Category Archives: Recurrent C. diff. Prevention Clinical Trials

Phase 1, Open Label, Single Group, Study Finds the Effect Of MET-2 Appears To Be Safe, Efficacious, and Well-Tolerated Among Patients with Recurrent C. difficile Infection

Background

Faecal microbiota transplantation (FMT) is highly effective for recurrent Clostridioides difficile infection but has inherent risks. Microbial Ecosystem Therapeutic 2 (MET-2) is an oral encapsulated formulation of 40 lyophilised bacterial species initially isolated from the stool of a healthy donor, but subsequently manufactured independently of donors, eliminating potential risks introduced by changes in donor health. The aim of this study was to determine MET-2 activity, safety, and tolerability.

Methods

This phase 1, open-label, single-group feasibility study was done in Alberta, Canada. The main inclusion criteria were mild to moderate C difficile infection and at least one episode of C difficile infection recurrence (ie, two episodes of C difficile infection) within 12 months. Initial daily treatment was ten oral capsules for 2 days, then three capsules for 8 days. If C difficile infection recurred, a higher dose was offered: 20 capsules for 2 days, then three capsules for 8 days. Patients were followed for adverse events and C difficile infection recurrence up to day 130. The primary outcome was the absence of C difficile infection recurrence (fewer than three unformed bowel movements in 24 h persisting for at least 2 days) at day 40 by intention-to-treat analysis. Secondary outcomes were mortality or hospitalisation due to C difficile infection, infections attributed to treatment, nausea, abdominal pain, vomiting, or diarrhoea during treatment, quality of life ( C difficile Health-Related Quality of Life Questionnaire) before and after treatment, and engrafted MET-2 bacteria in the patient stool. The absence of C difficile infection recurrence at day 130 was an exploratory outcome. This study is registered with ClinicalTrials.govNCT02865616

Findings

Between Sept 19, 2018, and Feb 28, 2020, we enrolled 19 adult patients with at least two episodes of mild to moderate C difficile infection (median age 65 years [IQR 56–67]; 12 women [63%], seven men [37%]). Recurrent C difficile infection was absent at day 40 in 15 (79%) of 19 patients after initial treatment, increasing to 18 (95%) 40 days after retreatment. No mortality associated with C difficile infection, infections associated with MET-2 treatment, or other serious adverse events were observed. The most common self-limited, mild to moderate symptoms reported during treatment were diarrhoea in 12 (63%) of 19 patients and abdominal cramps in 12 (63%). After MET-2 treatment, quality of life improved significantly, as did alpha diversity in stool microbial composition (p=1·93×10 −6). MET-2 associated taxa were found in greater abundance in most patients after treatment compared with baseline. 16 (84%) of 19 patients did not have a recurrence of C difficile infection by day 130.

Interpretation

MET-2 appears to be safe, efficacious, and well-tolerated among patients with recurrent
C difficile infection. Results must be validated in controlled studies.

Funding

NuBiyota.

 

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https://www.thelancet.com/journals/langas/article/PIIS2468-1253(21)00007-8/fulltext?rss=yes

Patient, Family, Caregiver January Symposium Broadcasts During March On C. diff. Spores and More Live Program

CDIFFRADIO.COM

 

 

 

 

 

 

 

SAVE THE DATES to listen in to the leading topic expert presentations

shared on January 15, 2021, at the Patient, Family, Caregiver Symposium:

Beginning Tuesday, March 9 from 1:00 p.m. – 2:00 p.m. EST following through on

March 16,  March 23, and  March 30.

A Symposium specifically developed for Patients Diagnosed With a C. diff. Infection, Being Treated For a Clostridioides diffiicile infection, Recovering From a Clostridioides difficile Infection and Recurrences with Family Members and Caregivers.

The Patient & Family C. diff. Symposium was a gathering of healthcare professionals, keynote speakers, health advocates, practitioners, educators, thought leaders, and patients who are transforming the patient experience and changing the way people experience
C. diff. infections worldwide.

Unlike other conferences on this topic, patients will share their C. diff. infection journeys, providing a real-world perspective on patient experience. Our attendees will learn more from this virtual-online symposium and gain knowledge on important topics that will better aid their care and recovery through tools and strategies delivered by keynote speakers.  

The Symposium followed the C Diff Foundation Mission statement –   Educating and Advocating for the prevention, treatments, clinical trials, diagnostics, and environmental safety of Clostridioides difficile
(C. diff.) infections worldwide.

Keynote speakers presented up-to-date data to expand on the existing knowledge and provide important information focused on, yet not limited to,  a Clostridioides difficile infection (also known as C. diff., C. difficile, CDAD, CDI) ……

  • Prevention
  • Treatments
  • Diagnostics
  • Research
  • Environmental Safety
  • Clinical trials and studies

WITH

  • Introduction to Microbiome Research and Studies
  • Infection Prevention
  • Fecal Microbiota Restoration and Transplants
  • Antibiotic Stewardship

We hope you enjoy the broadcasts!

 

Program Chair:  Paul Feuerstadt, MD, FACG

Barbara McGovern, MD     “Treatment of recurrent C. difficile infection with                                                                                        SER-109, an investigational microbiome drug.”

Paul Feuerstadt, MD          ” C. diff. Overview – What is a C. diff. Infection?”

Sahil Khanna, MD               “C. diff. Treatments + FMT Overview. “

 

 

 

Simon Cutting, Ph. D.         “Bacillus, and C. diff.  Spore Overview. “

Teena Chopra, MD                ” Introduction to Infection Prevention.”

Doe Kley, RN, MPH              “C. diff. Transitioning from Hospital to Home. “

Courtney Jones                    ” Microbiome, Microbiota, and Gut Health.”

Denise Cardo, MD                “Everyone Has a Role in Antibiotic Awareness.”

Larry Kociolek, MD              “C. diff. Infections in Pediatrics.”

Kathy Bischoff                        “My C. diff.  Journey.”

Renata Johnson                      “My C. diff. Journey.”

Paul Feuerstadt, MD      &    Barbara McGovern, MD

 

This Symposium was hosted by the C Diff Foundation and

Sponsored by Seres Therapeutics  

Please — Do Not Take Medicine Into Your Own Hands, You Are NOT Out Of Options

Do-It-Yourself Treatments Could Be Fatal……

You are NOT out of options………………………

During these unprecedented times, we understand the patient’s frustration and how this pandemic has created a halt to the readily accessible alternative treatment option in the FMT community.   The need for continued treatments for a C. diff. infection and recurrent C. diff. infections are real and necessary. We also understand how patients experiencing
recurrent C. difficile infections are desperately seeking the FMT alternative treatment.

C Diff Foundation is able to provide information about treatments available to safely treat  CDI’s and recurrent C. diff. infections.

Most home remedies or natural therapies, though, haven’t been put through the same rigorous clinical testing you expect from pharmaceutical medications.

In a world where you can fix almost anything with a do-it-yourself video on YouTube, you might think curing your own illness would be a piece of cake. It might be if it weren’t for a couple of (not so small) sticking points.  One, the home remedy recommended by your friend — or one of the many websites promoting “natural therapies” — might not work.1  Dr. Harriet Hall, a retired family physician, former Air Force flight surgeon, and author of the SkepDoc column in Skeptic magazine, is one of those leading the charge against medical “treatments” not supported by science.  Like others in the medical and scientific community, ……. There is the only medicine that has been tested and proven to work, and medicine that hasn’t,” Hall told Healthline. 1

Talk to your medical professional/s.

Discuss medications and clinical trials available.

Do Not Share Antibiotics.

Responses to an anonymous online questionnaire of 496 parents, researchers at the Cohen Children’s Medical Center of New York reported that 48 percent of the parents surveyed said they’ve held onto leftover antibiotics. More troubling to researchers was that of those parents, 73 percent reported giving those antibiotics to siblings, unrelated children, and unrelated adults.  This would sometimes occur months after the drugs were originally prescribed.
Dr. Ruth Milanaik, director of the neonatal neurodevelopment follow-up program at Cohen and senior author of the study, says the results show an “alarming” percentage of parents engaging in sharing or borrowing antibiotics, a practice known as prescription diversion.  “This is dangerous not only for those given antibiotics that weren’t prescribed for them but for entire populations of people who some antibiotics may no longer help when the bacteria they target become resistant to them,” Milanaik said in a statement. 2

Discuss Resources available.

Times are trying during these unprecedented times and you are not without hope – we would like to help you and not see you get hurt or even worse. Please take time to speak to your treating physician and consider contacting a C Diff Foundation Triage Nurse at 727-205-3922 to learn more about safe and effective treatments available and options available to you at this time of desperation.

Remember – You  Are Not Out of Options.

Stay safe – and please – Do NOT take medicine into your own hands.

Thank You!

Resources:
1 Foxnews.com
2 Healthline.com

 

 

Rebiotix and Ferring Pharmaceuticals Announced Positive Preliminary Findings From Their Ongoing Pivotal Phase 3 Trial Of the Investigational Microbiome-based Treatment RBX2660

This is a promising approach to managing CDI. Completion of a Phase 3 study, with positive results, is exciting and holds much promise for patients suffering with recurrent C. diff. infections.
We look forward to the final results and are truly grateful.

 

Rebiotix and Ferring announce world’s first with positive preliminary
pivotal Phase 3 data for investigational microbiome-based therapy RBX2660

Rebiotix and Ferring are the first to announce positive preliminary results on primary
efficacy endpoint from ongoing pivotal Phase 3 clinical trial for RBX2660

RBX2660 is an investigational, non-antibiotic, microbiome-based therapy, developed to
reduce Clostridiodes difficile (C. diff) infection recurrences

The CDC defines C. diff as a major burden to patients and doctors and an urgent healthcare
threat causing an estimated half a million illnesses and thousands of deaths annually in the
US alone ( 1 , 2)

Source:  Press Release
Roseville, Minnesota and Saint-Prex, Switzerland – 6 May, 2020, 07:00 EST –

Today, . These preliminary positive efficacy findings mark an important milestone, advancing RBX2660 in its clinical development program with a goal of bringing a US FDA approved therapy to patients. The clinical development program for RBX2660 is the most advanced in the world in evaluating the safety and efficacy of a standardized, non-antibiotic microbiome-based therapy.
RBX2660 is being developed to reduce C. diff infection recurrences, an urgent unmet need for
patients and healthcare providers worldwide. Antibiotics, the current standard of care, have been shown to disrupt the microbiome and increase the risk of C. diff recurrence. 3

C. diff causes nearly 30,000 deaths each year in the US; in Europe, the incidence of C. diff is increasing, with recurrent bouts of infection representing 10-15% of all healthcare-related infections in hospitals annually. 4 , 5

As a live biotherapeutic, aiming to help restore the gut microbiome community, RBX2660 may bring an innovative therapeutic option to patients suffering from this potentially deadly infection. “C. diff infection is a significant public health threat that has limited treatment options. These positive preliminary findings represent a major step forward towards bringing an innovative, non-antibiotic option to patients that may help restore their gut microbiome, said Per Falk, Ferring’s President and Chief Science Officer. With health systems under increasing pressure due to viruses like COVID-19 and the rising threat of antimicrobial resistance, the need for new therapies is greater than ever. We believe the power of the microbiome has great potential and we look forward to bringing RBX2660 to patients soon.”

“Since founding Rebiotix in 2011, our mission has been to harness the power of the microbiome to treat complex diseases. Our first goal was to address C. diff, which poses a significant health threat to thousands worldwide every year,” said Lee Jones, CEO and founder of Rebiotix, a Ferring company.

The positive preliminary data on the primary efficacy endpoint are a major stepping stone
for the RBX2660 development program, bringing us closer to an approved microbiome therapy
available for healthcare providers to help patients. As a first-in-class, potentially paradigm-changing technology, we look forward to discussing our final data with the FDA in the latter part of this year.” The ongoing Phase 3 trial is a randomized, multicenter, double-blinded, placebo-controlled study. The trial also incorporates a safety assessment intended to follow patients for several months after receiving the investigational drug. The safety data will provide insight into the potential of using microbes as a therapeutic intervention. The full data package is anticipated in the second half of 2020.

This trial builds on nearly a decade of research and evaluation of the formulation, with robust clinicaland microbiome data collected over multiple controlled trials under the proprietary MRT drug platform.

About Clostridioides difficile infection (C. diff)
C. diff is a bacterium that causes diarrhea and colitis (an inflammation of the colon). 6 It is estimated to cause up to half a million illnesses in the US alone every year and is considered an urgent threat to public health by the CDC, and can lead to severe complications, including hospitalization, surgery, and death. 2 While antibiotics are the standard of care to address the infection, they are also the primary risk factor for disease recurrence. 3 Recurrence of C. diff occurs in approximately 15- 50% of patients. 7

About the microbiome
The human microbiome is a complex community of microorganisms which live on every surface of the body. The microbiome aids in the maintenance and development of the immune system,
metabolism, and other functions essential to human life. 8 The gastrointestinal tract houses the most dense and complex population of microbiota, which has an incredible influence over daily health – from aiding in food digestion to fighting disease. Clinical and scientific studies indicate antibiotics, viruses, stress and other factors can disturb the gut microbiota. This disruption, often referred to as “dysbiosis,” may have negative health impacts, and promote conditions for infections like C. dif infection to take hold. 9

Rebiotix and Ferring believe there is tremendous potential in microbiota-based therapies to address such illnesses, and are evaluating this therapeutic option through their
pioneering microbiota-based MRT drug platform, beginning with recurrent C. diff infection.

About RBX2660

The investigational RBX2660 formulation is the first-in-class microbiota-based therapy to achieve positive preliminary Phase 3 study results. RBX2660 is being developed to help break the cycle of recurrent C. diff infection. The therapy has been granted Fast Track, Orphan, and Breakthrough Therapy designations from the US FDA. The RBX2660 ongoing pivotal Phase 3 trial, PUNCH CD3,  is a randomized, multicenter, double-blinded, placebo-controlled study. For more information about the RBX2660 Phase 3 study, visit http://www.clinicaltrials.gov (NCT03244644).

About Ferring Pharmaceutical Ferring Pharmaceuticals is a research-driven, specialty biopharmaceutical group committed to helping people around the world build families and live better lives. Headquartered in Saint-Prex,Switzerland, Ferring is a leader in reproductive medicine and maternal health, and in specialty areas within gastroenterology and urology. Founded in 1950, privately-owned Ferring now employs approximately 6,500 people worldwide, has its own operating subsidiaries in nearly 60 countries and markets its products in 110 countries.Learn more at http://www.ferring.com, or connect with us on Twitter, Facebook, Instagram, LinkedIn and YouTube.

About Rebiotix
Rebiotix Inc, part of the Ferring Pharmaceuticals Group, is a late-stage clinical microbiome
company focused on harnessing the power of the human microbiome to revolutionize the treatment of challenging diseases. Rebiotix has a diverse pipeline of investigational drug products built on its pioneering microbiota-based MRT drug platform. The platform consists of investigational drug technologies designed to potentially rehabilitate the human microbiome by delivering a broad consortium of live microbes into a patient’s intestinal tract. For more information on Rebiotix and its pipeline of human microbiome-directed therapies for diverse disease states, visit http://www.rebiotix.com, or connect with us on Twitter, Facebook, LinkedIn and YouTube.

For more information, please contact
Courtney Jones
Marketing Manager
Rebiotix Inc., a Ferring Company
+1 651 705 8774 (direct)
courtney.jones@ferring.com

Lindsey Rodger
Senior Manager, Corporate Communications
Ferring Pharmaceuticals
+41 58 451 4023 (direct)
+41 79 191 0486 (mobile)
lindsey.rodger@ferring.com

References
1 Centers for Disease Control and Prevention. What Is C. Diff?17 Dec. 2018. Available at:
https://www.cdc.gov/cdiff/what-is.html.
2 Centers for Disease Control and Prevention. Biggest Threats and Data, 14 Nov. 2019. Available at:
https://www.cdc.gov/drugresistance/biggest-threats.html.
3 Theriot CM, Young VB. Microbial and metabolic interactions between the gastrointestinal tract and
Clostridium difficile infection. Gut Microbes. 2013;5(1):86-95. doi:10.4161/gmic.27131.
4 Lessa FC, Mu Y, Bamberg WM, et al., Burden of Clostridium difficile Infection in the United States. New
England Journal of Medicine. 2015;372(9):825-834. doi:10.1056/nejmoa1408913.
5 DRG Report 2016 Clostridium Difficile.
6 Centers for Disease Control and Prevention. Clostridiodes difficile Fact Sheet. Available at:

PDF Document

7 Stevens VW, Nelson RE, Schwab-Daugherty EM, et al., Comparative Effectiveness of Vancomycin and
Metronidazole for the Prevention of Recurrence and Death in Patients with Clostridium difficile Infection.
JAMA Intern Med. 2017;177(4):546–553. doi:10.1001/jamainternmed.2016.9045.
8 Mohajeri MH, Brummer RJM, Rastall RA, et al., The role of the microbiome for human health: from basic
science to clinical applications. Eur J Nutr. 2018;57(Suppl 1):1–14. doi:10.1007/s00394-018-1703-4.
9 Quigley EM. Gut bacteria in health and disease. Gastroenterol Hepatol (N Y). 2013;9(9):560–569.

Seres Therapeutics Announced on March 30th, 2020, That the Company Has Completed Enrollment of its SER-109 Phase 3 Clinical Study, ECOSPOR III

On March 30th, 2020

Seres Therapeutics, Inc., announced that the Company has completed enrollment of its SER-109 Phase 3 clinical study, ECOSPOR III.

www.serestherapeutics.com

 

SER-109 is an oral, first-in-field microbiome therapeutic candidate that has been granted Orphan Drug and Breakthrough Therapy designations by the U.S. Food and Drug Administration (FDA), and is being investigated for use in preventing recurrent Clostridium difficile infection (CDI).

“We are pleased to have achieved this critically important corporate milestone. SER-109 has the potential to be the first FDA-approved therapy for C. difficile infection to treat the underlying cause of this disease, and the first approved microbiome drug for any human condition. We believe SER-109 could fundamentally transform the treatment of patients with recurrent C. difficile infection, a life-altering infectious disease, and we eagerly look forward to topline clinical results in the middle of this year. With compelling Phase 3 ECOSPOR III clinical data, we plan to engage in discussions with the FDA regarding a filing for product approval,” said Eric Shaff, President and Chief Executive Officer of Seres. “We are also working to advance our other promising clinical development candidates in light of the COVID-19 pandemic. This remains an evolving situation and we are carefully reviewing our development plans to determine how to rapidly advance our pipeline toward high-quality data readouts.”

SER-109 Study Updates

The SER-109 Phase 3 ECOSPOR III study (ClinicalTrials.gov identifier: NCT03183128) is a multicenter, randomized, placebo-controlled study which has enrolled 181 patients with multiply recurrent CDI to date. ECOSPOR III had been designed to enroll 188 patients. The Company has decided to halt enrollment as a result of the COVID-19 pandemic. Seres believes that ECOSPOR III remains well-powered to evaluate the efficacy of SER-109. The ECOSPOR III study’s primary endpoint is the reduction of CDI recurrence at up to eight weeks following SER-109 administration, and the Company expects to report study results in mid-2020 as had been planned.

Seres is grateful to the patients, principal investigators and clinical research teams who participated in ECOSPOR III, many of whom are now involved in the fight against COVID-19.

The SER-109 Phase 3 ECOSPOR III study includes use of an objective Clostridium difficile cytotoxin assay to ensure that all patients entering the study have active CDI, as well as to confirm CDI recurrences during the study (i.e., the ECOSPOR III primary endpoint).

Seres plans to initiate a SER-109 Expanded Access Program at selected clinical sites participating in the ongoing Phase 3 ECOSPOR III study, and the Company may also initiate the program at additional clinical sites for eligible patients to have access to SER-109.

Prior completed clinical studies have demonstrated SER-109 bacterial engraftment into the gastrointestinal microbiome, and that engraftment is associated with reduced recurrence of CDI. In all prior clinical studies, SER-109 was associated with a favorable safety profile.

The FDA has issued several safety alerts related to Fecal Microbiota Transplantation (FMT) and the risk of pathogen transmission including warnings related to Multi-Drug Resistant Organisms and SARS-CoV-2, the virus linked to COVID-19 (June 12, 2019Alert; March 12, 2020Alert; and March 23, 2020Alert). Unapproved FMT is widely used under an FDA Enforcement Discretion policy for the treatment of recurrent CDI that is not responsive to standard therapies.

In contrast to FMT, SER-109 is comprised of a highly purified consortia of spore-based commensal bacteria and is manufactured under Good Manufacturing Practices (GMP) conditions using stringent standards to ensure product quality and consistency. Seres utilizes a unique manufacturing process which has been demonstrated to inactivate numerous potential pathogens, including species of non-spore bacteria, such as Escherichia coli, and viruses. The Company’s manufacturing process inactivates many emerging potential pathogens where diagnostic assays may not yet be available, such as SARS-CoV-2. Seres has issued a position statement highlighting the criticality of including pathogen inactivation processes in the manufacture of microbiome therapeutics. Recent discussions with the FDA have indicated agency support regarding the fundamental differentiation between FMT and Seres’ product candidates.

COVID-19 Impact and Other Clinical Program Updates

Seres continues to monitor the impact of the COVID-19 pandemic on Company operations and ongoing clinical development activity, including the SER-287 Phase 2b study in ulcerative colitis, the SER-401 Phase 1b study in metastatic melanoma, and SER-301, a rationally designed, fermented development candidate for ulcerative colitis. Mitigation activities to minimize COVID-19-related operation disruptions are ongoing; however, given the severity and evolving nature of the situation, the timing of SER-287 Phase 2b and SER-401 Phase 1b clinical readouts is uncertain. Seres does not anticipate disruptions to the availability of its drug product candidates for ongoing studies.

The SER-287 Phase 2b study is currently approximately 60% enrolled based on the 201-patient target study size. SER-287 development activity has been adversely impacted by multiple clinical sites halting non-essential procedures, including endoscopies, which may make it difficult to achieve the original enrollment target in H2 2020 as planned. Seres is evaluating enrollment mitigation strategies and possible trial design modifications with the goal of obtaining a high-quality, clinically meaningful dataset within a timeframe consistent with Seres’ prior guidance for its cash runway extending into the second quarter of 2021. Furthermore, the Company is encouraged by the FDA’s indications of flexibility in light of the COVID-19 pandemic, and plans to engage the FDA in discussions regarding any potential trial modifications.

Seres continues to execute on activities to advance SER-301 clinical development and the planned initiation of patient dosing in Australia and New Zealand later this year.

 

SOURCE:  http://ir.serestherapeutics.com/news-releases/news-release-details/seres-therapeutics-announces-completion-enrollment-ser-109-phase