A Phase 2b/3, Multi-Center, Randomized, Double-Blind, Placebo Controlled Trial to Evaluate the Safety and Efficacy of Pagibaximab Injection in Very Low Birth Weight (VLBW) Neonates for the Prevention of Staphylococcal Sepsis

开始日期2009-12-22

申办/合作机构

Biosynexus, Inc.

NCT00646399 / Completed临床2/3期

Evaluate the safety, PK and efficacy comparing Pagibaximab Injection to placebo in preventing staphylococcal sepsis in very low birth weight infants. 1550 infants will be enrolled prior to 48 hours of life and will be randomized 1:1 to receive active drug or placebo on study days 0, 1, 2, 9, 16, and 23.

开始日期2009-03-01

申办/合作机构

Biosynexus, Inc.

NCT00631800 / Completed临床2期

Phase II Randomized, Double Blind, Placebo Controlled, Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity Study in VLBW Neonates of BSYX-A110, for the Prevention of Staphylococcal Infection

The purpose of this study is to evaluate the safety (including tolerability), pharmacokinetics, pharmacodynamics and clinical activity of BSYX-A110 administered in a 3-dose regimen on Study Days 0, 7, and 14.

开始日期2003-05-01

申办/合作机构

Biosynexus, Inc.

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2011-08-15·Open Antimicrobial Agents Journal

Lysostaphin Reduces the Production of Inflammatory Cytokines in Staphylococcus aureus Challenged Mice, and Prevents Systemic Shock

作者: Kokai-Kun, John F. ; Mond, James J. ; Sei, Clara ; Chanturiya, Tanya

Lysostaphin is being developed as a treatment for serious staphylococcal infections.Mice challenged with S. aureus produce inflammatory cytokines including, TNF-α and IL-6, and over-production of these cytokines can lead to shock and contribute to the lethality of staphylococcal infections.Two major components of the staphylococcal cell wall, peptidoglycan and lipoteichoic acid, are known to synergize to induce shock and organ failure in animal models, and we wished to determine whether the rapid lysostaphin-mediated degradation of peptidoglycan during treatment of systemic S. aureus infection could affect shock-associated parameters.We found that lysostaphin treatment of S. aureus-infected mice, which reduces bacteremia and organ infection, also reduced the serum levels of inflammatory cytokines and reversed the symptoms of S. aureus-induced shock.We compared the cytokine response of mice challenged with S. aureus to that of mice challenged with S. aureus and then treated with lysostaphin or nafcillin.Lysostaphin-treated mice, as compared with untreated mice or nafcillin-treated mice, had a blunted cytokine responses to S. aureus challenge.Core body temperature was used as a real time indicator for systemic shock in mice.Mice infected with S. aureus demonstrated a rapid drop in core body temperature, which was reversed by lysostaphin treatment.These studies demonstrated that lysostaphin treatment did not contribute to the induction of shock by rapidly releasing staphylococcal cell wall components, but rather it blunted the inflammatory cytokine response and ameliorated shock related symptoms.

2009-07-01·Antimicrobial agents and chemotherapy2区 · 医学

Phase 1/2 Double-Blind, Placebo-Controlled, Dose Escalation, Safety, and Pharmacokinetic Study of Pagibaximab (BSYX-A110), an Antistaphylococcal Monoclonal Antibody for the Prevention of Staphylococcal Bloodstream Infections, in Very-Low-Birth-Weight Neonates

2区 · 医学

Article

作者: Thackray, Helen M. ; Kramer, William G. ; Nesin, Mirjana ; Kokai-Kun, John F. ; Fretz, Jennifer ; Garcia-Prats, Joseph A. ; Mond, James J. ; Fischer, Gerald W. ; Schneider, Joseph H. ; Weisman, Leonard E.

ABSTRACT:

Staphylococcal sepsis is a major cause of morbidity and mortality in very-low-birth-weight (VLBW) infants. A human chimeric monoclonal antibody, pagibaximab, was developed against staphylococcal lipoteichoic acid. We evaluated the safety, tolerability, and pharmacokinetics of pagibaximab in VLBW neonates. A phase 1/2, randomized, double-blind, placebo-controlled, dose escalation study was conducted in VLBW infants (700 to 1,300 g) 3 to 7 days old. Patients received two doses 14 days apart of intravenous pagibaximab (10, 30, 60, or 90 mg/kg of body weight) or placebo in a 2:1 ratio. Blood and urine samples were obtained pre- and postinfusion for analysis of safety and pharmacokinetics, and data on adverse events were gathered. Staphylococcal organisms causing sepsis were collected and evaluated. Fifty-three patients received at least one dose of pagibaximab or placebo. The average gestational age was 27.6 weeks; the average birth weight was 1,003 g. All serious adverse events were deemed unrelated or probably not drug related. Morbidity and mortality were similar across treatment groups. No evidence of immunogenicity of pagibaximab was detected. Pagibaximab pharmacokinetics was linear. The mean clearance (CL), volume of distribution, and elimination half-life of pagibaximab were independent of dose. The serum half-life was 20.5 ± 6.8 days. Pagibaximab enhanced serum opsonophagocytic activity. All staphylococci causing sepsis were opsonizable by pagibaximab. Two infusions of pagibaximab, administered 2 weeks apart to high-risk neonates appeared safe and tolerable, and pharmacokinetics were linear. Evaluation of more frequent doses, at the highest doses tested, in neonates at high-risk of staphylococcal sepsis, is warranted.

2008-12-01·Journal of neuroinflammation1区 · 医学

Mannan-Abeta28conjugate prevents Abeta-plaque deposition, but increases microhemorrhages in the brains of vaccinated Tg2576 (APPsw) mice

1区 · 医学

ArticleOA

作者: Andrew Lees ; Anahit Ghochikyan ; Mikayel Mkrtichyan ; Grigor Mamikonyan ; Adrine Karapetyan ; Vitaly Vasilevko ; Michael G Agadjanyan ; Irina Petrushina ; Rodmehr Ajdari ; Nina Movsesyan ; David H Cribbs

Abstract:

Background:

New pre-clinical trials in AD mouse models may help to develop novel immunogen-adjuvant configurations with the potential to avoid the adverse responses that occurred during the clinical trials with AN-1792 vaccine formulation. Recently, we have pursued an alternative immunization strategy that replaces QS21 the Th1 type adjuvant used in the AN-1792 clinical trial with a molecular adjuvant, mannan that can promote a Th2-polarized immune response through interactions with mannose-binding and CD35/CD21 receptors of the innate immune system. Previously we established that immunization of wild-type mice with mannan-Aβ28conjugate promoted Th2-mediated humoral and cellular immune responses. In the current study, we tested the efficacy of this vaccine configuration in amyloid precursor protein (APP) transgenic mice (Tg2576).

Methods:

Mannan was purified, activated and chemically conjugated to Aβ28peptide. Humoral immune responses induced by the immunization of mice with mannan-Aβ28conjugate were analyzed using a standard ELISA. Aβ42and Aβ40amyloid burden, cerebral amyloid angiopathy (CAA), astrocytosis, and microgliosis in the brain of immunized and control mice were detected using immunohistochemistry. Additionally, cored plaques and cerebral vascular microhemorrhages in the brains of vaccinated mice were detected by standard histochemistry.

Results:

Immunizations with low doses of mannan-Aβ28induced potent and long-lasting anti-Aβ humoral responses in Tg2576 mice. Even 11 months after the last injection, the immunized mice were still producing low levels of anti-Aβ antibodies, predominantly of the IgG1 isotype, indicative of a Th2 immune response. Vaccination with mannan-Aβ28prevented Aβ plaque deposition, but unexpectedly increased the level of microhemorrhages in the brains of aged immunized mice compared to two groups of control animals of the same age either injected with molecular adjuvant fused with an irrelevant antigen, BSA (mannan-BSA) or non-immunized mice. Of note, mice immunized with mannan-Aβ28showed a trend toward elevated levels of CAA in the neocortex and in the leptomeninges compared to that in mice of both control groups.

Conclusion:

Mannan conjugated to Aβ28provided sufficient adjuvant activity to induce potent anti-Aβ antibodies in APP transgenic mice, which have been shown to be hyporesponsive to immunization with Aβ self-antigen. However, in old Tg2576 mice there were increased levels of cerebral microhemorrhages in mannan-Aβ28immunized mice. This effect was likely unrelated to the anti-mannan antibodies induced by the immunoconjugate, because control mice immunized with mannan-BSA also induced antibodies specific to mannan, but did not have increased levels of cerebral microhemorrhages compared with non-immunized mice. Whether these anti-mannan antibodies increased the permeability of the blood brain barrier thus allowing elevated levels of anti-Aβ antibodies entry into cerebral perivascular or brain parenchymal spaces and contributed to the increased incidence of microhemorrhages remains to be investigated in the future studies.

项与 Biosynexus, Inc. 相关的新闻（医药）

2021-09-22

·BioSpace

ImmunoGen Appoints Helen M. Thackray, MD to its Board of Directors

WALTHAM, Mass.--(BUSINESS WIRE)-- ImmunoGen Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, today announced the appointment of Helen M. Thackray, MD, FAAP to its Board of Directors. "Helen joins ImmunoGen's Board of Directors at an exciting time, as we advance multiple programs in the clinic and transform ImmunoGen into a fully integrated oncology company with the potential to launch two innovative ADCs next year," said Stephen McCluski, ImmunoGen's Chairman of the Board of Directors. "Her deep development and regulatory expertise will be invaluable in the near term, as we anticipate pivotal data and submission of a BLA for our lead program, mirvetuximab soravtansine, and progress the rest of our portfolio with a focus on a path to full approval for IMGN632 in blastic plasmacytoid dendritic cell neoplasm (BPDCN)." Dr. Thackray has over 25 years of biopharmaceutical, clinical research, and bench research experience. Currently, Dr. Thackray is the Chief Research and Development Officer for BioCryst Pharmaceuticals, Inc., where she oversees research and development activities from discovery through registration and defines the strategic direction of the Company's pipeline. Prior to joining BioCryst, Dr. Thackray served in various positions of increasing responsibility at GlycoMimetics, Inc., including ten years as Chief Medical Officer and Senior Vice President, Clinical Development. In this role, she led product development for a multinational program in AML (acute myeloid leukemia) and other hematologic malignancies from pre-IND through registration studies. Earlier in Dr. Thackray's career, she was Vice President, Clinical Product Development for Biosynexus, Inc., where she led the Company's development programs in orphan indications. Dr. Thackray is a board-certified pediatrician and, since 2002, has been an Assistant Clinical Professor in Pediatrics at George Washington University School of Medicine and Health Sciences. She holds a Doctor of Medicine degree from George Washington University, School of Medicine and Health Sciences, a Bachelor of Sciences degree from Stanford University, and is a Fellow of the American Academy of Pediatrics (FAAP). Dr. Thackray stated, "ImmunoGen has established a leadership position in ADCs and built a strong pipeline targeting solid tumors and hematologic malignancies. The Company is rapidly approaching the commercialization of two products in areas of significant unmet need, and I look forward to contributing my expertise and working with the rest of the Board and management team to deliver more good days for cancer patients and create long-term value for the business." ABOUT IMMUNOGEN ImmunoGen is developing the next generation of antibody-drug conjugates (ADCs) to improve outcomes for cancer patients. By generating targeted therapies with enhanced anti-tumor activity and favorable tolerability pro we aim to disrupt the progression of cancer and offer our patients more good days. We call this our commitment to TARGET A BETTER NOW™. Learn more about who we are, what we do, and how we do it at . FORWARD-LOOKING STATEMENTS This press release includes forward-looking statements based on management's current expectations. These statements include, but are not limited to, ImmunoGen's expectations related to: the occurrence, timing, and outcome of potential preclinical, clinical, and regulatory events related to the Company's product candidates, in particular with respect to mirvetuximab soravtansine and IMGN632, and the launch of those product candidates next year; and the presentation of preclinical and clinical data on the Company's product candidates, including with respect to mirvetuximab soravtansine and IMGN632. For these statements, ImmunoGen claims the protection of the safe harbor for forward-looking statements provided by the Private Securities Litigation Reform Act of 1995. Various factors could cause ImmunoGen's actual results to differ materially from those discussed or implied in the forward-looking statements, and you are cautioned not to place undue reliance on these forward-looking statements, which are current only as of the date of this release. Factors that could cause future results to differ materially from such expectations include, but are not limited to: the timing and outcome of the Company's preclinical and clinical development processes; the difficulties inherent in the development of novel pharmaceuticals, including uncertainties as to the timing, expense, and results of preclinical studies, clinical trials, and regulatory processes; the Company's ability to financially support its product programs; risks and uncertainties associated with the scale and duration of the COVID-19 pandemic and the resulting impact on ImmunoGen's industry and business; and other factors as set forth in the Company's Annual Report on Form 10-K filed with the Securities and Exchange Commission on March 1, 2021, and other reports filed with the Securities and Exchange Commission.

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