Tag Archives: C. diff. prevention clinical trials

Da Volterra Shared Results From Phase I Clinical Trial of DAV132 to Prevent Gut Microbiome Disruption Caused by Antibiotics and Prevent C. diff. Infections

DAV132 is a first-in-class product to protect the microbiome during antibiotic treatments and prevent Clostridium difficile infections.

French biotech Da Volterra is developing products to fight the rapidly rising rates of antibiotic resistance. During a Phase I study, the company’s medical device, DAV132, was used with the antibiotic, moxifloxacin, and successfully protected the intestinal microbiota from antibiotic residues. Overall, the product managed to reduce exposure of the microbiota to the antibiotic by 99% and maintain 97.8% of the microbiome’s genetic richness without affecting the drugs therapeutic efficacy.

In a randomized, controlled clinical trial performed in 44 healthy human volunteers, DAV132 was used in association with moxifloxacin, a widely used fluoroquinolone antibiotic. It was demonstrated that DAV132 is able to effectively capture residual antibiotics in the colon and reduce their concentration to very low levels. DAV132 reduced exposure of the intestinal microbiota to moxifloxacin by 99%. Meanwhile the plasma concentration of the antibiotic was essentially unaffected by the co-administration DAV132, meaning that its therapeutic efficacy will be maintained.

The ability of DAV132 to protect the intestinal microbiome was explored by identifying changes in bacterial gene richness as well as a detailed statistical analysis of the evolution of bacterial species throughout the study. In volunteers who received moxifloxacin alone, gene richness was drastically diminished to 54.6% of baseline after antibiotic treatment and failed to return to baseline even one month after treatment; 39% of bacterial species identified in the intestinal microbiota were affected. The co-administration of DAV132 with moxifloxacin largely protected the intestinal microbiome from disruption (97.8% of baseline for bacterial gene richness, and 93% of bacterial species protected).

The primary endpoints for the study were fully achieved and DAV132 showed an excellent tolerability profile.

Annie Ducher MD, Chief Medical Officer of Da Volterra, declared: “This clinical study is indicative of the potential of DAV132 to become one of the first preventative solutions to protect the intestinal microbiome and further avoid the detrimental consequences of antibiotic treatments, such as Clostridium difficile infections, for patients. We look forward to advancing the development of DAV132 in a pivotal patient study in 2018.”

Jean de Gunzburg PhD, Chief Scientific Officer of Da Volterra, added: “This study constitutes the first scientific demonstration of the protection of the intestinal microbiome from dysbiosis caused by a fluoroquinolone antibiotic treatment; our data suggests that this effect should be extendable to many different antibiotics from several therapeutic classes. The metagenomics analysis is outstanding and thoroughly convincing that DAV132 is highly effective at protecting the commensal bacteria in the intestines.”

The results are available under the reference: Gunzburg et al. Protection of the human gut microbiome from antibiotics. The Journal of Infectious Diseases, jix604, https://doi.org/10.1093/infdis/jix604.

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About DAV132:
With a novel and unique mechanism of action, DAV132 is a product candidate aiming to protect the intestinal microbiome from the side effects of antibiotics, hence preventing the onset of C. difficile infections. DAV132 is an adsorbent with a proprietary coating with colon targeted delivery. DAV132 has been tested in four Phase 1 clinical studies with no adverse safety events. DAV132 is currently entering a Phase 2 clinical trial.

About Da Volterra:
Da Volterra is a biopharmaceutical company based in France that develops new strategies aimed at protecting the intestinal microbiome from the deleterious effects of antibiotics, and preventing multi-resistant and life-threatening infections. Da Volterra’s innovative approaches promise a substantial medical progress to combat deadly pathogens. http://www.davolterra.com

(January 2018)

To read the article in its entirety, please click on the following link to be redirected:

https://www.businesswire.com/news/home/20180116005398/en/Da-Volterra-Announces-Publication-Full-Results-Clinical

Ribaxamase Protects the Gut Microbiome and Reduces Risk For New Opportunistic C.diff. Infections According To Phase 2b Study

From IDWeek  2017- SanD iego, CA

 

Ribaxamase is associated with reduced risk for new, opportunistic Clostridium difficile infections (CDI) in hospital patients, according to findings from a multinational, double-blind, placebo-controlled Phase 2b study presented at IDWeek 2017.

 

 

“These data support that ribaxamase can maintain the balance of the gut microbiome and thereby prevent opportunistic infections like CDI during IV beta-lactam treatment,” said lead study author John Kokai-Kun, PhD, of Synthetic Biologics, Inc., Rockville, MD.

“Ribaxamase also protected the diversity of the gut microbiome and reduced the emergence of antibiotic resistance in ceftriaxone-treated patients,” he said.

CDI represent an “urgent threat” but there are no FDA-approved drugs or vaccines to prevent infections, Dr. Kokai-Kun noted.

“SYN-004 (ribaxamase) is a beta-lactamase designed to be orally administered with IV beta-lactam antibiotics and remain localized in the intestine to degrade antibiotics excreted into the intestine,” he said. “This is expected to protect the gut microbiome from disruption thus preventing deleterious effects including, CDI, colonization by opportunistic pathogens and emergence of antibiotic resistance in the gut microbiome.”

“Ribaxamase was well tolerated and not systemically absorbed in Phase 1 studies and efficiently degraded ceftriaxone excreted into the human intestine while not altering the plasma pharmacokinetics of ceftriaxone in Phase 2a studies,” he told the IDWeek audience.

The researchers conducted their study to assess if ribaxamase prevents new-onset CDI. They also assessed non-CDI antibiotic-associated diarrhea, colonization by opportunistic pathogens, gut microbiome alterations and acquired antibiotic resistance.

Data from 412 patients (man age 70 years) in the intention-to-treat population “enriched for higher risk for CDI” were hospitalized for ≥5 days of IV ceftriaxone for treatment lower respiratory tract infections,” Dr. Kokai-Kun said. Patients were randomly assigned 1:1 to receive oral ribaxamase 150mg four times daily or placebo during IV ceftriaxone treatment and for an additional 72 hours.

“Fecal samples were collected at pre-specified points for determination of colonization by opportunistic pathogens and to examine changes in the gut microbiome,” Dr Kokai-Kun said. Patients were monitored for 6 weeks for CDI, defined as diarrhea plus the presence of C. difficile toxin.

Study participants saw a 71% relative risk reduction in CDI (P=0.045) and a statistically significant 44% relative risk reduction in new colonization by vancomycin-resistant enterococci (P=0.0002). Moreover, the respiratory infection was cleared in ~99% of cases demonstrating that concomitant ribaxamase did not impact the cure rate of ceftriaxone.

For continuous infectious disease news coverage from the IDWeek 2017, check back to MPR’s IDWeek page for the latest updates.

Reference: 

Kokai-Kun J, Roberts T, Coughlin O, Whalen H, Le C, Da Costa C, Sliman J. SYN-004 (ribaxamase) prevents New Onset Clostridium difficile Infection by Protecting the Integrity Gut Microbiome in a Phase 2b Study. Poster presented at IDWeek; October 4–8, 2017; San Diego, CA. http://www.idweek.org/.

 

 

Synthetic Biologics Announced Positive Topline Results From the Second Phase 2a Open-Label Clinical Trial of SYN-004, Prevention of C.diff. Infection (CDI) and Antibiotic-associated Diarrhea (AAD)

SYN-004 Degraded IV Ceftriaxone in the Presence of a Proton Pump Inhibitor in the Gastrointestinal Tract without Affecting Antibiotic Levels in the Bloodstream —

— Two Poster Presentations Planned for ASM Microbe 2016, Including Detailed Data from Two SYN-004 Phase 2a Open-Label Clinical Trials —

SyntheticBiologics2016LOGO

Synthetic Biologics, Inc. a clinical stage company focused on developing therapeutics to protect the gut microbiome, announced positive topline results from the second Phase 2a open-label clinical trial of SYN-004, the Company’s candidate designed to protect the gut microbiome from the unintended effects of certain commonly used intravenous (IV) beta-lactam antibiotics for the prevention of C. difficile infection (CDI), antibiotic-associated diarrhea (AAD) and the emergence of antibiotic-resistant organisms. Results from 14 participants who completed this clinical trial were analyzed to assess the ability of the 150 mg dose of SYN-004 to degrade ceftriaxone when administered alone and with the proton pump inhibitor (PPI), esomeprazole.

 

To read article in its entirety:

http://ir.syntheticbiologics.com/press-releases/detail/211

 

 

 

Synthetic Biologics Announced Positive Topline Results From the First Phase 2a Study Of SYN-004 For C. difficile Infection Prevention

syntheticbiologics
Synthetic Biologics Announces Positive Topline Results from First Phase 2a Clinical Trial of SYN-004, the Company’s Candidate for the Prevention of C. difficile Infection

Synthetic Biologics, Inc. a clinical stage company focused on developing therapeutics to protect the gut microbiome while targeting pathogen specific diseases, announced positive topline results from the first Phase 2a study of SYN-004, the Company’s candidate designed to protect the gut microbiome from the unintended effects of certain commonly used intravenous (IV) beta-lactam antibiotics for the prevention C. difficile infection (CDI) and antibiotic-associated diarrhea (AAD). Topline results from the ten ileostomized participants who completed the Phase 2a open-label study demonstrated that SYN-004 successfully degraded residual IV ceftriaxone in the chyme (digestive fluid in the small intestine) without affecting the intended level of ceftriaxone in the bloodstream.

Evaluation of the chyme from the ileostomized participants indicates that both dosage strengths of SYN-004 (75 mg and 150 mg) degrade residual IV ceftriaxone present in the chyme, supporting the mechanism of action of SYN-004. In addition, both dosage strengths of SYN-004 appear to be well tolerated by the participants in the study. Overall, the topline data support the hypothesis that SYN-004 has the capacity to degrade residual IV ceftriaxone in the GI tract, thereby preserving the balance of the gut microbiome for the prevention of CDI, AAD and emergence of antibiotic-resistant organisms, without affecting the antibiotic level in the bloodstream intended for treatment of a primary infection.

“The completion of the first Phase 2a clinical trial for SYN-004 is an important achievement for Synthetic Biologics. These positive topline results demonstrate the potential for SYN-004 to protect the gut microbiome from the damaging effects of certain IV beta-lactam antibiotics for the prevention of C. difficile infection and antibiotic-associated diarrhea,” stated Jeffrey Riley, President and Chief Executive Officer of Synthetic Biologics. “The second Phase 2a clinical trial for SYN-004 is currently ongoing to evaluate the GI antibiotic-degrading effects and the safety of SYN-004 in the presence of the proton pump inhibitor (PPI), esomeprazole, in participants with functioning ileostomies. We anticipate reporting topline results from the second Phase 2a of SYN-004 during the first half of 2016.”

Mr. Riley concluded, “We are pleased to report additional progress from our SYN-004 program. We have begun dosing patients in the SYN-004 Phase 2b proof-of-concept clinical trial that is intended to evaluate the effectiveness of SYN-004 to prevent C. difficile infection and C. difficile associated diarrhea, as well as antibiotic-associated diarrhea in up to 370 patients hospitalized for a lower respiratory tract infection and receiving IV ceftriaxone.”

 

First SYN-004 Phase 2a Clinical Trial Design

The Phase 2a randomized, multi-center, open-label study evaluated the ability of two different dose strengths of SYN-004 to degrade residual IV ceftriaxone in the GI tract of 10 healthy participants with functioning ileostomies, without affecting the concentrations of IV ceftriaxone in the bloodstream. The study consisted of two treatment phases for all participants: 1) the administration of IV ceftriaxone alone, and 2) the administration of IV ceftriaxone with one of two dosage strengths of oral SYN-004. Chyme samples were collected from the participants to measure the capability of SYN-004 to degrade the residual antibiotic in the GI tract. Participants were enrolled at two trial sites located in Canada.

 

To read the article in its entirety click on the link below:

http://money.cnn.com/news/newsfeeds/articles/prnewswire/CL69745.htm

 

— SYN-004 Degraded IV Ceftriaxone in Gastrointestinal Tract without Affecting
Antibiotic Levels in the Bloodstream —
— First Patients Dosed in Phase 2b Proof-of-Concept Clinical Trial for SYN-004 —
— SYN to Host Microbiome Clinical Program Seminar in NYC on Thursday, December 10, 2015

This release includes forward-looking statements on Synthetic Biologics’ current expectations and projections about future events. In some cases, forward-looking statements can be identified by terminology such as “may,” “should,” “potential,” “continue,” “expects,” “anticipates,” “intends,” “plans,” “believes,” “estimates,” and similar expressions. These statements are based upon current beliefs, expectations and assumptions and are subject to a number of risks and uncertainties, many of which are difficult to predict and include statements regarding the potential for SYN-004 to protect the gut microbiome from the damaging effects of certain IV beta-lactam antibiotics for the prevention of C. difficile infection and antibiotic-associated diarrhea, the timing of the reporting of topline results from the second Phase 2a of SYN-004, the potential market for SYN-004, and the intended therapeutics results of SYN-004 and SYN-010. The forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those set forth or implied by any forward-looking statements. Important factors that could cause actual results to differ materially from those reflected in Synthetic Biologics’ forward-looking statements include, among others, a failure to receive the necessary regulatory approvals for commercialization of Synthetic Biologics’ therapeutics, a failure of Synthetic Biologics’ clinical trials, and those conducted by investigators, to be commenced or completed on time or to achieve desired results, a failure of Synthetic Biologics’ clinical trials to receive anticipated funding, a failure of Synthetic Biologics’ products for the prevention and treatment of diseases to be successfully developed or commercialized, Synthetic Biologics’ inability to maintain its licensing agreements, or a failure by Synthetic Biologics or its strategic partners to successfully commercialize products and other factors described in Synthetic Biologics’ report on Form 10-K for the year ended December 31, 2014 and any other filings with the SEC. The information in this release is provided only as of the date of this release, and Synthetic Biologics undertakes no obligation to update any forward-looking statements contained in this release on account of new information, future events, or otherwise, except as required by law.

i  Leffler DA et al. N Engl J Med 2015; 372:1539-1548.

ii Leffler DA et al. N Engl J Med 2015; 372:1539-1548.

 

 

*Please note – The C Diff Foundation does not endorse this product or any product and this posting is strictly for informational purposes only.

 

C. diff. – Valneva Announced the Start of Phase II Clinical Trial of its C. diff. Vaccine Candidate

NewsSpeakerValneva Announces Start of Phase II Clinical Trial of its Clostridium difficile vaccine candidate

  • First Study participant(s) enrolled in Phase II trial which aims to enable Phase III entry upon successful completion
  • Study to enroll 500 healthy subjects aged 50 years and older in the United States and Germany
  • First results are expected in Q4 2015

                   * News Provided in English, French, and German *

Lyon (France), December 18, 2014European biotechnology company Valneva SE (“Valneva”) announced today the initiation of the Phase II clinical trial of its VLA84 prophylactic vaccine candidate against Clostridium difficile (C. difficile), the main cause of nosocomial diarrhea. Data from the Phase I study in healthy elderly and adults showed good safety and immunogenicity of the vaccine candidate, and indicated functionality of induced antibodies, supporting the Company`s decision to progress the vaccine candidate into Phase II

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Valneva annonce l`initiation de l`essai clinique de Phase II pour son candidat vaccin contre le Clostridium difficile

  • Premier volontaire recruté pour l`essai de Phase II qui, une fois achevé, devrait conduire à l`initiation de la Phase III
  • L`étude de Phase II vise à recruter 500 volontaires âgés de 50 ans et plus aux Etats-Unis et en Allemagne
  • Premiers résultats attendus au T4 2015

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Lyon (France), 18 décembre 2014 -La société de biotechnologie européenne Valneva SE (“Valneva”) annonce aujourd`hui le lancement de  l`essai clinique de Phase II de son candidat vaccin prophylactique VLA84 contre le Clostridium difficile (C. difficile), principale cause de diarrhée nosocomiale. Les données de Phase I chez des adultes et des personnes âgées en bonne santé ont démontré un bon profil d`innocuité et d`immunogénicité du candidat vaccin ainsi qu`un bon fonctionnement des anticorps produits, conduisant ainsi la société à faire progresser son candidat vaccin en Phase II.

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Valneva gibt den Start einer klinischen Phase-II Studie mit seinem Impfstoffkandidaten gegen Clostridium difficile bekannt

  • Erste(r) Studienteilnehmer wurde(n) in die Phase II-Studie aufgenommen, die nach erfolgreichem Abschluss eine Phase III-Studie ermöglichen soll
  • Studie wird 500 gesunde Probanden im Alter von 50 Jahren oder älter in den USA und Deutschland umfassen
  • Erste Ergebnisse werden im 4. Quartal 2015 erwartet

Lyon (Frankreich), 18. Dezember 2014 – Das europäische Biotech Unternehmen Valneva SE (“Valneva”) hat heute den Start der klinischen Phase II-Studie ihres prophylaktischen Impfstoffkandidaten VLA84 gegen Clostridum difficile (C. difficile), die Hauptursache von nosokomialen Durchfallerkrankungen, bekannt gegeben. Die Daten aus der vorangegangenen Phase I-Studie in gesunden jüngeren Erwachsenen und älteren Personen zeigten bereits erste gute Sicherheits-  und Immunogenitätsdaten des Impfstoffkandidaten, und deuteten auf die Funktionalität der induzierten Antikörper hin, weshalb sich das Unternehmen für die Weiterentwicklung des Impfstoffkandidaten  in einer Phase II entschieden hat.

*Please note – The C Diff Foundation does not endorse this product or any product and this posting is strictly for informational purposes only.

Synthetic Biologics, Inc. Is Issued a Notice of Allowance for a Composition of Matter Patent Application covering SYN-004, Leading Product in its C. difficile Program

* In the news *

Synthetic Biologics, Inc., a biotechnology company developing novel pathogen-specific therapies for serious infections and diseases, announced that as of October 22, 2014  the U.S. Patent and Trademark Office has issued a Notice of Allowance for a composition of matter patent application that covers the lead product in its C. difficile program, SYN-004. This is Synthetic Biologics’ first allowed patent application directly pertaining to SYN-004 in the U.S. and adds to the Company’s extensive C. difficile patent estate.

Synthetic Biologics, Inc. Logo

SYN-004 is Synthetic Biologics’ novel oral enzyme drug candidate designed as the first and only prophylactic treatment intended to prevent the development of C. difficile infections, by binding with and neutralizing certain intravenous (IV) beta-lactam antibiotics in the gut.

SYN-004 is intended to block the effects of antibiotics within the gastrointestinal (GI) tract, maintaining the natural balance of bacterial flora (the gut microbiome), potentially preventing the 1.1 million C. difficile infections in the U.S. each year.  The U.S. patent to be issued has claims to compositions of matter and pharmaceutical compositions of beta-lactamases, including SYN-004, and carries a patent term to at least 2031. In addition to the newly allowed patent, the Company has numerous related granted and pending U.S. and international patent applications that are central to the Synthetic Biologics’ intellectual property estate.

“This new patent will strengthen the protection of Synthetic Biologics’ SYN-004 and reiterates our position as a key player in the prevention of microbiome-based diseases,” said Jeffrey Riley, Chief Executive Officer of Synthetic Biologics. “We continue to bolster the Company’s patent estate while making progress towards our goals to initiate Phase Ia and Ib C. difficile clinical trials this quarter.”

 

Resource: Synthetic Biologics news release.

 

*Please note – The C Diff Foundation does not endorse this product or any product and this posting is strictly for informational purposes only.