorphic reaction]). The Koebner phenomenon manifests as depigmentation at sites of trauma, usually in a linear arrangement. Stable vitiligo is defined as an absence of signs of active disease. All participants who do not have the features of active vitiligo (defined above) are required to have stable disease. Eligibility is determined at Screening based on the resulting scores from the local in-person reads of F-VASI, T-VASI, and BSA. Other Inclusion Criteria: If receiving concomitant medications for any reason other than vitiligo, participant must be on a stable regimen, which is defined as not starting a new drug or changing dosage within 7 days or 5 half-lives (whichever is longer) prior to Day 1. Participant must be willing to stay on a stable regimen during the duration of the study. Must agree to stop all other treatments for vitiligo from Screening through the final follow-up visit. Exclusion Criteria: Any psychiatric condition including recent or active suicidal ideation or behavior that meets any of the following criteria: Suicidal ideation associated with actual intent and a method or plan in the past year: Yes answers on items 4 or 5 of the C-SSRS administered at the screening visit. Previous history of suicidal behaviors in the past 5 years: Yes answer (for events that occurred in the past 5 years) to any of the suicidal behavior items of the C-SSRS. For adults, any lifetime history of serious suicidal behavior or recurrent suicidal behavior. For adolescents, any previous lifetime history of suicidal behavior. Medical conditions pertaining to vitiligo and other diseases/conditions affecting the skin: Participants that have other types of vitiligo that do not meet criteria for active or stable vitiligo as noted in inclusion criterion #2 (including, but not limited to, segmental vitiligo and mixed vitiligo). Currently have active forms of other hypopigmentation (including but not limited to Vogt-Koyanagi-Harada disease, malignancy-induced hypopigmentation [melanoma and mycosis fungoides], post-inflammatory hypopigmentation, pityriasis alba [minor manifestation of atopic dermatitis], senile leukoderma [age-related depigmentation], chemical/drug-induced leukoderma, ataxia telangiectasia, tuberous sclerosis, melasma, and congenital hypopigmentation disorder including piebaldism, Waardenburg syndrome, hypomelanosis of Ito, incontinentia pigmenti, dyschromatosis symmetrica hereditarian, xeroderma pigmentosum, and nevus depigmentosus). NOTE: Coexistence of halo nevus/nevi (also known as Sutton nevus/nevi) is permitted. Currently have active forms of inflammatory skin disease(s) or evidence of skin conditions (for example, morphea, discoid lupus, leprosy, syphilis, psoriasis, seborrheic dermatitis) at the time of the Screening or Baseline Visit that in the opinion of the investigator would interfere with evaluation of vitiligo or response to treatment. Leukotrichia in more than 33% of the face surface area affected with vitiligo lesions OR leukotrichia in more than 33% of the total body surface area affected with vitiligo lesions. Have active acute or chronic skin infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 4 weeks prior to first dose on Day 1, or superficial skin infections within 2 weeks prior to first dose on Day 1. NOTE: participants may be rescreened after the infection resolves. General Infection History: Having a history of systemic infection requiring hospitalization, parenteral antimicrobial, antiviral (including biologic treatment), antiparasitic, antiprotozoal, or antifungal therapy, or as otherwise judged clinically significant by the investigator within 6 months prior to Day 1. Have active acute or chronic infection requiring treatment with oral antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 4 weeks prior to Day 1 or superficial skin infections within 2 weeks prior to first dose on Day 1. NOTE: participants may be rescreened after the infection resolves. Evidence or history of untreated, currently treated or inadequately treated active or latent infection with Mycobacterium TB Specific Viral Infection History: History (single episode) of disseminated herpes zoster or disseminated herpes simplex, or a recurrent (more than one episode of) localized, dermatomal herpes zoster. Infected with hepatitis B or hepatitis C viruses: all participants will undergo screening for hepatitis B and C for eligibility. Participants who are positive for HCVAb and HCV RNA will not be eligible for this study. Have a known immunodeficiency disorder (including positive serology for HIV at screening) or a first-degree relative with a hereditary immunodeficiency. Medical Conditions, Other: Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. Current or recent history of clinically significant severe, progressive, or uncontrolled renal (including but not limited to active renal disease or recent kidney stones), hepatic, hematological, gastrointestinal, metabolic, endocrine (eg, untreated hypovitaminosis D or hypothyroidism), pulmonary, cardiovascular, psychiatric, immunologic/rheumatologic or neurologic disease; or have any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration, or interfere with the interpretation of study results; or in the opinion of the investigator or Pfizer (or designee), the participant is inappropriate for entry into this study, or unwilling/unable to comply with study procedures and lifestyle requirements. Have hearing loss with progression over the previous 5 years, sudden hearing loss, or middle or inner ear disease such as otitis media, cholesteatoma, Meniere's disease, labyrinthitis, or other auditory condition that is considered current, fluctuating or progressive. Have a history of any lymphoproliferative disorder such as EBV-related lymphoproliferative disorder, history of lymphoma, history of leukemia, or signs and symptoms suggestive of current lymphatic or lymphoid disease. Abnormal findings on the Screening chest imaging (eg, chest x-ray) including, but not limited to, presence of active TB, general infections, cardiomyopathy, or malignancy. Chest imaging may be performed up to 12 weeks prior to screening. Documentation of the official reading must be located and available in the source documentation. Long QT Syndrome, a family history of Long QT Syndrome, or a history of TdP. Have any malignancies or have a history of malignancies with the exception of adequately treated or excised nonmetastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ. Prior/Concomitant Therapy: Have received any of the prohibited treatment regimens specified. Prior/Concurrent Clinical Study Experience: Previous administration with an investigational drug or vaccine within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). Diagnostic Assessments: Any of the following abnormalities in laboratory values at Screening, as assessed by the study-specific laboratory and, if deemed necessary, confirmed by a single repeat: Renal impairment Hepatic dysfunction Screening standard 12-lead ECG that demonstrates clinically relevant abnormalities Other Exclusion Criteria: Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blind, parallel-group, vehicle controlled.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ritlecitinib 50 mg<br>Ritlecitinib 50 mg QD (ritilecitinib 50 mg QD arm; approximately 400 participants) | Drug: Ritlecitinib<br>* 50 mg capsule<br>|
| Placebo Comparator: Placebo<br>Placebo (placebo arm; approximately 200 participants) | Drug: Placebo<br>* Matching capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| F-VASI75 and T-VASI50 comprise the primary endpoint family at 52 weeks | To evaluate the efficacy of ritlecitinib 50 mg QD compared to placebo in adult and adolescent participants with non segmental vitiligo. Proportion of participants achieving F-VASI75 (defined as at least 75% improvement in F-VASI from Baseline) and proportion of participants achieving T-VASI50 (defined as at least 50% improvement in T-VASI from Baseline). | 52 weeks | 
| For the EU: Proportion of participants achieving F-VASI75 at Week 52. | To assess the comparative efficacy of ritlecitinib 50 mg QD compared to placebo over a 52 week period in facial vitiligo. Proportion of participants achieving F-VASI75 (defined as at least 75% improvement in F-VASI from Baseline). | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| For the EU: Proportion of participants achieving T-VASI50 at Week 52 | To evaluate the efficacy of ritlecitinib 50 mg QD compared to placebo in adult and adolescent participants with non segmental vitiligo. Proportion of participants achieving T-VASI50 (defined as at least 50% improvement in T-VASI from Baseline). | 52 weeks | 
| Proportion of participants achieving F-VASI75 at Week 36. | To assess the comparative efficacy of ritlecitinib 50 mg QD compared to placebo over a 36 week period in facial vitiligo. Proportion of participants achieving F-VASI75 (defined as at least 75% improvement in F-VASI from Baseline). | 36 weeks | 
| Proportion of participants achieving F-VASI75 at Week 24. | To assess the comparative efficacy of ritlecitinib 50 mg QD compared to placebo over a 24 week period in facial vitiligo. Proportion of participants achieving F-VASI75 (defined as at least 75% improvement in F-VASI from Baseline). | 24 weeks | 
| Patient Global Impression of Severity-Face | To assess the effect of ritlecitinib 50 mg QD compared to placebo on the PGIS-F at Week 52 | 52 weeks | 
| Patient Global Impression of Severity-Overall Vitiligo | To assess the effect of ritlecitinib 50 mg QD compared to placebo on the PGIS-V at Week 52 | 52 weeks | 
| Patient Global Impression of Change-Overall Vitiligo | To assess the effect of ritlecitinib 50 mg QD compared to placebo on the PGIC-V at Weeks 36 and 52. For EU only | 36 and 52 weeks | 
| Patient Global Impression of Severity-Overall Vitiligo | To assess the effect of ritlecitinib 50 mg QD compared to placebo on the PGIS-V at Weeks 36 and 52. For EU only | 36 and 52 weeks | 
| Stabilization of disease | The difference in the proportion of participants with stable disease at all timepoints in participants with non segmental vitiligo treated with ritlecitinib 50 mg QD compared to placebo. | 52 Weeks | 
| CDLQI/DLQI | To evaluate the change from baseline in DLQI or CDLQI at weeks 36 and 52 in participants with non segmental vitiligo treated with ritlecitinib 50 mg QD compared to placebo | 36 and 52 weeks | 
| Patient Global Impression of Change-Face | To evaluate the proportion of responders based on achieving at least moderately better on PGIC-F at weeks 36 and 52 in participants with non segmental vitiligo treated with ritlecitinib 50 mg QD compared to placebo | 36 and 52 weeks | 
| Patient Global Impression of Severity-Face | To evaluate the proportion of responders based on achieving improvment in PGIS-F at weeks 36 and 52 in participants with non segmental vitiligo treated with ritlecitinib 50 mg QD compared to placebo | 36 and 52 weeks | 
| Hospital Anxiety and Depression Scale | To assess the effect of ritlecitinib 50 mg QD compared to placebo on depression and anxiety subscales of the HADS at weeks 36 and 52 | 36 and 52 weeks | 
| Incidence of TEAEs, SAEs, and AEs leading to discontinuation. Incidence of clinically significant laboratory abnormalities | To evaluate the safety and tolerability of ritlecitinib in adult and adolescent participants with non segmental vitiligo | 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-segmental vitiligo (both active and stable vitiligo)