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    Originally posted by Jim View Post
    John, the data from the Phase 2 trial in Hong Kong/China will be available in November. This data is necessary for approval from the U.S. FDA to begin trials here. Recruitment won't be until 2013.
    Ok great, thanks. I saw Wise mention looking for recruits for the 2014 trial and thought recruitment for this one had begun

    Comment


      wasnt it understood that the data would be necessary for trials in the US from the beginning? and that the data wouldnt be available until novemeber? but yet it was stated over and over that trials would begin in 2012? even recently (within a month or 2 ago)

      Comment


        Barrington, the US Trials were projected to start in '12. There have been delays. Here's what Dr. Young posted a few months ago-


        A major part of the delay resulted from the Chinese Ministry of Health putting the first of their freezes on cell transplant trials in 2009. This forced us to change our plans to do the trial in Kunming and start it instead in Hong Kong. We lost over a year because of this delay and we started the trial in Hong Kong in the Fall of 2010.

        From October 2010 to October 2011, our teams in Hong Kong could only recruit 8 subjects that met the eligibility criteria. In the meantime, China gave permission and we started the trials in Kunming for the trial in Fall of 2011. Kunming just did their 20th patient. We have decided to close recruitment for both trials.

        I had hoped that we would have completed CN102B by Fall 2011 and that we could have started the phase 3 trials in 2012. We need the 6-month follow up data from CN102B to apply for the clinical trials in the U.S. and Europe. This data will be available 6 months from now.

        There is much to do in the meantime. We must raise the funds for the trials in China, U.S., and Europe. In China, we are working with investigators to apply for grants in China. In the U.S., we are raising funds through JustADollarPlease, Boyd Melson's boxing, Lone Star, and other approaches. In Europe, we are hoping to raise the money from the government of Norway.

        I am coming to India in September and hope to talk to investigators in to see if we can get the trials moving in India. As you know, the Apollo Hospital would like to go ahead and several other centers are interested. Again, funding is an unresolved issue. To tell you the truth, lack of funding is the major issue. If we had the funds, we would simply pay for the trials.

        But the news is otherwise good. So far, the therapy appears to be safe. Our surgeons feel comfortable with the procedure and believe that it is feasible. None of the subjects have lost significant function and some have gotten some function back. It is still too early to know how significant the improvements are but I believe that it is sufficient to justify going ahead with a phase 3 trial in China, U.S., Europe, and India.

        The symposium in Xi'an was really quite exciting. We now have several promising candidate therapies and viable sources of these therapies.

        Wise

        Comment


          Originally posted by JohnMarz View Post
          Has recruitment begun for the umcb+lithium trial in the US?
          JohnMarz,

          We are not looking for "people candidates". We are looking for "therapy candidates" that we can put into trial in 2014.

          Wise.

          Comment


            Originally posted by Barrington314mx View Post
            wasnt it understood that the data would be necessary for trials in the US from the beginning? and that the data wouldnt be available until novemeber? but yet it was stated over and over that trials would begin in 2012? even recently (within a month or 2 ago)
            The Phase III trial is planned to start mid-2013 in the United States and China, assuming that we get the clinical trials approved by the regulatory authorities. We were hoping that we could get the safety data to allow us to get the Phase II trial in Brackenridge Hospital in Austin started in 2012. However, it is beginning to look as if this is not possible. I recently learned the Brackenridge Hospital just lost their rehabilitation doctor who was going to be the investigator of our trial there and we are still struggling to raise the funds for the trial. I am not sure that we will be able to identify a new investigator and get the regulatory approval for a phase II trial in Austin within 2012. We are considering all the options right now, including starting a phase II trial in New Jersey instead.

            Wise.

            Comment


              thanks for the replys. hope all the pieces begin to fall in place.

              Comment


                Dr. Young.. Phase 2 at kessler? Would a C4-5 Asaia A 22 yo man be elgible? We live in Fort Lee

                Comment


                  Originally posted by okwjoe View Post
                  Dr. Young.. Phase 2 at kessler? Would a C4-5 Asaia A 22 yo man be elgible? We live in Fort Lee
                  Hi. I have started posting things relevant to SCINetUSA in its own topic /forum/showthread.php?t=117784.

                  Wise.

                  Comment


                    Regarding ChinaSCINet, several things have been going on in the past month:

                    1. We have had several meetings now with the senior leadership of the Ministry of Health in China. They have given us some good and frank advice that we are now scrambling to implement, including setting up facilities in China to process cells and identifying a Chinese principal investigator for the trial.

                    2. A major fundraiser is being planned for March 2013 in Hong Kong. We are applying for several possible grants from China.

                    3. I will be attending the “The International Neural Regeneration Symposium 2012 (INRS2012)” to be held in Shenyang on September 22-25. Further options for the therapies to be tested in 2014 will be discussed.

                    Wise.

                    Comment


                      Originally posted by Wise Young View Post

                      1. We have had several meetings now with the senior leadership of the Ministry of Health in China. They have given us some good and frank advice that we are now scrambling to implement, including setting up facilities in China to process cells and identifying a Chinese principal investigator for the trial.
                      Who are currently performing these functions?

                      Comment


                        Wise will you be starting phase3 trials in India or phase2? Are u thinking to include lower lumbar injuries in india trial or not yet?

                        Can foreign patients join trials in india or norway?

                        Researchers at Silk Institute have produced neurons from Umbilical cells recently. Hope you read at carecure. If so umbilical cells can be tested in lower injuries too.

                        Comment


                          Jawaid theres no stemcell trials in Norway for all I know. One year ago I damaged my spinal cord and was at the biggest rehab centre for sci patients in scandinavia here in Norway. No one talked about coming stem cells trials, although my neighbour patient got injected with stem cells at stem cells inc and participated in their trials.

                          Comment


                            Hi Dr Young
                            Is it possible to get a list of the exercises regime that was done in the china trial. I would like to do at home. I already do quite a bit of pt at home including treadmill, recumbent bike, leg press, leg raises etc. I walk now full time with crutches and progress has been continuous but slow. I'd like to see if there is more I can be doing to speed my recovery.

                            Thanks

                            James

                            Comment


                              Originally posted by Wise Young View Post
                              My specific comments are embedded and my general comments follow.

                              Originally Posted by paolocipolla [IMG]/forum/images/buttons/viewpost.gif[/IMG]
                              Wise,

                              I'l try to be more clear on sevral points.

                              1) I didn't say that recruitment of chronic spinal cord injury patients is easy.
                              I agree it is still a lot of work, but think it is much easier than with acute SCI as you have an existing population with chronic SCI that can travel etc..
                              About the Hong Kong trial you had been able to recuit just 8 patients in two years because you couldn't accept patients non Hong Kong resident.
                              @ I agree.
                              Good


                              I think it was a mistake to run a trial in a place wher you can't accep patients from other countries. Many CC members are willing to parteciapate to your trial and willing to come back for examinations when needed, but they can't because you can't accept patients from around the world. I think it is quite clear that to accelate SCI clinical trial for chronic SCI at this stage it very important to have a center that can accept candidates from around the world.
                              @ Why would the Hong Kong government pay for treatments of patients from other countries? You have the cart before the horse. If we had a billion dollars to do the trial, perhaps we can do something like that what you suggest. Otherwise, we have to follow where opportunity leads us and circumstances restrict us to do.
                              A non profit org could sposnsor the non resident patients, like "just a dollar please" for example


                              2) I have 2 questions here:
                              How many patients per arm would you need in a phase III ACUTE SCI
                              trial?
                              How many patients per arm would you need in a phase III CHRONIC SCI trial?
                              This is of course what phase 2 trials are intended to find out. We would need to estimate the variability (i.e. standard error of mean) of treated and control populations and then do a power analysis to find out how many subjects are needed to detect X percent change in the outcome measure. We know from the methylprednisolone trial that about 60 subjects per treatment arm were necessary to detect 10% differences in motor and sensory score changes. We don't yet have that data from our phase 2 trials. I am hoping that that number will be lower for chronic ASIA A subjects.

                              So it seems we agree that in a trial for chronic SCI likely you need fewer patients per arm than in an acute trial.


                              3) You say:
                              "Will everybody who travels to join a clinical trial be ready to give up 3 months of their lives and to return again at 6 months and a year (or more) after the treatment? Some might but I suspect that many would not be able to do it."
                              Ask for a deposit to the partecipants before they join the trial.
                              Interesting idea. I am not sure that institutional review boards would approve such a proposal. They would approve, however, a payment incentive, i.e. pay subjects to come back. Again, this is a question of funding and not a question of possibility.
                              Good, so let's work out some solutions here for a quicker trial next time.

                              4) You say:
                              "You assume that the results of a single trial center would be credible to the rest of the world."

                              Well if you have enrolled patients with Thoracic SCI, with no function below the level of injury and now some of them are walking I belive it shoud NOT be difficult to convivnce doctors the the therapy is working.

                              @ The Kunming group did a study showing that approximately 50% of 30 subjects with ASIA A recovered ability to walk unassisted when they were treated with intradural decompression. The study did not do a control. Over half of the subjects had ASIA A thoracic spinal cord injuries. The study was turned down by the two major neurosurgery journals. The reviewers said that they did not believe the results, which is tantamount to saying that they thought we were lying.

                              Even when the results were published by a multicenter study from the United States, doctors may not believe. Take a look at the National Acute Spinal Cord Injury Study (NASCIS II), where we did a double-blind randomized placebo-controlled trial involving 487 subjects published in the New England Journal of Medicine (the most prestigious medical journal in the world). During the two years that followed publication of that study in 1990, less than a third of patients with acute spinal cord injury in the United States received the high-dose methylprednisolone (MP) therapy. It took several years of concerted effort to increase the usage rate of MP to 90% by the mid-1990's. But, once that effort slackens, doctors stop using the drug, even though there has been no new information from clinical trials indicating that the drug is ineffective or unsafe. Today, less than 50% of spinal cord injured patients in the United States and Europe are receiving MP. In 1991, the investigators of NASCIS decided that the data was too strong to allow us to conduct a second placebo-controlled trial of MP. The FDA requires two phase 2 randomized controlled trial for approval of a therapy. In some ways, I wish that we had gone ahead to a second phase III trial and gotten the spinal cord injury approved as an indication for MP. Many thousands of patients would have received the drug and gotten an average of 20% better recovery. But, such a trial would have been impossible to do after the publication of the first trial.

                              Let me give you another example from another field. Jaing, et al. from the Chang Gung Memorial Hospital in Taiwan (one of the best and most respected hospital in Taiwan) published a paper in 2010 reporting that he had 88% survival and disease-free survival in 74% of 35 kids with thalassemia treated with umbilical cord blood from Stemcyte. Thalassemia is a genetic disease that is easily documented. In 2011, Ruggeri, et al. from Italy published a study which reported the European experience using umbilical cord blood from multiple cord blood banks and they found only 67% total survival and 23% disease-free survival in 35 kids of thalassemia. Ruggeri, et al. recommended that umbilical cord blood cells not be used to treat kids of thalassemia except in a clinical trial setting. These kinds of differences happen amongst clinical trials. Many doctors around the world still refuse to use umbilical cord blood to treat thalassemia, even when they cannot find HLA-identical siblings to donate bone marrow, relegating the child to a life-time of blood transfusions every two or three weeks, along with all the expense and complications that such frequent transfusions bring.
                              You are talking about acute SCI here. May I suggest you not to mix acute trials with chronic trials? They are two very different "business" & people get esily confused especially if you mention walking.. unless that would be the goal

                              I also assume you can show medical examinations (done by indipendent examiners) of the patients before and after the treatment with the motor scores etc., or the medical community will considere your claims at the level of the ones of Geeta Shroff end others (NO COMPARISON INTENDED HERE).
                              In our Hong Kong trials, we had OT/PT examiners at each hospital as well as well as third-party examiners at the MacLehose rehabilitation center. In Kunming, we have designated nurse-doctor teams of experienced examiners (who are actually going to the homes of the patients to examine them because many cannot come back to the hospital for the followup exams). Credibility is not easy to achieve.
                              If you can get few people out of w/c I think it's easy, or at least if you show me the data and the people I will believe you.

                              Finally I want phase III trial of therapies that can restore significant functions, not something that has the same efficacy of pacebo even less,
                              That is the pharma business and I am not intersted in that.
                              @ What you want is not always what you get in trials. Of course, all of us would love to see significant functional improvements from a therapy. I don't know where you get the impression (as indicated by your signature quotes) that "pharma business" wants something less. In fact, approval of third party re-imbursement for therapies now require not only significant evidence of improvement but the improvement must be meaningful. So, let me assure that pharmaceutical industry want treatments that produce functionally significant improvement.

                              But investors wants to make money, so once they invest money in a therapy they will try to push it to the market even if there is something better getting ready.


                              Paolo




                              Clinical trials have two purposes. The first if of course to show that treatments are safe and effective. The second is to show that the treatments are not safe or are not effective. The latter should not need to be said but people (including most scientists and clinicians) forget this. Right now, many medical tourism clinics around the world are offering umbilical cord blood cell therapy of spinal cord injury, pointing to animal studies that show efficacy. If our trials show that umbilical cord blood mononuclear cells transplanted into the injury site, with or without lithium, do not change neurological function in patients, we can say definitively that the therapy does not work and recommend against its use. On the other hand, if the treatment does work, either with or without lithium, we want to be able to strongly recommend its use and back up that recommendation with global phase III trials.

                              Phase II trials are not sufficiently powered to be statistically convincing. On the other hand, they can show trends and, based on those trends, I believe that it is worthwhile going ahead to phase III trials. You will see the data from the trends as soon as all the data is collected and we submit the data for publication. Usually journals allow scientists and clinicians to share data before publication in symposia but premature publication of the data on internet may harm the chances of the data being accepted for publication in the best possible journal. That is the reason why I cannot present the data here.

                              Wise.
                              See in blue my comments.

                              Paolo
                              In God we trust; all others bring data. - Edwards Deming

                              Comment


                                Originally posted by Imight View Post
                                So the person you had in the bw photo, is acute? I thought most of your patients were chronic. I also thought they were walking unassisted. It sounds like you've already taken note that they DO need stem cell therapy AND her training to walk again. She's clearly not accomplishing the results without the injection.

                                I guess I'm just doing this for endurance at this point. That hurts.
                                Wise,

                                here above is an example of how people can get confused hearing/reading what you say.
                                You can always say that people misunderstand, but that is not how the "communication process" works.

                                Paolo
                                In God we trust; all others bring data. - Edwards Deming

                                Comment

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