섬유증을 동반한 비알코올성 지방간염 치료를 위한 사로글리타자르 마그네슘 (NASH)
비알코올성 지방간염 및 섬유증 환자에서 사로글리타자르 마그네슘의 효능 및 안전성을 평가하기 위한 2b상, 전향적, 다기관, 무작위, 이중맹검, 위약 대조 연구
Saroglitazar Magnesium for the Treatment of Nonalcoholic Steatohepatitis
연구 개요
상태
정황
상세 설명
A Phase 2b, Prospective, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate Efficacy and Safety of Saroglitazar Magnesium in Subjects with Nonalcoholic Steatohepatitis and Fibrosis.
연구 유형
등록 (실제)
단계
- 2 단계
연락처 및 위치
연구 장소
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Alabama
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Birmingham, Alabama, 미국, 35294
- Zydus US032
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Homewood, Alabama, 미국, 35209
- Zydus US079
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Arizona
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Phoenix, Arizona, 미국, 85013
- Zydus US047
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Tucson, Arizona, 미국, 85712
- Zydus US025
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Tucson, Arizona, 미국, 85712
- Zydus US087
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Tucson, Arizona, 미국, 85724
- Zydus US029
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California
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Chula Vista, California, 미국, 91911
- Zydus US118
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Fresno, California, 미국, 93720
- Zydus US041
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Gardena, California, 미국, 90247
- Zydus US111
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Huntington Park, California, 미국, 90255
- Zydus US013
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La Jolla, California, 미국, 92037
- Zydus US065
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Lancaster, California, 미국, 93534
- Zydus US094
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Long Beach, California, 미국, 90808
- Zydus US080
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Long Beach, California, 미국, 90815
- Zydus US090
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Los Angeles, California, 미국, 90027
- Zydus US022
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Los Angeles, California, 미국, 90033
- Zydus US062
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Murrieta, California, 미국, 92563
- Zydus US023
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Orange, California, 미국, 92868
- Zydus US052
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Panorama City, California, 미국, 91402
- Zydus US012
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Colorado
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Aurora, Colorado, 미국, 80045
- Zydus US039
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Florida
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Clearwater, Florida, 미국, 33761
- Zydus US122
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Fort Myers, Florida, 미국, 33907
- Zydus US057
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Hallandale, Florida, 미국, 33009
- Zydus US108
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Hialeah Gardens, Florida, 미국, 33016
- Zydus US096
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Lakeland, Florida, 미국, 33803
- Zydus US003
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Lakewood Rch, Florida, 미국, 34211
- Zydus US016
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Largo, Florida, 미국, 33777
- Zydus US125
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Maitland, Florida, 미국, 32751
- Zydus US001
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Maitland, Florida, 미국, 32751
- Zydus US124
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Miami, Florida, 미국, 33014
- Zydus US007
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Miami, Florida, 미국, 33135
- Zydus US024
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Miami, Florida, 미국, 33136
- Zydus US034
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Miami, Florida, 미국, 33136
- Zydus US038
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Miami, Florida, 미국, 33155
- Zydus US121
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Miami, Florida, 미국, 33173
- Zydus US054
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Miami Lakes, Florida, 미국, 33016
- Zydus US098
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Naples, Florida, 미국, 34102
- Zydus US099
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Ocala, Florida, 미국, 34471
- Zydus US081
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Orlando, Florida, 미국, 32806
- Zydus US085
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Port Orange, Florida, 미국, 32127
- Zydus US104
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Winter Park, Florida, 미국, 32789
- Zydus US004
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Georgia
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Dalton, Georgia, 미국, 30720
- Zydus US107
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Gainesville, Georgia, 미국, 30501
- Zydus US113
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Marietta, Georgia, 미국, 30060
- Zydus US114
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Savannah, Georgia, 미국, 31406
- Zydus US119
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Indiana
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Indianapolis, Indiana, 미국, 46202
- Zydus US020
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Iowa
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West Des Moines, Iowa, 미국, 50652
- Zydus US100
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Kansas
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Kansas City, Kansas, 미국, 66160
- Zydus US049
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Louisiana
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Houma, Louisiana, 미국, 70363
- Zydus US071
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Marrero, Louisiana, 미국, 70072
- Zydus US014
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West Monroe, Louisiana, 미국, 71291
- Zydus US123
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Massachusetts
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Boston, Massachusetts, 미국, 02215
- Zydus US017
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Michigan
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Chesterfield, Michigan, 미국, 48047
- Zydus US092
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Wyoming, Michigan, 미국, 49519
- Zydus US019
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Minnesota
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Saint Paul, Minnesota, 미국, 55101
- Zydus US115
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Missouri
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Columbia, Missouri, 미국, 65201
- Zydus US074
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Kansas City, Missouri, 미국, 64131
- Zydus US120
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Nevada
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Reno, Nevada, 미국, 89511
- Zydus US116
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New Jersey
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Sparta, New Jersey, 미국, 07871
- Zydus US077
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New York
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Manhasset, New York, 미국, 11030
- Zydus US069
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New York, New York, 미국, 10033
- Zydus US066
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North Carolina
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Asheville, North Carolina, 미국, 28801
- Zydus US018
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Charlotte, North Carolina, 미국, 28204
- Zydus US027
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Ohio
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Cincinnati, Ohio, 미국, 45044
- Zydus US010
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Cincinnati, Ohio, 미국, 45267-0595
- Zydus US009
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Cleveland, Ohio, 미국, 44109
- Zydus US035
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Springboro, Ohio, 미국, 45066
- Zydus US072
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Pennsylvania
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Hershey, Pennsylvania, 미국, 17033
- Zydus US060
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Philadelphia, Pennsylvania, 미국, 19141
- Zydus US053
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South Carolina
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Charleston, South Carolina, 미국, 29401
- Zydus US015
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Charleston, South Carolina, 미국, 29425
- Zydus US030
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Columbia, South Carolina, 미국, 29204
- Zydus US073
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Greenwood, South Carolina, 미국, 29646
- Zydus US075
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Summerville, South Carolina, 미국, 29485
- Zydus US112
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Tennessee
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Hermitage, Tennessee, 미국, 37067
- Zydus US011
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Nashville, Tennessee, 미국, 37232
- Zydus US028
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Texas
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Arlington, Texas, 미국, 76012
- Zydus US002
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Austin, Texas, 미국, 78745
- Zydus US051
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Austin, Texas, 미국, 78757
- Zydus US101
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Bellaire, Texas, 미국, 77401
- Zydus US089
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Brownsville, Texas, 미국, 78520
- Zydus US105
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Edinburg, Texas, 미국, 78539
- Zydus US095
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Edinburg, Texas, 미국, 78539
- Zydus US106
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Fort Worth, Texas, 미국, 76104
- Zydus US061
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Houston, Texas, 미국, 77030
- Zydus US067
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Houston, Texas, 미국, 77030
- Zydus US109
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Houston, Texas, 미국, 77058
- Zydus US005
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Houston, Texas, 미국, 77079
- Zydus US110
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Katy, Texas, 미국, 77084
- Zydus US117
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San Antonio, Texas, 미국, 78215
- Zydus US031
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San Antonio, Texas, 미국, 78222
- Zydus US103
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San Antonio, Texas, 미국, 78229
- Zydus US036
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San Antonio, Texas, 미국, 78229
- Zydus US102
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San Antonio, Texas, 미국, 78234
- Zydus US043
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San Antonio, Texas, 미국, 78240
- Zydus US008
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Waco, Texas, 미국, 76712
- Zydus US078
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Wichita Falls, Texas, 미국, 76301
- Zydus US076
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Utah
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Ogden, Utah, 미국, 84405
- Zydus US088
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Virginia
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Manassas, Virginia, 미국, 20110
- Zydus US070
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Richmond, Virginia, 미국, 23236
- Zydus US082
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Richmond, Virginia, 미국, 23298
- Zydus US021
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Buenos Aires, 아르헨티나, B1629ODT
- Zydus AR004
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CABA, 아르헨티나, C1056ABJ
- Zydus AR001
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CABA, 아르헨티나, C1180AAX
- Zydus AR013
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CABA, 아르헨티나, C1199ABB
- Zydus AR007
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CABA, 아르헨티나, C1221ADC
- Zydus AR006
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CABA, 아르헨티나, C1264AAA
- Zydus AR005
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CABA, 아르헨티나, C1425AGC
- Zydus AR008
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CABA, 아르헨티나, C1426ABP
- Zydus AR012
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CABA, 아르헨티나, CP143CKE
- Zydus AR003
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Mar del Plata, 아르헨티나, B7600
- Zydus AR009
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Mar del Plata, 아르헨티나
- Zydus AR011
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Ramos Mejía, 아르헨티나
- Zydus AR002
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Rosario, 아르헨티나, S2002KDS
- Zydus AR010
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Adana, 터키 (Türkiye), 01240
- Zydus TR003
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Ankara, 터키 (Türkiye), 06230
- Zydus TR002
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Ankara, 터키 (Türkiye), 06800
- Zydus TR001
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Bursa, 터키 (Türkiye), 16059
- Zydus TR004
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Gaziantep, 터키 (Türkiye), 27310
- Zydus TR005
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Istanbul, 터키 (Türkiye), 34093
- Zydus TR009
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Istanbul, 터키 (Türkiye), 34760
- Zydus TR008
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Izmir, 터키 (Türkiye), 35100
- Zydus TR007
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Izmir, 터키 (Türkiye), 35150
- Zydus TR006
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Kayseri, 터키 (Türkiye), 38039
- Zydus TR011
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Kocaeli, 터키 (Türkiye), 41000
- Zydus TR010
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Mersin, 터키 (Türkiye), 33110
- Zydus TR012
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Rize, 터키 (Türkiye), 53020
- Zydus TR013
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Trabzon, 터키 (Türkiye), 61080
- Zydus TR014
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Puerto Rico
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San Juan, Puerto Rico, 푸에르토 리코, 00927
- Zydus US097
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- Males or females, between 18 and 75 years of age, both inclusive at screening.
- BMI ≤45 kg/m²
- Histological confirmation of NASH with liver fibrosis by central pathologist on a diagnostic liver biopsy with a NAS ≥4 with at least one-point score in each of the three components of the NAFLD activity score [NAS] (steatosis scored 0-3, ballooning degeneration scored 0-2, and lobular inflammation scored 0-3) and NASH by pattern recognition Note: The biopsy must not have been performed more than 24 weeks before randomization.
- The subjects must have a stable body weight (no more than 5% change) between the time of biopsy and randomization.
- Fibrosis stage 2 and 3, according to the NASH CRN fibrosis staging, reported by central pathologist.
- If the subjects have type 2 diabetes mellitus, then it must be moderately controlled with HbA1c ≤ 9.5% and on a stable dose of permitted anti-diabetic medication for at least 90 days before screening until randomization.
- If the subjects are taking vitamin E > 400 IU/day, then it must be on a stable dose for at least 24 weeks prior to screening or, if a historical biopsy is used, at least 24 weeks prior to baseline liver biopsy until randomization.
- Must provide written informed consent and agree to comply with the trial protocol.
Exclusion Criteria:
-
Consumption of >2 units of alcohol per day (>14 units per week) if male and >1 units of alcohol per day (>7 units per week) if female for at least 12 consecutive weeks within 5 years before screening (Note: 1 unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits/hard liquor)
-
History or presence of other concomitant liver diseases at screening:
- Chronic hepatitis B (HBV) or hepatitis C virus (HCV) infection (However, If the subject has been treated for the HCV infection and has been cured at least 5 years from screening, such subjects can be enrolled in the study)
- Primary biliary cholangitis (PBC)
- Primary sclerosing cholangitis (PSC)
- Definite autoimmune liver disease or overlap syndrome
- Alcoholic liver disease
- Hemochromatosis
- Wilsons disease
- Alpha-1 antitrypsin deficiency
-
Subject with known cirrhosis, either based on histology, clinical criteria or any non-invasive diagnostic modality, within 24 weeks prior to the randomization.
-
Evidence of portal hypertension (low platelet count, esophageal varices, ascites, history of hepatic encephalopathy, splenomegaly) at screening.
-
Treatment with glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium glucose cotransporter- 2 (SGLT-2) inhibitors, and dipeptidyl peptidase 4 inhibitors (gliptins) unless stable for 120 days prior to screening or, if a historical biopsy is used, from 120 days prior to baseline liver biopsy until randomization.
-
Use of concurrent medications prior to screening including:
- Anti-NASH therapy(s) including S-adenosyl methionine (SAMe), ursodeoxycholic acid (UDCA), and obeticholic acid in the period from 90 days prior to screening or, if a historical biopsy is used, from 90 days prior to baseline liver biopsy until randomization. For resmetirom; 120 days prior to screening or if a historical biopsy is used, from 120 days prior to baseline liver biopsy until randomization.
- Antidiabetic mediation which may impact NASH histology including thiazolidinediones (pioglitazone, rosiglitazone) in the period from 90 days prior to screening or, if a historical biopsy is used, from 90 days prior to baseline liver biopsy until randomization.
- Immune modulatory agents including anti-TNF-α therapies (infliximab, adalimumab, etanercept) or anti-integrin therapy (namixilab) in the period from 28 days prior to screening or if a historical biopsy is used from 28 days prior to baseline liver biopsy until randomization.
- Any treatment or anticipated initiation (intended use for more than 14 consecutive days) of medications known to have an effect on steatosis (e.g. treatment with corticosteroids [topical and inhaled are allowed]), methotrexate, tamoxifen, valproic acid, amiodarone or tetracycline, estrogens in doses higher than used in oral contraceptives, vitamin A, L-asparaginase, valproate, chloroquine, or antiretroviral drugs in the period from 28 days prior to screening or, if a historical biopsy is used, from 28 days prior to baseline liver biopsy until randomization.
- Treatment with orlistat, zonisamide, topiramate, phentermine, lorcaserin, bupropion, or naltrexone alone, or in combination or any other medication, that could promote weight loss, in the opinion of the investigator, in the period from 28 days prior to screening or if a historical biopsy is used from 28 days prior to baseline liver biopsy until randomization.
-
Changing doses of statins (simvastatin, pitavastatin, pravastatin, atorvastatin, fluvastatin, lovastatin, rosuvastatin) or fibrates (clofibrate, Fenofibrate) in the 90 days preceding screening until randomization.
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Use of drugs that are known CYP2C8 inhibitors/substrate in the 28 days preceding screening until randomization.
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History of liver transplant
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Any weight reduction surgery in the 2 years prior to screening or planned during the study (weight reduction surgery is disallowed during the study), and malabsorptive weight loss surgery (Rouxen-Y or distal gastric bypass) at any time prior to screening.
Note: Lap banding, if the band has been removed >6 months before baseline liver biopsy, or intragastric balloon, if the balloon has been removed > 6 months before baseline liver biopsy, is allowed.
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Type 1 diabetes mellitus
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History of stomach or intestinal surgery or resection within the six months prior to screening that would potentially alter absorption and/or excretion of orally administered drugs as judged by the investigator.
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Unstable cardiovascular disease, including:
- unstable angina, (i.e., new or worsening symptoms of coronary heart disease) in the 90 days before screening and throughout the screening period; acute coronary syndrome in the 24 weeks before screening and throughout the screening period;
- acute myocardial infarction in the 90 days before screening and throughout the screening period; or heart failure of New York Heart Association class (III - IV), worsening congestive heart failure, or coronary artery intervention, in the 24 weeks before screening and throughout the screening period.
- history of unstable cardiac dysrhythmias
- uncontrolled hypertension at screening
- stroke or transient ischemic attack in the 24 weeks before screening
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History of myopathies or evidence of active muscle disease demonstrated by CPK ≥ 5 times ULN at screening.
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For subjects with elevated baseline ALT, AST, or ALP; ALT, AST, or ALP exceeding by more than 50% at Visit 2 reading compared to Visit 1 Note: If the ALT, AST or ALP values at Visit 2 exceed by more than 50% from Visit 1, then a third value will be measured to assess for the trend. If the third value shows continued increase ≥ 10%, then subject is considered ineligible for randomization.
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Any of the following laboratory values at screening:
- Hemoglobin <9 g/dL
- WBC count <2.5 × 103/µL
- Neutrophil count <1.5 × 103/µL
- Platelets <140 × 103/µL [if low platelet count is due to reasons other than liver disease as assessed by a hematologist, participants may be eligible if the platelet count is > 75 x 103/µL] as per investigator's discretion]
- INR ≥ 1.3 (in the absence of anticoagulants)
- Total bilirubin > ULN except in Gilbert's syndrome. In subjects with known Gilbert's syndrome, direct bilirubin > 2 x ULN
- Albumin <3.5 g/dL
- eGFR <60 mL/min/1.73 m2
- ALP ≥ 2x ULN
- ALT or AST ≥ 250 U/L
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Participation in any other therapeutic clinical study and on active treatment in the past 90 days of the screening.
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History of benign or malignant bladder tumors, and/or hematuria or has current hematuria except due to a urinary tract infection.
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History of malignancy in the past 5 years and/or active neoplasm with the exception of resolved superficial nonmelanoma skin cancer.
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Known allergy, sensitivity or intolerance to the study drug, comparator or formulation ingredients.
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Pregnancy-related exclusions, including:
- Pregnant/lactating female (including positive pregnancy test at screening)
- Pregnancy should be avoided by male and female participants either by true abstinence or the use of an acceptable effective contraceptive measures for the duration of the study and for at least 1 month after the end of the study treatment
-
History or other evidence of severe illness or any other conditions that would make the subject, in the opinion of the investigator, unsuitable for the study (such as poorly controlled psychiatric disease, HIV, coronary artery disease or active gastrointestinal conditions that might interfere with drug absorption)
-
Receiving an elemental diet or parenteral nutrition.
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Chronic pancreatitis or pancreatic insufficiency.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 네 배로
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: Saroglitazar Magnesium 2 mg
Saroglitazar Magnesium 2 mg tablet orally administered once daily in the morning before breakfast without food, for the duration of treatment. |
Patients randomly assigned to this group will receive Saroglitazar Magnesium 2 mg tablet orally once daily in the morning before breakfast without food, for the duration of treatment.
다른 이름들:
|
|
실험적: Saroglitazar Magnesium 4 mg
Saroglitazar Magnesium 4 mg tablet orally administered once daily in the morning before breakfast without food, for the duration of treatment. |
Patients randomly assigned to this group will receive Saroglitazar Magnesium 4 mg tablet orally once daily in the morning before breakfast without food, for the duration of treatment.
다른 이름들:
|
|
위약 비교기: Placebo
Placebo tablet orally administered once daily in the morning before breakfast without food, for the duration of treatment. |
Patients randomly assigned to this group will receive Placebo tablet orally once daily in the morning before breakfast without food, for the duration of treatment.
다른 이름들:
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Resolution of steatohepatitis with no worsening of fibrosis
기간: 52 Weeks/EOT
|
Resolution of steatohepatitis is defined as absent fatty liver disease or isolated or simple steatosis without steatohepatitis and a NAS of 0-1 for inflammation, 0 for ballooning, and any value for Steatosis |
52 Weeks/EOT
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Improvement in liver fibrosis with no increase in NAS for ballooning, inflammation or steatosis
기간: Week 52/EOT
|
Proportion of subjects achieving improvement in liver fibrosis (reduction of at least one stage) with no increase in NAS for ballooning, inflammation or steatosis |
Week 52/EOT
|
|
2 points improvement in NAS
기간: Week 52/EOT
|
Proportion of subjects with at least 2 points improvement in NAS at Week 52/EOT with at least 1-point improvement in either ballooning or inflammation and no worsening of liver fibrosis |
Week 52/EOT
|
|
Improvement in steatosis, ballooning, inflammation and fibrosis from liver biopsy
기간: Week 52/EOT
|
Proportion of subjects with ≥1 point improvement in steatosis, ballooning, inflammation and fibrosis |
Week 52/EOT
|
|
Decrease in SAF score on liver biopsy
기간: Week 52/EOT
|
Proportion of subjects with decrease in SAF score ≥2 combining hepatocellular inflammation and ballooning without worsening of fibrosis |
Week 52/EOT
|
|
Histological score changes in steatosis, ballooning, inflammation, and fibrosis
기간: Week 52/EOT
|
Change from baseline in steatosis, ballooning, inflammation, and fibrosis |
Week 52/EOT
|
|
Change in liver enzyme parameters including (ALT, AST, ALP, GGT, total bilirubin, albumin)
기간: Week 52/EOT
|
Change from baseline in liver enzyme parameters (ALT, AST, ALP, GGT, total bilirubin, albumin) |
Week 52/EOT
|
|
Change in non-invasive markers of steatosis
기간: Week 52/EOT
|
Change from baseline in non-invasive markers of steatosis (Enhanced Liver Fibrosis [ELF] test, Fibrosis 4 [FIB 4], APRI [AST to Platelet Ratio Index], NFS [NAFLD Fibrosis Score], PRO-C3) |
Week 52/EOT
|
|
Change in n lipid parameters including (TG, LDLC, TC, HDL-C, non-HDL-C, VLDL-C
기간: Week 52/EOT
|
Change from baseline in lipid parameters (TG, LDLC, TC, HDL-C, non-HDL-C, VLDL-C) |
Week 52/EOT
|
|
Change in body weight (any change from baseline)
기간: Week 52/EOT
|
Change from baseline in body weight |
Week 52/EOT
|
|
Change in insulin resistance marker, HOMA-IR
기간: Week 52/EOT
|
Change from baseline in insulin resistance marker (HOMA-IR) |
Week 52/EOT
|
|
Change in inflammatory markers including (CK-18 [M30], IL-6, CRP)
기간: Week 52/EOT
|
Change from baseline in inflammatory markers (CK-18 [M30], IL-6, CRP) |
Week 52/EOT
|
|
Change in glucose homeostasis markers including (HbA1c, FPG)
기간: Week 52/EOT
|
Change from baseline in glucose homeostasis markers (HbA1c, FPG) |
Week 52/EOT
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공동 작업자 및 조사자
수사관
- 연구 책임자: Deven V. Parmar, MD, FCP, Zydus Therapeutics Inc.
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- SARO.20.002
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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