“A phase 2 multi-center study investigating the efficacy, safety and tolerability of pioglitazone in adult participants with non-segmental vitiligo”

Trial ID: 2025-523266-24-00
Protocol: 2025-523266-24-00
Sponsor: I.F.O. Istituti Fisioterapici Ospitalieri

Trial statistics

science

test molecule

location_city

research sites

public

country

medical_information

disease

person_search

investigators

Diseases & Conditions

Vitiligo

Objectives

The primary objective of this phase 2 multicenter study is to evaluate the efficacy, safety, and tolerability of pioglitazone, a selective peroxisome proliferator-activated receptor gamma (PPARγ) activator from the thiazolidinedione class, when administered concurrently with phototherapy for the treatment of non-segmental vitiligo in adult participants. This investigation addresses the clinical need for therapeutic interventions targeting the pathophysiological mechanisms underlying vitiligo through PPARγ activation, which may influence melanocyte function and autoimmune processes characteristic of this depigmentation disorder.

Participants

The sponsor did not provide information regarding the total number of participants enrolled in this clinical trial. The study population consisted of adults aged between **18 and 65 years** of **all genders**, both male and female participants were eligible for enrollment. Participants were required to have a clinical diagnosis of **non-segmental vitiligo** with **depigmented areas** and specific involvement criteria including facial involvement with a body surface area of at least 0.3%. The trial population was selected based on disease severity measures, including a **Total Vitiligo Scoring Index** of at least 3 and a **Facial Vitiligo Area Scoring Index** of at least 0.3 at both screening and baseline. Eligible participants had previously experienced treatment failure with at least one first-line therapy such as **topical corticosteroids** or **calcineurin inhibitors**. Female participants of childbearing potential were required to use highly effective contraception methods throughout the study duration and for at least 30 days following the last dose of study medication, with negative pregnancy test results confirmed at regular intervals. The trial excluded vulnerable populations.

Plans and Procedures

This is a **phase 4**, **multi-center clinical trial** evaluating the efficacy, safety, and tolerability of **pioglitazone** in adult participants with **non-segmental vitiligo**. The study employs a therapeutic strategy where the assignment of subjects to treatment is decided in advance and does not fall within the normal clinical practice. The investigational medicinal product is **Pioglitazone Mylan 15 mg tablets**, administered via **oral use** as a selective **PPARγ activator** from the **thiazolidinediones** class. The active substance is **pioglitazone**, which is of chemical origin. The maximum daily dose is 15 mg, with a maximum total dose of 960 mg over the treatment period. The treatment duration is 16 weeks, during which pioglitazone will be used simultaneously with **phototherapy**.

The primary objective is to assess the use of a PPARγ selective activator for the treatment of vitiligo, specifically non-segmental vitiligo, when combined with phototherapy. The **primary endpoint** is the proportion of subjects achieving **F-VASI50**, defined as at least 50% improvement in **Facial Vitiligo Area Scoring Index** from baseline at Week 16. The trial is designed to evaluate participants with a clinical diagnosis of non-segmental vitiligo who have **depigmented areas** and previous failure of at least one first-line treatment such as **topical corticosteroids** or **calcineurin inhibitors**.

The study involves a sequence of visits beginning with a **screening visit** where eligibility is assessed. Key inclusion criteria require adults between 18 and 65 years of all genders with face involvement **Body Surface Area** ≥0.3%, **Total Vitiligo Scoring Index** (T-VASI) ≥3, and F-VASI ≥0.3 at both screening and baseline. Participants must provide signed informed consent and agree to discontinue all other vitiligo treatments from screening until the final follow-up visit according to specified washout periods. Female subjects of childbearing potential must use highly effective contraception throughout the study and for at least 30 days after the last dose, with negative pregnancy tests required at visit 1 and every 4 weeks during the study. Female subjects of non-childbearing potential must meet criteria including postmenopausal status confirmed by cessation of menses for at least 12 consecutive months or documented **hysterectomy** and/or bilateral **oophorectomy**.

The estimated recruitment start date is December 9, 2025, with an estimated end date of March 31, 2027. The expected length of participant involvement is 16 weeks of active treatment. Conditions that may lead to early termination from the study include failure to meet eligibility criteria, withdrawal of consent, pregnancy during the study period, or other safety concerns as determined by the investigator. All participants must agree to discontinue other vitiligo treatments during their involvement in accordance with protocol-specified washout requirements.

Treatment

The experimental medication utilized in this clinical trial is **pioglitazone**, marketed as Pioglitazone Mylan 15 mg compresse. Pioglitazone is a **thiazolidinedione** (TZD) that functions as a selective **PPARγ activator**. The **active substance** is pioglitazone of chemical origin. The investigational medicinal product is supplied in **tablet** form for **oral administration**. The dosage strength is **15 mg** per tablet. The maximum daily dose administered is **15 mg**, with a maximum total dose of **960 mg** over the course of treatment. The maximum treatment period is **16 weeks**. The experimental medication is administered simultaneously with **phototherapy treatment** as part of the therapeutic regimen for **non-segmental vitiligo** in adult participants. The product is manufactured by MYLAN S.P.A. and is authorized for use in this investigation. Participant compliance monitoring throughout the treatment period will be conducted to ensure adherence to the prescribed dosing schedule and administration protocol.

Efficacy

Efficacy will be assessed using the Facial Vitiligo Area Scoring Index (F-VASI) as the primary parameter. The primary endpoint is defined as the proportion of subjects achieving F-VASI50, which represents at least 50% improvement in F-VASI from baseline, evaluated at Week 16. At screening and baseline, subjects must have a F-VASI of at least 0.3 and a Total Vitiligo Scoring Index (T-VASI) of at least 3 to be eligible for enrollment. The body surface area (BSA) involvement of the face must be at least 0.3% at screening and baseline, with the face assessment excluding the scalp, ears, neck, and surface area of the lips, but including the nose and eyelids. The treatment period for efficacy assessment is 16 weeks.

Inclusion and Exclusion Criteria

check_circle

Inclusion Criteria

Subjects must meet all the following inclusion criteria at both screening and baseline to be eligible for enrollment into the study: i) Adults between 18 years and 65 years of all genders; ii) Has a clinical diagnosis of non-segmental vitiligo with depigmented areas; iii) Has a face involvement BSA ≥0.3% at screening and baseline. The face will not include the scalp, ears, neck, or surface area of the lips but will include the nose and the eyelids; iv) Has a Total Vitiligo Scoring Index (T-VASI) ≥3 at screening and baseline; v) Has a Facial Vitiligo Area Scoring Index (F-VASI) ≥0.3 at screening and baseline. vi) Previous failure of at least one first-line treatment (e.g. topical corticosteroids or calcineurin inhibitors). vii) Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study; viii) Agree to discontinue all other vitiligo treatments from screening until the final follow-up visit in accordance with the washout times reported below in Table 2. ix) Female subjects of childbearing potential (WOCBP) and at risk for pregnancy must agree to use a highly effective method of contraception (confirmed by the investigator) throughout the study and for at least 30 days after the last PGZ dose of assigned treatment and have a negative pregnancy test result on visit 1 and each 4 weeks during the entire study; x) Female subjects of non-childbearing potential must meet at least 1 of the following criteria: • Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed with a serum follicle-stimulating hormone (FSH) level confirming the postmenopausal state; • Have undergone a documented hysterectomy and/or bilateral oophorectomy; • Have medically confirmed ovarian failure. • All other female subjects (including female subjects with tubal ligations) are considered childbearing potential.

cancel

Exclusion Criteria

i. Unable to consent (adults lacking capacity); ii. Participants that have a diagnosis of other types of vitiligo including segmental and mixed vitiligo; iii. Has ≥50% leukotrichia on face or body; iv. Unable to return for follow-up visits; v. Pregnant women and/or breastfeeding, or those who have recently delivered a baby within the past 6 months; vi. Has any other dermatological diseases that would interfere with vitiligo assessments; vii. History of type I or II diabetes viii. Has a transplanted organ, which requires continued immunosuppression; ix. Has a history of any oncological malignancy; x. Familiar atypical multiple mole and melanoma (FAMMM) syndrome; xi. Systemic lupus erythematosus; xii. Dermatomyositis; xiii. Genetic conditions that predispose an individual to skin cancer (Gorlin syndrome, xeroderma pigmentosum); xiv. Bloom syndrome or Cockayne syndrome; xv. Has had major surgery within 3 months before Screening OR has a major surgery planned during the study; xvi. Has hypersensitivity to the active substance or to any of the excipients; xvii. Has cardiac failure or history of cardiac failure (NYHA stages I to IV); xviii. Has current bladder cancer or a history of bladder cancer xix. Has uninvestigated macroscopic haematuria. xx. Any evidence of fluid overload xxi. Prior/Concurrent investigational clinical study experience; xxii. Enrolled in a clinical study of any other investigational drug or device; xxiii. Liver disease, or kidney disease; xxiv. Hypoglycemia as defined by fasting blood glucose <70 mg/dL assessed at a fasting study visit; xxv. ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study-specific laboratory and confirmed by a single repeat, if deemed necessary: xxvi. Absolute neutrophil count of <2.5 x 109/L (<2500/mm3); xxvii. Hemoglobin <10.0 g/dL or hematocrit <30%; xxviii. Platelet count below the lower limit of normal (LLN) at Screening; xxix. Absolute lymphocyte count of <0.8 x 109 /L (<800/mm3); xxx. Serum creatinine > upper limit of normal (ULN) or eGFR <60 ml/min/1.73m2 based on the age-appropriate calculation. xxxi. Enzymes aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values >2 times the ULN; xxxii. Total bilirubin 1.5 times the ULN; subjects with a history of Gilbert's syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin is ULN; xxxiii. Creatine kinase (CK) >3 times the ULN and positive urine myoglobin; xxxiv. In the opinion of the investigator, have any uncontrolled clinically significant laboratory abnormality that would affect interpretation of study data or the subject’s participation in the study. xxxv. Patients who, in the opinion of the investigator, are unable or unlikely to comply with the administration schedule and study evaluation.