The Experts below are selected from a list of 315 Experts worldwide ranked by ideXlab platform

Kevan C Herold - One of the best experts on this subject based on the ideXlab platform.

  • Teplizumab treatment may improve C-peptide responses in participants with type 1 diabetes after the new-onset period: a randomised controlled trial.
    Diabetologia, 2012
    Co-Authors: Kevan C Herold, Steven M Willi, Peter A Gottlieb, Stephen E Gitelman, Lesley Devine, Frank Waldron-lynch, Jennifer L Sherr, Stephen M Rosenthal, Saleh Adi, My Jalaludin
    Abstract:

    Aims/hypothesis Type 1 diabetes results from a chronic autoimmune process continuing for years after presentation. We tested whether treatment with teplizumab (a Fc receptor non-binding Anti-CD3 Monoclonal Antibody), after the new-onset period, affects the decline in C-peptide production in individuals with type 1 diabetes.

  • exendin 4 improves reversal of diabetes in nod mice treated with anti cd3 Monoclonal Antibody by enhancing recovery of β cells
    Endocrinology, 2007
    Co-Authors: Nicole A Sherry, Wei Chen, Jake A Kushner, Mariela Glandt, Qizhi Tang, Sue Tsai, Pere Santamaria, Jeffrey A Bluestone, Annemarie B Brillantes, Kevan C Herold
    Abstract:

    Immune modulators can arrest loss of insulin secretion in type 1 diabetes mellitus (T1DM), but they have not caused permanent disease remission or restored normal insulin secretion. We tested whether exendin-4, a glucagon-like peptide-1 receptor agonist, would enhance remission of T1DM in NOD mice treated with Anti-CD3 Monoclonal Antibody (mAb) and studied the effects of exendin-4 treatment on cellular and metabolic responses of β-cells. Diabetic NOD mice treated with Anti-CD3 mAb and exendin-4 had a higher rate of remission (44%) than mice treated with Anti-CD3 mAb alone (37%) or exendin-4 (0%) or insulin or IgG alone (0%) (P < 0.01). The effect of exendin-4 on reversal of diabetes after Anti-CD3 mAb was greatest in mice with a glucose level of less than 350 mg/dl at diagnosis (63 vs. 39%, P < 0.05). Exendin-4 did not affect β-cell area, replication, or apoptosis or reduce the frequency of diabetogenic or regulatory T cells or modulate the antigenicity of islet cells. Reversal of T1DM with Anti-CD3 mAb w...

  • a single course of anti cd3 Monoclonal Antibody hokt3γ1 ala ala results in improvement in c peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes
    Diabetes, 2005
    Co-Authors: Kevan C Herold, William Hagopian, David Donaldson, Stephen E Gitelman, David M Harlan, Brygida Bisikirska, Umesh Masharani, Kristina I Rother, Beverly Diamond, Jeffrey A Bluestone
    Abstract:

    Despite advances in understanding autoimmune diabetes in animal models, there has been little progress in altering the natural course of the human disease, which involves progression to insulin deficiency. Studies with immunosuppressive agents have shown short-term effectiveness, but they have not induced tolerance, and continuous treatment is needed. We studied the effects of hOKT3γ1(Ala-Ala), a humanized Fc mutated Anti-CD3 Monoclonal Antibody, on the progression of type 1 diabetes in patients with recent-onset disease in a randomized controlled trial. In general, the drug was well tolerated. A single course of treatment, within the first 6 weeks after diagnosis, preserved C-peptide responses to a mixed meal for 1 year after diagnosis (97 ± 9.6% of response at study entry in drug-treated patients vs. 53 ± 7.6% in control subjects, P < 0.01), with significant improvement in C-peptide responses to a mixed meal even 2 years after treatment ( P < 0.02). The improved C-peptide responses were accompanied by reduced HbA1c and insulin requirements. Clinical responses to drug treatment were predicted by an increase in the relative number of CD8+ T-cells in the peripheral blood after the lymphocyte count recovered 2 weeks after the last dose of drug. We conclude that treatment with the Anti-CD3 Monoclonal Antibody hOKT3γ1(Ala-Ala) results in improved C-peptide responses and clinical parameters in type 1 diabetes for at least 2 years in the absence of continued immunosuppressive medications.

  • use of anti cd3 Monoclonal Antibody to induce immune regulation in type 1 diabetes
    Annals of the New York Academy of Sciences, 2004
    Co-Authors: Brygida Bisikirska, Kevan C Herold
    Abstract:

    : Achieving immunologic tolerance to autoimmune diabetes is the goal of therapies for treatment and prevention of the disease. However, whether this can be achieved with an antigen-specific approach is still unproven in humans. Other approaches, including treatment with Anti-CD3 Monoclonal Antibody, have focused on regulation of an active immune response. Preclinical studies with Anti-CD3 mAb showed the ability to reverse diabetes and induce tolerance to autoimmunity, even at the time of presentation with hyperglycemia. These studies also suggested that mAb treatment induced an active regulatory process. Based on these and other preclinical data, we have carried out a Phase I/II trial of the humanized FcR non-binding Anti-CD3 mAb hOKT3gamma1(Ala-Ala) in patients with new-onset type 1 diabetes. mAb treatment prevented the loss of insulin production over the first two years of the disease with reduced hemoglobin A1c levels and insulin usage. Studies have suggested that the mechanism of drug action involves induction of regulatory cells. CD4(+)IL-10(+) T cells can be found in patients after treatment; in addition, the CD8(+) T cells are induced by the mAb, and these cells may regulate antigen- specific responses. These initial studies have shown clinical efficacy of treatment with Anti-CD3 mAb and suggest a novel mechanism that may account for the lasting effects of treatment.

  • treatment of type 1 diabetes with anti cd3 Monoclonal Antibody
    Reviews in Endocrine & Metabolic Disorders, 2003
    Co-Authors: Mariela Glandt, William Hagopian, Kevan C Herold
    Abstract:

    Anti-CD3 Monoclonal antibodies (MAbs) were developed as a way of inducing immune suppression of T cells. More recent studies have indicated that Anti-CD3 MAbs can affect immune responses by inducing immune regulation. We recently reported that a single course of treatment with a non-FcR binding Anti-CD3 MAb, hOKT3γ1 (Ala-Ala), can lead to preservation of insulin production in patients with new-onset Type 1 diabetes for even beyond 1 yr after treatment. The sustained insulin production was accompanied by improvement in glucose control and reduced use of insulin. Our studies of the mechanism of the non-FcR binding Anti-CD3 MAb indicate that the MAb delivers an activation signal to T cells resulting in disproportionate production of interleukin-10 (IL-10) relative to interferon-γ(IFN-γ) in vitro compared with FcR binding Anti-CD3 MAb, and detectable levels of IL-10, IL-5, but rarely IFN-γ or IL-2 in the serum after treament. In addition, the drug induces a population of CD4+IL-10+ CCR4+ cells in vivo. Preclinical data suggest that Anti-CD3 MAb induces a population of regulatory T cells that can prevent or lead to reversal of Type 1 diabetes. The induction of cells with a regulatory phenotype may account for the ability of Anti-CD3 MAb to induce immune regulation.

Scott E Plevy - One of the best experts on this subject based on the ideXlab platform.

  • a phase i study of visilizumab a humanized anti cd3 Monoclonal Antibody in severe steroid refractory ulcerative colitis
    Gastroenterology, 2007
    Co-Authors: Scott E Plevy, Bruce Salzberg, Gert Van Assche, Miguel Regueiro, Daniel W Hommes, William J Sandborn, Stephen B Hanauer, Stephan R Targan, Lloyd Mayer, Uma Mahadevan
    Abstract:

    Background & Aims: To evaluate the safety and biological activity of visilizumab (a humanized Anti-CD3 Monoclonal Antibody) and to determine a maximum tolerated dose in patients with severe ulcerative colitis that had not responded to 5 days of treatment with intravenous corticosteroids. Methods: In this open-label phase 1 study, 32 subjects received visilizumab at a dose of 10 or 15 μg/kg, administered intravenously on 2 consecutive days. Clinical response was defined as a Modified Truelove and Witts Severity Index 30 days in 2 of 8 patients), the dose was reduced to 10 μg/kg in 24 patients. On day 30, 84% of patients demonstrated a clinical response, 41% achieved clinical remission, and 44% achieved endoscopic remission. Forty-five percent of patients did not require salvage therapies or colectomy during the first year postdose. Mild to moderate symptoms of cytokine release occurred in 100% and 83% of patients in the 15- and 10-μg/kg dose groups, respectively. All patients exhibited a rapid decrease in circulating CD4+ T-cell counts, which returned to baseline values by day 30 in 26 of 30 evaluable patients (86%). There were no serious infections. Conclusions: Visilizumab had an acceptable safety profile at the 10-μg/kg dose level and may be clinically beneficial in patients with severe intravenous corticosteroid–refractory ulcerative colitis.

  • a humanized anti cd3 Monoclonal Antibody visilizumab for treatment of severe steroid refractory ulcerative colitis preliminary results of a phase i study
    Gastroenterology, 2003
    Co-Authors: Scott E Plevy, Bruce Salzberg, Miguel Regueiro, William J Sandborn, Stephen B Hanauer, Stephan R Targan, Lloyd Mayer, Ian Walters
    Abstract:

    Purpose: In severe, steroid-resistant ulcerative colitis (UC), therapeutic approaches have involved targeting T-cells to control excess inflammation. We hypothesize that the humanized Anti-CD3 Monoclonal Antibody, visiliaumab (Protein Design Labs, Inc., Fremont, CA), may provide therapeutic benefit in UC Methods: We report preliminary results from multicenter, phase I dose-escalation study of visilianmab in patients with severe UC whose disease has not responded to a minimum of 5 days of intravenous (IV) corticosteroids. Seven patients have been enrolled to date; five patients (reported here) have passed the day 30 evaluation. All patients received an IV infusion of visilizumab at 15 p,/kg on study days 1 and 2. Results: At enrollment, the first 5 patients had a median modified Truelove and Witts (MTWS]) score of 13 (range 11-16); all had an endoscopy score of 3 (scale 0-3, 3 = severe disease), with >60 cm of colon involvement by endoscopy. At day 30, these 5 patients all achieved clinical and endoscopic remLssion (defined as an MTWSI of <3) and an endoscopy score of 0 or 1. Patients have continued to maintain clinical improvement for several months following treatment. The first 3 patients are now beyond 90 days and have been tapered off steroids onto 5-ASA's or are receiving no additional therapy. Transient (1-4 week) decreases in T-lymphocyte counts from peripheral blood were observed. Moderate cytokine release symptoms (nausea, vomiting, chifis, arthmlgias) were observed in four patients, and one patient had severe dehydration that required fluid support. These symptoms were transient, resolving within 1-2 hours and occurred predominantly on day 1. Two patients had transienL low-level Epstein-Barr titers (3640, 5153 copies/m1) in whole-blood detected by PCR that were not associated with clinical symptoms. There have been no documented infectious complications. Conclusions: This preliminary analysis of an open-label phase [ study of visilizumab in patients with severe UC has demonstrated potential tolerahility and clinical activity at a very low dose. Enrollment into this study continues and the data will be updated at the meeting.

  • A humanized Anti-CD3 Monoclonal Antibody, visilizumab, for treatment of severe steroid-refractory ulcerative colitis: Preliminary results of a phase I study
    Gastroenterology, 2003
    Co-Authors: Scott E Plevy, Bruce Salzberg, Miguel Regueiro, William J Sandborn, Stephen B Hanauer, Stephan R Targan, Lloyd Mayer, Ian B. Walters
    Abstract:

    Purpose: In severe, steroid-resistant ulcerative colitis (UC), therapeutic approaches have involved targeting T-cells to control excess inflammation. We hypothesize that the humanized Anti-CD3 Monoclonal Antibody, visiliaumab (Protein Design Labs, Inc., Fremont, CA), may provide therapeutic benefit in UC Methods: We report preliminary results from multicenter, phase I dose-escalation study of visilianmab in patients with severe UC whose disease has not responded to a minimum of 5 days of intravenous (IV) corticosteroids. Seven patients have been enrolled to date; five patients (reported here) have passed the day 30 evaluation. All patients received an IV infusion of visilizumab at 15 p,/kg on study days 1 and 2. Results: At enrollment, the first 5 patients had a median modified Truelove and Witts (MTWS]) score of 13 (range 11-16); all had an endoscopy score of 3 (scale 0-3, 3 = severe disease), with >60 cm of colon involvement by endoscopy. At day 30, these 5 patients all achieved clinical and endoscopic remLssion (defined as an MTWSI of

Bruce Salzberg - One of the best experts on this subject based on the ideXlab platform.

  • a phase i study of visilizumab a humanized anti cd3 Monoclonal Antibody in severe steroid refractory ulcerative colitis
    Gastroenterology, 2007
    Co-Authors: Scott E Plevy, Bruce Salzberg, Gert Van Assche, Miguel Regueiro, Daniel W Hommes, William J Sandborn, Stephen B Hanauer, Stephan R Targan, Lloyd Mayer, Uma Mahadevan
    Abstract:

    Background & Aims: To evaluate the safety and biological activity of visilizumab (a humanized Anti-CD3 Monoclonal Antibody) and to determine a maximum tolerated dose in patients with severe ulcerative colitis that had not responded to 5 days of treatment with intravenous corticosteroids. Methods: In this open-label phase 1 study, 32 subjects received visilizumab at a dose of 10 or 15 μg/kg, administered intravenously on 2 consecutive days. Clinical response was defined as a Modified Truelove and Witts Severity Index 30 days in 2 of 8 patients), the dose was reduced to 10 μg/kg in 24 patients. On day 30, 84% of patients demonstrated a clinical response, 41% achieved clinical remission, and 44% achieved endoscopic remission. Forty-five percent of patients did not require salvage therapies or colectomy during the first year postdose. Mild to moderate symptoms of cytokine release occurred in 100% and 83% of patients in the 15- and 10-μg/kg dose groups, respectively. All patients exhibited a rapid decrease in circulating CD4+ T-cell counts, which returned to baseline values by day 30 in 26 of 30 evaluable patients (86%). There were no serious infections. Conclusions: Visilizumab had an acceptable safety profile at the 10-μg/kg dose level and may be clinically beneficial in patients with severe intravenous corticosteroid–refractory ulcerative colitis.

  • a humanized anti cd3 Monoclonal Antibody visilizumab for treatment of severe steroid refractory ulcerative colitis preliminary results of a phase i study
    Gastroenterology, 2003
    Co-Authors: Scott E Plevy, Bruce Salzberg, Miguel Regueiro, William J Sandborn, Stephen B Hanauer, Stephan R Targan, Lloyd Mayer, Ian Walters
    Abstract:

    Purpose: In severe, steroid-resistant ulcerative colitis (UC), therapeutic approaches have involved targeting T-cells to control excess inflammation. We hypothesize that the humanized Anti-CD3 Monoclonal Antibody, visiliaumab (Protein Design Labs, Inc., Fremont, CA), may provide therapeutic benefit in UC Methods: We report preliminary results from multicenter, phase I dose-escalation study of visilianmab in patients with severe UC whose disease has not responded to a minimum of 5 days of intravenous (IV) corticosteroids. Seven patients have been enrolled to date; five patients (reported here) have passed the day 30 evaluation. All patients received an IV infusion of visilizumab at 15 p,/kg on study days 1 and 2. Results: At enrollment, the first 5 patients had a median modified Truelove and Witts (MTWS]) score of 13 (range 11-16); all had an endoscopy score of 3 (scale 0-3, 3 = severe disease), with >60 cm of colon involvement by endoscopy. At day 30, these 5 patients all achieved clinical and endoscopic remLssion (defined as an MTWSI of <3) and an endoscopy score of 0 or 1. Patients have continued to maintain clinical improvement for several months following treatment. The first 3 patients are now beyond 90 days and have been tapered off steroids onto 5-ASA's or are receiving no additional therapy. Transient (1-4 week) decreases in T-lymphocyte counts from peripheral blood were observed. Moderate cytokine release symptoms (nausea, vomiting, chifis, arthmlgias) were observed in four patients, and one patient had severe dehydration that required fluid support. These symptoms were transient, resolving within 1-2 hours and occurred predominantly on day 1. Two patients had transienL low-level Epstein-Barr titers (3640, 5153 copies/m1) in whole-blood detected by PCR that were not associated with clinical symptoms. There have been no documented infectious complications. Conclusions: This preliminary analysis of an open-label phase [ study of visilizumab in patients with severe UC has demonstrated potential tolerahility and clinical activity at a very low dose. Enrollment into this study continues and the data will be updated at the meeting.

  • A humanized Anti-CD3 Monoclonal Antibody, visilizumab, for treatment of severe steroid-refractory ulcerative colitis: Preliminary results of a phase I study
    Gastroenterology, 2003
    Co-Authors: Scott E Plevy, Bruce Salzberg, Miguel Regueiro, William J Sandborn, Stephen B Hanauer, Stephan R Targan, Lloyd Mayer, Ian B. Walters
    Abstract:

    Purpose: In severe, steroid-resistant ulcerative colitis (UC), therapeutic approaches have involved targeting T-cells to control excess inflammation. We hypothesize that the humanized Anti-CD3 Monoclonal Antibody, visiliaumab (Protein Design Labs, Inc., Fremont, CA), may provide therapeutic benefit in UC Methods: We report preliminary results from multicenter, phase I dose-escalation study of visilianmab in patients with severe UC whose disease has not responded to a minimum of 5 days of intravenous (IV) corticosteroids. Seven patients have been enrolled to date; five patients (reported here) have passed the day 30 evaluation. All patients received an IV infusion of visilizumab at 15 p,/kg on study days 1 and 2. Results: At enrollment, the first 5 patients had a median modified Truelove and Witts (MTWS]) score of 13 (range 11-16); all had an endoscopy score of 3 (scale 0-3, 3 = severe disease), with >60 cm of colon involvement by endoscopy. At day 30, these 5 patients all achieved clinical and endoscopic remLssion (defined as an MTWSI of

Lloyd Mayer - One of the best experts on this subject based on the ideXlab platform.

  • a phase i study of visilizumab a humanized anti cd3 Monoclonal Antibody in severe steroid refractory ulcerative colitis
    Gastroenterology, 2007
    Co-Authors: Scott E Plevy, Bruce Salzberg, Gert Van Assche, Miguel Regueiro, Daniel W Hommes, William J Sandborn, Stephen B Hanauer, Stephan R Targan, Lloyd Mayer, Uma Mahadevan
    Abstract:

    Background & Aims: To evaluate the safety and biological activity of visilizumab (a humanized Anti-CD3 Monoclonal Antibody) and to determine a maximum tolerated dose in patients with severe ulcerative colitis that had not responded to 5 days of treatment with intravenous corticosteroids. Methods: In this open-label phase 1 study, 32 subjects received visilizumab at a dose of 10 or 15 μg/kg, administered intravenously on 2 consecutive days. Clinical response was defined as a Modified Truelove and Witts Severity Index 30 days in 2 of 8 patients), the dose was reduced to 10 μg/kg in 24 patients. On day 30, 84% of patients demonstrated a clinical response, 41% achieved clinical remission, and 44% achieved endoscopic remission. Forty-five percent of patients did not require salvage therapies or colectomy during the first year postdose. Mild to moderate symptoms of cytokine release occurred in 100% and 83% of patients in the 15- and 10-μg/kg dose groups, respectively. All patients exhibited a rapid decrease in circulating CD4+ T-cell counts, which returned to baseline values by day 30 in 26 of 30 evaluable patients (86%). There were no serious infections. Conclusions: Visilizumab had an acceptable safety profile at the 10-μg/kg dose level and may be clinically beneficial in patients with severe intravenous corticosteroid–refractory ulcerative colitis.

  • a humanized anti cd3 Monoclonal Antibody visilizumab for treatment of severe steroid refractory ulcerative colitis preliminary results of a phase i study
    Gastroenterology, 2003
    Co-Authors: Scott E Plevy, Bruce Salzberg, Miguel Regueiro, William J Sandborn, Stephen B Hanauer, Stephan R Targan, Lloyd Mayer, Ian Walters
    Abstract:

    Purpose: In severe, steroid-resistant ulcerative colitis (UC), therapeutic approaches have involved targeting T-cells to control excess inflammation. We hypothesize that the humanized Anti-CD3 Monoclonal Antibody, visiliaumab (Protein Design Labs, Inc., Fremont, CA), may provide therapeutic benefit in UC Methods: We report preliminary results from multicenter, phase I dose-escalation study of visilianmab in patients with severe UC whose disease has not responded to a minimum of 5 days of intravenous (IV) corticosteroids. Seven patients have been enrolled to date; five patients (reported here) have passed the day 30 evaluation. All patients received an IV infusion of visilizumab at 15 p,/kg on study days 1 and 2. Results: At enrollment, the first 5 patients had a median modified Truelove and Witts (MTWS]) score of 13 (range 11-16); all had an endoscopy score of 3 (scale 0-3, 3 = severe disease), with >60 cm of colon involvement by endoscopy. At day 30, these 5 patients all achieved clinical and endoscopic remLssion (defined as an MTWSI of <3) and an endoscopy score of 0 or 1. Patients have continued to maintain clinical improvement for several months following treatment. The first 3 patients are now beyond 90 days and have been tapered off steroids onto 5-ASA's or are receiving no additional therapy. Transient (1-4 week) decreases in T-lymphocyte counts from peripheral blood were observed. Moderate cytokine release symptoms (nausea, vomiting, chifis, arthmlgias) were observed in four patients, and one patient had severe dehydration that required fluid support. These symptoms were transient, resolving within 1-2 hours and occurred predominantly on day 1. Two patients had transienL low-level Epstein-Barr titers (3640, 5153 copies/m1) in whole-blood detected by PCR that were not associated with clinical symptoms. There have been no documented infectious complications. Conclusions: This preliminary analysis of an open-label phase [ study of visilizumab in patients with severe UC has demonstrated potential tolerahility and clinical activity at a very low dose. Enrollment into this study continues and the data will be updated at the meeting.

  • A humanized Anti-CD3 Monoclonal Antibody, visilizumab, for treatment of severe steroid-refractory ulcerative colitis: Preliminary results of a phase I study
    Gastroenterology, 2003
    Co-Authors: Scott E Plevy, Bruce Salzberg, Miguel Regueiro, William J Sandborn, Stephen B Hanauer, Stephan R Targan, Lloyd Mayer, Ian B. Walters
    Abstract:

    Purpose: In severe, steroid-resistant ulcerative colitis (UC), therapeutic approaches have involved targeting T-cells to control excess inflammation. We hypothesize that the humanized Anti-CD3 Monoclonal Antibody, visiliaumab (Protein Design Labs, Inc., Fremont, CA), may provide therapeutic benefit in UC Methods: We report preliminary results from multicenter, phase I dose-escalation study of visilianmab in patients with severe UC whose disease has not responded to a minimum of 5 days of intravenous (IV) corticosteroids. Seven patients have been enrolled to date; five patients (reported here) have passed the day 30 evaluation. All patients received an IV infusion of visilizumab at 15 p,/kg on study days 1 and 2. Results: At enrollment, the first 5 patients had a median modified Truelove and Witts (MTWS]) score of 13 (range 11-16); all had an endoscopy score of 3 (scale 0-3, 3 = severe disease), with >60 cm of colon involvement by endoscopy. At day 30, these 5 patients all achieved clinical and endoscopic remLssion (defined as an MTWSI of

Stephan R Targan - One of the best experts on this subject based on the ideXlab platform.

  • a phase i study of visilizumab a humanized anti cd3 Monoclonal Antibody in severe steroid refractory ulcerative colitis
    Gastroenterology, 2007
    Co-Authors: Scott E Plevy, Bruce Salzberg, Gert Van Assche, Miguel Regueiro, Daniel W Hommes, William J Sandborn, Stephen B Hanauer, Stephan R Targan, Lloyd Mayer, Uma Mahadevan
    Abstract:

    Background & Aims: To evaluate the safety and biological activity of visilizumab (a humanized Anti-CD3 Monoclonal Antibody) and to determine a maximum tolerated dose in patients with severe ulcerative colitis that had not responded to 5 days of treatment with intravenous corticosteroids. Methods: In this open-label phase 1 study, 32 subjects received visilizumab at a dose of 10 or 15 μg/kg, administered intravenously on 2 consecutive days. Clinical response was defined as a Modified Truelove and Witts Severity Index 30 days in 2 of 8 patients), the dose was reduced to 10 μg/kg in 24 patients. On day 30, 84% of patients demonstrated a clinical response, 41% achieved clinical remission, and 44% achieved endoscopic remission. Forty-five percent of patients did not require salvage therapies or colectomy during the first year postdose. Mild to moderate symptoms of cytokine release occurred in 100% and 83% of patients in the 15- and 10-μg/kg dose groups, respectively. All patients exhibited a rapid decrease in circulating CD4+ T-cell counts, which returned to baseline values by day 30 in 26 of 30 evaluable patients (86%). There were no serious infections. Conclusions: Visilizumab had an acceptable safety profile at the 10-μg/kg dose level and may be clinically beneficial in patients with severe intravenous corticosteroid–refractory ulcerative colitis.

  • a humanized anti cd3 Monoclonal Antibody visilizumab for treatment of severe steroid refractory ulcerative colitis preliminary results of a phase i study
    Gastroenterology, 2003
    Co-Authors: Scott E Plevy, Bruce Salzberg, Miguel Regueiro, William J Sandborn, Stephen B Hanauer, Stephan R Targan, Lloyd Mayer, Ian Walters
    Abstract:

    Purpose: In severe, steroid-resistant ulcerative colitis (UC), therapeutic approaches have involved targeting T-cells to control excess inflammation. We hypothesize that the humanized Anti-CD3 Monoclonal Antibody, visiliaumab (Protein Design Labs, Inc., Fremont, CA), may provide therapeutic benefit in UC Methods: We report preliminary results from multicenter, phase I dose-escalation study of visilianmab in patients with severe UC whose disease has not responded to a minimum of 5 days of intravenous (IV) corticosteroids. Seven patients have been enrolled to date; five patients (reported here) have passed the day 30 evaluation. All patients received an IV infusion of visilizumab at 15 p,/kg on study days 1 and 2. Results: At enrollment, the first 5 patients had a median modified Truelove and Witts (MTWS]) score of 13 (range 11-16); all had an endoscopy score of 3 (scale 0-3, 3 = severe disease), with >60 cm of colon involvement by endoscopy. At day 30, these 5 patients all achieved clinical and endoscopic remLssion (defined as an MTWSI of <3) and an endoscopy score of 0 or 1. Patients have continued to maintain clinical improvement for several months following treatment. The first 3 patients are now beyond 90 days and have been tapered off steroids onto 5-ASA's or are receiving no additional therapy. Transient (1-4 week) decreases in T-lymphocyte counts from peripheral blood were observed. Moderate cytokine release symptoms (nausea, vomiting, chifis, arthmlgias) were observed in four patients, and one patient had severe dehydration that required fluid support. These symptoms were transient, resolving within 1-2 hours and occurred predominantly on day 1. Two patients had transienL low-level Epstein-Barr titers (3640, 5153 copies/m1) in whole-blood detected by PCR that were not associated with clinical symptoms. There have been no documented infectious complications. Conclusions: This preliminary analysis of an open-label phase [ study of visilizumab in patients with severe UC has demonstrated potential tolerahility and clinical activity at a very low dose. Enrollment into this study continues and the data will be updated at the meeting.

  • A humanized Anti-CD3 Monoclonal Antibody, visilizumab, for treatment of severe steroid-refractory ulcerative colitis: Preliminary results of a phase I study
    Gastroenterology, 2003
    Co-Authors: Scott E Plevy, Bruce Salzberg, Miguel Regueiro, William J Sandborn, Stephen B Hanauer, Stephan R Targan, Lloyd Mayer, Ian B. Walters
    Abstract:

    Purpose: In severe, steroid-resistant ulcerative colitis (UC), therapeutic approaches have involved targeting T-cells to control excess inflammation. We hypothesize that the humanized Anti-CD3 Monoclonal Antibody, visiliaumab (Protein Design Labs, Inc., Fremont, CA), may provide therapeutic benefit in UC Methods: We report preliminary results from multicenter, phase I dose-escalation study of visilianmab in patients with severe UC whose disease has not responded to a minimum of 5 days of intravenous (IV) corticosteroids. Seven patients have been enrolled to date; five patients (reported here) have passed the day 30 evaluation. All patients received an IV infusion of visilizumab at 15 p,/kg on study days 1 and 2. Results: At enrollment, the first 5 patients had a median modified Truelove and Witts (MTWS]) score of 13 (range 11-16); all had an endoscopy score of 3 (scale 0-3, 3 = severe disease), with >60 cm of colon involvement by endoscopy. At day 30, these 5 patients all achieved clinical and endoscopic remLssion (defined as an MTWSI of