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News Article | December 13, 2016
Site: www.businesswire.com

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Acer Therapeutics Inc., a pharmaceutical company developing therapies for serious rare diseases with significant unmet medical need, today announced the signing of an agreement with the Greater Paris University Hospitals AP-HP (via its Department of Clinical Research and Development*) granting the company exclusive rights to access and use data from a randomized controlled clinical study of celiprolol.1 The company will use this pivotal clinical data to support a New Drug Application (NDA) regulatory filing for its lead product, VASEBRA™ (celiprolol), for the treatment of vascular Ehlers-Danlos Syndrome (vEDS). “We have studied celiprolol for nearly two decades in vEDS patients and this is the only drug ever to demonstrate a clinical benefit in a randomized, controlled clinical study,” said Pierre Boutouyrie M.D., Ph.D., co-director of the clinical pharmacology service at the Georges-Pompidou European Hospital AP-HP and Principal Investigator for the celiprolol study. “Having established celiprolol as a standard of care in France for vEDS patients, we are excited to partner with Acer to help bring celiprolol to members of the U.S. patient community who are suffering from this devastating, life-threatening disease.” “We are committed to bringing VASEBRA™ to vEDS patients who currently do not have access to this treatment,” said Robert D. Steiner, M.D., Chief Medical Officer of Acer. “This pivotal clinical data from AP-HP will represent a critical element of the clinical module in our NDA, which we are diligently building along with manufacturing, non-clinical and other components of the regulatory package.” “This collaboration between AP-HP and Acer is a fantastic example of academic-industry partnership,” said Chris Schelling, CEO and Founder of Acer. “The signing of this agreement marks an important corporate milestone as it will enable us to continue to rapidly advance our lead candidate VASEBRA™, a potential life-saving therapy for patients with vEDS, towards an NDA filing.” About VASEBRA™ and Vascular Ehlers-Danlos Syndrome (vEDS) Ehlers-Danlos Syndrome (EDS) is a group of hereditary disorders of connective tissue. Vascular EDS (vEDS) is the most severe subtype where patients suffer from life threatening arterial dissections and ruptures, as well as intestinal and uterine ruptures. The average mortality is 51 years of age. There are approximately 2,000 people in the U.S. diagnosed with vEDS, though experts estimate as many as 5,000 patients may be affected. There are currently no FDA-approved therapies for vEDS.2 Acer is advancing VASEBRA™ (celiprolol), a new chemical entity (NCE), for the treatment of vEDS and plans to file an NDA based on a randomized controlled clinical study of celiprolol.1 In 2015, the U.S. Food and Drug Administration (FDA) granted VASEBRA™ orphan drug designation for the potential treatment of vEDS. *The Office for Technology Transfer & Industrial Ventures of the AP-HP's Department of Clinical Research and Development, protects and enhances the innovations and clinical expertise of medical personnel by setting up privileged partnerships with healthcare companies. Nearly half of the patented innovations are transferred to companies all over the world and, in particular, the creation of nearly 70 young companies. The AP-HP organizes each year the APinnov Technology Transfer Meetings. About Greater Paris university hospitals AP-HP AP-HP (Greater Paris University Hospitals) is a European world-renowned university hospital. Its 39 hospitals treat 8 million people every year: in consultation, emergency, during scheduled or home hospitalizations. The AP-HP provides a public health service for everyone, 24 hours a day. This mission is a duty as well as a great source of pride. AP-HP is the leading employer in the Greater Paris area: 100,000 staff members – doctors, researchers, paramedical staff, administrative personnel and workers – work there. About Acer Therapeutics Acer Therapeutics, headquartered in Cambridge, MA, is developing therapies with established clinical proof-of-concept for the treatment of serious, ultra-rare diseases with critical unmet medical need. The company’s late-stage clinical pipeline includes two candidates for severe genetic disorders for which there are currently no FDA-approved treatments: VASEBRA™ for vascular Ehlers-Danlos Syndrome (vEDS), and ACER-001 for Maple Syrup Urine Disease (MSUD) and Urea Cycle Disorders (UCD). 1. Ong KT, et al. Effect of celiprolol on prevention of cardiovascular events in vascular Ehlers-Danlos syndrome: a prospective randomised, open, blinded-endpoints trial. Lancet. 2010; 376: 1476–84. 2. Pepin MG, et al. Survival is affected by mutation type and molecular mechanism in vascular Ehlers–Danlos syndrome (EDS type IV) Genet Med. 16: 881-888.

Santagostino E.,Maggiore Hospital Policlinico | Negrier C.,University of Lyon | Klamroth R.,Vivantes Hospital | Tiede A.,Hannover Medical School | And 4 more authors.
Blood | Year: 2012

A recombinant fusion protein linking coagulation factor IX (FIX) with human albumin (rIX-FP) has been developed to facilitate hemophilia B treatment by less frequent FIX dosing. This first-in-human dose-escalation trial in 25 previously treated subjects with hemophilia B (FIX ≤ 2 IU/dL) examined the safety and pharmacokinetics of 25, 50, and 75 IU/kg rIX-FP. Patients in the 50-IU/kg cohort underwent a comparative pharmacokinetics assessment with their previous FIX product (plasma-derived or recombinant). No allergic reactions or inhibitors were observed. Four mild, possibly treatmentrelated adverse events were reported. In the 50-IU/kg cohort (13 subjects), the mean half-life of rIX-FP was 92 hours, more than 5 times longer than the subjects' previous FIX product. After 25 or 50 IU/kg rIX-FP administration, the baseline-corrected mean FIX activity remained elevated at day 7 (7.4 IU/dL and 13.4 IU/dL, respectively) and day 14 (2.5 IU/dL and 5.5 IU/dL, respectively). The incremental recovery of rIX-FP was higher than both recombinant and plasma-derived FIX (1.4 vs 0.95 and 1.1 IU/dL per IU/kg, respectively). These results demonstrated both the safety and improved pharmacokinetics of rIX-FP, thus indicating this new product with extended half-life as possibly able to control and prevent bleeding with less frequent injection. The trial was registered at www.clinicaltrials.gov as no. NCT01233440. © 2012 by The American Society of Hematology.

Qaqundah P.Y.,Hoag Medical Group | Taveras H.,Clinical Research and Development | Iverson H.,Teva Pharmaceuticals | Shore P.,Clinical Research and Development
Allergy and Asthma Proceedings | Year: 2016

Background: Many children struggle with albuterol hydrofluoroalkane (HFA) inhalers. Albuterol multidose dry powder inhaler (MDPI) may simplify rescue bronchodilator use in children. Objective: To demonstrate the comparability of albuterol MDPI and albuterol HFA in children with asthma. Methods: This phase II, multicenter, double-blind, double-dummy, single-dose, five-period, crossover study randomized patients (ages 4-11 years) with persistent asthma and prestudy forced expiratory volume in 1 second (FEV1) of 60-90% of predicted to 1 of 10 treatment sequences that contained albuterol MDPI (90 and 180 μg), albuterol HFA (90 and 180 μg), and placebo MDPI and placebo HFA. Efficacy was evaluated by measuring the area under the baseline-adjusted percent-predicted FEV1-time curve over 6 hours (PPFEV1 AUC0-6) after dosing. Safety was evaluated by adverse events. Results: The full analysis set included 61 patients. Albuterol MDPI and albuterol HFA significantly improved PPFEV1 AUC0-6 versus placebo (p ≤ 0.0107). Mean improvement (± standard error [SE]) in PPFEV1 AUC0-6 versus placebo with albuterol MDPI at 90 and 180 μg was similar (21.2 ± 4.87 [95% confidence interval {CI}, 11.60 -30.81], and 22.6 ± 4.87 [95% CI, 13.00 -32.20], %•hour, respectively). Mean improvement (± SE) with albuterol HFA 180 μg was significantly (p = 0.0226) greater versus albuterol HFA 90 μg (23.7 ± 4.85 [95% CI, 14.13-33.23], and 12.5 ± 4.85 [95% CI, 2.93-22.05], %•hour, respectively). All doses of albuterol were well tolerated. Conclusion: Albuterol MDPI 90 and 180 μg and albuterol HFA 180 μg provided similar and significant FEV1 improvements versus placebo; albuterol HFA 90 μg was significant versus placebo but seemed less effective based on absolute improvements in FEV1. ©2016, OceanSide Publications, Inc., U.S.A.

Busso C.,IVI Valencia | Fernandez-Sanchez M.,IVI Seville | Garcia-Velasco J.A.,University of Santiago de Compostela | Landeras J.,IVI Murcia | And 6 more authors.
Human Reproduction | Year: 2010

Background Ovarian hyperstimulation syndrome (OHSS) seems to be induced by the ovarian release of vascular endothelial growth factor (VEGF), which increases vascular permeability. Dopamine agonists inhibit VEGF receptor phosphorylation and thereby decrease vascular permeability.Method SA randomized, double-blind, placebo-controlled, multicentre study assessing three oral doses (50, 100, 200 ≥g/day) of the non-ergot derived dopamine agonist quinagolide started on the day of human chorionic gonadotrophin (hCG) and continued for 17-21 days without dose-titration in comparison to placebo in preventing moderate/severe early OHSS (onset ≤9 days after hCG administration) in 182 IVF patients with ≥20 but less than 30 follicles ≥10 mm.Result SThe incidence of moderate/severe early OHSS was 23 (12/53) in the placebo group and 12 (6/51), 13 (7/52) and 4 (1/26) in the quinagolide 50, 100 and 200 g/day groups, respectively. The moderate/severe early OHSS rate was significantly lower with all quinagolide groups combined compared with placebo [P = 0.019; OR = 0.28 (0.09-0.81)]. The incidence of ultrasound evidence of ascites among patients with no clinical pregnancy was significantly reduced from 31 (8/26) with placebo to 11 (8/70) with all quinagolide groups combined [P = 0.033; OR = 0.29 (0.10-0.88)], although there was no difference for those with clinical pregnancy. Quinagolide did not have a detrimental effect on pregnancy or live birth rates. The incidence of gastrointestinal and central nervous system adverse events increased with increasing doses of quinagolide.Conclusion SQuinagolide appears to prevent moderate/severe early OHSS while not affecting treatment outcome. The effect is more marked in patients who did not achieve a clinical pregnancy. Quinagolide administered in high doses without dose-titration is associated with poor tolerability.

Ratnayake A.,Allergy Immunology and Respiratory Studies | Taveras H.,Clinical Research and Development | Iverson H.,Frazer | Shore P.,Clinical Research and Development
Allergy and Asthma Proceedings | Year: 2016

Background: Many children struggle with the use of albuterol hydrofluoroalkane (HFA) inhalers. Albuterol multidose dry powder inhaler (MDPI) may simplify rescue bronchodilator use in children. Objective: To compare the pharmacokinetics (PK), pharmacodynamics (PD), and tolerability of albuterol MDPI and albuterol HFA after a single inhaled dose in children with asthma. Methods: This single-center, open-label, two-period crossover study randomized children to albuterol MDPI or HFA 180 μg on two treatment days with a 4- to 14-day washout. Plasma albuterol concentrations were measured before the dose and up to 10 hours after the dose to determine the primary PK values of area under the plasma concentration-versus-time curve from time 0 to the last measurable concentration (AUC0-t), maximum observed concentration (Cmax), and AUC from time 0 extrapolated to infinity (AUC0-inf). Heart rate and blood pressure before the dose and after the dose were monitored for PD effects, and adverse events (AE) were monitored for overall safety. Results: Fifteen children, ages 6-11 years, were included (PK, n = 13 for time to Cmax and terminal half-life of elimination; n = 12 for AUC and Cmax due to incomplete data). AUC0-t (geometric mean ratio [GMR] 1.056 [90% confidence interval {CI}, 0.88 -1.268]) and AUC0-inf (GMR 0.971 [90% CI, 0.821-1.147]) were comparable between treatments. Cmax was larger for albuterol MDPI versus HFA (GMR 1.340 [90% CI, 1.098 -1.636]). PD parameters between the treatments were comparable. No deaths, serious AEs, treatment-emergent AEs, or withdrawals due to AEs were reported for either treatment. Conclusion: Albuterol MDPI and albuterol HFA had comparable PK and PD in children after a single 180-μg dose. ©2016, OceanSide Publications, Inc., U.S.A.

Seidner D.L.,Vanderbilt University | Joly F.,University Paris Diderot | Youssef N.N.,Clinical Research and Development
Clinical and Translational Gastroenterology | Year: 2015

OBJECTIVES: In clinical trials, treatment with the glucagon-like peptide 2 analog teduglutide was associated with improved fluid and nutrient absorption and increased intestinal villus height and crypt depth in patients with short bowel syndrome (SBS). Plasma citrulline, an amino acid produced by enterocytes, is considered a measure of enterocyte mass. This analysis assessed changes in plasma citrulline levels in patients with SBS in 2 phase III clinical studies of teduglutide. METHODS: Both teduglutide studies (0.05 or 0.10mg/kg/day in CL0600-004 and 0.05 mg/kg/day in CL0600-020) were phase III, 24-week, double-blind, and placebo controlled. Plasma citrulline levels were analyzed and validated by liquid chromatography coupled to tandem mass spectrometry. RESULTS: In both the CL0600-004 and CL0600-020 studies, change in mean plasma citrulline concentrations at Week 24 vs. baseline was significantly greater with teduglutide compared with placebo (10.9 (0.05-mg/kg/day dose) and 15.7 (0.10-mg/kg/day dose) vs. 2.0μmol/L and 20.6 vs. 0.7μmol/L, respectively, for each study (P≤ 0.0001 for each comparison with placebo)). Teduglutide treatment was associated with reductions from baseline in PS (parenteral support) volume requirements; however, a significant correlation between PS reduction and increase in plasma citrulline at Week 24 was observed in only one out of the three teduglutide treatment groups. CONCLUSIONS: In 2 phase III studies, patients receiving teduglutide had significant increases in plasma citrulline at Week 24 compared with patients receiving placebo. Increases in plasma citrulline concentrations likely reflect enterocyte mass expansion, but no clear correlation was detected between change in plasma citrulline and change in weekly PS volume. © 2015 the American College of Gastroenterology All rights reserved.

Robbie G.J.,Clinical Pharmacology and DMPK | Criste R.,Clinical Pharmacology and DMPK | Dall'Acqua W.F.,Protein Discovery | Jensen K.,Biostatistics | And 3 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2013

The study objective was to evaluate the pharmacokinetics (PK), antidrug antibody (ADA), and safety of motavizumab-YTE (motavizumab with amino acid substitutions M252Y/S254T/T256E [YTE]), an Fc-modified anti-respiratory syncytial virus (RSV) monoclonal antibody. Healthy adults (n=31) were randomized to receive a single intravenous (i.v.) dose of motavizumab- YTE or motavizumab (0.3, 3, 15, or 30 mg/kg) and followed for 240 days. Clearance of motavizumab-YTE was significantly lower (71% to 86%) and the half-life (t1/2) was 2- to 4-fold longer than with motavizumab. However, similar peak concentrations and volume-of-distribution values, indicative of similar distribution properties, were seen at all dose levels. The sustained serum concentrations of motavizumab-YTE were fully functional, as shown by RSV neutralizing activity that persisted for 240 days with motavizumab-YTE versus 90 days postdose for motavizumab. Safety and incidence of ADA were comparable between groups. In this first study of an Fc-modified monoclonal antibody in humans, motavizumab-YTE was well tolerated and exhibited an extended half-life of up to 100 days. Copyright © 2013, American Society for Microbiology. All Rights Reserved.

Bensen-Kennedy D.,Clinical Research and Development
Thrombosis Research | Year: 2013

In patients with hemophilia A, outcomes have improved dramatically over the last few decades due to several advances in care, including the availability of factor VIII (FVIII) concentrates. Current research has focused on enhancing the properties of FVIII concentrates and other coagulation factor products using recombinant DNA technology. However, there are several challenges to the development of new products for hemophilia patients, including the relative rarity of the disease, rapidly evolving standards of care, and the varying requirements of regulatory authorities around the world. In the development of two innovative coagulation factor products (recombinant single-chain factor VIII [rVIII-SingleChain] and a recombinant fusion protein linking coagulation factor VIIa with albumin [rVIIa-FP]), these issues have been addressed through novel clinical trial designs, including an ongoing three-part study evaluating the safety, efficacy, and pharmacokinetics of rVIII-SingleChain in patients with severe hemophilia A, and a randomized, placebo-controlled, dose-escalation study of rVIIa-FP in healthy volunteers. The design of these trials is intended to answer as many important clinical questions as possible while limiting the burden on hemophilia patients. © 2013 Elsevier Ltd.

Hayden M.E.,Pate Rehabilitation | Plenger P.,Clinical Research and Development | Bison K.,Program Development | Kowalske K.,University of Texas Southwestern Medical Center | And 2 more authors.
PM and R | Year: 2013

Objective: To evaluate functional improvement following a traumatic brain injury (TBI) after admission to a postacute treatment facility, focusing on the time since injury and analysis of recovery by degree of impairment at admission. Design: A retrospective study of patients who received treatment at a postacute rehabilitation facility. Setting: Postacute rehabilitation for persons with acquired brain injury that involved transdisciplinary teams. Patients: Patients (n = 1274) were admitted for treatment less than 5 years after TBI and were assessed on our outcome measures at least 3 times. The patients were then grouped by the time since injury and the severity of impairment at admission. Methods: Patients received comprehensive multidisciplinary treatment 5 days per week, 6 hours per day. Main Outcome Measurements: Function was assessed by using the Pate Environmentally Relevant Program Outcome System (PERPOS) scale at admission, discharge, and approximately every 2 weeks during treatment. By using these assessment scores, the rate and degree of improvement were monitored. Results: Postacute rehabilitation yielded significant gains in functioning, with 69% of all patients who demonstrated clinically meaningful gains. The time since injury had a significant impact on gains made in rehabilitation (Ftime × time-since-treatment group interaction = 17.75; P < .001), with the 0-3 months post injury group outperforming each other group (P < .001 for each comparison). This effect was statistically significant (P < .001) for each of the 3 severity-at-intake subgroups analyzed but was stronger for the severe (F314 = 9.05) and moderate-to-severe (F425 = 7.32) than for the mild-to-moderate (F533 = 2.95) severity-at-intake groups. Conclusions: Postacute rehabilitation is associated with functional gains for individuals with TBI beyond what can be explained by undirected recovery. These findings provide evidence for postacute rehabilitation as effective care after TBI. © 2013 American Academy of Physical Medicine and Rehabilitation.

WASHINGTON, DC--(Marketwired - Nov 17, 2016) - The Alliance for Regenerative Medicine (ARM), the international advocacy organization representing the gene and cellular therapies and broader regenerative medicine sector, announced it will hold its Inherited Blood Disorders Clinical and Patient Education Roundtable December 13 in Washington, D.C., the third event in its patient roundtable series. ARM's patient roundtable series is intended to serve as an educational resource for the broader patient community and to help bridge the gap between industry and patient groups who are working towards the common goal of durable, and potentially curative, therapies. Held in partnership with the Hemophilia Federation of America and the National Hemophilia Foundation, and sponsored by Shire, Sangamo BioSciences and uniQure, this event will focus on educating multi-sector stakeholders about the latest scientific progress and delivery challenges associated with hemophilia and other inherited blood disorders. "Many gene and cell therapies developers are advancing transformative approaches to treating and potentially curing inherited blood disorders, including hemophilia, beta-thalassemia, sickle cell disease and more," said Morrie Ruffin, ARM managing director. "We are pleased to serve an educational role to provide patients with information on the latest advances and potential impact of these technologies, especially as several therapies are moving through late-stage clinical evaluation." This roundtable discussion is expected to attract more than 100 individuals, including patient advocates, industry leaders and clinicians. 1:40 - 2:10pm Featured Talk: Gene Therapy 101 and Clinical Outlook Steven Pipe, M.D. Director, Division of Pediatric Hematology & Oncology Pediatric Medical Director, Hemophilia & Coagulation Disorders Program University of Michigan 2:10 - 3:05pm Roundtable Discussion: State of the State of Gene Therapy for Inherited Blood Disorders Daniel Leonard Director of Global Patient Advocacy uniQure 3:20 - 4:15pm Roundtable Discussion: Clinical Trial Recruitment and Interaction with Patient Community John Chapin, M.D. Medical Director, Clinical Research and Development - Hematology Shire This preliminary agenda is available online, with additional details to be added over the coming weeks. This event will take place at the Carnegie Library at Mt. Vernon Square, 801 Mt. Vernon Square NW, Washington, D.C. 20001. Registration is now open. The cost of attendance is $150 for industry attendees; $75 for non-profit and government attendees. The event is complimentary for patients, patient advocates, clinician attendees and members of the media. For more information and to register, please visit http://alliancerm.org/event/clinical-patient-education-inherited-blood-disorder-roundtable. For questions regarding this event, please contact ARM's Patient Advocacy & Events Manager Chelsey Hathaway, chathaway@alliancerm.org. For media interested in attending this event, please contact ARM's Senior Director of Communications Lyndsey Scull, lscull@alliancerm.org. About The Alliance for Regenerative Medicine The Alliance for Regenerative Medicine (ARM) is an international multi-stakeholder advocacy organization that promotes legislative, regulatory and reimbursement initiatives necessary to facilitate access to life-giving advances in regenerative medicine worldwide. ARM also works to increase public understanding of the field and its potential to transform human healthcare, providing business development and investor outreach services to support the growth of its member companies and research organizations. Prior to the formation of ARM in 2009, there was no advocacy organization operating in Washington, D.C. to specifically represent the interests of the companies, research institutions, investors and patient groups that comprise the entire regenerative medicine community. Today, ARM has more than 250 members and is the leading global advocacy organization in this field. To learn more about ARM or to become a member, visit http://www.alliancerm.org.

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