Results 1 to 8 of 8

Thread: Clinical Trial Question

  1. #1
    Senior Member Schmeky's Avatar
    Join Date
    Sep 2002
    Location
    West Monroe, LA, USA
    Posts
    3,415

    Clinical Trial Question

    Dr. Young,

    I know you have been very busy. When you have time, I have question concerning combinational therapies for future treatment of SCI.

    In order to introduce single treatments such as Cethrin, or Nogo blockers, or Chondroitinase into combination therapies, I understand these modalities will have to complete their own individual clinical trials.

    Therefore, if for instance, using your pending Lithium/HLA matched Umbilical Cord Blood stem cell treatment gives "good" results in humans, but in lab testing Cethrin (or Nogo or Chondriotinase) added gives excellent results, then obviously two things would have to happen before Cethrin (for example) could be part of a combination trial.

    1) Cethrin would have to complete all three clincal trial phases
    2) Useage of Cethrin would have to be licensed through the developer

    Correct?

  2. #2
    I've often thought and worried about the same probability...
    which makes me want a cocktail/combination of a different type!

    Schmeky, I can't imagine that you're not right, unfortunately.

  3. #3
    Quote Originally Posted by Schmeky
    Dr. Young,

    I know you have been very busy. When you have time, I have question concerning combinational therapies for future treatment of SCI.

    In order to introduce single treatments such as Cethrin, or Nogo blockers, or Chondroitinase into combination therapies, I understand these modalities will have to complete their own individual clinical trials.

    Therefore, if for instance, using your pending Lithium/HLA matched Umbilical Cord Blood stem cell treatment gives "good" results in humans, but in lab testing Cethrin (or Nogo or Chondriotinase) added gives excellent results, then obviously two things would have to happen before Cethrin (for example) could be part of a combination trial.

    1) Cethrin would have to complete all three clincal trial phases
    2) Useage of Cethrin would have to be licensed through the developer

    Correct?
    Schmeky,

    We would like to take one or more of the axon growth inhibitor blockers to clinical trial, in combination with a cell transplantation and growth factor stimulant. We are discussing this with several companies. The Bioaxone's phase 1 trial suggests that Cethrin is safe and well-tolerated. It obvious has been applied only to subacute spinal cord injury and not yet to chronic spinal cord injury. I have long thought that this would be a good treatment option because the spinal cord will be exposed and Cethrin can be administered at the same time as the cell transplant.

    You seem to be discussing drug evaluation and clinical trials as if there are hard "rules" that govern them. The FDA approves clinical trials and give final approval of drugs based on data from the clinical trials. If they perceive that a drug is risky, they may require phase 1 clinical trials to collect certain data to evaluate the risk. To approve a drug, they generally require two confirming phase 3 trials based on a scientifically acceptable clinical trial design with a well-defined primary outcome measure.

    Other than the above, I don't think that the FDA dictates the design of non-pivotal phase 2 clinical trials or that individual components of a therapy must be tested through phase 3 before the combination is allowed. If a rational argument is made for the benefit of the combination, I think that that FDA will accept it. However, it does seem reasonable that there be phase 1 and 2 studies of the treatment combination to show safety and feasibility before a commitment is made to a pivotal phase 3 trial. I don't think that cethrin alone or umbilical cord blood + lithium must both be shown to be effective before they can be combined. It would help of course.

    Much depends on the company and what risks they are willing to take. A company's first concern is limitation of risk to its primary asset. Many companies are risk-averse and will impose a rigid plan of drug development and testing. They often do not want the drug to go into clinical trials for other indications (e.g, chronic spinal cord injury) because such trials may reveal safety issues that may complicate the filing for the primary indication (subacute spinal cord injury)

    The route of administration is important. In their phase 1 trial, they gave Cethrin intraspinally. It is not clear that the drug is as safe or effective when given intrathecally. If it is to be given intrathecally, Bioxone may want to partner with Medtronics and do a phase 1/2 intrathecal Cethrin trial first. However, if the company decides that they want to try intraspinal injection of Cethrin into the spinal cord during cell transplantation, this is something that ChinaSCINet can help them do very rapidly and efficiently.

    The availability of funds is also important. In any case, the success of the Cethrin phase 1 trial is good news and I suspect that the company will be working very hard to raise the additional funds needed to take it to phase 2 and 3 trials. If another corporation were to approach Bioaxone with money for a clinical trial in combination with their therapy, I suspect that Bioaxone will consider such an offer seriously.

    Wise.
    Last edited by Wise Young; 12-17-2006 at 08:07 PM.

  4. #4
    Wise, my question probably has been answered in some form or other... speaking hypothetically, let's say TRIAL X has finished phase 3 and is proved to be both safe and effective through the ChinaSCInet. would this trial need to be replicated in the United States for the FDA to approve it even after undergoing international standards?

  5. #5
    Senior Member Schmeky's Avatar
    Join Date
    Sep 2002
    Location
    West Monroe, LA, USA
    Posts
    3,415
    Quote Originally Posted by Wise Young
    Schmeky,

    We would like to take one or more of the axon growth inhibitor blockers to clinical trial, in combination with a cell transplantation and growth factor stimulant. We are discussing this with several companies. The Bioaxone's phase 1 trial suggests that Cethrin is safe and well-tolerated. It obvious has been applied only to subacute spinal cord injury and not yet to chronic spinal cord injury. I have long thought that this would be a good treatment option because the spinal cord will be exposed and Cethrin can be administered at the same time as the cell transplant.

    You seem to be discussing drug evaluation and clinical trials as if there are hard "rules" that govern them. The FDA approves clinical trials and give final approval of drugs based on data from the clinical trials. If they perceive that a drug is risky, they may require phase 1 clinical trials to collect certain data to evaluate the risk. To approve a drug, they generally require two confirming phase 3 trials based on a scientifically acceptable clinical trial design with a well-defined primary outcome measure.

    Other than the above, I don't think that the FDA dictates the design of non-pivotal phase 2 clinical trials or that individual components of a therapy must be tested through phase 3 before the combination is allowed. If a rational argument is made for the benefit of the combination, I think that that FDA will accept it. However, it does seem reasonable that there be phase 1 and 2 studies of the treatment combination to show safety and feasibility before a commitment is made to a pivotal phase 3 trial. I don't think that cethrin alone or umbilical cord blood + lithium must both be shown to be effective before they can be combined. It would help of course.

    Much depends on the company and what risks they are willing to take. A company's first concern is limitation of risk to its primary asset. Many companies are risk-averse and will impose a rigid plan of drug development and testing. They often do not want the drug to go into clinical trials for other indications (e.g, chronic spinal cord injury) because such trials may reveal safety issues that may complicate the filing for the primary indication (subacute spinal cord injury)

    The route of administration is important. In their phase 1 trial, they gave Cethrin intraspinally. It is not clear that the drug is as safe or effective when given intrathecally. If it is to be given intrathecally, Bioxone may want to partner with Medtronics and do a phase 1/2 intrathecal Cethrin trial first. However, if the company decides that they want to try intraspinal injection of Cethrin into the spinal cord during cell transplantation, this is something that ChinaSCINet can help them do very rapidly and efficiently.

    The availability of funds is also important. In any case, the success of the Cethrin phase 1 trial is good news and I suspect that the company will be working very hard to raise the additional funds needed to take it to phase 2 and 3 trials. If another corporation were to approach Bioaxone with money for a clinical trial in combination with their therapy, I suspect that Bioaxone will consider such an offer seriously.

    Wise.

    Thank you very much for this insightful response. I am of the "opinion" that axon growth inhibitor blockers in conjunction with cell transplantation and a lab proven growth factor could potentially result in truly significant results.

    I know little of "hard rules", so thank you for pointing this out. It is encouraging to know that it is possible to even obtain the newer classes of treatments (Cethrin as an example) under the right circumstances.

    It is also good to hear you state the ChinsSCINET can test such combinations quickly and efficiently.

    Again, thank you, and forgive my ignorance.

  6. #6
    Quote Originally Posted by Chaz19
    Wise, my question probably has been answered in some form or other... speaking hypothetically, let's say TRIAL X has finished phase 3 and is proved to be both safe and effective through the ChinaSCInet. would this trial need to be replicated in the United States for the FDA to approve it even after undergoing international standards?
    The US FDA will approve drugs on the basis of clinical trials carried out overseas, as long as the clinical trial centers are approved by the FDA and the trial is registered with the FDA (i.e. approved by the FDA). Drug companies are now carrying out many clinical trials all over the world for US FDA approval. For example, India has become a very popular place for clinical trials by large pharmaceutical companies. The Clinical Trial Centre at Hong Kong University (which is organizing and helping run the ChinaSCINet trials) has been site-visited by the US FDA and is running over 100 clinical trials for US drug companies and US FDA approval.

    We are planning to get our phase 3 trials registered with the US FDA and the China sFDA. To do so, we have to ensure that all our participating clinical trial centers are GCP-certified (Good Clinical Practices certification is now required for all clinical trial centers in China), submit the protocol for approval by the US FDA, and submit all the paperwork. Because the FDA requires two phase 3 trials showing positive results for approval, it makes sense to do it with registered trials, one in an overseas country and the other in the United States. Because the ethics of "equipoise" in clinical trials make it difficult to do a placebo-controlled trial to assess a therapy that has strong evidence for efficacy (because the placebo group would be deprived of the effective therapy), it is desirable to carry out the two phase 3 trials in parallel.

    Having one trial in China and one trial in the US would be very helpful in getting the treatment approved in both countries. Note that China is rapidly becoming the second largest medical market in the world and may soon overtake the United States in terms of size. In my travels in China, doctors have been telling me that as many as 90% of their patients in big cities are now covered by insurance. Insurance in China has a much higher co-pay provision (often 50%) than the U.S. but with a population of 1.2 billion people, the volume of covered medical care exceeds that of the U.S.

    Also, certain conditions are more prevalent in China than in the United States. While I have been conservatively using the figure of 1 million people with chronic spinal cord injury in China, some of our investigators have been using the figure of 3 million people with spinal cord injury in China. If so, the market for covered spinal cord injury therapies may be 3-12x greater than that in the U.S. Hopefully, these kinds of numbers will put spinal cord injury on therapeutic target lists for pharmaceutical companies and lead to greater investment of companies into clinical trials for spinal cord injury therapies.

    Doing clinical trials in China, however, is not easy. The medical care system is in a state of massive transformation, from a completely government supported system to one that is covered by private insurance. For a while, several years ago, before the insurance system was set up, it was a cash-based medical care system. The Chinese sFDA has also imposed very strict regulations on "foreign drugs", requiring evidence that such drugs are shown to be safe and efficaceous before they can be tested in China. Approval times of clinical trials in China are slow (over 9 months). One way around this is to have the clinical trials and drug sponsored by a Chinese company and hence the drug falls under less strict rules governing domestic drugs and treatments.

    Wise.

  7. #7
    I read that China has 80 million disable people, many of them are elderly.

  8. #8
    Wise-
    thanks so much for your thorough and clear response...Im slowly beginning to understand the Great complexity of ' clinical trial' process and the varying factors.
    thanks again.
    Chaz

Similar Threads

  1. Replies: 6
    Last Post: 03-24-2009, 01:22 AM
  2. Replies: 34
    Last Post: 10-05-2006, 05:48 PM
  3. Trial participation
    By Eric.S in forum Cure
    Replies: 16
    Last Post: 09-03-2006, 07:02 PM
  4. Aeolus Receives Approval From FDA for Launch of ALS Clinical Trial
    By golanbenoni in forum Health & Science News
    Replies: 0
    Last Post: 09-08-2004, 12:32 PM
  5. Replies: 1
    Last Post: 12-05-2002, 09:51 AM

Posting Permissions

  • You may not post new threads
  • You may not post replies
  • You may not post attachments
  • You may not edit your posts
  •