France - Grave ​accident in the context of a clinical trial in Rennes

[Pathfinder]

Translation Google

Grave accident in the context of a clinical trial in Rennes

published le15.01.16
News

The Ministry of Social Affairs, Health and Women's Rights was informed last night of the occurrence of a serious accident as part of a Phase 1 clinical trial, conducted on a drug taken orally, being developed by a European laboratory. Marisol Touraine, Minister of Social Affairs, Health and Women's Rights, visited this afternoon at the University Hospital (CHU) for Rennes meet the families of vicitimes. The Minister made this occasion a point of information to clarify the circumstances of the accident and present the measures undertaken independently of judicial proceedings.

This test was performed in a licensed private institution specializing in the conduct of clinical trials in order to evaluate the safety, tolerability, pharmacological profiles of this molecule in healthy volunteers.

This accident resulted in the hospitalization of six of the volunteers at the University Hospital of Rennes. One of them in intensive care, is brain dead.

The company informed the Agence fran?aise de s?curit? sanitaire des produits de sant? (MSNA) the interruption of the trial and currently is recalling all the volunteers who participated.

The MSNA has decided to conduct a technical inspection on the site to which these clinical trials. As soon as she was informed, Marisol Touraine, Minister of Social Affairs, Health and Women's Rights, took the General Inspectorate of Social Affairs (IGAS) to conduct an inspection on the organization, means, and the conditions of intervention of this institution in the realization of the clinical trial.

- Consult the speech by Marisol Touraine at Rennes University Hospital
- Consult the press release of the Ministry of Social Affairs, Health and Women's Rights


http://social-sante.gouv.fr/actualit...nique-a-rennes

-------------------------------------------------------------------------------------------------------------------------------------------------------

Intervention by Marisol Touraine
Minister of Social Affairs, Health and Women's Rights
Press conference
Rennes
Friday, January 15, 2016

Ladies and gentlemen,

An exceptionally serious accident occurred in the context of a trial
Phase 1 clinical realized in Rennes. 6 people were hospitalized at University Hospital
Rennes since last Sunday. They are all men, aged 28-49 years. TO
the time when I speak, one of them is in critical condition, qualified by
brain dead doctors. The five others are hospitalized in Neurology
CHU, two of them are in a serious situation. With a degree of seriousness
different in different cases, these patients have neurologic manifestations
same type.

First I want to address my thoughts to these five people, their families and their
family. And I mean my confidence and support to the CHU health professionals
Rennes who support them now.

I just met the victims of this clinical trial accident, and their
family. I wanted to do to express their first my support and my
absolute commitment to shed light on what happened. The shock is all
greater than accidents of such gravity do not seem to be documented. Ace
now I do not know of any comparable event. What happened is
new and, we wish the greatest vigilance. I remember that they are
healthy people who volunteer for clinical trials Phase 1. They
could not expect - let alone their families - that their health is in
danger. Families are obviously collapsed. They ask questions, I
pledge that all the answers they are made. Under the circumstances
tragic they face, they show a dignity to which I want to
tribute. Now I would like to provide you with the information available at this
moment.

1 / First I will return to the chronology of events in a very
factual.

The laboratory Biotrial filed April 30, 2015 a trial record
Phase 1 for a new molecule developed by BIAL laboratory. This
molecule intended to treat mood disorders and anxiety and movement disorders
related to neurodegenerative diseases. At this point, the directions of a medicament
are very general. Contrary to what I read, this drug contains
no cannabis, is not a derivative of cannabis. It acts on the natural systems that
help fight against pain, this is called the system
endocannabinoid. The National Agency of Drug Safety (MSNA) authorized
clinical trial June 26, 2015, in accordance with the procedure in force. The trial
started July 9, 2015 in the premises of Biotrial, a private institution
authorized, specialized in conducting clinical trials.

What is a Phase 1 clinical trial? This is the first administration
medication in humans to evaluate the safety and the characteristics of a
molecule. This phase necessarily comes after the validation of tests conducted
on animals. In this case, tests were conducted on different species
animal including chimpanzees. This procedure is framed, it responds to
strict rules laid down in Articles L 1121-13 and R. 1121-11 to R.1121-16 the code
public health :

- The test must be conducted in licensed premises after inspection by
Regional health agencies.
- There must be prior authorization of the MSNA and the advice of a
Personal protection committee, composed of volunteers from civil society
and health professions, which assess the ethical conduct of the trial
in humans.
- A national database identifies healthy volunteers who can participate in these
tests.
The test is now at issue provided included 128 healthy volunteers, men
and women aged 18-55 years. To date, 90 people were administered this
molecule at varying doses. Others have received placebo. This test was to evaluate
the drug effects:
- First single doses, that is to say, administered at once
- Then in multiple doses, that is to say, the repeated use of the tablet on
several days
- And finally, as part of a concomitant to the meal.
These are people who took the drug repeatedly are
Victims of serious adverse events occurred.
According to the information that was given to me, they would have started
taking the drug Thursday, January 7th. The first symptoms would have appeared
Sunday, January 10 on a first person. The other 5 were hospitalized
gradually since.

The laboratory reported having interrupted this test Monday, January 11.

That is the chronology of events as it can be established at this time.

2 / As soon as I learned of the accident, I hired the first actions,
regardless of the legal proceedings by the prosecution of Rennes
and the Public Health pole of the Paris prosecutor.

The MSNA was forthwith launched a technical inspection procedure on the site, to
in particular to verify compliance with regulatory procedures and good practices
clinics. The Deputy Director of the inspection of that agency and two of its
Inspectors are already on site.

I have also asked that are identified and contacted without delay all
volunteers who were exposed to this product in the context of this trial since July 9
2015. It is for the Regional Health Agency of Britain to ensure that all
the volunteers who participated in this trial are the subject of specific information,
personalized and appropriate medical examination at the University Hospital of Rennes. They must be
personally contacted and a phone number is available to them
as part of the hospital: it is 02 99 28 24 47. I want to say very clearly to
the attention of our fellow citizens no marketed drug is involved.

Finally, I immediately seized the General Inspectorate of Social Affairs (IGAS)
for her diligent inspection on the site. This will verify compliance with the
current regulations :
- In the conduct of clinical trials
- At the place of this achievement
- Compliance with the rules of conduct of a study, particularly as regards the
volunteer recruitment, administration of the product, reporting
serious adverse events and information.
IGAS inspectors will be there tomorrow.

I asked that a first step Note I be delivered before the end of the month,
and that the final report be made before the end of March. All responsibilities
possible should be established.

I thank you


http://social-sante.gouv.fr/IMG/pdf/...ave_rennes.pdf

 

[Pathfinder]

Translation Google

Clinical trials: "The Rennes accident remains incomprehensible"

Good connoisseur of clinical trials, Professor Bernard B?gaud expressed his perplexity after the grave side effects that occurred in a study on a drug in Rennes.

By Pierre BIENVAULT on 01/17/2016 at 15h35

Four people remained hospitalized Sunday, January 17 at Rennes University Hospital after participating in a clinical trial phase 1. During the day we learned of the death of a patient who was brain dead. Professor Bernard B?gaud directs at the University of Bordeaux an Inserm unit responsible for assessing the impact of drugs on the population. From 1994-2008, he also chaired the committee of clinical trials of Afssaps, the drug agency, which now is called ANSM.

What is your reaction after the Rennes accident? Were there ever in France or in the world as grave of incidents with a Phase 1 trial?

Bernard B?gaud: We are facing an accident quite unusual, even rare. Since Friday, several foreign colleagues called me, they are as perplexed as I. One can speculate. At this stage, what happened is rather incomprehensible. The only somewhat comparable precedent goes back in 2006 in Britain with a drug trial against Parkinson's disease. Six people were hospitalized in intensive care but had been finally able to be got out of trouble. When I chaired the committee on clinical trials to Afssaps, for fifteen years, I have of course paid great attention to all the side effects related to phase testing 1. There was only once a case of encephalopathy with neurological sequelae with an essay on an anti-Alzheimer vaccine. But never such a "hecatomb", with as many people as severely affected.

How does a Phase 1 unfold and what is its goal?

BB: This is the first trial of a drug in humans. The point is not whether the product is effective against the disease concerned but to evaluate its safety and maximum dose that can then be administered to patients. Before a phase 1 trial, several toxicity studies were conducted in animals. We take into account what has been observed to move to Phase 1 in humans, always in early, very low doses. Take, for example, a product which has shown toxicity in animals with a dose of 40 mg per kilogram. In humans, we will give a starting dose of 4 mg per kilogram. Then increased gradually and in a controlled manner, looking at the effects that may appear in volunteers: vomiting, dizziness, headaches or stomach pain, dilated pupils, effect on heart rate. And as soon as one or more effects appear, the test is stopped. In the vast majority of cases, these are mild reactions and consequences.
What is the profile of people who participate in these trials? Do they do it for the money?

B.B: Officially not. All the talk of the promoters of these tests is to say that there are rules to prevent people from becoming professionals in clinical trials. It is true that there is a financial limit (no more than ? 4,500 in a year) that a volunteer can not exceed. There is also a national registry of volunteers to ensure that no one has several tests simultaneously with different laboratories.
There is also a period to be observed between two tests. But the financial motivation is paramount. It should be understood that these volunteers are healthy and therefore have no direct benefit to participate in the trial. This is different from a phase 2 or 3 where one includes patients who hope that the drug tested will benefit them.

In a Phase 1, volunteers have the constraints and risks. Some people make ideal testing to advance science. Or because a family member has been affected by such a disease. But in the vast majority of cases, the financial motivation is the main driver. 20 years ago, I myself did testing phase 1. And the people we recruited were often young people or students who were improving their ordinary well.

Pierre BIENVAULT

http://www.la-croix.com/Sciences-et...emeure-incomprehensible-2016-01-17-1200731774

 

[Pathfinder]

Translation Google

Accident during a clinical trial: Death of the brain-dead patient

CHU Rennes - Sunday, January 17, 2016.

"The patient brain dead died at midday. The health status of the other 5 inpatients is stationary." informed the Rennes University Hospital in his second statement dated Sunday, January 17, 2016.

This is the second point on the health status of patients hospitalized at the University Hospital of Rennes after the accident as part of the clinical trial conducted by Biotrial private research company on behalf of Bial.

Teams of the CHU contacted for a rapid response, the remaining 84

The CHU states that they contacted , for a rapid response, the 84 other volunteers who were exposed to the test drug. Already, 10 of them were received in consultation and underwent an examination at the University Hospital of Rennes on Saturday 16 afternoon. Clinical and radiological abnormalities present in hospitalized patients has not been found in these 10 volunteers.

Among the contacted persons, 5 of them have expressed the desire for care close to home. The Rennes University Hospital organizes coordination with the other hospitals involved.

Meanwhile 66 calls were received at the hotline set up by the CHU namely on 02 99 28 24 47.

First release of Rennes University Hospital

Recall of facts

In a phase 1 clinical trial conducted by Biotrial private research company of Rennes on behalf of the Portuguese company Bial, six healthy volunteers, men aged 28 to 49 years, were hospitalized. One of them is brain-dead, the other 5 are cared in service Neurology at the University Hospital of Rennes. To date 90 individuals have received this molecule at varying doses. The victims took the drug repeatedly since January 7. The first symptoms date back to Sunday, January 10. The trial was interrupted on January 11. (Ed)


http://www.reseau-chu.org/article/a...e-deces-du-patient-en-etat-de-mort-cerebrale/

 

[Pathfinder]

Translation Google

Rennes accident: it is urgent to learn more

We better known the nature of the terrible brain damage victims of this tragic accident. But their exact causes are yet to be determined.

BY ANNE JEANBLANC
Published on 01/20/2016 at 12:17 | The Point.fr

First, the news about the first 90 volunteers who had tested relatively low doses BIA compound 10-2474 (an inhibitor of degradation of endocannabinoids developed by the laboratory Portuguese Bial) are good. All were contacted in the days following the tragedy. MRI scans of their brains and neurological assessments performed on a number of them did not reveal any particular problems. The Pontchaillou Hospital Rennes obviously continuing its investigations with other people involved in this clinical trial. Tuesday night, officials Biotrial (the research company that conducted the tests) were meant reassuring.

However, although improving, the assessment of four of the six volunteers who received the highest doses of the molecule remains terrible. We know a little more about the deceased patient: Europe 1 revealed that it was an artist of 49 years, father of four children. Information that brings nothing to the file, if not a human side to these "guinea pigs" often faceless who agree to test drugs so that sick people can possibly, one day, get better. According to the Rennes University Hospital, only one patient is still under observation in the neurology department. Three others, whose state improved, are going to be able to be transferred in establishments closer to their residence. One suffers from hemiplegia, the second of amnesia ant?rograde, and the third presents important brain damages but without clinical repercussion according to a competent source joined Sunday by the MPA news agency. As for the one who has never presented symptom, he is going home.

Neighboring molecules in development

The time is now to questions. We must first understand why this tragedy occurred. Assumptions are numerous: an action different from the one , by means of another receiver than the one originally targeted, under the effect of repeated and cumulative doses; a production dosing error; or contamination (the test compound was manufactured in Italy from raw materials produced in Hungary). The need for transparency is all the more pressing as other neighboring molecules are under studies or have already been developed. And none of them has caused similar side effects to those observed during the test on the BIA 10-2474.

Other astonishment: the number of volunteers "enlisted" in this work. All drug specialists recall that Phase 1 trials typically cover about ten people, never women, contrary to what happened this time. According to Le Figaro, "Biotrial claims to have conducted pregnancy tests two days before the first administration of the product." Furthermore, these trials intended mainly to test the tolerance (and not to highlight a therapeutic effect) are never made against placebo. However, two people received a fake medication in the group of eight who took the highest dose. It remains to assess the consequences of this tragic accident on clinical trials in our country. They greatly depend on the results of ongoing investigations.

http://www.lepoint.fr/editos-du-poi...nt-d-en-savoir-plus-20-01-2016-2011297_57.php

---------------------------------------------------------------------------------------------------------------------------------------

JAN 20, 2016 @ 10:18 AM

Janssen Voluntarily Suspends FAAH Inhibitor Phase 2 Trials In Wake Of Bial Tragedy

David Kroll , CONTRIBUTOR

The research and development arm of Janssen Pharmaceuticals, a Johnson & Johnson JNJ -2.11% company, announced on Sunday (January 17) their voluntary suspension of dosing in two Phase 2 clinical trials of their FAAH inhibitor.

Janssen spokesperson Greg Panico confirmed yesterday that the experimental drug is JNJ-42165279.

Following a Phase 1 trial where few, mild side effects were reported, Janssen had launched Phase 2 trials of the compound in patients with social anxiety disorder or major depressive disorder with anxious distress...

Janssen?s decision is a precautionary response to January 15 reports of severe adverse reactions in a Phase 1 clinical trial of another company?s experimental drug in the same general class.
...
Recognizing that volunteers in Phase 2 clinical trials are suffering from disorders the experimental drug is intended to treat, Janssen also advised investigators to have study participants seek guidance from their treating physicians about existing FDA-approved medications to manage their respective conditions.

Janssen ?will reevaluate our decision to suspend dosing in these clinical trials when we have additional information,? according to their press release.
...
http://www.forbes.com/sites/davidkr...ss=pharma-healthcare#2715e4857a0b24f91b9d68bb

 

[Pathfinder]

French drug trial scandal: 'dogs died in pre-clinical test'

Laboratory involved in drug trial that left one person dead and others seriously injured says industrial secrecy prevents publication of earlier testing

Kim Willsher
Thursday 25 February 2016 06.36 EST Last modified on Thursday 25 February 2016 17.01 EST

A drug that left one person dead and four others with suspected brain damage in a controlled trial had killed several dogs in a previous test, it has been claimed.

However, the laboratory involved and France?s drug safety agency say details of earlier testing of the molecule cannot be published because of industrial secrecy.

Le Figaro said it had information suggesting a pre-clinical trial of the drug had left ?a number? of dogs dead and others with neurological damage.

When news of the incident was revealed, Marisol Touraine, the French health minister, said 108 people had taken part in the trial for Portuguese pharmaceutical company Bial at a French clinic in January. Ninety of them were given varying doses of the drug while the rest took a placebo.
...

https://www.theguardian.com/science...-trial-scandal-dogs-died-in-pre-clinical-test
----------------------------------------------------------------------------------------------------------------

Man who died in French drug trial had ?unprecedented? reaction, say experts

Experts investigating the French drug trial that left one man dead and five hospitalised have published a report laying blame on the substance tested

AFP in Paris
Monday 7 March 2016 18.10 EST Last modified on Monday 7 March 2016 18.43 EST

Experts investigating the death of a man in a drug trial in France have concluded that the compound being tested had caused an ?astonishing and unprecedented? reaction in the brain.

Six people were hospitalised and one died in January after taking part in a Phase I trial for a new pain and mood disorder medication at the Biotrial research institute, in western France, on behalf of Portuguese pharmaceutical company Bial.

In a report published on Monday, a group of experts put together by the National Agency for Drug Safety said the problem clearly lay with the substance being tested ? BIA 10-2474.

They underlined ?the astonishing and unprecedented nature? of the accident, which caused a reaction in the brain ?unlike anything seen before?.
...


https://www.theguardian.com/science...man-dead-expert-report-unprecidented-reaction

------------------------------------------------------------------------------------------------------------------------------------------------------

Read the ANSM report here:

Minutes of the Temporary Specialist Scientific Committee (TSSC) meeting on "FAAH (Fatty Acid Amide Hydrolase) Inhibitors" of 15/02/2016 (08/03/2016) (195 ko)