Category Archives: Clinical Trials

Acurx Pharmaceuticals LLC Lead Product ACX-362E Has Successfully Completed First-In-Man Phase I Clinical Trial To Treat C.difficile Infection

 Acurx Pharmaceuticals, LLC is, a privately-held, clinical stage, biopharmaceutical company developing new antibiotics for difficult-to-treat bacterial infections, announced that its lead product candidate, ACX-362E, has successfully completed the 32-subject, double-blinded, placebo-controlled, single-ascending dose portion of this first-in-man Phase 1 clinical trial. ACX-362E is a novel, oral antibacterial agent for the treatment of Clostridioides difficile infection (CDI), an acute, serious, potentially life-threatening, intestinal infection.

ACX-362E is Acurx’s lead compound in a pipeline of molecules that target a previously unexploited mechanism of action, namely, inhibition of the bacterial enzyme DNA polymerase IIIC (pol IIIC).  Pol IIIC is required for DNA replication of many Gram-positive pathogens, including not only Clostridioides but also Enterococcus, Staphylococcus, and Streptococcus.  Although the trial data remain blinded, ongoing monitoring of the data show dose levels up to 600mg have been generally well tolerated. Blood levels of ACX-362E show low systemic exposure, as predicted by prior animal studies and desirable in treating CDI.  Additionally, fecal concentrations of ACX-362E at higher dose levels have exceeded the concentrations known to inhibit C. difficile by several hundred-fold.

“We are very encouraged by these initial data which corroborate our nonclinical findings, showing that at well-tolerated doses ACX-362E reaches concentrations in the colon that are projected to be therapeutically relevant for patients with CDI” said Robert J. DeLuccia, Co-Founder and Managing Partner of Acurx.  “This gives us confidence that the ongoing multiple-dose segment of the trial will provide data to guide selection of our Phase 2 dose and improve the probability of success and timeline efficiency of our Phase 2 clinical trial planned to start later this year.”

Dr. Kevin Garey, Professor, University of Houston College of Pharmacy and the Principal Investigator for microbiomic aspects of the Phase 1 clinical trial said: “The emerging fecal concentration data are comparable to those observed with precedent products that have advanced to demonstrate clinical success. I look forward to the multiple-dose safety data and to the results of the microbiomic analyses that our laboratory is performing which will form a template for a new paradigm in microbiome studies associated with drug discovery and development of CDI-directed antibiotics.”

About the Phase 1 Clinical Trial
This Phase 1 trial, conducted in the U.S., is a double-blinded, placebo-controlled study to determine safety, tolerability, pharmacokinetics and fecal concentrations of ACX-362E in healthy volunteers.  It is being conducted in two parts; first, single ascending doses are administered to four cohorts of 8 subjects each, and second, multiple ascending doses are given that simulate the anticipated clinical treatment regimen. Safety information is analyzed through assessment of adverse events and other standard safety measures, while concentrations of ACX-362E are determined in both the blood and the feces, the latter being the critical site of drug delivery for treating CDI.  In addition, Acurx has partnered with the laboratory of Dr. Kevin Garey at the University of Houston to perform state-of-the-art microbiomic testing of gastrointestinal flora in trial subjects.

About ACX-362E, FDA QIDP and Fast Track Designation
FDA Fast Track Designation is a process designed to facilitate the development and expedite the regulatory pathway of new drugs to treat serious or life-threatening conditions and that fill a high unmet medical need. ACX-362E is a novel, first-in-class, orally-administered antibacterial.  It is the first of a novel class of DNA polymerase IIIC inhibitors under development by Acurx to treat bacterial infections. Acurx acquired ACX-362E from GLSynthesis, Inc. in February 2018.

ACX-362E is a Qualified Infectious Disease Product (QIDP) for the treatment of patients with Clostridium difficile infection (CDI).  Under QIDP designation, ACX-362E will now be eligible to benefit from certain incentives for the development of new antibiotics provided under the Generating Antibiotic Incentives Now Act (the GAIN Act). These incentives include Priority Review and eligibility for Fast Track status. Further, if ultimately approved by the FDA, ACX-362E is eligible for an additional five-year extension of Hatch-Waxman marketing exclusivity. ACX-362E is being developed as a targeted, narrow spectrum oral antibiotic for the treatment of patients with CDI.  Acurx anticipates completing the Phase 1 clinical trial in the second quarter of 2019 and is planning to advance ACX-362E into a Phase 2 clinical trial in the fourth quarter of 2019. The CDC (Centers for Disease Control & Prevention) has designated Clostridium difficile bacteria as an urgent threat highlighting the need for new antibiotics to treat CDI.

RESOURCE:  https://www.acurxpharma.com/news-media/press-releases/detail/8/acurx-announces-first-in-man-clinical-trial-data-of

 

 

Deinove Phase II DNV3837 for C.difficile Infection Clinical Trial To Begin Mid 2019

Deinove is preparing initiation of Phase II for DNV3837 in Clostridium difficile infections, with a key partner

  • The test design has been improved for a better assessment of DNV3837 effectiveness in treating Clostridium difficile infections,
  • This will be a multicenter trial, taking place mostly in the United States, where the prevalence of the disease is high,
  • DEINOVE has chosen Medpace as its Clinical Research Organization (CRO)1 to prepare and oversee the trial, notably because of their experience with the target disease,
  • The trial is scheduled to begin mid-2019,
  • This clinical program will be the focal point of DEINOVE’s antibiotic strategy in the coming months, as the Company has decided not to exercise its option on the NBTI program.

DEINOVE (Euronext Growth Paris: ALDEI), a French biotech company that uses a disruptive approach to develop innovative antibiotics and bio-based active ingredients for cosmetics and nutrition, is preparing the Phase II study that will test DNV3837, its most advanced antibiotic candidate, for use against Clostridium difficile infections (CDI). DEINOVE has chosen Medpace (NASDAQ: MEPD) to act as its CRO and to oversee the clinical trial scheduled to begin in 2019.

DNV3837 is a first-in-class antibiotic candidate targeting the treatment of Clostridium difficile infections (CDIs), a disease classified as a priority by the WHO and one of the leading causes of healthcare-associated infections2. DNV3837 has demonstrated a promising efficacy profile and acceptable tolerance in Phase I trials. The FDA3 has already approved the start of a Phase II study and has granted the DNV3837 program the Qualified Infectious Disease Product (QIDP) designation and Fast Track status4 for accelerated product development.

DEINOVE acquired the DNV3837 program in the 1st half of 2018. Since then, their clinical development team has worked with a group of healthcare experts in CDI to prepare for the start of a Phase II clinical trial whose purpose is to demonstrate the efficacy of DNV3837 in patients suffering from CDI. Several aspects of the trial design, which had been presented to the FDA prior to the acquisition, have been improved:

  • the target patient population was expanded and now covers moderate to severe CDIs for greater progressiveness in treatment assessment;
  • it will be a multicenter trial with a major part taking place in the United States, where there is greater prevalence and the regulatory authorities are looking for new treatment options.

The design of the trial has now been finalized for submission of the updated version to the FDA. The selection process of clinical investigation centers is underway. The trial is scheduled to begin mid-year.

DEINOVE has chosen Medpace to oversee the trial. Medpace is an internationally-recognized full-service CRO that notably has a great deal of experience in infectious diseases, especially gastrointestinal infections like CDIs.

Its mission includes support for the clinical trial’s design and set-up (protocol review, contacting the clinical investigation centers, etc.), gathering and analyzing data, and interacting with the FDA.

Georges Gaudriault, Scientific Director at DEINOVE, said: “Preparations for the Phase II clinical trial for DNV3837 are moving forward as planned and we are delighted to have executed such an agreement with Medpace for this trial’s oversight. Their experience in both the pathology and American regulatory procedures will help us to secure and maximize this trial’s progress.”

The DNV3837 program is followed by the AGIR program (backed by Bpifrance), whose aim is to add to the portfolio of new molecules from DEINOVE’s biodiversity. The option on the NBTI5 program will indeed not be exercised, as the data gathered during the assessment phase were not considered to be in line with DEINOVE’s expectations for pursuing the program.

Emmanuel Petiot, CEO of DEINOVE, added: “The antibiotics field is a priority for DEINOVE and the DNV3837 program is our spearhead. Furthermore, we have decided not to exercise our option on the NBTI program with REDX Pharma, insofar as our teams’ assessment showed obstacles to its development without further optimization. We want to respond quickly and effectively to the health emergency and the lack of innovative antibiotics, and we are focusing our efforts on those programs with the highest possible probability of success.”

 

DNV3837 – a prodrug 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 Clostridium difficile.

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

DNV3837 is administered intravenously and is able to cross the gastrointestinal barrier, allowing it to precisely target the infection site. Several Phase I trials (on approx. one 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 C. diff. bacteria without altering the gut microbiota in the long term, a definite advantage for patient prognosis. It has also shown an acceptable tolerance profile.

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

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

https://globenewswire.com/news-release/2019/01/31/1708049/0/en/Deinove-is-preparing-initiation-of-Phase-II-for-DNV3837-in-Clostridium-difficile-infections-with-a-key-partner.html

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.

Ferring Pharmaceuticals Acquires Rebiotix, Inc.

Ferring acquires innovative biotechnology company and microbiome pioneer Rebiotix Inc.

  • Rebiotix’s RBX2660 is a non-antibiotic treatment in Phase 3 development for the prevention of recurrent Clostridium difficile infection (CDI) and has the potential to be the world’s first approved human microbiome product
  • CDI is one of the most common healthcare-associated infections in the US, affecting more than 500,000 people and causing approximately 29,000 deaths each year.1
  • Ferring’s global capabilities ensure broader patient access to any future approved human microbiome treatments derived from Rebiotix’s Microbiota Restoration Therapy™ (MRT™) drug platform

Saint-Prex, Switzerland & Roseville, MN, US – 05 April, 2018 — Ferring Pharmaceuticals* and Rebiotix Inc.  announce that they have agreed to the acquisition of Rebiotix by Ferring. This acquisition brings together two innovative healthcare companies that share a common commitment to exploring and understanding the human microbiome to develop new solutions for patients.

The most advanced investigational microbiome treatment from Rebiotix is RBX2660, a non-antibiotic treatment currently in Phase 3 development for the prevention of recurrent CDI. RBX2660 has the potential to be the first human microbiome product approved anywhere in the world. In the US, RBX2660 has received FDA Fast Track, Breakthrough Therapy and Orphan Drug Designations, which means the FDA considers it eligible for Expedited Review, once the submission has been made.

“The scientific advances Rebiotix has made add significant strategic value to Ferring’s leadership in gastroenterology,” said Michel Pettigrew, President of the Executive Board and Chief Operating Officer, Ferring Pharmaceuticals. “Therapies targeted towards the microbiome have the potential to transform healthcare. Together, we have a unique opportunity to help people living with debilitating and life-threatening conditions like Clostridium difficile infection.”

Rebiotix’s proprietary MRT drug platform delivers healthy, live, human-derived microbes into the gastrointestinal tract. It provides a standardised, stabilised product that is ready-to-use in an easy-to-administer format. The MRT pipeline consists of a number of investigational treatments including RBX7455, a non-frozen, lyophilised oral capsule formulation, in development for the prevention of recurrent CDI.

“Ferring shares our passion for understanding the role the microbiome plays in human health and has global capabilities that offer huge potential for the investigational therapies that we have in development,” said Lee Jones, Founder, President and Chief Executive Officer, Rebiotix, Inc. “Rebiotix was founded to revolutionise healthcare by harnessing the power of the human microbiome and this is a significant milestone in achieving that goal.”

“This acquisition strengthens our innovation pipeline and complements our own ongoing microbiome research as well as our partnerships with world-leading organisations in this area,” said Per Falk, Chief Science Officer, Ferring Pharmaceuticals. “Rebiotix’s culture and passion for high quality, innovative research fits with our own and complements our existing R&D capabilities.”

In addition to the acquisition of Rebiotix, Ferring, as a leader in gastroenterology, is supported by ongoing partnerships with world-leading research organisations in the field of microbiome research including the Karolinska Institutet and Science for Life Laboratory, the Centre for Translational Microbiome Research, Intralytix, The Institut Pasteur, the University of Lille, MyBiotics Pharma, March of Dimes and Metabogen.


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 women’s health, and in specialty areas within gastroenterology and urology. Ferring has been developing treatments for mothers and babies for over 50 years. Today, over one third of the company’s research and development investment goes towards finding innovative and personalised healthcare solutions to help mothers and babies, from conception to birth. Founded in 1950, 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 www.ferring.com, or connect with us on Twitter, Facebook, Instagram, LinkedIn and YouTube.

About Rebiotix Inc.

Rebiotix Inc. is a late-stage clinical microbiome company focused on harnessing the power of the human microbiome to revolutionise the treatment of challenging diseases. Rebiotix possesses a deep and diverse clinical pipeline targeting several other disease states with drug products built on its pioneering MRT platform. The MRT platform is a standardised, stabilised drug technology that is designed to rehabilitate the human microbiome by delivering a broad consortium of live microbes into a patient’s intestinal tract via a ready-to-use and easy-to-administer format. For more information on Rebiotix and its pipeline of human microbiome-directed therapies, visit www.rebiotix.com.

About RBX2660

RBX2660 is the most advanced product utilising Rebiotix’s proprietary MRT drug platform. RBX2660 is in Phase 3 development for the prevention of recurrent CDI and has the potential to be the first human microbiome product approved anywhere in the world. It consists of a microbiota suspension of intestinal microbes and is administered via enema.

*Ferring Holding Inc. signed the agreement as part of Ferring Pharmaceuticals Group

Immuron Announced First Patients Enrolled In Phase 1/2 (first-in-human) Clinical Trials For Immuron’s IMM-529 For Treatment of C.difficile Infections

The Australian biopharmaceutical company Immuron announced that the first patients have enrolled in phase 1/2 (first-in-human) clinical trials for Immuron’s IMM-529, an oral immunotherapeutic medication for treatment of Clostridium difficile infections (CDI).

As published in MD Mag February 16, 2018

To review this publication in its entirety please click on the following link to be redirected:

http://www.mdmag.com/medical-news/a-powerful-new-weapon-in-the-fight-against-clostridium-difficile-infection

According to Dan Peres, MD, senior vice president and head of medical development at Immuron, IMM-529 “has shown promise in successfully treating Clostridium-difficile” through its “unique delivery of antibodies.”

If the trials are successful, IMM-529 may be a powerful new weapon in the global fight against CDI. Peres reports that IMM-529 that has been effective in preclinical studies for prophylactic use, treatment of disease, and the prevention of recurrence in relation to CDI, and that the company is excited to enroll the first patients.

The placebo-controlled study to test the safety, tolerability and efficacy of IMM-529 will take place at Hadassah Medical Center in Jerusalem and include 60 CDI diagnosed patients in the 28 day study.

Patients enrolled in the study, led by Yoseph Caraco, MD, head of the clinical pharmacology unit at Hadassah Medical Center, will receive IMM-529 or a placebo 3 times a day during the 28 -day trial period, and be monitored for 2 additional months, determining any recurrence of the disease.

In a statement, Caraco said that he was optimistic about IMM-529 based on pre-clinical trial results and that IMM-529 could “be the answer we’re all looking for” when it comes to treatment of CDI.

IMM-529 targets CDI in 2 ways: by neutralizing toxin B (TcdB), a cytotoxin responsible for inflammation and diarrhea that characterizes CDI, and by binding Clostridium difficile spores and vegetative cells preventing further colonization. Caraco reported that IMM-529 approaches CDI by “targeting the main virulence factors of the disease with only minor disturbance to the natural biome” which could be extremely valuable in treating CDI.

In the earlier pre-clinical proof-of-concept study by led by Dena Lyras, MD, PhD with Monash University in Melbourne, Australia, IMM-529 was shown to be 80% effective in both the treatment of and prevention of CDI without the use of antibiotics.

In a December 2015 statement from Immuron, Lyras stated that she was “excited by the potential of these therapeutics in treating patients with both the acute and the relapse phase, of the disease.”

According to data supplied by the American Gastroenterological Association, approximately 500,000 people in the US are diagnosed with CDI each year, and CDI-associated deaths range from 14,000 to 30,000 per year.

In the European Union, according to a 2016 study led by Alessandro Cassini, MD, with the European Centre for Disease Prevention and Control in Stockholm, Sweden, more than 150,000 cases of hospital-acquired CDI infections (134,053–173,089; 95% CI) occur each year.

According to Immuron, the cost of CDI globally (calculated by CIDRAP, the Center for Infectious Disease and Policy at the University of Minnesota) is an estimated annual economic burden of more than $10 billion and increases in hypervirulent and antibiotic-resistant strains have led to CDI becoming a major medical concern.

Caraco stated that CDI poses “a growing risk amongst a greater population of patients, including those recently treated with antibiotics, the elderly, institutionalized and hospitalized.”

If IMM-529 is found to be safe and effective in clinical trials, it could prove a significant boon to the global fight against CDI at all 3 stages of the disease.

Learn More About Clostridium difficile (C.diff., C.difficile) infection and Recurrent CDI Clinical Trials In Progress

 

 

 

The C Diff Foundation has implemented a global campaign to raise awareness of Clostridium difficile infection (C.difficile) clinical trials, clinical studies, clinical research and observational studies evaluating interventions for C. difficile prevention, treatments, and environmental safety.

In the USA: Nearly half a million Americans suffer from Clostridium difficile (C. diff.) infections in a single year according to a study released in 2015 by the Centers for Disease Control and Prevention (CDC). Approximately 29,000 patients died within 30 days of the initial diagnosis of C. difficile. Of those, about 15,000 deaths were estimated to be directly attributable to C. difficile infections making C. difficile a very important cause of infectious disease death in the United States.

“Clostridium difficile infections are not only the most common cause of healthcare-acquired infections in the United States but also very common in the community in younger patients who previously were thought to be less susceptible to C. difficile. The rate of recurrent C. difficile infections is increasing tremendously and this increase is higher than the rate of primary C. difficile infections,” stated Sahil Khanna, MD, Assistant Professor of Medicine Division of Gastroenterology and Hepatology, Director of the C. difficile Clinic, Fecal Microbiota Transplantation program and C. difficile related Clinical Trials, Mayo Clinic, Rochester, MN.

Dr. Khanna also added, “It is imperative and important for clinical trials to be done to advance the development of new treatments, new medications, and new ways to prevent and treat Clostridium difficile infections.”

Individuals volunteer to participate in clinical trials in hopes of improving their own health, to access treatments that might not be available otherwise, often because they are new and not yet widely available. They help others by contributing to advances in medicine. There can also be potential risks participating in clinical trials and clinical studies. All of the known risks associated with a particular trial and or study will be discussed during the informed consent process. It will be thoroughly explained in the informed consent document that a volunteer will receive from the research staff prior to participating in any study.

To learn more about clinical research (e.g., Clostridium difficile, C.difficile) visit the U.S. Food and Drug Administration http://www.fda.gov or telephone 1-800-835-4709, The National Institutes of Health (NIH) http://www.nih.gov and ClinicalTrials.gov.

“Clinical trials are vital to improving our knowledge about how best to prevent and treat C. difficile infections. Informing patients of clinical trials is important, and in recent years several clinical trials have led to significant improvements in the treatments available for patients with C. difficile infections,” stated Mark Wilcox, MD, FRCPath, Consultant Microbiologist, Head of Microbiology and Academic Lead of Pathology Leeds Teaching Hospitals, Professor of Medical Microbiology University of Leeds Institute of Biomedical and Clinical Sciences, Lead on Clostridium difficile for Public Health England, UK.

About the U.S. Food and Drug Administration (FDA):
The FDA is responsible for protecting the public health by assuring that foods are safe, wholesome, sanitary and properly labeled; ensuring that human and veterinary drug, and vaccines and other biological products and medical devices intended for human use are safe and effective. FDA’s responsibilities extend to the 50 United States, the District of Columbia, Puerto Rico, Guam, the Virgin Islands, American Samoa, and other U.S. territories and possessions.

About the National Institutes of Health (NIH):
The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the nation’s medical research agency making important discoveries that improve health and save lives.

About ClinicalTrials.gov
ClinicalTrials.gov is a Web-based resource that provides patients, their family members, health care professionals, researchers, and the public with easy access to information on publicly and privately supported clinical studies on a wide range of diseases and conditions.

Sanofi Pasteur Ends Development of C. difficile Vaccine

Sanofi Pasteur SA  Pharmaceutical company announced on Friday, December 1, 2017  that it had ended development of an experimental vaccine for Clostridium difficile infection, after an early look at late-stage trial results indicated a low probability for success.

About three million Americans are infected annually with the bacterium – also known as C. diff – ———

The move marks the second blow in a week to Sanofi’s vaccine program after the Paris-based company on Wednesday said use of its new dengue vaccine will be strictly limited due to evidence it can worsen the disease in people who have not previously been exposed to the mosquito-borne virus.

Sanofi’s Dengvaxia vaccine is the world’s first approved shot for preventing dengue infection, which kills about 20,000 people a year and infects hundreds of millions.

The company said in a statement that all data from vaccinated volunteers in the C. diff trial will continue to be analyzed for more information and shared with the scientific community.

As many as 30,000 Americans die each year from the bacterium, usually after recurrences of infection. The infections are typically the result of taking antibiotics, which wipe out friendly bacteria in the colon that normally keep C. diff under control.

Sanofi said it will continue to focus on six other vaccine projects in development.

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

https://www.reuters.com/article/markets-swiss-stocks/swiss-stocks-factors-to-watch-on-dec-4-idUSL8N1O14KZ