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 (Tranquillo)
A 52-Week Study of Ritlecitinib Oral Capsules in Adults and Adolescents With Vitiligo (Active and Stable) (Tranquillo)
Kawai Norisuke
Pfizer R&D Japan G.K.
Shinjuku Bunka Quint Bldg., 3-22-7 Yoyogi, Shibuya-ku, Tokyo
+81-3-5309-7000
clinical-trials@pfizer.com
Clinical Trials Information Desk
Pfizer R&D Japan G.K.
Shinjuku Bunka Quint Bldg., 3-22-7 Yoyogi, Shibuya-ku, Tokyo
+81-3-5309-7000
clinical-trials@pfizer.com
Complete
Dec. 23, 2022
Dec. 23, 2022
600
Interventional
randomized controlled trial
double blind
placebo control
parallel assignment
treatment purpose
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. Adolescent participants will not be enrolled in the United States.
Disease Characteristics:
2. 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, 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 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); 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.
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 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:
- 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 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) that may increase the risk associated with study participation 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.
1. US only Co-Primary Endpoints: Response based on F-VASI75 (defined as at least 75% improvement in F-VASI from Baseline) at Week 52 and T-VASI50 (defined as at least 50% improvement in T-VASI from Baseline) at Week 52 (Proportion of participants achieving F-VASI75 and T-VASI50)
2. Global (Other than US): Response based on F-VASI75) at Week 52 (Proportion of participants achieving F-VASI75)
3. Incidence of Treatment Emergent Adverse Events, Serious Adverse Events, Adverse Events leading to discontinuation, and clinically significant laboratory abnormalities (Safety and tolerability of ritlecitinib in participants with nonsegmental vitiligo)
1. US-Only: Response based on F-VASI75 at Weeks 24 and 36 (Proportion of participants achieving F-VASI75)
2. US-Only: Response based on T-VASI50 at Weeks 24 and 36 (Proportion of participants achieving T-VASI50)
3. US-Only: Response based on T-VASI75 (defined as at least 75% improvement in T-VASI from Baseline) at Week 52 (Proportion of participants achieving T-VASI75)
4. US-Only: Median Percentage change from baseline (%CFB) in F-VASI at Weeks 24, 36, and 52
5. US-Only: Median %CFB in T-VASI at Weeks 24, 36, and 52
6. US-Only: Proportion of responders based on Patient Global Impression of Severity-Face (PGIS-F) Week 52
7. US-Only: Proportion of responders based on Patient Global Impression of Severity-Overall Vitiligo (PGIS-V) at Week 52
8. Global (Other than US): Response based on F-VASI75 at Weeks 24 and 36 (Proportion of participants achieving F-VASI75)
9. Global (Other Than US): Response based on T-VASI50 at Weeks 24, 36, and 52 (Proportion of participants achieving T-VASI50)
10. Global (Other than US): Median %CFB in F-VASI at Weeks 24, 36, and 52
11. Global (Other than US): Median %CFB in T-VASI at Weeks 24, 36, and 52
12. Global (Other than US): Proportion of responders based on PGIS-F at Weeks 24, 36, and 52
13. Global (Other than US): Proportion of responders based on PGIS-V at Weeks 24, 36, and 52
14. All Countries: Proportion of participants achieving disease stabilization (Proportion of participants with stable disease at all timepoints through Week 52)
15. Response based on T-VASI50 at Weeks 4, 8, 12, and 48 (Proportion of participants achieving T-VASI50)
16. Response based on F-VASI75 at Weeks 4, 8, 12, and 48 (Proportion of participants achieving F-VASI75)
17. Response based on T-VASI75 at Weeks 4, 8, 12, 24, 36, and 48, (Proportion of participants achieving T-VASI75)
18. Proportion of participants with sustained improvement in T-VASI (Defined as maintenance of >=T-VASI50 from Week 36 to Week 52)
19. Proportion of participants with sustained improvement in F-VASI (Defined as maintenance of >=F-VASI75 from Week 36 to 52)
20. All Countries: Time to rescue medication (Comparing time to rescue medication curves and difference in probabilities of using rescue medication)
21. Median %CFB in F-VASI at timepoints through Week 52
22. Median %CFB in T-VASI at timepoints through Week 52
23. Response based on T-VASI90 (defined as at least 90% improvement in T-VASI from Baseline) at timepoints through Week 52 (Proportion of participants achieving T-VASI90)
24. Response based on T-VASI100 (defined as 100% improvement in T-VASI from Baseline) at timepoints through Week 52 (Proportion of participants achieving T-VASI100)
25. Response based on F-VASI50 (defined as as at least 50% improvement in F-VASI from Baseline) at timepoints through Week 52 (Proportion of participants achieving F-VASI50)
26. Response based on F-VASI90 (defined as at least 90% improvement in F-VASI from Baseline) at timepoints through Week 52 (Proportion of participants achieving F-VASI90)
27. Response based on F-VASI100 (defined as 100% improvement in F-VASI from Baseline) at timepoints through Week 52 (Proportion of participants achieving F-VASI100)
28. Proportion of responders based on PGIS-F at Weeks 24 and 36
29. Proportion of responders based on PGIS-V at Weeks 24 and 36
30. Proportion of responders based on Patient Global Impression of Change-Face (PGIC-F) at Weeks 24, 36, and 52
31. Proportion of responders based on Patient Global Impression of Change- Overall Vitiligo (PGIC-V) at Weeks 24, 36, and 52
32. Change from baseline (CFB) in DLQI or CDLQI at Week 52
33. CFB in HADS (depression and anxiety subscales) at Week 52
34. Response based on a 'normal' subscale score indicative of an absence of depression at Week 52 (in participants with baseline HADS subscale scores indicative of depression) (Proportion of participants achieving absence of depression on HADS depression subscale)
35. Response based on a 'normal' subscale score indicative of an absence of anxiety at Week 52 (in participants with baseline HADS subscale scores indicative of anxiety) (Proportion of participants achieving absence of anxiety on HADS anxiety subscale)
Pfizer Japan Inc.
Nippon Medical School Hospital IRB
1-1-5 Sendagi, Bunkyo-ku, Tokyo
+81-3-3822-2131
clinicaltrial@nms.ac.jp
Approval
Nov. 25, 2022
Yes
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.
NCT05583526
ClinicalTrials.gov
Australia/Bulgaria/Canada/China/Germany/Italy/Korea, Republic of/Mexico/Poland/South Africa/Spain/Turkey/United Kingdom/United States
