Tag Archives: Are there clinical trials for C.diff?

DEINOVE: DNV3837 Antibiotic Candidate: the Phase II Clinical Trial to Treat CDI Continues in the USA

DEINOVE is a French biotech company that uses its lead generation platform to develop innovative anti-infective drugs, is pursuing the Phase II clinical trial of its antibiotic candidate DNV3837, in a context where U.S. hospitals are still fighting the COVID-19 pandemic. The Company thanks the clinicians for their commitment to this trial, as they face an unprecedented health crisis.

DNV3837 targets the treatment of Clostridioides difficile gastrointestinal infections (CDI), a pathogen classified as urgent threat by the U.S. Centers for Disease Control and Prevention (CDC). A Phase II clinical trial, launched in early 2020 in the United States, is evaluating the efficacy of DNV3837 in patients, following promising Phase I data. To date, DEINOVE is the only French biotech with a small molecule in clinical development, fully owned by the company, in the field of antibiotics.

This trial continues in the United States despite the COVID-19 outbreak. Several of the investigation centers have maintained their clinical research activities and continue to screen and include patients. DEINOVE scientific team and the CRO Medpace are closely monitoring the situation.

« We are grateful to the clinicians for doing their utmost to ensure that the clinical trial runs smoothly. We are surrounded by a team that is aware of the therapeutic stakes and the potential of our solution in development, and we thank them for this. In the current health conditions in the United States, where hospitals are overcrowded, we could have feared a suspension of the trial, » says Dr. Yannick Plétan, Acting Chief Medical Officer responsible for the clinical trial. «Conversely, the COVID-19 outbreak – which mainly affects the elderly – and the heavy antibiotic treatments administered to combat possible bacterial co-infections, are factors conducive to the development of severe Clostridioides difficile infections targeted by DNV3837. We are concerned, however, about the irrational use of antibiotics, which would have long-term public health consequences. »

On June 1st of this year, the WHO warned of the increasing rates of antimicrobial resistance, boosted by the current health crisis. ” The COVID19 pandemic has led to an increased use of antibiotics, which ultimately will lead to higher bacterial resistance rates that will impact the burden of disease and deaths during the pandemic and beyond,”worried Dr Tedros Adhanom Ghebreyesus, WHO Director-General1. According to him, the threat of antimicrobial resistance is “one of the most urgent challenges of our time “. He also recalled that only small proportion of COVID-19 patients need antibiotics to treat subsequent bacterial infections.

ABOUT CLOSTRIDIOIDES DIFFICILE INFECTIONS (CDI)

40% of patients suffering a Clostridioides difficile infection (CDI) have severe forms, with mortality rates as high as 50%. Over the past 20 years, CDIs tended to increase significantly in incidence and severity, particularly due to the development of new hypervirulent strains and the high risk of recurrence. The US Center for Disease Control and Prevention (CDC) recently identified CDIs as one of the leading causes of healthcare-associated infections before Staphylococcus aureus (MRSA2) infections. In 2017, in the United States, there were an estimated 223,900 cases in hospitalized patients and 12,800 deaths3. This disease does not affect the United States only, recent studies4 show that the incidence of this type of infection is vastly underestimated in other parts of the world such as Europe and Asia.

To date, there are no therapeutic solutions for patients with severe gastrointestinal infections. Since the oral route is compromised, the available treatments, which are mostly oral treatments, struggle to reach the intestine because of the patient’s pathological condition (reduced gastrointestinal motility, intubation, intestinal perforation, etc.), and the few antibiotics that could be administered intravenously (IV), do not cross the gastrointestinal barrier and therefore do not reach the site of infection.

ABOUT THE DNV3837 ANTIBIOTIC CANDIDATE

DNV3837 – a prodrug5 of the DNV3681 molecule (also known as MCB3681) – is a narrow-spectrum, hybrid oxazolidinone-quinolone synthetic antibiotic targeting only Gram-positive bacteria. It is developed as a highly active 1st line treatment targeting Clostridioides difficile.

It has demonstrated significant efficacy and superiority to reference treatments (fidaxomicin in particular) against isolates of C. difficile, regardless of their virulence (including the hyper virulent BI/NAP1/027 strain).

DNV3837 is an intravenous antibiotic that, when converted to its active form DNV3681, crosses the gastrointestinal barrier and accumulates in the intestinal lumen, allowing it to precisely target the infection site. Several Phase I trials (on approx. a hundred healthy volunteers) have shown a high concentration of the antibiotic in stools, a strong marker of its presence in the intestine. It has also demonstrated its ability to eliminate Clostridioides bacteria without affecting the gut microbiota. It has also shown an acceptable tolerance profile.

FDA granted the DNV3837 drug with Qualified Infectious Disease Product (QIDP) designation and Fast Track status.

ABOUT THE PHASE II CLINICAL TRIAL TESTING DNV3837 IN CDI

The antibiotic candidate DNV3837 has been in a Phase II trial since the end of January 2020. The purpose of this trial is to evaluate its efficacy in CDI (through monitoring of symptoms, stool analysis, etc.), as well as to consolidate the safety and pharmacokinetic data.

This trial is taking place in the United States in two stages:

  • In the first phase, a cohort of 10 patients with moderate to severe CDI is treated with DNV3837. At the end of this phase, the DSMB6 has scheduled to review the interim results.
  • The second phase involves 30 patients with severe CDI. This is an open-label randomized trial testing DNV3837 (in 2/3 of patients) against an approved standard of care7 (1/3 of patients) for comparison purposes.

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

https://www.businesswire.com/news/home/20200715005695/en/DEINOVE-DNV3837-Antibiotic-Candidate-Phase-II-Trial

Summit Therapeutics plc Phase 2 Clinical Trial Ridinilazole In Development For the Treatment of C. difficile Infection

Summit Announces Publication of Phase 2 Clinical Analyses of Gut Microbiome Health

July 13, 2020 – Summit Therapeutics plc announced the publication of data from the Phase 2 clinical trial of the company’s precision antibiotic, ridinilazole, in development for the treatment of C. difficile infection (‘CDI’) in the American Journal of Physiology – Gastrointestinal and Liver Physiology. The data published in collaboration with researchers at Tufts University and Tufts Medical Center demonstrated that ridinilazole’s microbiome preservation resulted in a gut environment expected to inhibit the growth of C. difficile. In contrast, vancomycin treatment resulted in a gut environment that may more highly favor the growth of C. difficile. The difference in gut environment could explain the approximately 60% relative reduction in recurrence observed in patients treated with ridinilazole over vancomycin in the Phase 2 trial.

“This is the first scientific article ever to show the effect of antibiotics treating CDI on the bile acid composition in the human gut. In addition, CoDIFy is the first clinical study to highlight the differential effects of antibiotics on bile acids, which are known to create environments that can either promote or protect against CDI,” said Dr. Ventzislav Stefanov, Executive Vice President and President of Discuva. “The protective gut environment observed after ridinilazole treatment, compared to vancomycin, provides a strong rationale for the higher sustained clinical response observed in patients taking ridinilazole in the CoDIFy clinical trial.”

The Phase 2 clinical trial enrolled 100 patients, half of whom received ridinilazole and the other half vancomycin. The publication, “Ridinilazole, a narrow spectrum antibiotic for treatment of Clostridioides difficile infection, enhances preservation of microbiota-dependent bile acids,” was authored by X. Qian, K. Yanagi, A. Kane, N. Alden, M. Lei, D. Snydman, R. Vickers, K. Lee and C. Thorpe. In the published data, there was a higher ratio of pro-C. difficile to anti C.-difficile bile acids at the start of treatment for both ridinilazole- and vancomycin-treated patients. This was expected, as patients who get CDI have perturbed microbiomes. However, during treatment, patients treated with vancomycin showed a further decrease in anti-C. difficile bile acids and had stools dominated by pro-C. difficile bile acids. In contrast, this did not occur in ridinilazole-treated patients. By the end of the study period, ridinilazole-treated patients’ bile acid ratios trended towards a healthy, non-CDI state. These results support the data from the Phase 2 clinical trial, in which patients receiving ridinilazole showed a statistically significant improvement in sustained clinical responses.

SOURCE: https://seekingalpha.com/pr/17929120-summit-announces-publication-of-phase-2-clinical-analyses-of-gut-microbiome-health

Seres Therapeutics To Host a Virtual Webcast Focused on SER-109 on May 27, 2020

In The News:

Seres Therapeutics to Host Virtual SER-109 Focused Symposium on May 27, 2020, Ahead of Phase 3 ECOSPOR III Study Read-Out

– Data from SER-109 Phase 3 study in recurrent C. difficile infection expected mid-2020 –

Seres Therapeutics, Inc.  announced that it will host a virtual webcast symposium focused on SER-109 as a potential new therapeutic option for recurrent Clostridioides difficile infection (CDI) on Wednesday,  May 27, 2020 from 8:30 to 9:30 a.m. ET.

During the event, Mark Wilcox, M.D., Professor of Medical Microbiology, University of Leeds, and Seres’ management will discuss the CDI patient burden, the ongoing SER-109 Phase 3 ECOSPOR III study and the potential for SER-109 to become the standard of care for recurrent CDI.

SER-109 is being evaluated in an ongoing Phase 3 study for the prevention of recurrence of CDI. SER-109 has obtained both Breakthrough Therapy Designation and Orphan Drug Designation from the U.S. Food and Drug Administration (FDA).

Seres previously reported the completion of enrollment in the Phase 3 ECOSPOR III study (ClinicalTrials.gov identifier: NCT03183128), a multicenter, randomized 1:1, placebo-controlled study in patients with multiply recurrent CDI. ECOSPOR III has enrolled 182 patients. Seres expects to report SER-109 Phase 3 top-line results in mid-2020.

Based on prior discussions with the FDA, Seres believes that ECOSPOR III has the potential to be the single pivotal study supporting product registration; however, this will depend on the strength of the data, and additional safety data may be required. If approved, SER-109 has the potential to be the first FDA-approved therapy for CDI to treat the underlying cause of this disease, and the first approved microbiome drug for any human condition.

To join the live webcast, on May 27, 2020 at 8:30 a.m. ET, including presentation slides, please visit the “Investors & Media” section of the Seres website at www.serestherapeutics.com. To access the conference call, please dial 844-277-9450 (domestic) or 336-525-7139 (international) and reference the conference ID number 4884302.                                                                                Webcast Link: https://edge.media-server.com/mmc/p/3qo4hxiv.

A webcast replay will be available on the Seres website beginning approximately two hours after the event and will be archived for approximately 21 days.

To view press release in its entirety please click on the following link:

http://ir.serestherapeutics.com/news-releases/news-release-details/seres-therapeutics-host-virtual-ser-109-focused-symposium-may-27#

 

 

Rebiotix, a Ferring Company, Completes Enrollment for First-Ever, Pivotal Phase 3 Clinical Trial RBX2660

Rebiotix, a Ferring Company, completes enrollment for first-ever, pivotal Phase 3 Clinical Trial of Microbiota -based RBX2660

Enrollment completion for the first Phase 3 clinical trial in microbiome industry

 The largest randomized, double-blinded study, with over 300 patients enrolled aimed to demonstrate the potential benefit of RBX2660 in reducing rates of recurrent Clostridioides difficile (C. diff) infection

 Rebiotix intends to use the results from the Phase 3 trial to serve as the basis for licensure application to the US Food and Drug Admin (FDA)

 Saint-Prex, Switzerland – On February 4, 2020

Rebiotix, a Ferring company, announced today that it has completed enrollment of the pivotal Phase 3 clinical trial for RBX2660, an investigational therapy aimed at breaking the cycle of recurrent Clostridioides difficile (C. diff) infection, which is responsible for the deaths of thousands of people in the US alone. The Centers for Disease Control and Prevention (CDC) has classified C. diff as an urgent public health threat, with limited options for treatment.

 

RBX2660 was developed under Rebiotix’s investigational microbiota-based MRT™ drug platform with the goal of delivering standardized, stabilized formulations to meet unmet medical needs. Conducted in the US and Canada, this is the first Phase 3 trial of its kind to be completed using a broad consortia microbiota-based formulation.

 

“Rebiotix was founded to harness the power of the human microbiome to treat debilitating diseases,” said Lee Jones, Rebiotix Founder, and CEO. “Microbiota-based therapies have shown tremendous potential as an innovative, non-antibiotic therapy, starting with C. diff. The completion of enrollment of this trial is a critical next step in making microbiota-based products accessible to patients – we are excited about this important milestone and look forward to sharing results later this year.”

 

The Phase 3 trial builds on the company’s extensive history with the formulation, including several hundred participants previously enrolled in multiple Phase 2 clinical trials. The robust data collected over the course of the company’s multi-year clinical development program will be eventually presented to the US FDA as part of a Biological License Application (BLA).

 

Ferring Pharmaceuticals, also with a rich and vast history of microbiome research of its own, led the industry by becoming the first major pharmaceutical company to acquire a microbiome therapeutics company in April 2018. Headquartered in Saint-Prex, Switzerland, Ferring is expected to have the first regulatory approved microbiota-based therapeutic in the world through the potential approval of the RBX2660 in the US.

 

About Clostridioides difficile Infection

Clostridioides difficile (also known as C. diff) is a bacterium that causes diarrhea and colitis (inflammation of the colon). C. diff, impacts nearly a half a million people each year in the United States; of those impacted, up to one in five patients will experience a recurrent episode.1 In 2019, the U.S. Centers for Disease Control listed C. diff as an urgent threat to public health.2

 

About RBX2660

RBX2660 is currently in Phase 3 clinical development for the reduction of recurrent Clostridioides difficile (C. diff) infection. RBX2660 has been granted Fast Track, Orphan, and Breakthrough Therapy Status designations from the US FDA. For more information about the RBX2660 Phase 3 study, visit http://www.clinicaltrials.gov (NCT03244644).

 

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.

 

About Ferring Pharmaceuticals

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.

 

References:

1Centers for Disease Control and Prevention. What Is C. Diff?,17 Dec. 2018. Available at: https://www.cdc.gov/cdiff/what-is.html.

2Centers for Disease Control and Prevention. Biggest Threats and Data, 14 Nov. 2019. Available at: https://www.cdc.gov/drugresistance/biggest-threats.html.

 

Source:  Rebiotix, Press Release

http://www.rebiotix.com

Contagion® Interview with Ken Blount, PhD Chief Scientific Officer at Rebiotix, a Ferring Company, and Discussed the Phase II Microbiota Based RBX2660 Clinical Trial Results and Plans for Next Steps

OCT 03, 2019 | ALEXANDRA WARD

Contagion Live

To read the interview in its entirety – click on the following link to be redirected:

https://www.contagionlive.com/news/phase-2-results-microbiotabased-rbx2660-safe-efficacious-for-preventing-c-diff-recurrence

Investigators at IDWeek 2019 presented the final, 24-month analysis of data from a phase 2 open-label trial of RBX2660 for the prevention of CDI recurrence. Patients with multi-recurrent CDI were enrolled in the multicenter study and received > 2 doses of RBX2660 delivered via enema 7 days apart.

The research team defined efficacy as absence of CDI recurrence through 56 days after the last dose, and durability as continued absence of CDI episodes beyond 8 weeks. Results were compared with the 8-week recurrence-free rates for a historical control cohort that received standard-of-care antibiotic therapy.

Participant stool samples were collected prior to and for up to 720 days after treatment, and safety and durability assessments were performed at 3, 6 ,12, and 24 months. Investigators assessed microbiome changes via shallow shotgun sequencing.

https://www.contagionlive.com/news/phase-2-results-microbiotabased-rbx2660-safe-efficacious-for-preventing-c-diff-recurrence