Tag Archives: C. diff research and development

Rebiotix, Inc. announces results of Phase 2 Punch(TM) CD Study for Treatment of Recurrent C. difficile infections

In The News*

Rebiotix Inc. announced today that results of the Phase 2 PUNCH™ CD Study found that the overall efficacy of RBX2660 in the treatment of recurrent Clostridium difficile infection was 87.1%. The study also found that administration of RBX2660 was well-tolerated and demonstrated satisfactory safety in the 60-day interim analysis.

The results of a 60-day interim analysis of the PUNCH CD study, the first prospective multi-center study of a next generation, standardized, commercially prepared microbiota restoration therapy for recurrent CDI were presented at IDWeek 2014.

Clostridium difficile infection, characterized by severe diarrhea, is a leading healthcare acquired infection and is linked to 14,000 deaths in the U.S. annually. The U.S. Centers for Disease Control recently termed CDI an urgent public health threat. Recurrent CDI is especially challenging to treat, and there are no indicated drugs for the condition.

The primary objective of the PUNCH CD study was product-related adverse events (AEs). A secondary objective was CDI resolution.  A total of 40 patients at 11 centers in the U.S. were enrolled in the study. All of the patients had multi-recurrent CDI and had failed standard therapy.  The PUNCH CD patient population was primarily elderly and female with multiple co-morbidities, thus reflecting the real-world population of patients with recurrent CDI who present with unmet medical needs.

A total of 34 patients received at least one dose of RBX 2660 administered via enema.  A second dose was permitted if CDI recurred

“Years of experience indicate microbiota therapy is highly efficacious for treatment of recurrent CDI. However, adequate data have been lacking on safety,” said Erik R. Dubberke, MD, MSPH, a PUNCH CD investigator and Director, Section of Transplant Infectious Diseases at Washington University School of Medicine, St. Louis, MO. “The phase 2 study indicates RBX2660 efficacy is consistent with past studies, and it is safe and easy to administer.”

The study represents a significant step forward in Rebiotix’s efforts to develop a durable cure for recurrent CDI that is debilitating to patients. RBX2660 will undergo further study in a Phase 2B randomized controlled trial scheduled to begin later this fall.

About Rebiotix Inc.
Rebiotix Inc. is a results-oriented biotechnology company revolutionizing the treatment of challenging gastrointestinal diseases by harnessing the power of the human microbiome. The Roseville, Minn. based company is pioneering Microbiota Restoration Therapy to restore healthy gut flora through the transplantation of live microorganisms. For more information, visit  http://www.rebiotix.com

Rebiotix is the only company that has a microbiota therapy with FDA orphan-drug designation for treatment of recurrent C. diff. infection. Orphan drugs are those intended for the safe and effective treatment, diagnosis or prevention of rare diseases and/or disorders that affect fewer than 200,000 people in the US. The FDA has also designated RBX2660 as a Fast Track product for the treatment of recurrent C. diff. infection. This designation underscores the urgent need for a new therapy to treat patients who have this debilitating and potentially life-threatening disease and means that FDA will act to expedite the development and review of the application for the product, as appropriate.


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Clostridium difficile Research and Development Community – September 2014


Here is the latest from the                              Clostridium difficile research community:

The role of host factors especially those involved in the intestinal inflammatory response and pathogenesis of against Clostridium difficile is not well understood. Trindade et all looked at the role of leukotrienes in modulating host susceptibility to CDI in C57BL/6 mice. Leukotrienes are proinflammatory lipid mediators which are not involved in the pathogenesis of CDI.


Scientists from Dr. Rupnik’s group in Slovenia describe the sequence diversity of 16S-23S rRNA intergenic spacer region of 43 C difficile strains representing different PCR ribotypes. Her groups suggests that homologous recombination as a possible mechanism responsible for the evolution of 16S-23S rRNA intergenic spacer region. Diversity in sequence length, the presence or absence of different sequence modules; tRNAAla genes and different combinations of spacers of different lengths (33 bp, 53 bp or 20 bp) and 9 bp direct repeats separating the spacers could be used to describe 22 different structural groups.


The use of the bacterial second messenger cyclic di-GMP (c-di-GMP) as an adjuvant to stimulate inflammation by initiating innate immune cell recruitment and triggering the release of pro-inflammatory cytokines and chemokines was studied in the context of a C.difficile toxin expressed from an adenovirus vaccine. Although co-expression of the cyclic di-GMP via an Ad5 vector expressing diguanylate cyclase lead to modest imcrease in T cell responses, antibody titers were not boosted.



Lipotechoic acids (LTA) are novel targets for vaccination against C.difficile. LTA is expressed on spores as well as vegetative cells. In this study, the authors report on the isolation fo 5 LTAs from C. difficile as a microheterogenous mixture, differing in size and composition, structure–activity relationship studies impossible. The authors describe the synthesis of these LTAs and their functions.


The microbiome of the infant gut is established very early following birth. In this study the authors report on the resistome of the infant gut consists of aminoglycoside and β-lactam resistance reservoir even in the absence of pathogens that could provide the needed evolutionary pressure. The resistome of the infant gut is also established very early in the life of the infant, probably at birth.


Chandrabali Ghose-Paul,MS,PhD, Chairperson of Research and Development


C Diff Foundation Welcomes Dr. Simon Cutting, MS, PhD

welcome1We are pleased to welcome                              Dr. Simon Cutting, , from the School of Biological Sciences at the Royal Holloway University of London  to the  C Diff Foundation’s

Research and Development Committee and  Research Community.

Professor Simon M. Cutting is a bacterial geneticist with over 25 years of experience with Bacillus since graduating from Oxford University with a D. Phil in 1986. His D.Phil was on understanding the genetic control of spore formation in Bacillus subtilis. After spending 7 years in the renowned laboratory of Professor Richard Losick at Harvard University Biological Laboratories (USA) he spent 3 years as an Assistant Professor at the University of Pennsylvania Medical School in Philadelphia.
He returned to the UK in 1996 and since then has worked on developing bacterial spores as novel oral vaccines at the Royal Holloway, University of London. The Cutting lab has developed a number of prototype oral vaccines and is now entering a ‘first in man’ phase 1/IIa clinical trial of a prototype oral vaccine to Clostridium difficile (see www.cdvax.org).
His work on Bacillus probiotics provides another area of his research interests and he was the first to address the fundamental mechanisms that might enable these bacteria to promote potential health benefit (SporeGen.com)

C Diff Foundation Welcomes Dr. Martha R. J. Clokie, MS, PhD

Welcome cloudWe are pleased to welcome                              Dr. Martha R. Clokie, from the Department of Microbiology and Immunology at the University of Leicester, UK to the C Diff Foundation’s Research and Development Committee and Research Community.

Dr. Clokie obtained a BSc in Biology (1st class hons) from the University of Dundee in 1996. An interest in ecology and molecular biology led her to an MSc at Edinburgh (1997) and a PhD at Leicester (2001) where she focused on designing molecular tools in order to establish the basis of plant biogeography.   ” I then wanted to study a system which evolved more rapidly than plants, so in Jan 2001 I started to work on cyanobacteria and viruses with Prof Nick Mann at the University of Warwick. I stayed in this field for 6 years during which time I became fascinated at the extent to which phages impacted the evolution and ecology of their cyanobacterial hosts.”

After a fellowship at the Scripps Research Institute, La Jolla, San Diego, Dr. Clokie started her own research group at the University of Leicester in 2006.  “I have focused on the gut pathogen Clostridium difficile where I have isolated and sequenced novel phages in order to determine how they are shaping populations in natural settings and to establish how we might be able to better understand these phages in order to develop them for therapeutic and diagnostic purposes.”

Her work has focused on Clostridium difficile as is the major cause of bacterial infectious diahorrea in the western world. The pathogen is difficult to diagnose and to treat as there are complications associated with the only 3 antibiotics that are effective against it.

Meridien Research in Tampa Bay – Florida, Seeking Volunteers For C. diff. Vaccine Clinical Research Trial

Sanofi Pasteur MeridienH-030-014_CDIF10010A-1_ STP

Are You at Risk for C. Diff?

C. diff is a bacterium that can cause mild diarrhea to life-threatening bowel disease. The risk of  acquiring C. diff. increases with age, the use of antibiotics and time spent in hospitals or in nursing homes.

Volunteers are needed for research study being conducted to evaluate the effects of an investigational vaccine for C.diff infections. You may qualify if you are 50 years old or older, are planning a hospitalization, and/or have had at least 2 recent hospital stays within the past year.

Qualified participants may receive at no cost study-related:
     ● Evaluations, physical exams, routine lab work
     ● Investigational medication or placebo

Compensation for time and travel may be available. No medical insurance is necessary.

Call 1-727-347-8839 (USA) for more information.

  About Meridien

Meridien Research  provides patients and families in the Tampa Bay area an opportunity to take part in clinical research trials for a wide variety of medical conditions. These research trials are usually offered at University or large research institutions, but with offices in Tampa, St. Petersburg, Brooksville, Bradenton and Lakeland, area residents can have access to the latest in medical research without leaving home.

Stephanie Jones, Director of Marketing



Insearch Group

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St. Petersburg, FL 33702







Clostridium difficile Research and Development; April/May 2014

Here’s the latest from the Clostridium difficile research community:

April/May 2014
The role of probiotics in the treatment or the prevention of C. difficile infection (CDI) has not been clearly defined as yet. To study the role of Lactobacillus strains on the quorum-sensing signals and toxin production of C. difficile, Yun et al. looked at in vitro and in vivo effects of L. acidophilus strain or cell extracts. The results show that L. acidophilus GP1B can inhibit the growth of C. difficile and contribute to the survival of mice given C.difficile.

The endospores of Bacillus subtilis (B. subtilis) can serve as a tool for surface presentation of heterologous proteins in addition to acting in the role of a probiotic. The utility of B .subtilis as a probiotic was studied in a mouse model of CDI to show that oral administration of B. subtilis spores, especially when administered post infection, was able to attenuate symptomatic disease.
C. difficile flagellar proteins play a myriad role in pathogenesis from adherence, toxin production, and biofilm formation. Barketi-Klai et al looked at the global gene expression profiles of C.difficile fliC mutants and compared gene expression levels to those of the parent wild-type strain. fliC mutants strains led to the up-regulation of genes involved in mobility, expression of virulence factors and sporulation which was not seen with the wild-type mutant strain. The authors conclude that deregulation of fliC expression could lead to the upregulation or deregulation of other genes that enhance the pathogenecity of such strains.
In addition to a patient’s health, CDI is also a huge financial burden to patients, hospital and society. A recent study looked at the added costs of CDI on cardiac surgical patients using the Nationwide Inpatient Sample (NIS) database, and reported that in cardiac surgery alone, CDI adds an incremental cost of $212 million/year.
The spores of C.difficile are important in the pathogenesis of CDI. Spore proteins present on the outer layer of spore may be essential for CDI. The BclA proteins are glycolipids present on the spore surface and may be glycosylated by sgtA, which is cotranscribed with BclA3. Mutant strains of sgtA were not different from wild-type strains in terms of sensitivity to ethanol or lysozyme, but showed a change in heat-resistance and the ability to be internalized by macrophages.


Chandrabali Ghose-Paul,MS,PhD,  Chairperson of Research and Development

Clostridium difficile; Research and Development April 2014

Here’s the latest from the Clostridium difficile research community:
The importance of biofilm formation in chronic and recurrent infections across a cross-section of pathogens, including C. difficile has been studied in great detail. Whether biofilm formation in CDI is an important marker for recurrence is not clearly understood. Crowther et al compared germination, proliferation and toxin production between planktonic and sessile communities of C.difficile in a triple-stage chemostat gut model and here have reported that planktonic populations of C.difficile may be a reservoir for spore persistence and recurrence.
Ransom et al have identified a gene cluster that is found exclusively in C.difficile and some closely-related species of bacteria that encode three cell division proteins: MldA, MldB and MldC. Mutant strains that lack the Mld proteins are severely attenuated for pathogenesis in a hamster model of CDI and thus are potential targets for therapeutics that can disrupt the spread of CDI.
C.difficile are spores formers and the infectious unit for CDI is the spore. The proteins present on the outerlayer of the spores can be used as potential vaccine targets. Spore proteins present on the outer layer of spores, the exosporium, may be essential for the initiation and persistence of CDI. Three C.difficile collagen-like exosporium proteins (BclA) are expressed on the exosporium of the spore. Mutants of BclA proteins were reported to have aberrant structure and faster germination rates than wild type strains. Infection experiments done in mice suggest that BclA1 plays a role in the early stages of infection.
C.difficile strains express three highly complex cell-surface polysaccharides (PSI, PSII and PSIII). PSII is the more abundantly expressed by most strains and is a potential target for vaccine development. The efficacy of PSII glycoconjugate-based vaccine using recombinant fragments of toxin A and toxin B were studied in mice. This vaccine was immunogenic and able to illicit toxin neutralizing antibody, one of the correlates of protection against CDI.
The last decade has seen a rapid change in the epidemiology of CDI due to the emergence of so called ”hypervirulent”strains of C. difficile BI/NAP1/027 . Although it is still unclear what exactly contributes to this rapid spread of this strain, Robinson et al hypothesize that the rapid spread of these hypervirulent ribotype 027strains is due to increased fitness over the historic strains such as ribotypes (001, 002, 014, and 053). Looking at in vitro as well as an in vivo model of competition in mice, data suggests that these hypervirulent strains may be able to outcompete historic strains in a mixed infection/complex microbiota environment.

Chandrabali Ghose-Paul,MS,PhD, Chairperson of Research and Development