Category Archives: C. diff. prevention clinical trials

Rebiotix Features Three Posters Highlighting RBX2660 Clinical and Microbiome Data at ID Week™ 2017 in San Diego, October 4th – 8th

Positive Topline Data from Open-Label Phase 2 Trial of RBX2660 in Recurrent Clostridium
difficile to be Presented for First Time

 

 

 

Rebiotix Inc., a clinical-stage microbiome company focused
on harnessing the power of the human microbiome to treat challenging diseases, today announced that three posters highlighting RBX2660 clinical and microbiome data will be featured at ID Week™ 2017 in San Diego, Oct. 4th to the 8th.

The posters describe clinical findings that highlight the key changes to
the human microbiome profiles of patients who received RBX2660, Rebotix’s Phase 3 drug candidate.

For the first time, researchers will discuss findings from the open-label Phase 2 trial of RBX2660 for the prevention of recurrent Clostridium difficile (C. diff.) infection. Data indicated that RBX2660 was well tolerated and achieved the primary efficacy endpoint of preventing C. diff. recurrence; patients treated with RBX2660 exhibited a treatment success rate of 78.8% compared with a historical control of 51.8% (p<0.0001, N=242). These results demonstrate a 55% reduction in recurrence for those patients treated with RBX2660 compared to the historical controls reflecting standard-of-care antibiotics today.

RBX2660 is currently being evaluated in a multinational Phase 3 clinical trial for the prevention of recurrent C. diff.  Researchers will also be presenting two posters on the microbiome analyses of the Phase 2B  randomized, placebo-controlled, double-blind clinical trial of RBX2660. The analyses, utilizing leading  edge genomic sequencing technology to measure the patient’s microbiome, provide measurable  evidence of RBX2660’s rehabilitative effect on human microbiome profiles of patients who were successfully treated with Rebiotix’s microbiota drug technology.

“The clinical potential of RBX2660 has been highlighted in multiple trials, including our recently
completed open-label Phase 2 study, and the data being presented at ID Week enables us to more fully understand RBX2660’s ability to rehabilitate a dysbiotic intestinal microbiome,” commented Lee Jones, president and CEO of Rebiotix. “These findings are important in that not only can we observe the clinical 2 effect of RB X2660, such as in the open-label Phase 2 study, but by analyzing the microbiota of RBX2660-treated patients, we can see how the microbiome changes in response to RBX2660 treatment and how those changes correlate to treatment success and to the microbiomes of healthy individuals.”

The first poster (#1863; to be presented Friday, Oct. 6th), titled RBX2660 is Safe, Superior to Antibiotic- Treated Controls for Preventing Recurrent Clostridium difficile, and May Rehabilitate Patient Microbiomes:  Open Label Trial Results, reported data from an open-label Phase 2 study of RBX2660 that included 242 subjects. Data from the study indicated that RBX2660’s efficacy in preventing recurrent Clostridium difficile infection (rCDI) was higher (78.8%) than CDI-free rates in the Historical Control Group (51.8%, p<0.0001). The reduction in recurrence of C. diff between these two arms is approximately 55%. Moreover, the safety profile of RBX2660 was consistent with results from previous clinical trials, and microbiota analysis suggested that RBX2660 may rehabilitate patient microbiota as RBX2660-treated subjects’ microbiomes were significantly altered compared to baseline and more closely resembled the RBX2660 microbiome profile than at baseline (p<0.05 by Dirichlet multinomial Wald-type pairwise hypothesis test).

The second poster (#1267; to be presented Saturday, Oct, 7th), titled Successful Response to
Microbiota-Based Drug RBX2660 in Patients with Recurrent Clostridium Difficile Infection is Associated with More Pronounced Alterations in Microbiome Profile, involved an analysis of 58 patients whose stool samples were collected in the randomized Phase 2B clinical trial to determine the effect of RBX2660 on rCDI patient microbiomes. 16s RNA sequencing analyses of patients’ microbiomes indicated that RBX2660 treatment shifted the relative microbiome densities, with taxa-specific increase in Bacteroidia, Clostridia, and decrease in Gamma-proteobacteria abundance. Importantly, a larger shift from baseline microbiome was seen in responders to RBX2600 compared to non-responders, and RBX2660 treatment appears to increase microbiome diversity.

 

The third poster (#1870; to be presented Saturday, Oct. 7th), titled Microbiome Profile is Distinct in Patients with Successful Response to Microbiota-Based Drug RBX2660 Relative to Placebo Responders involved a sub-analysis of 57 patients who participated in the randomized Phase 2B clinical trial of RBX2660. 16s rRNA sequencing analysis was used to compare the microbiome changes from baseline of patients classified as responders to RBX2660 vs placebo. Investigators determined that RBX2660 treatment for rCDI is associated with greater changes in patient microbiomes than placebo treatment. Notably, at 7, 30 and 60 days, microbiomes from RBX2660-treated patients had high Kullback-Leibler divergence from baseline and significantly different means from baseline (p<0.001). Further, active responders trended toward higher Bacteroides and lower Gamma-proteobacteria and Bacilli after treatment, both of which are characteristic of a healthier microbiome. According to the 3 researchers, these changes are consistent with the hypothesis that RBX2660 can restore a healthier microbiome in rCDI patients.

Rebiotix, Inc. funded all three studies.

For More Information About Rebiotix Please

Click On the Following Link:

http://www.rebiotix.com

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/.

 

 

SYN-004 (ribaxamase) For C. difficile Prevention Advances; U.S. Food and Drug Administration (FDA) Has Granted A Breakthrough Therapy Designation

On May 11, 2017 Synthetic Biologics, Inc. a late-stage clinical company developing therapeutics that preserve the microbiome to protect and restore the health of patients, announced that the U.S. Food and Drug Administration (FDA) has granted a Breakthrough Therapy Designation for SYN-004 (ribaxamase) for the prevention of Clostridium difficile infection.

SYN-004 (ribaxamase) is the Company’s first-in-class oral enzyme designed to protect the gut microbiome from disruption caused by certain intravenous (IV) beta-lactam antibiotics.

The Breakthrough Therapy Designation is based on data from the successful Phase 2b clinical trial of ribaxamase, which met its primary endpoint of significantly reducing CDI. FDA Breakthrough Therapy Designation is intended to expedite development and review timelines when preliminary clinical evidence indicates that a drug may demonstrate substantial improvement on one or more clinically significant endpoints over available therapies for serious or life threatening diseases. If approved by the FDA, SYN-004 (ribaxamase) would be the first available drug designed to prevent Clostridium difficile infection by protecting the gut microbiome from antibiotic-mediated dysbiosis.

“We are delighted by the FDA’s recognition of ribaxamase’s potential to prevent CDI, and the dire need to fill the current void of an approved intervention,” said Jeffrey Riley, President and Chief Executive Officer. “Following this announcement, we have been asked and anticipate requesting a Type-B multidisciplinary meeting with the Agency for a comprehensive discussion on the overarching, high-level drug development plan and pathway to licensure for ribaxamase. We look forward to working closely with the FDA throughout the development and review process and remain dedicated to bringing this potentially paradigm-shifting approach to antibiotic therapy to patients in critical need.”

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C. diff. Spores and More Global Broadcasting Network 

www.cdiffradio.com

Protecting the Gut Microbiome: A Paradigm Shift in Managing GI Disorders

Live Broadcast On Tuesday, May 16th Join us with our guest, Dr. Joseph Sliman, MD, MPH, Chief Medical Officer of Synthetic Biologics.  Dr. Sliman will be discussing  the protection of the natural gut microbiome from the unintended consequences of intravenous (IV) antibiotics which are excreted into the gut is expected to protect against opportunistic enteric infections. Synthetic Biologics is developing two microbiome-focused drug candidates in Phase 3 development including, SYN-004 (ribaxamase) which is designed to protect the gut microbiome by degrading certain IV beta-lactam antibiotics for the prevention of Clostridium difficile infection (CDI), pathogenic
overgrowth and the emergence of antimicrobial resistance, and SYN-010 which is intended to reduce the impact of methane producing organisms in the gut microbiome to treat an underlying cause of irritable bowel syndrome with constipation (IBS-C).

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To learn more about Synthetic Biologics, please click on the link provided below

.http://www.syntheticbiologics.com/about/overview

Source:  Synthetic Biologics

Synthetic Biologics – Protecting the Gut Microbiome: A Paradigm Shift in Managing GI Disorders