Current Clinical Trial Status and Future Prospects of PPAR-Targeted Drugs for Treating Nonalcoholic Fatty Liver Disease
Abstract
:1. Introduction
2. PPAR Agonists in the Past and Current Clinical Trials against NASH
2.1. Lanifibranor (PPAR Pan Agonist)—Under Consideration for Treating NAFLD/NASH
2.2. Chiglitazar (PPAR Pan Agonist)—Under Consideration in China
2.3. Elafibranor (PPARα/δ Dual Agonist)—Discontinued
2.4. Saroglitazar (PPARα/γ Dual Agonist)—Under Consideration
2.5. Seladelpar (PPARδ-Selective Agonist)—Interrupted
2.6. Fenofibrate (PPARα(/γ Dual) Agonist)—Discontinued
2.7. Pemafibrate (PPARα-Selective Agonist)—Under Consideration in Japan
2.8. Pioglitazone (PPARγ-Selective Agonist)—Under Consideration
2.9. Rosiglitazone (PPARγ-Selective Agonist)—Discontinued
2.10. Lobeglitazone (PPARγ Agonist)—Under Consideration in Korea
3. Future Prospects of PPAR Agonists for NAFLD/NASH
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Drug | NCT Number | Phase | Status | Participants | End Date | Liver Histology | Non-Invasive Tests | Blood Tests | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Steatosis | Ballooning | Inflammation | Fibrosis | Total Score | Fat Content | Stiffness | ALT | AST | ||||||
PPARα/δ/γ pan agonist | ||||||||||||||
Lanifibranor | NCT03008070 (https://classic.clinicaltrials.gov/ct2/show/NCT03008070) | 2 | Completed | 247 | 2020/3/16 | ↓ | ↓ | NS | ↓ | ↓ | ↓ | ↓ | ||
PPARα/δ dual agonist | ||||||||||||||
Elafibranor | NCT01694849 (https://classic.clinicaltrials.gov/ct2/show/NCT01694849) | 2 | Completed | 275 | 2015/12 | ↓ | ↓ | NS | ↓ | ↓ | ↓ | |||
NCT02704403 (https://classic.clinicaltrials.gov/ct2/show/NCT02704403) | 3 | Terminated | 2157 | 2020/10/28 | NS | |||||||||
NCT03883607 (https://classic.clinicaltrials.gov/ct2/show/NCT03883607) | 2 | Terminated | 10 | 2020/6/16 | No description (pharmacokinetics, pharmacodynamics, safety, and tolerability data only) | |||||||||
NCT03953456 (https://classic.clinicaltrials.gov/ct2/show/NCT03953456) | 2 | Terminated | 17 | 2020/7/14 | No description | |||||||||
PPARα/γ dual agonist | ||||||||||||||
Saroglitazar | NCT02265276 (https://classic.clinicaltrials.gov/ct2/show/NCT02265276) | 3 | Unknown | 100 | 2015/9 | No description | ||||||||
NCT03061721 (https://classic.clinicaltrials.gov/ct2/show/NCT03061721) | 2 | Completed | 106 | 2020/12/15 | ↓ | ↓ | ||||||||
NCT03863574 (https://classic.clinicaltrials.gov/ct2/show/NCT03863574) | 2 | Completed | 16 | 2020/10/30 | No description | |||||||||
NCT04193982 (https://classic.clinicaltrials.gov/ct2/show/NCT04193982) | 3 | Unknown | 250 | 2021/10/31 | No description | |||||||||
PPARα agonists | ||||||||||||||
Fenofibrate (α/γ) | NCT00252499 (https://classic.clinicaltrials.gov/ct2/show/NCT00252499) | NA | Terminated | 13 | 2010/8 | No description (protocol drug change required new clinicaltrails.gov entry) | ||||||||
NCT00262964 (https://classic.clinicaltrials.gov/ct2/show/NCT00262964) | NA | Completed | 51 | 2008/12 | No description | |||||||||
NCT01289639 (https://classic.clinicaltrials.gov/ct2/show/NCT01289639) | NA | Terminated | 11 | 2014/8 | No description | |||||||||
NCT02354976 (https://classic.clinicaltrials.gov/ct2/show/NCT02354976) | 2 | Completed | 78 | 2016/5/26 | ↑ | NS | ↑ | |||||||
NCT02781584 (https://classic.clinicaltrials.gov/ct2/show/NCT02781584) | 2 | Completed | 220 | 2020/12/17 | No description (safety and tolerability data only) | |||||||||
NCT02891408 (https://classic.clinicaltrials.gov/ct2/show/NCT02891408) | 1 | Completed | 74 | 2019/5/13 | No description (pharmacokinetics data only) | |||||||||
Pemafibrate | NCT03350165 (https://classic.clinicaltrials.gov/ct2/show/NCT03350165) | 2 | Completed | 118 | 2020/6/30 | NS | ↓ | ↓ | NS | |||||
PPARδ agonist | ||||||||||||||
Seladelpar | NCT03551522 (https://classic.clinicaltrials.gov/ct2/show/NCT03551522) | 2 | Terminated | 181 | 2020/8/10 | No description | ||||||||
PPARγ agonists | ||||||||||||||
Pioglitazone | NCT00013598 (https://classic.clinicaltrials.gov/ct2/show/NCT00013598) | 2 | Completed | 30 | 2004/3 | No description | ||||||||
NCT00062764 (https://classic.clinicaltrials.gov/ct2/show/NCT00062764) | 2 | Completed | 18 | 2009/2 | No description | |||||||||
NCT00063622 (https://classic.clinicaltrials.gov/ct2/show/NCT00063622) | 3 | Completed | 247 | 2009/9 | ↓ | ↓ | ↓ | NS | ↓ | ↓ | ||||
NCT00227110 (https://classic.clinicaltrials.gov/ct2/show/NCT00227110) | 4 | Completed | 55 | 2006/1 | ↓ | ↓ | ↓ | NS | ↓ | ↓ | ↓ | |||
NCT00441272 (https://classic.clinicaltrials.gov/ct2/show/NCT00441272) | 2 | Completed | 100 | NP | No description | |||||||||
NCT00633282 (https://classic.clinicaltrials.gov/ct2/show/NCT00633282) | 2 | Completed | 184 | 2011/8 | No description (only in combination with lifestyle intervention; PMID: 26252777) | |||||||||
NCT00994682 (https://classic.clinicaltrials.gov/ct2/show/NCT00994682) | 4 | Completed | 176 | 2014/12 | ↓ | ↓ | ↓ | NS | ↓ | ↓ | ↓ | ↓ | ||
NCT01289639 (https://classic.clinicaltrials.gov/ct2/show/NCT01289639) | NA | Terminated | 11 | 2014/8 | No description (only baseline data published; PMID: 24360972, 24740208) | |||||||||
NCT01002547 (https://classic.clinicaltrials.gov/ct2/show/NCT01002547) | 4 | Completed | 105 | 2016/12/31 | No description (only in combination with vitamin E; PMID: 31332029) | |||||||||
NCT01068444 (https://classic.clinicaltrials.gov/ct2/show/NCT01068444) | 2 | Completed | 90 | 2020/7 | ↓ | NS | ↓ | NS | ↓ | ↓ | ↓ | ↓ | ||
NCT01431521 (https://classic.clinicaltrials.gov/ct2/show/NCT01431521) | 1 | Completed | 31 | 2012/10/1 | No description | |||||||||
NCT01703260 (https://classic.clinicaltrials.gov/ct2/show/NCT01703260) | 2 | Terminated | 20 | 2014/9 | No description | |||||||||
NCT02265276 (https://classic.clinicaltrials.gov/ct2/show/NCT02265276) | 3 | Unknown | 100 | 2015/9 | No description | |||||||||
NCT02365233 (https://classic.clinicaltrials.gov/ct2/show/NCT02365233) | 4 | Terminated | 5 | 2016/12/31 | No description | |||||||||
NCT02875821 (https://classic.clinicaltrials.gov/ct2/show/NCT02875821) | 4 | Completed | 44 | 2017/6/7 | No description | |||||||||
NCT03646292 (https://classic.clinicaltrials.gov/ct2/show/NCT03646292) | 4 | Unknown | 60 | 2021/2 | No description | |||||||||
NCT03796975 (https://classic.clinicaltrials.gov/ct2/show/NCT03796975) | 4 | Completed | 120 | 2019/11/20 | No description | |||||||||
NCT03910361 (https://classic.clinicaltrials.gov/ct2/show/NCT03910361) | 4 | Completed | 51 | 2020/7/2 | No description | |||||||||
NCT03950505 (https://classic.clinicaltrials.gov/ct2/show/NCT03950505) | 4 | Unknown | 60 | 2020/12 | No description | |||||||||
NCT05521633 (https://classic.clinicaltrials.gov/ct2/show/NCT05521633) | 3 | Completed | 96 | 2022/5/24 | No description | |||||||||
Rosiglitazone | NCT00252499 (https://classic.clinicaltrials.gov/ct2/show/NCT00252499) | NA | Terminated | 13 | 2010/8 | No description (protocol drug change required new clinicaltrails.gov entry) | ||||||||
NCT00492700 (https://classic.clinicaltrials.gov/ct2/show/NCT00492700) | 2 | Completed | 63 | NP | ↓ | NS | NS | NS | NS | ↓ | ↓ | |||
NCT00699036 (https://classic.clinicaltrials.gov/ct2/show/NCT00699036) | 2 | Unknown | 165 | 2009/8 | No description | |||||||||
NCT01406704 (https://classic.clinicaltrials.gov/ct2/show/NCT01406704) | 4 | Terminated | 26 | 2013/12 | No description | |||||||||
Lobeglitazone | NCT02285205 (https://classic.clinicaltrials.gov/ct2/show/NCT02285205) | 4 | Completed | 38 | 2015/11 | ↓ | NS | ↓ | ↓ |
Drug | NCT Number | Phase | Status | Participants | Subject | Start Date | ESC Date |
---|---|---|---|---|---|---|---|
PPARα/δ/γ pan agonists | |||||||
Chiglitazar | NCT05193916 (https://classic.clinicaltrials.gov/ct2/show/NCT05193916) | 2 | Recruiting | 100 | NASH with elevated triglyceride and insulin resistance | 2022/3/21 | (2023/11) |
Lanifibranor | NCT03459079 (https://classic.clinicaltrials.gov/ct2/show/NCT03459079) | 2 | Recruiting | 54 | T2DM and NAFLD | 2018/8/14 | (2024/4/14) |
NCT04849728 (https://classic.clinicaltrials.gov/ct2/show/NCT04849728) | 3 | Recruiting | 1000 | NASH with F2/F3 stage of liver fibrosis | 2021/8/19 | (2026/9/30) | |
NCT05232071 (https://classic.clinicaltrials.gov/ct2/show/NCT05232071) | 2 | Recruiting | 63 | T2DM and NASH | 2022/6/29 | (2023/12/31) | |
PPARα/γ dual agonist | |||||||
Saroglitazar | NCT03617263 (https://classic.clinicaltrials.gov/ct2/show/NCT03617263) | 2 | Recruiting | 90 | NAFLD in women with polycystic ovarian syndrome | 2018/12/4 | (2024/7) |
NCT03639623 (https://classic.clinicaltrials.gov/ct2/show/NCT03639623) | 2 | Recruiting | 15 | Liver transplant recipients with NAFLD | 2019/2/25 | 2023/6 | |
NCT04469920 (https://classic.clinicaltrials.gov/ct2/show/NCT04469920) | 1 | Recruiting | 100 | NASH with advanced fibrosis | 2020/7/16 | (2024/10) | |
NCT05011305 (https://classic.clinicaltrials.gov/ct2/show/NCT05011305) | 2 | Recruiting | 240 | NASH | 2021/8/18 | (2023/12) | |
NCT05211284 (https://classic.clinicaltrials.gov/ct2/show/NCT05211284) | 2 | Recruiting | 160 | NASH with human immunodeficiency virus | 2022/9/26 | (2025/3/1) | |
NCT05872269 (https://classic.clinicaltrials.gov/ct2/show/NCT05872269) | 4 | Not yet | 1500 | NAFLD with comorbidities (obesity, T2DM, dyslipidemia, or metabolic syndrome) | 2023/7/20 | (2025/6/10) | |
PPARγ agonist | |||||||
Pioglitazone | NCT04501406 (https://classic.clinicaltrials.gov/ct2/show/NCT04501406) | 2 | Recruiting | 166 | NASH in T2DM | 2020/12/15 | (2027/8/31) |
NCT04976283 (https://classic.clinicaltrials.gov/ct2/show/NCT04976283) | 4 | Recruiting | 123 | Liver fat in T2DM and NAFLD | 2021/9/15 | (2023/11/15) | |
NCT05254626 (https://classic.clinicaltrials.gov/ct2/show/NCT05254626) | 4 | Recruiting | 100 | NASH | 2022/8/1 | (2025/8) | |
NCT05305287 (https://classic.clinicaltrials.gov/ct2/show/NCT05305287) | 4 | Recruiting | 60 | NAFLD in T2DM | 2022/11/1 | (2027/3/31) | |
NCT05422092 (https://classic.clinicaltrials.gov/ct2/show/NCT05422092) | NA | Not yet | 80 | NAFLD in T2DM | 2022/9/20 | (2023/12) | |
NCT05513729 (https://classic.clinicaltrials.gov/ct2/show/NCT05513729) | NA | Recruiting | 80 | NAFLD in T2DM | 2022/8/18 | (2024/3/1) | |
NCT05605158 (https://classic.clinicaltrials.gov/ct2/show/NCT05605158) | 3 | Not yet | 56 | NASH | 2022/11 | (2024/11) | |
NCT05813249 (https://classic.clinicaltrials.gov/ct2/show/NCT05813249) | 4 | Recruiting | 180 | NAFLD in obesity and/or T2DM | 2023/2/15 | (2024/8/15) | |
NCT05942963 (https://classic.clinicaltrials.gov/ct2/show/NCT05942963) | 4 | Not yet | 240 | NAFLD and T2DM | (2023/10) | (2024/4) |
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Share and Cite
Kamata, S.; Honda, A.; Ishii, I. Current Clinical Trial Status and Future Prospects of PPAR-Targeted Drugs for Treating Nonalcoholic Fatty Liver Disease. Biomolecules 2023, 13, 1264. https://doi.org/10.3390/biom13081264
Kamata S, Honda A, Ishii I. Current Clinical Trial Status and Future Prospects of PPAR-Targeted Drugs for Treating Nonalcoholic Fatty Liver Disease. Biomolecules. 2023; 13(8):1264. https://doi.org/10.3390/biom13081264
Chicago/Turabian StyleKamata, Shotaro, Akihiro Honda, and Isao Ishii. 2023. "Current Clinical Trial Status and Future Prospects of PPAR-Targeted Drugs for Treating Nonalcoholic Fatty Liver Disease" Biomolecules 13, no. 8: 1264. https://doi.org/10.3390/biom13081264