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

• ClinicalTrials.gov Identifier: NCT05583526
• Recruitment Status: Recruiting
• First Posted: October 17, 2022
• Last Update Posted: February 5, 2024
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: October 6, 2022
• First Posted Date: October 17, 2022
• Last Update Posted Date: February 5, 2024
• Actual Study Start Date: December 1, 2022
• Estimated Primary Completion Date: June 27, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 1, 2024)

• US only Co-Primary Endpoints: Response based on Total body Vitiligo Area Scoring Index 75 (T-VASI75) at Week 52 and T-VASI50 at Week 52 [ Time Frame: Week 52 ]
  Proportion of participants achieving T-VASI75 (defined as at least 75% improvement in T-VASI from Baseline) and T-VASI50 (defined as at least 50% improvement in T-VASI from Baseline)
• Global (Other than US): Response based on Facial Vitiligo Area Scoring Index 75 (F-VASI75) at Week 52 [ Time Frame: Week 52 ]
  Proportion of participants achieving F-VASI75 (defined as at least 75% improvement in F-VASI from Baseline).
• Incidence of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Adverse Events (AEs), leading to discontinuation, and clinically significant laboratory abnormalities [ Time Frame: Baseline through Week 52 ]
  safety and tolerability of ritlecitinib in participants with nonsegmental vitaligo

Original Primary Outcome Measures (submitted: October 13, 2022)

• F-VASI75 and T-VASI50 comprise the primary endpoint family at 52 weeks [ Time Frame: 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).
• For the EU: Proportion of participants achieving F-VASI75 at Week 52. [ Time Frame: 52 weeks ]
  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).

Current Secondary Outcome Measures (submitted: February 1, 2024)

• US-Only: Response based on F-VASI75 at 24, 26 and 52 weeks [ Time Frame: 24, 36 and 52 Weeks ]
  Proportion of participants achieving at least a 75% improvement in F-VASI from Baseline.
• US-Only: Response based on T-VASI50 at 24 and 36 weeks [ Time Frame: 24 and 36 weeks ]
  Proportion of participants achieving T-VASI50 (defined as at least 50% improvement in T-VASI from Baseline).
• Global (Other than US):Patient Global Impression of Severity-Face (PGIS-F) [ Time Frame: Week 36 and week 52 ]
  To assess the effect of ritlecitinib compared to placebo on the PGIS-F at Week 36 and 52
• Global (Other than US): Patient Global Impression of Severity-Overall Vitiligo (PGIS-V) [ Time Frame: Week 36 and week 52 ]
  To assess the effect of ritlecitinib compared to placebo on the PGIS-V at Week 36 and 52
• Global (Other Than US): Response based on T-VASI50 at Week 52 [ Time Frame: Week 52 ]
  Proportion of participants achieving T-VASI50 (defined as at least 50% improvement in T-VASI from Baseline).
• Patient Global Impression of Change-Face (PGIC-F) [ Time Frame: Week 36 and week 52 ]
  To assess the effect of ritlecitinib compared to placebo on the PGIC-F at Weeks 36 and 52.
• Patient Global Impression of Change- Overall vitiligo(PGIC-V) [ Time Frame: Week 36 and week 52 ]
  To assess the effect of ritlecitinib compared to placebo on the PGIC-V at Weeks 36 and 52.
• Global (Other than US): Response based on F-VASI75 at 24 and 36 weeks [ Time Frame: Week 24 and week 36 ]
  Proportion of participants achieving F-VASI75 (defined as at least 75% improvement in F-VASI from Baseline).
• Global (Other than US): Response based on PGIS-V [ Time Frame: 36 and 52 weeks ]
  Proportion of participants achieving PGIC-V response
• Global (Other than US): Response based on F-VASI75 [ Time Frame: 24 and 36 weeks ]
  Proportion of participants achieving F-VASI75 (defined as at least 75% improvement in F-VASI from Baseline)
• Change from baseline in Dermatology Life Quality Index (DLQI) or Children Dermatology Life Quality Index (CDLQI) [ Time Frame: Week 52 ]
  To evaluate the change from baseline in DLQI or CDLQI at week 52
• Proportion of participants achieving disease stabilization [ Time Frame: Baseline through week 52 ]
  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 and 100mg compared to placebo
• Response based on T-VASI50 [ Time Frame: Baseline through week 4, week 8, week 12, week 48. ]
  Proportion of participants achieving T-VASI50 (defined as at least 50% improvement in T-VASI from Baseline)
• Response based on F-VASI75 [ Time Frame: Baseline through week 4, week 8, week 12, week 48. ]
  Proportion of participants achieving F-VASI75 (defined as at least 75% improvement in F-VASI from Baseline)
• US only: Response based on T-VASI75 [ Time Frame: Baseline through week 4, week 8, week 12, week 24, week 36, week 48. ]
  Proportion of participants achieving T-VASI75 (defined as at least 75% improvement in T-VASI from Baseline)
• Global (Other than US): Response based on T-VASI75 [ Time Frame: Baseline through week 52 ]
  Proportion of participants achieving T-VASI75 (defined as at least 75% improvement in T-VASI from Baseline)
• All Countries: Time to rescue medication [ Time Frame: Baseline through week 52 ]
• Percentage change from baseline in F-VASI [ Time Frame: Baseline through week 52 ]
• Percentage change from baseline in T-VASI [ Time Frame: Baseline through week 52 ]
• Response based on T-VASI90 [ Time Frame: Baseline through week 52 ]
  Proportion of participants achieving T-VASI90 (defined as at least 90% improvement in T-VASI from Baseline)
• Response based on T-VASI100 [ Time Frame: Baseline through week 52 ]
  Proportion of participants achieving T-VASI100 (defined as at least 100% improvement in T-VASI from Baseline)
• Response based on F-VASI50 [ Time Frame: Baseline through week 52 ]
  Proportion of participants achieving F-VASI50 (defined as at least 50% improvement in F-VASI from Baseline).
• Response based on F-VASI90 [ Time Frame: Baseline through week 52 ]
  Proportion of participants achieving F-VASI90 (defined as at least 50% improvement in F-VASI from Baseline).
• Response based on F-VASI100 [ Time Frame: Baseline through week 52 ]
  Proportion of participants achieving F-VASI100 (defined as at least 100% improvement in F-VASI from Baseline).
• Change from baseline in the Hospital Anxiety and Depression Scale (HADS) [ Time Frame: Week 52 ]
  To assess the effect of ritlecitinib compared to placebo on depression and anxiety subscales of the HADS at week 52
• The proportion of patients achieving absence of depression on HADS depression subscale [ Time Frame: Week 52 ]
  Response based on a 'normal' subscale score indicative of an absence of depression (in participants with baseline HADS subscale scores indicative of depression)
• The proportion of patients achieving absence of anxiety on HADS anxiety subscale [ Time Frame: Week 52 ]
  Response based on a 'normal' subscale score indicative of an absence of anxiety (in participants with baseline HADS subscale scores indicative of anxiety)
• US-Only: Patient Global Impression of Severity-Face (PGIS-F) [ Time Frame: Week 52 ]
  To assess the effect of ritlecitinib compared to placebo on the PGIS-F at 52
• US-Only: Patient Global Impression of Severity-Overall Vitiligo (PGIS-V) [ Time Frame: Week 52 ]
  To assess the effect of ritlecitinib compared to placebo on the PGIS-V at 52

Original Secondary Outcome Measures (submitted: October 13, 2022)

• For the EU: Proportion of participants achieving T-VASI50 at Week 52 [ Time Frame: 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 T-VASI50 (defined as at least 50% improvement in T-VASI from Baseline).
• Proportion of participants achieving F-VASI75 at Week 36. [ Time Frame: 36 weeks ]
  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).
• Proportion of participants achieving F-VASI75 at Week 24. [ Time Frame: 24 weeks ]
  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).
• Patient Global Impression of Severity-Face [ Time Frame: 52 weeks ]
  To assess the effect of ritlecitinib 50 mg QD compared to placebo on the PGIS-F at Week 52
• Patient Global Impression of Severity-Overall Vitiligo [ Time Frame: 52 weeks ]
  To assess the effect of ritlecitinib 50 mg QD compared to placebo on the PGIS-V at Week 52
• Patient Global Impression of Change-Overall Vitiligo [ Time Frame: 36 and 52 weeks ]
  To assess the effect of ritlecitinib 50 mg QD compared to placebo on the PGIC-V at Weeks 36 and 52. For EU only
• Patient Global Impression of Severity-Overall Vitiligo [ Time Frame: 36 and 52 weeks ]
  To assess the effect of ritlecitinib 50 mg QD compared to placebo on the PGIS-V at Weeks 36 and 52. For EU only
• Stabilization of disease [ Time Frame: 52 Weeks ]
  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.
• CDLQI/DLQI [ Time Frame: 36 and 52 weeks ]
  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
• Patient Global Impression of Change-Face [ Time Frame: 36 and 52 weeks ]
  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
• Patient Global Impression of Severity-Face [ Time Frame: 36 and 52 weeks ]
  To evaluate the proportion of responders based on achieving improvement in PGIS-F at weeks 36 and 52 in participants with non segmental vitiligo treated with ritlecitinib 50 mg QD compared to placebo
• Hospital Anxiety and Depression Scale [ Time Frame: 36 and 52 weeks ]
  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
• Incidence of TEAEs, SAEs, and AEs leading to discontinuation. Incidence of clinically significant laboratory abnormalities [ Time Frame: 52 weeks ]
  To evaluate the safety and tolerability of ritlecitinib in adult and adolescent participants with non segmental vitiligo

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A 52-Week Study of Ritlecitinib Oral Capsules in Adults and Adolescents With Nonsegmental Vitiligo (Active and Stable) Tranquillo
• Official Title: 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 NONSEGMENTAL VITILIGO
• Brief Summary: A 52-Week Study of Ritlecitinib Oral Capsules in Adults and Adolescents with Nonsegmental Vitiligo (Active and Stable) Tranquillo
• Detailed Description: 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 nonsegmental vitiligo (both active and stable vitiligo).
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Double-blind, parallel-group, vehicle controlled.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Condition

• Stable Nonsegmental Vitiligo
• Active Nonsegmental Vitiligo

Intervention

• Drug: Ritlecitinib
  50 mg capsule
• Drug: Placebo
  Matching capsule

Study Arms

• Experimental: Ritlecitinib 50 mg
  Ritlecitinib 50 mg QD (ritilecitinib 50 mg QD arm; approximately 400 participants)
  Intervention: Drug: Ritlecitinib
• Placebo Comparator: Placebo
  Placebo (placebo arm; approximately 200 participants)
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 13, 2022): 600
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 27, 2025
• Estimated Primary Completion Date: June 27, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Participants ≥18 years of age at Screening. 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.

   Disease Characteristics:

2. Eligible participants must have at both Screening and Baseline:

   • A clinical diagnosis of nonsegmental vitiligo for at least 3 months; and
   • BSA involvement 4%-60% inclusive, excluding involvements at palms of the hands, 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 cheek 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 nonsegmental 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); Confetti-like depigmentation is characterized by the presence of numerous 1-mm to 5-mm depigmented macules in clusters;
   • Trichrome lesion(s);Trichrome lesions have a hypopigmented zone of varying width between normal and completely depigmented skin, resulting in 3 different hues of skin;
   • 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 and Baseline based on the resulting scores from the local in-person reads of F-VASI, T-VASI, and BSA.

   Other Inclusion Criteria:

3. 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.
4. Must agree to stop all other treatments for vitiligo from Screening through the final follow-up visit.

Exclusion Criteria:

1. 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 ideation or behavior or recurrent suicidal behavior. For adolescents, any previous lifetime history of suicidal behavior.

2. 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 disorders of pigmentation (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 (all types, including mixed), 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 a superficial skin infections within 2 weeks prior to first dose on Day 1. NOTE: participants may be rescreened after the infection resolves.

3. 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. 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

4. 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.

5. Medical Conditions, Other:

   • 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.
   • History of severe allergic or anaphylactoid reaction to any kinase inhibitor or a known allergy/hypersensitivity to any component (including excipients) of the study intervention.
   • 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 acute, 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.
   • Significant trauma or major surgery within 1 month of the first dose of study drug or considered in imminent need for surgery or with elective surgery scheduled to occur during the study.

   Prior/Concomitant Therapy:

6. Have received any of the prohibited treatment regimens specified.

   Prior/Concurrent Clinical Study Experience:

7. Previous administration with an investigational drug or vaccine that do not affect vitiligo within 4 weeks of Day 1 [Baseline] or within 5 half-lives, whichever is longer.

   Diagnostic Assessments:

8. 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

9. Screening standard 12-lead ECG that demonstrates clinically relevant abnormalities

   Other Exclusion Criteria:

10. 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.

11. Adolescent participants 12 to <18 years of age without one of the following:

    • Documented evidence from a health professional of having received varicella vaccination (2 doses); or
    • Evidence of prior exposure to VZV based on serological testing (ie, a positive VZV IgG Ab result) at Screening.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Pfizer CT.gov Call Center; 1-800-718-1021; ClinicalTrials.gov_Inquiries@pfizer.com

• Listed Location Countries: Australia, Bulgaria, Canada, China, Germany, Italy, Japan, Korea, Republic of, Mexico, Poland, South Africa, Spain, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT05583526
• Other Study ID Numbers: B7981040; Tranquillo ( Other Identifier: Alias Study Number ); 2022-501668-16-00 ( Registry Identifier: CTIS (EU) )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: January 2024