Efficacy and Safety Study of Apremilast to Treat Active Ulcerative Colitis

Phase 2

Completed

Conditions: Ulcerative Colitis

Interventions: Drug: Apremilast
Drug: Placebo

Registration Number: NCT02289417

Lead Sponsor: Amgen

Brief Summary: The purpose of the study is to evaluate the clinical efficacy, safety and tolerability of apremilast (30 mg twice daily \[BID\] and 40 mg BID), compared with placebo, in participants with active Ulcerative Colitis (UC).

Detailed Description: Approximately 165 participants (55 subjects per arm) will be randomized in a 1:1:1 ratio to receive oral apremilast (30 mg BID or 40 mg BID), or identically appearing placebo BID for up to 12 weeks, followed by 40 weeks of blinded treatment with apremilast (30 mg BID or 40 mg BID).

At the end of the Blinded Active-treatment Phase (Week 52), participants who have a Mayo endoscopy score ≤ 1 will have the opportunity to participate in the Extension Phase. Participants enrolled in the Extension Phase will receive apremilast for an additional 52 weeks (Weeks 52 to 104). With the implementation of Amendment 4, participants entering the Extension Phase will receive apremilast 30 mg BID. Subjects currently in the Extension Phase who are receiving apremilast 40 mg BID will be switched to 30 mg BID at the next scheduled visit.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 170

Inclusion Criteria

Subjects must satisfy the following criteria to be enrolled in the study:

Male or female aged 18 and over at the time of signing the informed consent.
Must understand and voluntarily sign an informed consent form prior to any study related assessments/procedures being conducted.
Diagnosis of ulcerative colitis (UC) with a duration of at least 3 months prior to the Screening Visit..
Total Mayo Score (TMS) ≥ 6 to ≤ 11 (range: 0-12) at baseline, prior to randomization in the study.
Endoscopic subscore ≥ 2 (range: 0-3) on the Mayo score prior to randomization in the study.
Subjects must have had a therapeutic failure, been intolerant to, or have a contraindication to, at least one of the following: oral aminosalicylates (ie, 5-aminosalicylic acid [5-ASA] compounds or sulfasalazine [SSZ]), budesonide, systemic corticosteroids, or immunosuppressants (eg, 6-mercaptopurine [6-MP], azathioprine [AZA], or methotrexate [MTX]).

Exclusion Criteria

The presence of any of the following will exclude a subject from enrollment:

Diagnosis of Crohn's disease, indeterminate colitis, ischemic colitis, microscopic colitis, radiation colitis or diverticular disease-associated colitis.
Ulcerative colitis restricted to the distal 15 cm or less (eg, ulcerative proctitis).
Subjects who have had surgery as a treatment for UC or who, in the opinion of the Investigator, are likely to require surgery for UC during the study.
Clinical signs suggestive of fulminant colitis or toxic megacolon.
Prior use of any tumor necrosing factor (TNF) inhibitor (or any biologic agent).
Prior use of mycophenolic acid, tacrolimus, sirolimus, cyclosporine or thalidomide.
Use of intravenous (IV) corticosteroids within 2 weeks of the Screening Visit.
Use of immunosuppressants (AZA, 6-MP or MTX) within 8 weeks of the Screening Visit.
Use of topical treatment with 5-ASA or corticosteroid enemas or suppositories within 2 weeks of the Screening Visit.
History of any clinically significant neurological, renal, hepatic, gastrointestinal, pulmonary, metabolic, cardiovascular, psychiatric, endocrine, hematological disorder or disease, or any other medical condition that, in the investigator's opinion, would preclude participation in the study.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Apremilast 40 mg PO BID	Apremilast	Apremilast 40 mg by mouth (PO) twice a day (BID) for 12 weeks After 12 weeks, participants assigned to the 40 mg BID dose of apremilast at baseline will continue to receive apremilast 40 mg BID for an additional 40 weeks (Wk 52) After 52 weeks, participants who are eligible for the extension Phase will continue to receive apremilast 40 mg BID for an additional 52 weeks (Wk 104)
Placebo BID	Placebo	Identically matching placebo by mouth (PO) twice a day (BID) for 12 weeks. After 12 weeks all participants randomized to placebo at baseline will be re-randomized to receive apremilast 30 mg or 40 mg BID for an additional 40 weeks (Wk 52) After Wk 52, participants who are eligible for the extension phase will continue to receive the same dose of apremilast assigned at Wk 12 (30 mg BID or 40 mg BID) for an additional 52 weeks (Wk 104)
Apremilast 30 mg PO BID	Apremilast	Apremilast 30 mg by mouth (PO) twice a day (BID) for 12 weeks After 12 weeks: * Participants who achieve at least a 20% decrease from baseline in the total Mayo score (TMS) will continue to receive apremilast 30 mg BID for an additional 40 weeks. (Wk 52) * Participants who do not achieve at least a 20% decrease from baseline in the TMS will receive apremilast 40 mg BID for an additional 40 weeks (Wk 52) After 52 weeks, participants who are eligible for the Extension Phase will continue to receive the same dose of apremilast assigned at Wk 12 (30 mg BID or 40 mg BID) for an additional 52 weeks (Wk 104)
Placebo BID	Apremilast	Identically matching placebo by mouth (PO) twice a day (BID) for 12 weeks. After 12 weeks all participants randomized to placebo at baseline will be re-randomized to receive apremilast 30 mg or 40 mg BID for an additional 40 weeks (Wk 52) After Wk 52, participants who are eligible for the extension phase will continue to receive the same dose of apremilast assigned at Wk 12 (30 mg BID or 40 mg BID) for an additional 52 weeks (Wk 104)

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved a Clinical Remission by Total Mayo Score (TMS) at Week 12	Week 12	Clinical remission was defined as a total Mayo score ≤ 2 points, with no individual subscore exceeding 1 point. The TMS is an instrument designed to measure disease activity of UC. The Mayo score ranges from 0 to 12 points. It consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease. * Stool Frequency Subscore (SFS) * Rectal Bleeding Subscore (RBS) * Endoscopy Subscore * Physician's Global Assessment (PGA). Two-sided 95% confidence intervals (CI) for the within-group percentages are based on the Wilson score method.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved a Clinical Response by Total Mayo Score and the Reduction in the Rectal Bleeding Subscore at Week 12	Week 12	Clinical response was defined as a decrease from baseline in the TMS of at least 3 points and at least 30%, along with a reduction in the rectal bleeding subscore (RBS) of at least 1 point or an absolute RBS of ≤ 1. The TMS is an instrument designed to measure disease activity of UC. The Mayo score ranges from 0 to 12 points. It consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease. * Stool Frequency Subscore (SFS) * Rectal Bleeding Subscore * Endoscopy Subscore * Physician's Global Assessment (PGA) Rectal bleeding (subscore 0-3) was defined as: 0 = No blood seen 1. = Streaks of blood with stool less than half the time 2. = Obvious blood with stool 3. = Blood alone passes Two-sided 95% CI for the within-group percentages are based on the Wilson score method.
Percentage of Participants Who Achieved an Endoscopic Remission at Week 12	Week 12	An endoscopic remission was defined as a Mayo endoscopic subscore (MES) of 0 at Week 12. The MES subscore findings were defined as: 0 = Normal or inactive disease 1. = Mild Disease (erythema, decreased vascular pattern, mild friability) 2. = Moderate Disease (marked erythema, lack of vascular pattern, friability erosions) 3. = Severe Disease (spontaneous bleeding, ulceration) The endoscopy subscores consisted of findings that were centrally read through proctosigmoidoscopy, graded from 0 to 3 with higher scores indicating more severe disease. Two-sided 95% CIs for the within-group percentage were based on the Wilson score method.
Percentage of Participants Who Achieved an Endoscopic Response at Week 12	Week 12	An endoscopic response is defined as a decrease from baseline of at least 1 point in the MES at Week 12. The Mayo endoscopy subscore findings were defined as: 0 = Normal or inactive disease 1. = Mild Disease (erythema, decreased vascular pattern, mild friability) 2. = Moderate Disease (marked erythema, lack of vascular pattern, friability erosions) 3 = Severe Disease (spontaneous bleeding, ulceration). The endoscopy subscores consisted of findings that were centrally read through proctosigmoidoscopy, graded from 0 to 3 with higher scores indicating more severe disease. Two-sided 95% CIs for the within-group percentage were based on the Wilson score method.
Percentage of Participants Who Achieved Clinical Remission in the Modified Mayo Subscore (MMS) at Week 12	Week 12	Clinical remission was defined as a modified Mayo score of ≤ 2, with no individual subscore \> 1, at Week 12. The MMS was based on a modification of the total Mayo score (TMS) which included the stool frequency, rectal bleeding, and endoscopic subscores of the TMS and excluded the Physician's Global Assessment (PGA) subscore, since this was a global measure that is subjective in nature. The MMS ranges from 0 to 9 points with higher scores indicating greater disease severity. The endoscopy subscores was centrally reviewed. Two-sided confidence intervals for the within-group percentage were based on the Wilson score method.
Percentage of Participants Who Achieved a Rectal Bleeding Subscore (RBS) of ≤ 1 at Week 12	Week 12	The RBS was measured as: 0 = No blood seen 1. = Streaks of blood with stool less than half the time 2. = Obvious blood with stool most of the time 3. = Blood alone passes The daily bleeding score represents the most severe bleeding of the day. Two-sided 95% CI for the within-group proportions are based on the Wilson score method.
Percentage of Participants Who Achieved Clinical Response in the Partial Mayo Subscore at Week 8	Week 8	Clinical response in the PMS was defined as a decrease from baseline in PMS of at least 2 points and at least 25%, with an accompanying decrease in the RBS of at least 1 point or an absolute RBS of 0 or 1. The PMS score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease). Two-sided 95% CI for the within-group proportions are based on the Wilson score method.
The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase	From the first dose of investigational product (IP) and no later than 28 days after the last dose of IP for those who had completed the study or discontinued (D/C) early; maximum duration of exposure to treatment was 12.00 weeks	A TEAE was defined as any adverse event (AE) occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain
The Number of Participants Who Discontinued Apremilast Due to Treatment Emergent Adverse Events During the Placebo-Controlled Period	From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early; median duration of exposure to treatment was 12.00 weeks	A TEAE was defined as any AE occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain.
Percentage of Participants Who Achieved Clinical Response in the Modified Mayo Subscore (MMS) at Week 12	Week 12	Clinical response in the MMS was defined as a decrease from baseline in the MMS of at least 2 points and at least 25%, along with a reduction in the RBS of at least 1 point or an absolute RBS ≤ 1. The MMS was based on the stool frequency, rectal bleeding, and endoscopic subscores of the TMS and excluded the PGA subscore. The MMS ranges from 0 to 9 points with higher scores indicating greater disease severity. The RBS was measured as: 0 = No blood seen 1. = Streaks of blood with stool less than half the time 2. = Obvious blood with stool most of the time 3. = Blood alone passes The daily bleeding score represents the most severe bleeding of the day. The endoscopy subscores was centrally reviewed. Two-sided confidence intervals for the within-group percentage were based on the Wilson score method.
Percentage of Participants Who Achieved Clinical Remission in the Partial Mayo Subscore (PMS) With no Individual Subscore >1 at Week 8	Week 8	Clinical remission in the partial Mayo subscore was defined as a PMS of 2 points or lower, with no individual subscore \>1. The PMS is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease). Two-sided 95% CI for the within-group proportions are based on the Wilson score method.
The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52	From first dose of IP and no later than 28 days after last dose of IP for those who completed the active treatment phase or D/C early; median duration of exposure = 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms	A TEAE was defined as any AE occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain
The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase)	From the first dose of IP at Week 52 and no later than 28 days after the last dose of IP for those who completed the study or had discontinued early; median exposure of apremilast for the total apremilast group was 52 weeks.	A TEAE was defined as any AE occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain

Trial Locations

Locations (99): Southern California Research Institute Medical Group, Inc.
🇺🇸
Los Angeles, California, United States
NYU Langone Long Island Clinical Research Associates
🇺🇸
Great Neck, New York, United States
Precision Clinical Research, LLC
🇺🇸
Lauderdale Lakes, Florida, United States
Gastroenterology Group of Naples
🇺🇸
Naples, Florida, United States
Avail Clinical Research, LLC
🇺🇸
DeLand, Florida, United States
Gastrointestinal Associates PA
🇺🇸
Flowood, Mississippi, United States
Pharmax Research Clinic, Inc.
🇺🇸
Miami, Florida, United States
Harborview Medical Center
🇺🇸
Seattle, Washington, United States
Hopital Beaujon
🇫🇷
Clichy, France
CHRU Nancy
🇫🇷
Vandoeuvre les Nancy, France
Nemocnice Slany
🇨🇿
Slany, Czechia
Winnipeg Regional Health Authority - Health Sciences Centre
🇨🇦
Winnipeg, Manitoba, Canada
University of Washington Medical Center
🇺🇸
Seattle, Washington, United States
Medical Center Asklepion - Humane Medicine Research EOOD
🇧🇬
Sofia, Bulgaria
Complesso Integrato Columbus
🇮🇹
Roma, Italy
Hepato-Gastroenterologie HK, s. r. o.
🇨🇿
Hradec Králové, Czechia
Crohn-Colitis-Centre Rhein-Main
🇩🇪
Frankfurt, Germany
Universitatsklinikum Schleswig-Holstein
🇩🇪
Keil, Germany
Hamilton Health Sciences Corporation, McMaster University Medical Centre
🇨🇦
Hamilton, Ontario, Canada
ENDOMEDIX Kft.
🇭🇺
Budapest, Hungary
Liverpool Hospital
🇦🇺
Liverpool, New South Wales, Australia
Amiens University Hospital
🇫🇷
Amiens, France
Gastroenterologische Praxis Minden
🇩🇪
Minden, Germany
Pannónia Magánorvosi Centrum Kft.
🇭🇺
Budapest, Hungary
Fondazione PTV Policlinico Tor Vergata
🇮🇹
Roma, Italy
Ikazia Ziekenhuis
🇳🇱
Rotterdam, Netherlands
CHRU Nantes
🇫🇷
Nantes, France
Auckland City Hospital
🇳🇿
Auckland, New Zealand
Concord Repatriation General Hospital
🇦🇺
Concord, New South Wales, Australia
University Multiprofile Hospital for Active Treatment Sveti Ivan Rilski EAD
🇧🇬
Sofia, Bulgaria
Javorszky Odon Korhaz
🇭🇺
Vác, Hungary
Municipal Institution Odesa Regional Clinical Hospital
🇺🇦
Odesa, Ukraine
CHU de Nice Archet I
🇫🇷
Nice, France
Christchurch Hospital
🇳🇿
Christchurch, New Zealand
Universitair Medisch Centrum Groningen
🇳🇱
Groningen, Netherlands
IRCCS - Istituo Clinico Humanitas - Humanitas Cancer Center
🇮🇹
Milan, Italy
Dunedin Hospital
🇳🇿
Dunedin, New Zealand
Vinnytsia Regional Clinical Hospital n a M I Pyrohov
🇺🇦
Vinnytsia, Ukraine
University Multiprofile Hospital for Active Treatment ACIBADEM City Clinic Sofia
🇧🇬
Sofia, Bulgaria
Karolina Korhaz Rendelointezet
🇭🇺
Mosonmagyaróvár, Hungary
Tolna Megyei Balassa Janos Korhaz
🇭🇺
Szekszárd, Hungary
Royal Melbourne Hospital
🇦🇺
Parkville, Victoria, Australia
University Multiprofile Hospital for Active Treatment Tsaritsa Yoanna ISUL EAD
🇧🇬
Sofia, Bulgaria
Clinic of Gastroenterology
🇧🇬
Sofia, Bulgaria
Endoskopia Sp. z o.o.
🇵🇱
Sopot, Poland
Footscray Hospital
🇦🇺
Footscray, Victoria, Australia
Multiprofile Hospital for Active Treatment Sveta Marina EAD
🇧🇬
Varna, Bulgaria
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
🇭🇺
Szeged, Hungary
Russian Medical Military Academy na SMKirov
🇷🇺
St Petersburg, Russian Federation
Uniwersytecki Szpital Kliniczny w Bialymstoku
🇵🇱
Bialystok, Poland
Economicus - NZOZ ALL-MEDICUS
🇵🇱
Katowice, Poland
Private Enterprise Private Manufacture Company Acinus
🇺🇦
Kirovograd, Ukraine
Osrodek Badan Klinicznych CLINSANTE S.C.
🇵🇱
Bydgoszcz, Poland
Centrum Medyczne sw. Lukasza
🇵🇱
Czestochowa, Poland
Sonomed Sp. z o.o.
🇵🇱
Szczecin, Poland
Gastromed Kopon Zmudzinski i Wspolnicy Sp. j. Specjalistyczne Centrum Gastrologii i Endoskopii Spec. Gabinety Lekarskie
🇵🇱
Torun, Poland
Centrum Zdrowia Matki, Dziecka i Mlodziezy
🇵🇱
Warsaw, Poland
Republican Clinical Hospital
🇷🇺
Kazan, Russian Federation
Niepubliczny Zaklad Opieki Zdrowotnej VIVAMED
🇵🇱
Warszawa, Poland
Lexmedica Drubajlo Hanna
🇵🇱
Wroclaw, Poland
Ars Medica
🇵🇱
Wroclaw, Poland
SEIHPE Rostov State Medical University of MoH of RF
🇷🇺
Rostov on Don, Russian Federation
Stolitsa-Medikl, LLC
🇷🇺
Moscow, Russian Federation
Ivano-Frankivsk Central City Clinical Hospital
🇺🇦
Ivano-Frankivsk, Ukraine
Kharkiv City Clinical Hospital 2
🇺🇦
Kharkiv, Ukraine
Central City Clinical Hospital
🇺🇦
Uzhgorod, Ukraine
Kremenchuk City Hospital # 1 n.a O.T.Bohaievskyi
🇺🇦
Kremenchuk, Ukraine
Lviv Emergency Clinical Hospital, Therapeutics Department No. 1
🇺🇦
Lviv, Ukraine
Municipal Institution Zaporizhzhia
🇺🇦
Zaporizhzhia, Ukraine
Digestive Health Specialists of The Southeast
🇺🇸
Dothan, Alabama, United States
Consultants for Clinical Research of South Florida
🇺🇸
Boynton Beach, Florida, United States
Connecticut Clinical Research Foundation
🇺🇸
Bristol, Connecticut, United States
University of Iowa Hospitals and Clinics
🇺🇸
Iowa City, Iowa, United States
UMass Medical Center
🇺🇸
Worcester, Massachusetts, United States
Advanced Medical Research Center
🇺🇸
Port Orange, Florida, United States
University of Chicago Medical Center
🇺🇸
Chicago, Illinois, United States
Clinical Research Institute of Michigan, LLC
🇺🇸
Chesterfield, Michigan, United States
Consultants for Clinical Research
🇺🇸
Cincinnati, Ohio, United States
Quality Medical Research
🇺🇸
Nashville, Tennessee, United States
Center for Digestive Health Research
🇺🇸
Troy, Michigan, United States
Digestive Research Center/ Gastroenterology Consultants of San Antonio
🇺🇸
Live Oak, Texas, United States
San Antonio Gastroenterology
🇺🇸
San Antonio, Texas, United States
Digestive Health Specialist of Tyler
🇺🇸
Pasadena, Texas, United States
University of Utah
🇺🇸
Salt Lake City, Utah, United States
Mater Adult Hospital
🇦🇺
South Brisbane, Queensland, Australia
Multiprofile Hospital for Active Treatment Kaspela
🇧🇬
Plovdiv, Bulgaria
Fakultni nemocnice Hradec Kralove
🇨🇿
Hradec Kralove, Czechia
Fakultni nemocnice u sv Anny v Brne
🇨🇿
Brno, Czechia
Centre Hospitalier Lyon Sud
🇫🇷
Pierre Bénite, France
Centre Hospitalier Universitaire de Saint Etienne
🇫🇷
Saint Priest en Jarez, France
Vasútegészségügyi Nonprofit Kiemelten Közhasznú Kft. Debreceni Egészségügyi Központja
🇭🇺
Debrecen, Hungary
DRK Kliniken Berlin Westend
🇩🇪
Berlin, Germany
Azienda Ospedaliero Universitaria Di Bologna Policlinico Sorsola Malpighi
🇮🇹
Bologna, Italy
Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello
🇮🇹
Palermo, Italy
Waikato hospital
🇳🇿
Hamilton, New Zealand
Regional Clinical Hospital
🇷🇺
Saratov, Russian Federation
Regional Clinical Hospital, Gastroenterology department, State Higher Education Institute Ivano-Frankivsk National Medical University
🇺🇦
Ivano-Frankivsk, Ukraine
Ivano-Frankivsk Regional Clinical Hospital
🇺🇦
Ivano-Frankivsk, Ukraine
University of Louisville
🇺🇸
Louisville, Kentucky, United States