A Study of ATI-50002 Topical Solution for the Treatment of Vitiligo

Study Overview
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Brief Summary
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The main objective of this study is to assess the safety, tolerability and efficacy of ATI-50002 Topical Solution, 0.46% in subjects with non-segmental facial vitiligo.

Detailed Description
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This is a multicenter, open-label study designed to evaluate the safety, tolerability and efficacy of ATI-50002 Topical Solution 0.46% in subjects with non-segmental facial vitiligo. Subjects will be required to have a clinical diagnosis of non-segmental facial vitiligo effecting at least 0.25% of total body surface area (TBSA) (excluding upper and lower eyelids, mucosal lip areas, and forehead and chin areas covered by the stereotactic positioning device for photography) with at least one area of the face with normal pigmentation. Twenty-four eligible subjects will receive ATI-50002 Topical Solution, 0.46%, BID for 24 weeks.

Official Title
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An Open-Label Pilot Study of the Safety, Tolerability and Efficacy of ATI-50002 Topical Solution Administered Twice-Daily in Adult Subjects With Non-Segmental Facial Vitiligo

Conditions
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Vitiligo

Intervention / Treatment
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* Drug: ATI-50002 topical solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has a clinical diagnosis of new onset or actively progressing non-segmental facial vitiligo or worsening of existing facial lesions within the past 6 months. Subject has non-segmental facial vitiligo effecting at least 0.25% total body surface area (TBSA) (excluding the upper and lower eyelids, mucosal lip areas and forehead and chin areas covered by the stereotactic positioning device for photography) with at least one area of the face with normal pigmentation. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test at the baseline visit and must agree to use an approved method of highly effective birth control for the duration of the study and for 30 days after last study medication application. Subject is in good general health and free of any known disease state or physical condition which, in the opinion of the investigator, would interfere with the study assessments or put the subject at undue risk by study participation. Subject agrees to refrain from any other treatments for vitiligo from the screening visit through the final follow-up visit. Over the counter (OTC) preparations deemed acceptable by the investigator and camouflage makeups are permitted. Exclusion Criteria: Subject with evidence of poliosis (white hairs) in > 50% of their facial vitiligo lesions. Subject with total facial depigmentation. Subject with spontaneous ongoing repigmentation (documented based on the subject's reporting in the last 3 months). Subject who has segmental vitiligo. Subject who has failed phototherapy. Failed phototherapy is defined as failure to achieve satisfactory repigmentation following adequately delivered phototherapy as determined by the investigator. Subject currently has, or has a history of, skin disease (e.g., psoriasis, seborrheic dermatitis, etc.) that, in the opinion of the investigator, would interfere with the study medication application or study assessments. Subject has, or has a history of, severe, progressive or uncontrolled autoimmune, metabolic, renal, hepatic, gastrointestinal, pulmonary, cardiovascular, genitourinary (i.e.,renal disease), hematological disease, neurologic or cerebral disorders, infectious disease or coagulation disorders that, in the opinion of the investigator, would interfere with the study assessments or put the subject at undue risk by study participation. Subject currently has a history of, current, or suspected systemic or cutaneous malignancy and/or lymphoproliferative disease, other than a history of adequately treated, well healed and completely cleared non-melanoma skin cancers (e.g., basal or squamous cell carcinoma) treated successfully at least 1 year prior to study entry with no evidence of disease. Subject currently has evidence of active or latent bacterial (including tuberculosis) or viral infections at the time of enrollment, or a history of incompletely treated or untreated tuberculosis. Subjects who have initiated therapy for latent tuberculosis for at least 2 weeks and agree to continue their therapy through completion may participate. Subject has a history of serious local infection (e.g., cellulitis, abscess) or systemic infection, or history of treated infection (e.g., pneumonia, septicemia) within 3 months prior to the baseline visit. Subjects on an antibiotic for a nonserious, acute local infection must complete the course prior to enrollment into the study. Subject has herpes zoster or cytomegalovirus (CMV) that resolved within 8 weeks prior to Visit 1. Subject has a history of frequent outbreaks of oral Herpes Simplex Virus defined as more than 4 episodes per year. Subjects previously treated with depigmenting agents. Clinically significant laboratory abnormalities at screening that in the opinion of the investigator, would make the subject a poor candidate for the study. Subject who has an absolute neutrophil count <1,000/mm3, or platelet count < 50,000/mL. Subject unable to comply with the required washout periods Subject who has participated in any investigational drug or device trial, regardless of indication in which administration of an investigational drug or device occurred within 30 days or 5 half-lives (whichever is longer) of screening (Visit 1). Note that investigational treatment for vitiligo (in any body area) requires a longer washout Subjects with a clinically significant abnormal thyroid-stimulating hormone or free T4 at screening. Subjects under treatment with stable thyroid replacement who have a free T4 and TSH within the normal range may participate. Subject has history of sensitivity to any of the ingredients in the study medication. Subject has a history of, or current alcohol or drug abuse within 2 years of study enrollment. Screening ECG findings of: QTcF >450msec for males or >470msec for females (use of the ECG algorithm is acceptable for this purpose) Heart rate ≤ 45 or ≥ 100 beats/minutes Rhythm disturbance other than sinus arrhythmia or ectopic supraventricular rhythm (ectopic atrial rhythm) Conduction disturbance including PR >240msec, pre-excitation (delta wave and PR <120msec), second degree or higher AV block Acute or chronic signs of ischemia. Left Bundle Branch Block Prior myocardial infarction

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ATI-50002 Topical Solution<br>ATI-50002 topical solution, high dose active, twice-daily, 24 weeks | Drug: ATI-50002 topical solution<br>* Topical Solution administered twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Facial Depigmentation in the AOI (Area of Interest) Based on Canfield 2-D Photographic Analysis From Baseline to Week 24 | Mean change from baseline in facial depigmentation in quantified Area of Interest (AOI) using Canfield-2-D photographic image analysis from baseline (Visit 2) compared to Week 24. Facial depigmentation is measured on a scale of 0 to 100, with a score of 0 meaning no depigmentation and a score of 100 meaning total depigmentation. Lower scores represent better outcomes. | Baseline to 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Facial Depigmentation in the AOI (Area of Interest) Based on Canfield 2-D Photographic Analysis From Baseline Compared to Week 48 | Mean change from baseline in facial depigmentation in quantified Area of Interest (AOI) using Canfield-2-D photographic image analysis from baseline (Visit 2) compared to Week 48. Facial depigmentation is measured on a scale of 0 to 100, with a score of 0 meaning no depigmentation and a score of 100 meaning total depigmentation. Lower scores represent better outcomes. | Baseline to 48 Weeks | 
| Mean Change From Baseline in Facial Depigmentation in the AOI (Area of Interest) Based on Canfield 2-D Photographic Analysis From Baseline Compared to Week 4 | Mean change from baseline in facial depigmentation in quantified Area of Interest (AOI) using Canfield-2-D photographic image analysis from baseline (Visit 2) compared to Week 4. Facial depigmentation is measured on a scale of 0 to 100, with a score of 0 meaning no depigmentation and a score of 100 meaning total depigmentation. Lower scores represent better outcomes. | Baseline to 4 Weeks | 
| Mean Change From Baseline in Facial Depigmentation in the AOI (Area of Interest) Based on Canfield 2-D Photographic Analysis From Baseline Compared to Week 8 | Mean change from baseline in facial depigmentation in quantified Area of Interest (AOI) using Canfield-2-D photographic image analysis from baseline (Visit 2) compared to Week 8. Facial depigmentation is measured on a scale of 0 to 100, with a score of 0 meaning no depigmentation and a score of 100 meaning total depigmentation. Lower scores represent better outcomes. | Baseline to 8 Weeks | 
| Mean Change From Baseline in Facial Depigmentation in the AOI (Area of Interest) Based on Canfield 2-D Photographic Analysis From Baseline Compared to Week 12 | Mean change from baseline in facial depigmentation in quantified Area of Interest (AOI) using Canfield-2-D photographic image analysis from baseline (Visit 2) compared to Week 12. Facial depigmentation is measured on a scale of 0 to 100, with a score of 0 meaning no depigmentation and a score of 100 meaning total depigmentation. Lower scores represent better outcomes. | Baseline to 12 Weeks | 
| Mean Change From Baseline in Facial Depigmentation in the AOI (Area of Interest) Based on Canfield 2-D Photographic Analysis From Baseline Compared to Week 16 | Mean change from baseline in facial depigmentation in quantified Area of Interest (AOI) using Canfield-2-D photographic image analysis from baseline (Visit 2) compared to Week 4. Facial depigmentation is measured on a scale of 0 to 100, with a score of 0 meaning no depigmentation and a score of 100 meaning total depigmentation. Lower scores represent better outcomes. | Baseline to 16 Weeks | 
| Mean Change From Baseline in Facial Depigmentation in the AOI (Area of Interest) Based on Canfield 2-D Photographic Analysis From Visit 2 Compared to Week 20 | Mean change from baseline in facial depigmentation in quantified Area of Interest (AOI) using Canfield-2-D photographic image analysis from baseline (Visit 2) compared to Week 20. Facial depigmentation is measured on a scale of 0 to 100, with a score of 0 meaning no depigmentation and a score of 100 meaning total depigmentation. Lower scores represent better outcomes. | Baseline to 20 Weeks | 
| Mean Change From Baseline in Facial Depigmentation in the AOI (Area of Interest) Based on Canfield 2-D Photographic Analysis From Baseline Compared to Week 32 | Mean change from baseline in facial depigmentation in quantified Area of Interest (AOI) using Canfield-2-D photographic image analysis from baseline (Visit 2) compared to Week 4. Facial depigmentation is measured on a scale of 0 to 100, with a score of 0 meaning no depigmentation and a score of 100 meaning total depigmentation. Lower scores represent better outcomes. | Baseline to 32 Weeks | 
| Mean Change From Baseline in Facial Depigmentation in the AOI (Area of Interest) Based on Canfield 2-D Photographic Analysis From Baseline Compared to Week 40 | Mean change from baseline in facial depigmentation in quantified Area of Interest (AOI) using Canfield-2-D photographic image analysis from baseline (Visit 2) compared to Week 40. Facial depigmentation is measured on a scale of 0 to 100, with a score of 0 meaning no depigmentation and a score of 100 meaning total depigmentation. Lower scores represent better outcomes. | Baseline to 40 Weeks | 
| Mean Change From Baseline in Facial Depigmentation in the AOI (Area of Interest) Based on Canfield 2-D Photographic Analysis From Baseline Compared to Post-treatment Week 52 | Mean change from baseline in facial depigmentation in quantified Area of Interest (AOI) using Canfield-2-D photographic image analysis from baseline (Visit 2) compared to Week 52. Facial depigmentation is measured on a scale of 0 to 100, with a score of 0 meaning no depigmentation and a score of 100 meaning total depigmentation. Lower scores represent better outcomes. | Baseline to 52 Weeks | 
| Mean Change From Baseline in the Facial Assessment of the Vitiligo Area Scoring Index (F-VASI) Compared to Week 4 | The Facial Vitiligo Area Scoring Index (F-VASI) is an assessment of the subject's facial vitiligo modified from the Vitiligo Area Scoring Index for the face only at week 4. F-VASI is measured on a scale of 0 to 100, with a score of 0 meaning no depigmentation and a score of 100 meaning total depigmentation. Lower scores represent better outcomes. | Baseline to 4 Weeks | 
| Mean Change From Baseline in the Facial Assessment of the Vitiligo Area Scoring Index (F-VASI) Compared to Week 8 | The Facial Vitiligo Area Scoring Index (F-VASI) is an assessment of the subject's facial vitiligo modified from the Vitiligo Area Scoring Index for the face only at Week 8. F-VASI is measured on a scale of 0 to 100, with a score of 0 meaning no depigmentation and a score of 100 meaning total depigmentation. Lower scores represent better outcomes. | Baseline to 8 Weeks | 
| Mean Change From Baseline in the Facial Assessment of the Vitiligo Area Scoring Index (F-VASI) Compared to Week 12 | The Facial Vitiligo Area Scoring Index (F-VASI) is an assessment of the subject's facial vitiligo modified from the Vitiligo Area Scoring Index for the face only at week 12. F-VASI is measured on a scale of 0 to 100, with a score of 0 meaning no depigmentation and a score of 100 meaning total depigmentation. Lower scores represent better outcomes. | Baseline to 12 Weeks | 
| Mean Change From Baseline in the Facial Assessment of the Vitiligo Area Scoring Index (F-VASI) Compared to Week 16 | The Facial Vitiligo Area Scoring Index (F-VASI) is an assessment of the subject's facial vitiligo modified from the Vitiligo Area Scoring Index for the face only at week 16. F-VASI is measured on a scale of 0 to 100, with a score of 0 meaning no depigmentation and a score of 100 meaning total depigmentation. Lower scores represent better outcomes. | Week 16 | 
| Mean Change From Baseline in the Facial Assessment of the Vitiligo Area Scoring Index (F-VASI) Compared to Week 20 | The Facial Vitiligo Area Scoring Index (F-VASI) is an assessment of the subject's facial vitiligo modified from the Vitiligo Area Scoring Index for the face only at week 20. F-VASI is measured on a scale of 0 to 100, with a score of 0 meaning no depigmentation and a score of 100 meaning total depigmentation. Lower scores represent better outcomes. | Baseline to 20 Weeks | 
| Mean Change From Baseline in the Facial Assessment of the Vitiligo Area Scoring Index (F-VASI) Compared to Week 24 | The Facial Vitiligo Area Scoring Index (F-VASI) is an assessment of the subject's facial vitiligo modified from the Vitiligo Area Scoring Index for the face only at week 24. F-VASI is measured on a scale of 0 to 100, with a score of 0 meaning no depigmentation and a score of 100 meaning total depigmentation. Lower scores represent better outcomes. | Baseline to 24 Weeks | 
| Mean Change From Baseline in the Facial Assessment of the Vitiligo Area Scoring Index (F-VASI) Compared to Week 32 | The Facial Vitiligo Area Scoring Index (F-VASI) is an assessment of the subject's facial vitiligo modified from the Vitiligo Area Scoring Index for the face only at week 32. F-VASI is measured on a scale of 0 to 100, with a score of 0 meaning no depigmentation and a score of 100 meaning total depigmentation. Lower scores represent better outcomes. | Baseline to 32 Weeks | 
| Mean Change From Baseline in the Facial Assessment of the Vitiligo Area Scoring Index (F-VASI) Compared to Week 40 | The Facial Vitiligo Area Scoring Index (F-VASI) is an assessment of the subject's facial vitiligo modified from the Vitiligo Area Scoring Index for the face only at week 40. F-VASI is measured on a scale of 0 to 100, with a score of 0 meaning no depigmentation and a score of 100 meaning total depigmentation. Lower scores represent better outcomes. | Baseline to 40 Weeks | 
| Mean Change From Baseline in the Facial Assessment of the Vitiligo Area Scoring Index (F-VASI) Compared to Week 48 | The Facial Vitiligo Area Scoring Index (F-VASI) is an assessment of the subject's facial vitiligo modified from the Vitiligo Area Scoring Index for the face only at week 48. F-VASI is measured on a scale of 0 to 100, with a score of 0 meaning no depigmentation and a score of 100 meaning total depigmentation. Lower scores represent better outcomes. | Baseline to 48 Weeks | 
| Mean Change From Baseline in the Facial Assessment of the Vitiligo Area Scoring Index (F-VASI) Compared to Post-treatment Week 52 | The Facial Vitiligo Area Scoring Index (F-VASI) is an assessment of the subject's facial vitiligo modified from the Vitiligo Area Scoring Index for the face only at week 52. F-VASI is measured on a scale of 0 to 100, with a score of 0 meaning no depigmentation and a score of 100 meaning total depigmentation. Lower scores represent better outcomes. | Baseline to 52 Weeks | 
| Treatment Success Based on the Subject's Assessment of Vitiligo on the Vitiligo Noticeability Scale (VNS) at Week 4 | The Vitiligo Noticeability Scale (VNS) represents the subject's assessment of the noticeability of facial vitiligo during the study treatment period by means of answering the question, Compared to before treatment, how noticeable is the vitiligo now? Subject response options include, 1: More Noticeable, 2: As Noticeable, 3: Slightly Less Noticeable, 4: A Lot Less Noticeable, and 5: No Longer Noticeable. Treatment success will be defined as follows: VNS score of 1 or 2 = treatment not successful, VNS score of 3 = treatment partially successful, or VNS score of 4 or 5 = treatment successful. Higher scores represent better outcomes. | Baseline to 4 Weeks | 
| Treatment Success Based on the Subject's Assessment of Vitiligo on the Vitiligo Noticeability Scale (VNS) at Week 8 | The Vitiligo Noticeability Scale (VNS) represents the subject's assessment of the noticeability of facial vitiligo during the study treatment period by means of answering the question, Compared to before treatment, how noticeable is the vitiligo now? Subject response options include, 1: More Noticeable, 2: As Noticeable, 3: Slightly Less Noticeable, 4: A Lot Less Noticeable, and 5: No Longer Noticeable. Treatment success will be defined as follows: VNS score of 1 or 2 = treatment not successful, VNS score of 3 = treatment partially successful, or VNS score of 4 or 5 = treatment successful. Higher scores represent better outcomes. | Baseline to 8 Weeks | 
| Treatment Success Based on the Subject's Assessment of Vitiligo on the Vitiligo Noticeability Scale (VNS) at Week 12 | The Vitiligo Noticeability Scale (VNS) represents the subject's assessment of the noticeability of facial vitiligo during the study treatment period by means of answering the question, Compared to before treatment, how noticeable is the vitiligo now? Subject response options include, 1: More Noticeable, 2: As Noticeable, 3: Slightly Less Noticeable, 4: A Lot Less Noticeable, and 5: No Longer Noticeable. Treatment success will be defined as follows: VNS score of 1 or 2 = treatment not successful, VNS score of 3 = treatment partially successful, or VNS score of 4 or 5 = treatment successful. Higher scores represent better outcomes. | Baseline to 12 Weeks | 
| Treatment Success Based on the Subject's Assessment of Vitiligo on the Vitiligo Noticeability Scale (VNS) at Week 16 | The Vitiligo Noticeability Scale (VNS) represents the subject's assessment of the noticeability of facial vitiligo during the study treatment period by means of answering the question, Compared to before treatment, how noticeable is the vitiligo now? Subject response options include, 1: More Noticeable, 2: As Noticeable, 3: Slightly Less Noticeable, 4: A Lot Less Noticeable, and 5: No Longer Noticeable. Treatment success will be defined as follows: VNS score of 1 or 2 = treatment not successful, VNS score of 3 = treatment partially successful, or VNS score of 4 or 5 = treatment successful. Higher scores represent better outcomes. | Baseline to 16 Weeks | 
| Treatment Success Based on the Subject's Assessment of Vitiligo on the Vitiligo Noticeability Scale (VNS) at Week 20 | The Vitiligo Noticeability Scale (VNS) represents the subject's assessment of the noticeability of facial vitiligo during the study treatment period by means of answering the question, Compared to before treatment, how noticeable is the vitiligo now? Subject response options include, 1: More Noticeable, 2: As Noticeable, 3: Slightly Less Noticeable, 4: A Lot Less Noticeable, and 5: No Longer Noticeable. Treatment success will be defined as follows: VNS score of 1 or 2 = treatment not successful, VNS score of 3 = treatment partially successful, or VNS score of 4 or 5 = treatment successful. Higher scores represent better outcomes. | Baseline to 20 Weeks | 
| Treatment Success Based on the Subject's Assessment of Vitiligo on the Vitiligo Noticeability Scale (VNS) at Week 24 | The Vitiligo Noticeability Scale (VNS) represents the subject's assessment of the noticeability of facial vitiligo during the study treatment period by means of answering the question, Compared to before treatment, how noticeable is the vitiligo now? Subject response options include, 1: More Noticeable, 2: As Noticeable, 3: Slightly Less Noticeable, 4: A Lot Less Noticeable, and 5: No Longer Noticeable. Treatment success will be defined as follows: VNS score of 1 or 2 = treatment not successful, VNS score of 3 = treatment partially successful, or VNS score of 4 or 5 = treatment successful. Higher scores represent better outcomes. | Baseline to 24 Weeks | 
| Treatment Success Based on the Subject's Assessment of Vitiligo on the Vitiligo Noticeability Scale (VNS) at Week 32 | The Vitiligo Noticeability Scale (VNS) represents the subject's assessment of the noticeability of facial vitiligo during the study treatment period by means of answering the question, Compared to before treatment, how noticeable is the vitiligo now? Subject response options include, 1: More Noticeable, 2: As Noticeable, 3: Slightly Less Noticeable, 4: A Lot Less Noticeable, and 5: No Longer Noticeable. Treatment success will be defined as follows: VNS score of 1 or 2 = treatment not successful, VNS score of 3 = treatment partially successful, or VNS score of 4 or 5 = treatment successful. Higher scores represent better outcomes. | Baseline to 32 Weeks | 
| Treatment Success Based on the Subject's Assessment of Vitiligo on the Vitiligo Noticeability Scale (VNS) at Week 40 | The Vitiligo Noticeability Scale (VNS) represents the subject's assessment of the noticeability of facial vitiligo during the study treatment period by means of answering the question, Compared to before treatment, how noticeable is the vitiligo now? Subject response options include, 1: More Noticeable, 2: As Noticeable, 3: Slightly Less Noticeable, 4: A Lot Less Noticeable, and 5: No Longer Noticeable. Treatment success will be defined as follows: VNS score of 1 or 2 = treatment not successful, VNS score of 3 = treatment partially successful, or VNS score of 4 or 5 = treatment successful. Higher scores represent better outcomes. | Baseline to 40 Weeks | 
| Treatment Success Based on the Subject's Assessment of Vitiligo on the Vitiligo Noticeability Scale (VNS) at Week 48 | The Vitiligo Noticeability Scale (VNS) represents the subject's assessment of the noticeability of facial vitiligo during the study treatment period by means of answering the question, Compared to before treatment, how noticeable is the vitiligo now? Subject response options include, 1: More Noticeable, 2: As Noticeable, 3: Slightly Less Noticeable, 4: A Lot Less Noticeable, and 5: No Longer Noticeable. Treatment success will be defined as follows: VNS score of 1 or 2 = treatment not successful, VNS score of 3 = treatment partially successful, or VNS score of 4 or 5 = treatment successful. Higher scores represent better outcomes. | Baseline to 48 Weeks | 
| Mean Change From Baseline in Total VASI at Week 24 | The Vitiligo Area Scoring Index (VASI) is an assessment of the subject's Vitiligo Area Scoring Index. VASI is measured on a scale of 0 to 100, with a score of 0 meaning no depigmentation and a score of 100 meaning total depigmentation. Lower scores represent better outcomes. | Baseline to 24 Weeks | 
| Mean Change From Baseline in Total VASI at Week 48 | The Vitiligo Area Scoring Index (VASI) is an assessment of the subject's Vitiligo Area Scoring Index. VASI is measured on a scale of 0 to 100, with a score of 0 meaning no depigmentation and a score of 100 meaning total depigmentation. Lower scores represent better outcomes. | Baseline to 48 Weeks |