Recombinant human anti–transforming growth factor Β1 antibody therapy in systemic sclerosis: A multicenter, randomized, placebo-controlled phase I/II trial of CAT-192
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.
2007-01
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>
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.Publisher
Wiley Subscription Services, Inc., A Wiley Company
ISSN
0004-3591 1529-0131
Other DOIs
PMID
17195236
Types
Article
URI
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=17195236&dopt=citationMetadata
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