Recombinant human anti–transforming growth factor Β1 antibody therapy in systemic sclerosis: A multicenter, randomized, placebo-controlled phase I/II trial of CAT-192
dc.contributor.author | Denton, Christopher P. | en_US |
dc.contributor.author | Merkel, Peter A. | en_US |
dc.contributor.author | Furst, Daniel E. | en_US |
dc.contributor.author | Khanna, Dinesh | en_US |
dc.contributor.author | Emery, Paul | en_US |
dc.contributor.author | Hsu, Vivien M. | en_US |
dc.contributor.author | Silliman, Nancy | en_US |
dc.contributor.author | Streisand, James | en_US |
dc.contributor.author | Powell, John | en_US |
dc.contributor.author | Åkesson, Anita | en_US |
dc.contributor.author | Coppock, John | en_US |
dc.contributor.author | Hoogen, Frank van den | en_US |
dc.contributor.author | Herrick, Ariane | en_US |
dc.contributor.author | Mayes, Maureen D. | en_US |
dc.contributor.author | Veale, Douglas | en_US |
dc.contributor.author | Haas, Joanna | en_US |
dc.contributor.author | Ledbetter, Stephen | en_US |
dc.contributor.author | Korn, Joseph H. | en_US |
dc.contributor.author | Black, Carol M. | en_US |
dc.contributor.author | Seibold, James R. | en_US |
dc.date.accessioned | 2007-09-20T18:07:00Z | |
dc.date.available | 2008-04-03T18:47:58Z | en_US |
dc.date.issued | 2007-01 | en_US |
dc.identifier.citation | Denton, Christopher P.; Merkel, Peter A.; Furst, Daniel E.; Khanna, Dinesh; Emery, Paul; Hsu, Vivien M.; Silliman, Nancy; Streisand, James; Powell, John; Åkesson, Anita; Coppock, John; Hoogen, Frank van den; Herrick, Ariane; Mayes, Maureen D.; Veale, Douglas; Haas, Joanna; Ledbetter, Stephen; Korn, Joseph H.; Black, Carol M.; Seibold, James R. (2007). "Recombinant human anti–transforming growth factor Β1 antibody therapy in systemic sclerosis: A multicenter, randomized, placebo-controlled phase I/II trial of CAT-192." Arthritis & Rheumatism 56(1): 323-333. <http://hdl.handle.net/2027.42/55924> | en_US |
dc.identifier.issn | 0004-3591 | en_US |
dc.identifier.issn | 1529-0131 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/55924 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=17195236&dopt=citation | en_US |
dc.description.abstract | Objective To evaluate CAT-192, a recombinant human antibody that neutralizes transforming growth factor Β1 (TGFΒ1), in the treatment of early-stage diffuse cutaneous systemic sclerosis (dcSSc). Methods Patients with SSc duration of <18 months were randomly assigned to the placebo group or to 1 of 3 CAT-192 treatment groups: 10 mg/kg, 5 mg/kg, 0.5 mg/kg. Infusions were given on day 0 and weeks 6, 12, and 18. The primary objective of this study was to evaluate the safety, tolerability, and pharmacokinetics of CAT-192. Secondary outcomes included the modified Rodnan skin thickness score (MRSS), the Scleroderma Health Assessment Questionnaire, assessment of organ-based disease, serum levels of soluble interleukin-2 receptor, collagen propeptides (N propeptide of type I [PINP] and type III collagen), and tissue levels of messenger RNA for procollagens I and III and for TGFΒ1 and TGFΒ2. Results Forty-five patients were enrolled. There was significant morbidity and mortality, including 1 death in the group receiving 0.5 mg/kg of CAT-192 and 3 deaths in the group receiving 5 mg/kg of CAT-192. There were more adverse events and more serious adverse events in patients receiving CAT-192 than in those receiving placebo, although these events were not more frequent in the high-dose treatment group. The MRSS improved in all groups during the study, but there was no evidence of a treatment effect for CAT-192. Improvement in the MRSS correlated with the disease duration (r = −0.54, P = 0.0008). Changes in the PINP level from baseline correlated with changes in the MRSS (r = 0.37, P = 0.027). Conclusion We report the first evaluation of a systemically administered and repeatedly dosed anti-TGFΒ1 drug. In this pilot study, CAT-192, in doses up to 10 mg/kg, showed no evidence of efficacy. The utility of clinical and biochemical outcome measures and the feasibility of multicenter trials of early dcSSc were confirmed. | en_US |
dc.format.extent | 162817 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.title | Recombinant human anti–transforming growth factor Β1 antibody therapy in systemic sclerosis: A multicenter, randomized, placebo-controlled phase I/II trial of CAT-192 | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Geriatrics | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Royal Free Hospital, London, UK ; Boston University School of Medicine, Boston, Massachusetts ; University of California, Los Angeles ; Leeds University, Leeds, UK ; University of Medicine and Dentistry of New Jersey, New Brunswick ; Genzyme, Boston, Massachusetts ; Cambridge Antibody Technology, Cambridge, UK ; Lund University Hospital, Lund, Sweden ; Walsgrave Hospital, Coventry, UK ; University Hospital, Nijmegen, The Netherlands ; Hope Hospital, Salford, UK ; University of Texas Health Science Center at Houston ; St. Vincent's Hospital, Dublin, Ireland ; University of Michigan, Ann Arbor ; Dr. Korn is deceased. | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor | en_US |
dc.contributor.affiliationother | Royal Free Hospital, London, UK ; Centre for Rheumatology, Royal Free and University College Medical School, Royal Free Hospital, Pond Street, London NW3 2QG, UK | en_US |
dc.contributor.affiliationother | Boston University School of Medicine, Boston, Massachusetts | en_US |
dc.contributor.affiliationother | University of California, Los Angeles | en_US |
dc.contributor.affiliationother | University of California, Los Angeles | en_US |
dc.contributor.affiliationother | Leeds University, Leeds, UK | en_US |
dc.contributor.affiliationother | University of Medicine and Dentistry of New Jersey, New Brunswick | en_US |
dc.contributor.affiliationother | Genzyme, Boston, Massachusetts ; Drs. Silliman, Streisand, Haas, and Ledbetter own stock and/or hold stock options in Genzyme. Dr. Powell owns stock and/or holds stock options in Cambridge Antibody Technology. Dr. van den Hoogen has received consulting fees and/or honoraria (less than $10,000 each) from Abbott and Bristol-Myers Squibb. Dr. Mayes has received consulting fees or honoraria (less than $10,000 each) from Actelion, Encysive, and Novartis. | en_US |
dc.contributor.affiliationother | Genzyme, Boston, Massachusetts | en_US |
dc.contributor.affiliationother | Cambridge Antibody Technology, Cambridge, UK | en_US |
dc.contributor.affiliationother | Lund University Hospital, Lund, Sweden | en_US |
dc.contributor.affiliationother | Walsgrave Hospital, Coventry, UK | en_US |
dc.contributor.affiliationother | University Hospital, Nijmegen, The Netherlands | en_US |
dc.contributor.affiliationother | Hope Hospital, Salford, UK | en_US |
dc.contributor.affiliationother | University of Texas Health Science Center at Houston | en_US |
dc.contributor.affiliationother | St. Vincent's Hospital, Dublin, Ireland | en_US |
dc.contributor.affiliationother | Genzyme, Boston, Massachusetts | en_US |
dc.contributor.affiliationother | Genzyme, Boston, Massachusetts | en_US |
dc.contributor.affiliationother | Royal Free Hospital, London, UK | en_US |
dc.identifier.pmid | 17195236 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/55924/1/22289_ftp.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1002/art.22289 | en_US |
dc.identifier.source | Arthritis & Rheumatism | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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