Citations 2
Induction of Antigen-Specific T Cell Tolerance by CNP-104 Positively Affects Clinical Response in Primary Biliary Cholangitis (PBC) 9237
Elhofy, Adam, Frey, Molly , McCarthy, Derrick , Wambre, Erik , Caldwell, Stephen H. , Firpi-Morell, Roberto , Fortune, Brett E. , Galambos, Michael, Harnois, Denise M. , Hassanein, Tarek , Läwitz, E., Patel, Bhaktasharan, Phillips, Raymond E. , Pratt, Daniel S. , Pruthi, Jatinder, Rajendiran, Govarthanan , Reddy, Gautham, Rodrı́guez, Manuel, Silveira, Marina , Zervos, Bobby, Peloso, Paul M. , Gershwin, M. Eric, Bowlus, Christopher L. , Gordon, Stuart J. G. , Kappus, Matthew R. , Mchenry, Scott A. , Phillips, Raymond, Rodriguez, Manuel, Silveira, Marina
The Journal of Immunology | November 21, 2025 | Volume: 214 | Issue: Supplement_1 | Pages: No page available
Abstract Description PBC is an archetypal autoimmune disease where the dominant autoantigen is mitochondrial PDC-E2. Hitherto, PBC treatment has been neither specific nor directed toward restoration of tolerance. CNP-104, a tolerogenic nanoparticle encapsulating PDC-E2, is hypothesized to restore tolerance to pathogenic T cells. We conducted a Phase 2a First-in-Human randomized controlled trial of CNP-104 in PBC patients unresponsive/intolerant to ursodeoxycholic acid. The 42 enrolled subjects were randomized 2:1 to receive two doses of CNP-104 or placebo (PBO) one week apart and were followed for 120 days to assess safety and treatment durability. CNP-104 was safe and well-tolerated. Compared to PBO, the CNP-104 group had a reduced percentage of antigen-specific Th17 T cells and increased antigen-specific tolerogenic CD8+ T cell counts (TIGIT, GARP). ALP, ALT, and total bilirubin were similar between groups. Clinically relevant effects on albumin levels, liver stiffness, and the rate of change in 5-year UK-PBC risk for liver outcomes were improved in the CNP-104 group compared to PBO. This trial is limited by small size and data variability. Induction of antigen-specific T cell tolerance, shown by reduced Th17 cells and increased TIGIT and GARP cells correlates with improved liver stiffness, albumin, and UK-PBC. These findings suggest the CNP-104 tolerogenic mechanism of action translates to clinical benefits. These data support future studies with this unique therapeutic platform to treat PBC. Topic Categories Therapeutic Approaches to Autoimmunity (THER)
Risankizumab for Ulcerative Colitis
Louis, Edouard, Panaccione, Remo, Biedermann, Luc , Colombel, Jean–Frédéric, D’Haens, Geert , Hisamatsu, Tadakazu , Siegmund, Britta , Boland, Brigid S. , Melmed, Gil , Armuzzi, Alessandro , Levine, Phillip, Kalabic, Jasmina , Cheng, Ling, Shu, Lei , Duan, W. Rachel, Pivorunas, Valerie , González, Yuri Sánchez , D’Cunha, Ronilda , Neimark, Ezequiel, Wallace, Kori, Ferrante, Marc , Group, INSPIRE and COMMAND Study, Balderramo, Domingo , Goncalves, Silvina A., Lasa, Juan, Novillo, Abel, Ruffinengo, Orlando, Heeren, Sonja, Reinisch, Walter , Baert, Filip , Colard, A, Ferrante, Marc, Franchimont, Denis , Rahier, Jean‐François , Francesconi, Carlos Fernando de Magalhães , Stanchev, Desislav , Atkinson, Kenneth, Beaton, Melanie, Greenbloom, Susan, Lachance, Jean-Rene, Lim, Allen, Samson, Jean-Michel, Shulman, Scott, Siffledeen, Jesse, Alfaro, Ignacio , Valenzuela, Carlos , Walsen, Gustavo, An, Ping , Cao, Qian , Chen, Yan , Gao, Xiang , Hou, Xiaohua , Hu, Naizhong, Liu, Mei , Lungen, LU, Ran, Zhihua, Tang, Tongyu , Yang, Shaoqi , Zhan, Qiang , Zhang, Guoxin , Zhang, Xiaolan , Zhong, Jie , Zou, Xiaoping, Álvarez, Eligio, Ricaurte, Juan, Borzan, Vladimir , Puljiz, Željko , Svoboda, Pavel , Ulbrych, Jan, Vaňásek, Tomáš , Ali, Ezzat, Salem, Osama , Sawah, Hisham, Altwegg, Romain , Flamant, Mathurin, Hébuterne, Xavier , Deppe, Herbert, Klaus, Jochen , Kucharzik, Torsten , Mertens, Jessica, Mroß, Michael, Reindl, Wolfgang , Schiefke, Ingolf, Schreiber, Stefan, Sturm, Andreas , Bamias, Georgios, Manolakopoulos, Spilios , Mantzaris, Gerassimos J. , Tzouvala, Maria , Viazis, N. , Avni‐Biron, Irit , Goldin, Eran , Katz, Lior H. , Lahat-Zok, Adi, Segal, Arik, Colecchia, Antonio , Cosintino, R. , Geccherle, Andrea, Monteleone, Giovanni , Privitera, Antonino Carlo , Vangeli, Marcello, Abe, Yasuhiko , Aoyama, Nobuo , Endo, Yutaka , Esaki, Motohiro, Fujii, Toshimitsu , Fukuda, Katsuyuki , Hirai, Fumihito , Hisanaga, Yasuhiro, Horiki, Noriyuki , Iguchi, Mikitaka , Ishiguro, Yoh , Ito, Hiroaki , Kamikozuru, Koji , Kato, Jun , Kawanishi, Teruki, Kobayashi, Taku , Kuge, Hiroyuki , Masuda, Tomoyuki, Matsuoka, Katsuyoshi , Matsushima, Kayoko , Matsushima, Masashi, Motoya, Satoshi , Nakai, Katsuhiko, Nakajima, Koichi, Nakamura, Masanao, Nishida, Atsushi , Nishikawa, Takahiro , Nishimata, Nobuaki, Ochiai, Toshiaki, Ohmiya, Naoki , Ohnishi, Yoshifumi , Oka, Shiro , Ozeki, Keiji , Saito, Daisuke, Saruta, Masayuki, Sasaki, Makoto, Shimizu, Masahito , Sujino, Tomohisa , Takatori, Hajime , Takatsu, Noritaka , Tokito, Satoki, Endo, Toshiyuki, Toyokawa, Tatsuya , Uenoyama, Yoshito , Yamamoto, Takatsugu, Yasuda, Hiroshi , Yokoyama, Kaoru , Jonaitis, Laimas, Kazėnaitė, Edita, Te, Lourdes Lol-be Pinzon, Lutgens, Maurice, Brooker, James, Griffiths, Ben, Inns, Stephen , Schultz, Michael, Eszyk, Jerzy, Kleczkowski, D, Kopoń, Adam, Petryka, Robert, Romańczyk, Tomasz , Rydzewska-Wyszkowska, Grażyna , Sikorski, Piotr, Talarek, Michał, Ministro, Paula , Tavares, Helena, Diculescu, Mihai-Mircea, Goldiș, Adrian , Agafina, Alina, Edin, Anton, Gerasimova, Evgenia, Gettueva, Maryana, Кашников, В. Н. , Pirmagomedov, Albert , Rafalskiy, Vladimir , Шарапова, К. М., Varganova, Daria L , Grgov, Saša, Svorcan, Petar , Tarabar, Dino, Ling, Khoon Lin , Baláž, Jozef, Ďurina, J, Greguš, Miloš, Laclav, Martin , Deetlefs, Eduan, Peter, Jonny , Rajabally, Muhammad, Rosa, Jennifer, Zyl, JI van, Wright, John , Jang, Byung Ik , Kang, Sang-Bum, Kim, Duk-Hwan , Kim, Tae Oh , Kim, Young-Ho , Song, Geun Am , Laria, Luisa Castro, Piudo, Ana Echarri, Ramirez, Vincent Hernandez, Martín‐Arranz, María Dolores , Trastoy, Pilar Varela, Mendoza, M Vera, Lördal, Mikael, Chang, Chung-Hsin, Kuo, Chia-Jung , Lin, Ching‐Pin , Tu, Chia–Hung, Erzın, Yusuf , Soykan, İrfan , Kravchenko, Tetiana , Tsarynna, Nataliia, Vyshyvanyuk, Vira , Cummings, Fraser , Kapur, Kapil , Kaser, Arthur , Kent, Alexandra , Parkes, Gareth, Patel, Kamal , Steel, Alan , Aberra, Faten , Aguilar, Humberto , Al‐Bawardy, Badr , Barnes, Matthew D., Beck, Kendall , Berkelhammer, Charles , Bullock, Jeff, Chiplunker, Adeeti , Dalal, Robin, Dalal, Sushila , Delgado, Belkis, DiGiovanna, Michael P., Duvall, George, Freedland, Curtis, Friedenberg, Keith, Gaidos, Jill , Ginsburg, Philip, Hassanein, Tarek , Higgins, Peter , Hou, Jason K. , Huilgol, Vivek, Inamdar, Nikhil, Kapur, Saurabh, Kerman, David H., Levine, Henry, Lodhia, Nilesh, Mayoral, Jaime L., McNeil, Donald, Mushahwar, Andria M., Ojeas, Harry, Patel, Bhaktasharan, Phillips, Raymond E. , Pouzar, Joe, Sarles, H, Schock, Joel, Sedghi, Shahriar , Shah, Nirav V. , Stokesberry, David, Su, Le‐Chu, Verma, Dharmendra, Weber, John T. , Younes, Ziad , Zisman, Timothy L. , Melmed, Gil Y , Kobayashi, Taku , Siegmund, Britta , Schreiber, Stefan , Bossuyt, Peter , Parkes, Gareth, Peyrin‐Biroulet, Laurent , Wu, Kaichun , Chen, Su , Atreya, Raja Narayana , Loftus, Edward V. , Group, INSPIRE and COMMAND Study, Reinisch, Walter , Dewit, Olivier , Franchimont, Denis , Kaiser, Roberto Luiz , Parra, Rogério Serafim , Sassaki, Lígia Yukie , Пенчев, Пламен , Bessissow, Talat , Lachance, Jean-René, Panaccione, Remo , Walsen, Gustavo, Chen, Youxiang , Li, Yan , Liu, Fei , Wang, Xin , Zhan, Qiang, Zhang, Hu , Zhang, Jie , Ricaurte, Juan, Krznarić, Željko , Bortlík, Martin , Svoboda, Pavel, Kjeldsen, Jens , Munck, Lars Kristian , Poulsen, Anja, Waked, Imam A. , Fumery, Mathurin , Laharie, David , Roblin, Xavier , Tréton, Xavier , Deppe, Herbert, Hasselblatt, Peter , Kandulski, Arne , Krause, Thomas , Naumann, Axel, Schreiber, Stefan , Schubert, Stefan, Κoutroubakis, Ioannis E. , Ardizzone, Sandro , Cicala, Michele , Gasbarrini, Antonio , Giannini, Edoardo Giovanni , Gionchetti, Paolo , Luzza, Francesco , Saibeni, Simone , Abe, Yasuhiko, Asonuma, Kunio , Hisanaga, Yasuhiro, Ishigami, Keisuke, Kakuta, Yoichi , Maemoto, Atsuo , Nakajima, Koichi, Nishida, Atsushi, Sasaki, Makoto, Sugimoto, Ken , Suzuki, Takayoshi , Takedatsu, Hidetoshi , Takeuchi, Ken, Tanaka, Hiroki , Tokito, Satoki, Yamamoto, Takayuki , Derovs, Aleksejs , Puķītis, Aldis , Jonaitis, Laimas Virginijus , Gearry, Richard B. , Griffiths, Ben, Kierkuś, Jarosław , Reguła, Jarosław , Cerqueira, Rute Maria , Goncalves, Tiago, Lopes, Susana , Portela, Francisco , Seicean, Andrada , Gerasimova, Evgenia, Sharapova, Ksenia, Smolyarchuk, Е. А. , Jovanović, Igor , Balaz, Jozef, Drobne, David , Wright, John, Cheon, Jae Hee , Kim, Jee Hyun , Lee, Jong Hun , Lee, Kang‐Moon , Park, Dong Il , Argüelles‐Arias, Federico , Piudo, Ana Echarri, García‐López, Santiago , Ramirez, V Hernández, Misselwitz, Benjamin , Chou, Jen‐Wei , Tu, Chia‐Hung , Alkım, Hüseyin , Kravchenko, Tetiana, Ahmad, Tariq, Parkes, Gareth, Speight, Richard, Ananthakrishnan, Ashwin N. , Barnes, Matthew, Bullock, Jeff, DiGiovanna, Michael, Hong, John D. , Huilgol, V.R., Phillips, Raymond, Siddiqui, Junaid, Swaminath, Arun C. , Weber, John, Matsuoka, K
JAMA | July 22, 2024 | Volume: 332 | Issue: 11 | Pages: 881
Importance The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown. Objective To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis. Design, Setting, and Participants Two phase 3 randomized clinical trials were conducted. The induction trial was conducted at 261 clinical centers (in 41 countries) and enrolled 977 patients from November 5, 2020, to August 4, 2022 (final follow-up on May 16, 2023). The maintenance trial was conducted at 238 clinical centers (in 37 countries) and enrolled 754 patients from August 28, 2018, to March 30, 2022 (final follow-up on April 11, 2023). Eligible patients had moderately to severely active ulcerative colitis; a history of intolerance or inadequate response to 1 or more conventional therapies, advanced therapies, or both types of therapies; and no prior exposure to risankizumab. Interventions For the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks. Main Outcomes and Measures The primary outcome was clinical remission (stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability) at week 12 for the induction trial and at week 52 for the maintenance trial. Results Among the 975 patients analyzed in the induction trial (aged 42.1 [SD, 13.8] years; 586/973 [60.1%] were male; and 677 [69.6%] were White), the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (adjusted between-group difference, 14.0% [95% CI, 10.0%-18.0%], P < .001). Among the 548 patients analyzed in the maintenance trial (aged 40.9 [SD, 14.0] years; 313 [57.1%] were male; and 407 [74.3%] were White), the clinical remission rates at week 52 were 72/179 (40.2%) for 180 mg of risankizumab, 70/186 (37.6%) for 360 mg of risankizumab, and 46/183 (25.1%) for placebo (adjusted between-group difference for 180 mg of risankizumab vs placebo, 16.3% [97.5% CI, 6.1%-26.6%], P < .001; adjusted between-group difference for 360 mg of risankizumab vs placebo, 14.2% [97.5% CI, 4.0%-24.5%], P = .002). No new safety risks were detected in the treatment groups. Conclusion and Relevance Compared with placebo, risankizumab improved clinical remission rates in an induction trial and in a maintenance trial for patients with moderately to severely active ulcerative colitis. Further study is needed to identify benefits beyond the 52-week follow-up. Trial Registration ClinicalTrials.gov Identifiers: NCT03398148 and NCT03398135