Tag Archives: Cdiff reasearch

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

Medicine, Like All Science, Is Dynamic and Forever Evolving and Why It Is Regarded As “The Practice Of Medicine.”

Medicine, like all science, is dynamic and evolving—that’s why it is referred to as “the practice of medicine.”

Accepted treatments of one era might be discarded later as “pseudoscience.” What is considered “experimental” today might become the standard of treatment tomorrow.

Fortunately, there is something called peer review and scientific standards. Also, most health care providers have embraced the process of gathering as much evidence as possible instead of treating patients like lab rats.

There is no safe substitute for the intimate, one-on-one relationship between a patient and a physician. This will continue to be true as long as doctors remember that medicine is a science and an art, full of both expected outcomes and surprising solutions.

The phrase “Nine out of 10 doctors recommend…” is often used to promote widely accepted treatments, so that one outlier doctor must be responsible for all the rather wacky treatments that we other physicians get asked about every week. And although some of these treatments seem beyond bizarre, they can also be incredibly interesting.

At least they were to the three physicians listed in this article’s byline, including
Dr. H. Eric Bender, who says his fascination with peculiar medical practices started in medical school. During one of his early rotations, he was shocked to learn that not only could he order leeches for a patient in the hospital but he could specify where they were to be placed as well: left leg, right arm or whole body. (In case you’re wondering, to precisely “aim” a leech, place it in a small cup with a very small hole cut in the bottom. That hole is then aligned with the area on the patient requiring blood removal and voilà! Bloodthirsty segmented worms are suddenly hard at work.
(Dr. Bender does not recommend trying this at home.)

Now, thanks to our internet-sparked society of do-it-yourselfers, Bender’s fascination with the unconventional cure has continued to grow as he has contemplated conversations with his patients and researched a wide range of (seemingly) ridiculous but sometimes effective remedies.
“Unfortunately, the physician’s oath to “do no harm” has been replaced in many
clinics with “do clean up this mess.”

For example, a physician or two in the not so distant past recommended that children smoke tobacco to treat pica, a condition in which people feel compelled to chew on non-nutritious substances like rocks, sand or glass. Some doctors over the years suggested that patients use cocaine and heroin to remedy toothaches and persistent cough, respectively. (In addition to references, the book includes pictures as evidence.) Alcohol has been recommended to pregnant women for its health benefits—Guinness beer is rich in iron—and not just by Irish physicians. Others practicing medicine have suggested using hookworms to cure asthma (causing dangerous infections).

The list of dangerous substances, organisms and animal byproducts that people have used over the years to treat everything from low libido to sexually transmitted diseases goes on and on. Fortunately, most of the practices did not, as further research demonstrated the dangers of many of them.

“Weird medicine” is not limited to just medical practices and treatments. A look into the medical literature reveals that it is replete with research and studies that aren’t particularly well-designed or are far-fetched to the point of absurdity.

Some fascinating practices seemed like terrible ideas but are actually so well-supported by research that they are considered the gold standard for treatment of certain illnesses.

As an example, consider that antibiotics frequently kill good bacteria while also killing the bad bacteria doctors are trying to eliminate.

“Good” bacteria suppress the growth of bad bacteria. So when the good bacteria are wiped out, many individuals develop a type of intestinal infection known as Clostridium difficile
(or C. diff
). C. diff is often difficult to treat with antibiotics, since they typically caused the problem in the first place. Fortunately, one treatment has a  high rate of s
uccess: fecal transplantation. Yes, you read that correctly. Doctors place stool from a donor inside the patient’s gastrointestinal system. Intuitively, you might think putting my feces into your gut would cause serious infections, but the donated good bacteria help eradicate infection.

To learn more about FMT:  https://cdifffoundation.org/2016/03/02/fecal-transplants-fmt-treating-clostridium-difficile-infections-u-s-food-and-drug-administration-fda-seeks-comment-on-what-investigational-new-drug-ind-requirements-to-waive/

IHow about maggots instead? Maggot therapy involves using those little legless larvae to prevent a wound infection. Maggots selectively target and eat dead tissue that is difficult to remove surgically without taking healthy tissue with it. Although doctors have been aware of this fact since at least the 1930s, this treatment was not regularly used for decades, particularly as antibiotic use to treat and manage wounds rose in popularity. However, after a recent “rediscovery” of maggot therapy, more than 800 health care institutions use it today. You can be sure pharmaceutical companies are already working on a way to charge exorbitant prices for the little larvae.

Patients performing their own research online can spark informative conversations with their doctors, even if they do sometimes suggest things that make a person want to scream, or puke.

Nevertheless, although “Dr. Google” is punctual and doesn’t require a co-pay, it is still not qualified to diagnose and treat.

There is no safe substitute for the intimate, one-on-one relationship between a patient and a physician. This will continue to be true as long as doctors remember that medicine is a science and an art, full of both expected outcomes and surprising solutions.

So to our patients: Be wary of charlatans but keep an open mind. Bring all your questions to a physician and ask away. To our fellow physicians: Listen to your patients. Talk with them, not to them. And remember: If you can’t do any good, at least do no harm.

 

H. Eric Bender, Murdoc Khaleghi and Bobby Singh are the authors of 1 Out of 10 Doctors Recommends: Drinking Urine, Eating Worms, and Other Weird Cures, Cases, and Research from the Annals of Medicine.

 

To read this article in its entirety, click on the link below:

http://www.newsweek.com/2016/08/26/weird-medicine-doctor-google-pseudoscience-491240.html

Researchers at MGGen Are Part Of a Community Study In Flagstaff, AZ On Two Serious Infection-Causing Bacteria; Clostridium difficile and Staphylococcus aureus

RESEARCH

RESEARCH

Researchers at Northern Arizona University’s Center for Microbial Genetics and Genomics, or MGGen, are putting out a call for poop.

The request is part of a community study on two nasty infection-causing bacteria in order to identify how the bugs are being carried around Flagstaff,  AZ and how they are making their way into the hospital.

The researchers say the pathogens could be present on any number of things, from dogs to ground meat to humans themselves.

It is hoped that confirming those reservoirs and tracking how the bacteria are transmitted will lead to new recommendations for how people and hospitals can better prevent the infections, the researchers said.

DNA MAPPING

The two bacteria, Clostridium difficile, or C. diff, and Staphylococcus aureus, or Staph, are important to study because they are notorious for causing hospital-acquired infections that are often difficult to treat.

Staph can cause skin and respiratory infections while symptoms of C. diff infections include diarrhea and fever.

For the research project, MGGen scientists are comparing Staph and C. diff bacteria collected from sick patients at Flagstaff Medical Center to those bacteria carried by healthy people.

Samples of the latter come from volunteers willing to provide a swab from inside their nose and a swab of their fecal material from used toilet tissue. The researchers have received 65 healthy community member samples and their goal is to get 500 by next April.

MGGen’s specialty is whole genome sequencing, which allows scientists to compare even the tiniest genetic variations between the samples. With that, they can tell how closely the samples are related, indicating potential transmission paths.

The study has found:  that the bacteria strains in ill patients don’t match those found in other hospital cases, indicating the organisms aren’t lingering in the hospital and being transmitted from patient to patient but are being acquired by people before they get into the hospital, said Heidie Hornstra O’Neill, research project coordinator at MGGen.

both bacteria species can live on and in healthy people without causing any problems, one possibility is that the pathogen hangs out in people’s bodies without causing any symptoms and then proliferates when the immune systems is weakened.

It could also be that only certain strains of the bacteria cause disease while others do not. About a third of people carry Staph bacteria, for example, but only a small percentage of people get a Staph infection, which could mean only some strains are dangerous, said Paul Keim, lab director at MGGen.

The researchers are collecting demographic information as well to see if a person’s gender, ethnicity or access to healthcare plays a role in whether they carry the bacteria.

SIDEWALK SCANNING

DOG POO SAMPLES:   Another potential source of C. diff bacteria, especially in a place like Flagstaff, is dogs, said Nate Stone, a research specialist at MGGen. Stone searched the sidewalks of Flagstaff for four months in the fall of 2014, collecting samples of dog poop to test them for C. diff. He found the bacteria were present in 17 percent of the 200 samples and half of the strains found are common in human C. diff infections. 

“We don’t know if dogs are giving humans C. diff or humans are giving dogs C. diff, but we do know dogs are carrying C. diff strains that can cause infections in humans, so they are probably one part of the story,” Stone said.

Next up, he’ll use genetic analysis to see if any bacteria from the dog poop samples match human samples, suggesting direct transmission.

Another possible C. diff reservoir is meat, and that’s also on Stone’s future research agenda.

The end goal of providing more data on these infection-causing bacteria is to help everyone from ordinary citizens to medical organizations figure out better ways to prevent them, Stone and Keim said.

“The reservoir stuff is fascinating because we think we can affect the way people live,” Keim said.

 

To read article in its entirety:

http://azdailysun.com/news/local/nau-researchers-track-path-of-infection-causing-bugs/article_3c0e8bc9-b432-5e6d-988e-53eee1e47bd4.html