Tag Archives: Clostridium difficile clinical trials

Summit Therapeutics Doses First Patient in Global Phase 3 Clinical Trials Oral Antibiotic ridinilazole for C.difficile Infection Treatment

Summit Doses First Patient in Phase 3 Clinical Trials of Precision Antibiotic Ridinilazole for C. Difficile Infection

  • Trials Aim to Show Superiority of Ridinilazole Over Standard of Care Treatment Vancomycin
  • Health Economic Outcomes Included to Support Commercialisation

FROM PRESS RELEASE:

Oxford, UK, and Cambridge, MA, US, 13 February 2019 – Summit Therapeutics plc (NASDAQ: SMMT, AIM: SUMM), a leader in new mechanism antibiotic innovation, today announces it has dosed the first patient in the global Phase 3 clinical trials of its precision oral antibiotic, ridinilazole, for C. difficile infection (‘CDI’). The trials aim to show superiority of ridinilazole over the standard of care, vancomycin, in a measure that combines CDI cure and recurrence called sustained clinical response (‘SCR’). Ridinilazole achieved statistical superiority over vancomycin in SCR in a Phase 2 clinical trial.

“Starting our Phase 3 programme is an important milestone for Summit,” commented Mr Glyn Edwards, Chief Executive Officer of Summit. With positive results, we believe ridinilazole could be positioned as the drug of choice in the front-line treatment of CDI, which potentially provides patients with sustained cures and hospitals with compelling cost savings.”

“Ridinilazole is the trail-blazer in our growing pipeline of innovative product candidates targeting serious infectious diseases,” added Dr David Roblin, President of R&D of Summit. “Our Phase 3 programme exemplifies our broader strategy of demonstrating significant advantages over current standards of care by gathering a carefully considered package of clinical and economic data to address the needs of physicians, regulators, healthcare providers, payors and, above all, patients.”

The Phase 3 clinical programme comprises two global, randomised, double-blind, active-controlled clinical trials called Ri-CoDIFy 1 and Ri-CoDIFy 2. The trials will be run concurrently with each expected to enrol approximately 680 patients at sites in North America, Latin America, Europe, Australia and Asia. Upon confirmation of a positive CDI toxin test, patients will be randomised to receive either ridinilazole (200mg twice a day) or vancomycin (125mg four times a day) for ten days. The primary endpoint of both clinical trials will test for superiority in SCR, defined as cure at the end of treatment and no recurrence of CDI within 30 days post-treatment. Secondary endpoints include cure at the end of treatment and SCR at 60 days and 90 days post-treatment. Additional endpoints will evaluate the impact of ridinilazole and vancomycin on the gut microbiome, which is known to protect against CDI. The Phase 3 clinical trials also include health economic outcome measures, such as readmission rates and length of hospital stay, to help support the commercialisation of ridinilazole, if approved.

Top-line data from the Phase 3 programme are expected to be reported in the second half of 2021.

The clinical and regulatory development of ridinilazole is being funded in part with Federal funds from the US Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority (‘BARDA’), under Contract No. HHS0100201700014C. Summit is eligible to receive up to $62 million in funding from BARDA to support the clinical and regulatory development of ridinilazole.

About Ridinilazole
Ridinilazole is an oral small molecule new mechanism antibiotic that is designed to selectively kill C. difficile, thereby preserving patients’ protective gut microbiome and leading to sustained CDI cures. In a Phase 2 proof of concept trial in CDI patients, ridinilazole showed statistical superiority in sustained clinical response (‘SCR’) rates compared to the standard of care, vancomycin. In that trial, SCR was defined as clinical cure at end of treatment and no recurrence of CDI within 30 days of the end of therapy. Ridinilazole was also shown to be highly preserving of the gut microbiome in the Phase 2 proof of concept trial, which was believed to be the reason for the improved clinical outcome for the ridinilazole-treated patients. In addition, ridinilazole preserved the gut microbiome to a greater extent than the marketed narrow-spectrum antibiotic fidaxomicin in an exploratory Phase 2 clinical trial. Ridinilazole has received Qualified Infectious Disease Product (‘QIDP’) designation and has been granted Fast Track designation by the US Food and Drug Administration. The QIDP incentives are provided through the US GAIN Act and include a potential extension of marketing exclusivity for an additional five years upon FDA approval.

About Summit Therapeutics
Summit Therapeutics is a leader in antibiotic innovation. Our new mechanism antibiotics are designed to become the new standards of care for the benefit of patients and create value for payors and healthcare providers. We are currently developing new mechanism antibiotics for infections caused by C. difficile, N. gonorrhoeae and ESKAPE pathogens and are using our proprietary Discuva Platform to expand our pipeline.

For more information, visit www.summitplc.com

MGB Biopharma (MGB) Prepares To Launch a Phase II Clinical Trial Of Its Anti-bacterial Agent MGB-BP-3

A new drug aimed at treating potentially deadly Clostridium difficile (C. diff) infections is set to be tested on patients for the first time.

Glasgow-based life sciences firm MGB Biopharma (MGB) said it was preparing to launch a Phase II clinical trial of its anti-bacterial agent MGB-BP-3.

The trial is expected to involve 30 patients based in North America.

All have been diagnosed with C.diff-associated disease (CDAD).

C.diff infections can cause diarrhoea and fever.

They have been a major problem in hospitals around the world, with thousands of deaths in the US alone linked to the bug each year.

The bacteria are able to take over the gut when a course of antibiotics kills off the bugs that normally live there.

MGB’s announcement came after it raised £1.3m from investors for trials of the new drug, which was invented at the University of Strathclyde.

The funding round was led by Edinburgh-based Archangels, with co-funding from a range of sources, including the Scottish Investment Bank, Barwell and Melrose-based Tri Capital.

The cash supplements a £2.7m grant awarded earlier this year by Innovate UK.

SOURCE:  https://www.bbc.com/news/uk-scotland-scotland-business-45508036

MGB said its trial would “evaluate safety and tolerability, efficacy and in particular look for improvement in global (or sustained) cure rates”.

Chief executive Dr Miroslav Ravic said: “We are already witnessing renewed interest in our new anti-bacterial agent and its trial in key medical centres in North America where CDAD is particularly prevalent.

“This offers opportunities both to progress the study rapidly and to attract increased attention to the results for this important trial.”

The company said it was aiming to start the trials in areas of the US and Canada with a high incidence of CDAD early next year.

Extended-pulsed fidaxomicin Found Superior to Standard-dose vancomycin To Treat C.difficile Infection In Older Adults

In a randomized, controlled, open label phase 3b/4 trial (ClinicalTrials.gov identifier: NCT02254967), hospitalized patients age 60 years and older with confirmed C difficile infection were recruited from 86 European hospitals. Patients were randomly assigned to receive extended-pulsed fidaxomicin (200-mg oral tablets, twice daily on days 1–5, then once daily on alternate days on days 7-25) or vancomycin (125-mg oral capsules, 4 times daily on days 1-10).

Of the 177 patients receiving fidaxomicin, 124 (70%) achieved the primary end point of sustained clinical cure 30 days posttreatment, compared with 106 (59%) of 179 who received vancomycin (odds ratio 1.62; 95% CI 1.04-2.54, P =.03).

Multivariate analysis, which included treatment arm and baseline stratification factors (infection severity, cancer presence, age, and number of previous C difficile infection occurrences) as covariates, also indicated fidaxomicin to be superior (P =.035). A subanalysis of microbiota diversity concluded that microbiota recovery was greater in the fidaxomicin group, and a Cox proportional hazards model suggested that the hazard of infection recurrence in the vancomycin group was 3.8 times greater.

This study demonstrates the superiority of extended-pulsed fidaxomicin treatment over standard treatment with vancomycin. The researchers note the absence of blinding and racial diversity in the study group as limitations and recommend that future investigations should study this treatment course in patients age 60 years and younger and should compare this treatment course with standard fidaxomicin treatment protocols.

Disclosure

The study was funded by Astellas Pharma Inc, who were involved in all stages of the study, including manuscript preparation.

Reference

Guery B, Menichetti F, Anttila V-J, et al.; for the EXTEND Clinical Study Group. Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients 60 years and older (EXTEND): a randomised, controlled, open-label, phase 3b/4 trial. [published online December 19, 2017]. Lancet Infect Dis. doi: 10.1016/S1473-3099(17)30751-X

 

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

https://www.infectiousdiseaseadvisor.com/clostridium-difficile/extended-pulsed-fidaxomicin-vs-vancomycin-sustained-clostridium-difficile-infection-cure/article/738757/

Ridinilazole Compared With Vancomycin For Efficacy and Safety For Treatment of C. difficile Infection; A Phase 2 Randomized,Double-Blind,Active-Controlled,Non-Inferiority Study

Article Summary:

Background

Clostridium difficile infection is the most common health-care-associated infection in the USA. We assessed the safety and efficacy of ridinilazole versus vancomycin for treatment of C difficile infection.

Methods

We did a phase 2, randomized, double-blind, active-controlled, non-inferiority study. Participants with signs and symptoms of C difficile infection and a positive diagnostic test result were recruited from 33 centres in the USA and Canada and randomly assigned (1:1) to receive oral ridinilazole (200 mg every 12 h) or oral vancomycin (125 mg every 6 h) for 10 days. The primary endpoint was achievement of a sustained clinical response, defined as clinical cure at the end of treatment and no recurrence within 30 days, which was used to establish non-inferiority (15% margin) of ridinilazole versus vancomycin. The primary efficacy analysis was done on a modified intention-to-treat population comprising all individuals with C difficile infection confirmed by the presence of free toxin in stool who were randomly assigned to receive one or more doses of the study drug. The study is registered with ClinicalTrials.gov, number NCT02092935.

Findings

Between June 26, 2014, and August 31, 2015, 100 patients were recruited; 50 were randomly assigned to receive ridinilazole and 50 to vancomycin. 16 patients did not complete the study, and 11 discontinued treatment early. The primary efficacy analysis included 69 patients (n=36 in the ridinilazole group; n=33 in the vancomycin group). 24 of 36 (66·7%) patients in the ridinilazole group versus 14 of 33 (42·4%) of those in the vancomycin group had a sustained clinical response (treatment difference 21·1%, 90% CI 3·1–39·1, p=0·0004), establishing the non-inferiority of ridinilazole and also showing statistical superiority at the 10% level. Ridinilazole was well tolerated, with an adverse event profile similar to that of vancomycin: 82% (41 of 50) of participants reported adverse events in the ridinilazole group and 80% (40 of 50) in the vancomycin group. There were no adverse events related to ridinilazole that led to discontinuation.

Interpretation

Ridinilazole is a targeted-spectrum antimicrobial that shows potential in treatment of initial C difficile infection and in providing sustained benefit through reduction in disease recurrence. Further clinical development is warranted.

Funding

Wellcome Trust and Summit Therapeutics.

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

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(17)30235-9/fulltext

Dr Richard J Vickers, PhD'Correspondence information about the author Dr Richard J Vickers
Glenn S Tillotson, PhD

,

Richard Nathan, MD

,

Sabine Hazan, MD

,

John Pullman, MD

,

Christopher Lucasti, DO

,

Kenneth Deck, MD

,

Prof Bruce Yacyshyn, MD

,

Benedict Maliakkal, MD

,

Yves Pesant, MD

,

Bina Tejura, MD

,

Prof David Roblin, FRCP

,

Prof Dale N Gerding, MD

,

Prof Mark H Wilcox, MD

for the

See appendix for full details of the CoDIFy study group
Published: 28 April 2017
Open Access Article has an altmetric score of 76

Open access funded by Wellcome Trust

Seres Therapeutics Announces a New SER-109 Phase 2 Clinical Study (ECOSPOR III) For Patients With Multiple Recurrent C. diff. Infections (CDI’s)

Seres Therapeutics Inc. a leading microbiome therapeutics platform company, announced on March 16th, 2017 plans to initiate a new SER-109 Phase 2 clinical study (ECOSPOR III) in patients with multiply recurrent Clostridium difficile (C. difficile) infection. The ECOSPOR III study design was finalized following a positive Type B meeting with the U.S. Food and Drug Administration (FDA). In a separate announcement today, Seres reported fourth quarter and full year 2016 financial results and provided an update on multiple ongoing microbiome clinical programs.

Seres plans to initiate a new SER-109 clinical study in approximately 320 patients with multiply recurrent C. difficile infection. Study participants will be randomized 1:1 between SER-109 and placebo. To ensure accurate measurement of C. difficile infection, diagnosis of recurrent C. difficile infection for both study entry and for endpoint analysis will be confirmed by C. difficile cytotoxin assay. Patients in the SER-109 arm will receive a total SER-109 dose, administered over three days, approximately 10-fold higher than the dose used in the prior ECOSPOR study. ECOSPOR III will evaluate patients for 24 weeks and the primary endpoint will compare the C. difficile recurrence rate in subjects who receive SER-109 verses placebo at up to eight weeks after dosing. The FDA has agreed that this new trial may qualify as a pivotal study with achievement of a persuasive clinical effect and addressing FDA requirements, including clinical and statistical factors, an adequately sized safety database, and certain CMC parameters.

“We are pleased to have received highly constructive guidance from the FDA regarding further SER-109 clinical development and we plan to initiate a new clinical study as soon as possible,” said Roger J. Pomerantz, M.D., President, CEO and Chairman of Seres. “Our prior SER-109 studies provided important new biological and clinical data that have advanced our pioneering microbiome therapeutic efforts. Based on our learnings and dialogue with the FDA, we believe that we are now positioned to initiate a robust clinical study that may provide the basis for SER-109 approval. There is an urgent need for improved treatments for C. difficile infection, and we believe SER-109 has great potential to address the underlying cause of the disease and become the first approved microbiome therapeutic in this new field of medicine.”

About SER-109

SER-109, an oral capsule, is Seres’ lead Ecobiotic® microbiome therapeutic for the treatment of multiply recurrent C. difficile infection. SER-109 is a biologically sourced consortium of bacterial spores designed to catalyze a shift in a dysbiotic gastrointestinal microbiome to a healthier state.

About Seres Therapeutics

Seres Therapeutics, Inc. is a leading microbiome therapeutics platform company developing a novel class of biological drugs that are designed to treat disease by restoring the function of a dysbiotic microbiome, where the natural state of bacterial diversity and function is imbalanced. The Phase 2 study of Seres’ program SER-109 has been completed in multiply recurrent Clostridium difficile infection. Seres’ second clinical candidate, SER-287, is being evaluated in a Phase 1b study in patients with mild-to-moderate ulcerative colitis (UC). Seres is also developing SER-262, the first ever synthetic microbiome therapeutic candidate, in a Phase 1b study in patients with primary CDI. For more information, please visit www.serestherapeutics.com. Follow us on Twitter @SeresTx.

Forward-looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding SER-109 development plans, the timing, design, and results of the ECOSPOR III study , the potential for ECOSPOR III to provide different results than the previous ECOSPOR study, the impact analysis of prior clinical studies may have on clinical outcomes, the potential for ECOSPOR III to qualify as a Pivotal Study, dysbiosis as an underlying cause of C. difficile and other diseases.

To Read article in its entirety please click on the link below:

http://finance.yahoo.com/news/seres-therapeutics-initiate-ser-109-110000650.html;_ylt=AwrBT.EHTNBYMRUAv3hXNyoA;_ylu=X3oDMTEzbjcwdjAxBGNvbG8DYmYxBHBvcwM4BHZ0aWQDVUkwMkM0XzEEc2VjA3Ny

 

 

MGB Biopharma Announced That the US FDA Has Granted Qualified Infectious Disease Product Designation For Treatment Of Clostridium difficile-associated Diarrhea (CDAD)

MGB Biopharma, a biopharmaceutical company developing a novel class of anti-infectives to address the major global problem of antibiotic resistance, announced that the US Food and Drug Administration (FDA) has granted MGB-BP-3, MGB Biopharma’s lead product, Qualified Infectious Disease Product (QIDP) designation for the treatment of Clostridium difficile-associated Diarrhoea (CDAD). The FDA grants QIDP designations to drugs intended to treat serious or life-threatening infections, caused by “qualified pathogens”.

MGB-BP-3 is an antibiotic that has shown to be active against a broad range of important multi-resistant and susceptible Gram-positive pathogens. The oral formulation of MGB-BP-3 is being developed by MGB Biopharma specifically for the treatment of Clostridium difficile, a Gram-positive bacterium responsible for the majority of cases of infectious hospital-acquired diarrhoea in developed countries.

Successful completion of the clinical phase I study of MGB-BP-3 confirmed the compound was well tolerated in healthy volunteers, was not systemically absorbed, had no effect on intestinal permeability, and had a noted effect on the Clostridium class of normal gut flora. MGB is preparing to initiate the phase II clinical study for MGB-BP-3 and investigate the safety and efficacy in patients with CDAD, caused by the most virulent ribotype of C. difficile B1/NAP1/027. This ribotype is shown to cause the highest morbidity and mortality in CDI patients, where the current therapy has only moderate efficacy.

Dr Miroslav Ravic, CEO of MGB Biopharma, said, “We are very pleased with the FDA’s decision to grant QIDP designation to MGB-BP-3 as we believe this drug has the potential to provide a significant benefit in the treatment of Clostridium difficile-associated Diarrhoea (CDAD). Granting of the QIDP designation highlights the potential of MGB-BP-3 to address serious and life-threatening infections and is an important milestone in the development of our lead product, as we prepare to initiate the phase II clinical trial.”

Dr Ravic, added, “Around the world, governments and global organisations are calling for new anti-bacterial drugs and are introducing incentives to reward companies for delivering these products; only last week antimicrobial resistance (AMR) was on the agenda of the G20 Summit. Our MGB-based anti-infectives have the potential to deliver significant advantages over current approaches.”

While pursuing its clinical development activities, MGB Biopharma is now evaluating partnering and funding sources for its lead compound MGB-BP-3, which has the potential to offer a clear differentiated treatment option for patients with life threatening infections caused by resistant and susceptible Clostridium difficile strains.

 

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

http://www.pharmabiz.com/NewsDetails.aspx?aid=97421&sid=2

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