The Results:

The trial did not demonstrate an appreciable difference between patients treated with CERE-120 versus those in the control group. Both groups showed an approximate 7 point improvement in the protocol-defined primary endpoint (Unified Parkinson's Disease Rating Scale- motor off score at 12 months), relative to a mean at baseline of approximately 39 points. Both groups had a substantial number of patients who demonstrated a meaningful clinical improvement from baseline. CERE-120 appeared to be safe and well tolerated.

Now I am awake (look out everyone!!!). After these results were announced, I was stunned. Ceregene is a very impressive company. They did an amazing job meeting the timelines promised and I have a tremendous amount of respect and gratitude for their desire to find an effective treatment so this is not a "sour grapes" comment. It is extremely important that everyone stop what they are doing, put their pencils down and hear this:

If Patient #1 in the real treatment group reduced their meds in a dramatic fashion and demonstrated a 7 point improvement and Patient #1 in the placebo group demonstrated the same 7 point improvement but increased their meds (which was permitted as long as the sponsor was notified in advance) how is this considered the same result? Please tell me the results were weighted in some way to account for this. If not, then a major injustice has occurred here!!!

Thanks so much for joining in and your question [if i had been holding a pencil, i would have put it down!] is almost so simple it's hard to believe something like that could be overlooked. We have been puzzled by the wording of this announcement all along.

In your first post, another interesting thought:

"Putting placebo patients through great emotional and physical trauma and taking every precaution to make the experience feel as real as possible does one thing to a clinical trial - it corrupts the results by producing an abnormally powerful placebo response."

This might be especially true with sham surgery.

Talking about your son brings the story home to all of us. So many other people are stressing right along with us.

I will ask you the same question as Dottie. If they go to phase III, are you entitled to the treatment? Does the Informed Consent address this?

paula

Thank you for asking Paula. From the consent form:

"If results confirm the continued safety and efficacy of CERE-120 following the conclusion of the trial, another study will be opened to allow subjects who received the sham surgery to receive the study drug CERE-120. Participation will be made available to all subjects deemed suitable for the surgical procedure by the subjects study neurologist and neurosurgeon."

It would be tragic if those that received the sham are not given the option of receiving the real treatment.

Found on the Alzheimer's Forum dated Jan 9, 2009 under PD news (scroll down to middle of page--
"In the meantime, the JAMA study may help soften the blow from the disappointing Phase 2 trial of CERE-120, a PD gene therapy approach. Unlike DBS, which can relieve symptoms but does nothing to slow neuronal death, gene therapy strategies aim to rescue dying neurons by delivering growth factors to brain regions affected by disease. Such methods have shown some success in AD (see ARF related conference story"

"CERE-120, an adeno-associated viral vector developed by San Diego, California-based Ceregene, Inc., carries the growth factor neurturin to dopamine-producing nigral neurons that degenerate in PD. In a November news release, the company announced that CERE-120 showed no clinical benefit in a Phase 2 study of 58 patients with advanced PD. The trial did have a silver lining. “We saw no product-related side effects at all,” said Ray Bartus, the company’s chief scientific officer, in an interview with ARF.

Based on autopsy data his team has analyzed from two patients in the recent trial, he thinks the gene delivery procedure could be at fault. While it appeared that neurturin DNA was taken up at the injection site—the terminal fields of nigral neurons—the researchers saw no evidence of the target protein in nigral cell bodies. To work in advanced PD patients, Bartus said the therapy should target both terminal fields and cell bodies. Based on this working hypothesis, he hopes the company can launch a trial that includes those adjustments later this year."

http://www.alzforum.org/new/detail.asp?id=2012

This is the first i've read about this explanation. Has anyone else?

Hadn't heard that Linda; the plot just thickened, but I'm not surprised. The statement for cancellation was too vague. They haven't abandoned it - they have a record for moving quickly - so does this mean we can be cautiously optimistic?

Anyone that can explain these results? It would be helpful to understand.

paula

Wow Linda, great find!!! To speculate, maybe Phase III will be new and improved version with a design that minimizes the placebo effect. Hope its true.

I found this in my Informed Consent:

If it is determined at the conclusion of this study that it is appropriate to provide CERE-120 to people with Parkinson's disease, those assigned to the sham surgery group may be permitted to enroll into an open-label follow-up study in which CERE-120 will be given"

The Questionnaire has this:

After the study is completed, you will be informed about which groiup (active treatment with Cere- 120 or sham surgery) you were assigned. If you were assigned to the sham surgery group, are you aware that you will
have the option to receive active treatment with CERE-120? Yes/No

I sent the coordinator the following:
" Someone asked me about the option of having the surgery - did that end with the completion of phase 2 or does it carry over to phase ?

Her reply:

"...I have not heard anything regarding a possible phase 3. I was told the last time I inquired that they were still in discussions as to what and if there
would be a next step even with the sham group".

Thanks much Dottie. It's understandable that they wouldn't know yet. The open label in your informed consent is different than a phase III tho don't you think? That raises another question that maybe they are still working on.

paula

oh i thought about that more....lol....you would have to be in a follow up study I guess because you certainly don't want to end up with the placebo again!

In my opionion, if Phase III becomes a reality, the fair thing to do would be to offer the sham group the real treatment in a separate open label study. If the procedure is modified, maybe we can be the group to prove the treatment is safe before it is rolled out to a larger group in Phase III. It probably won't happen that way but its a nice thought. In reality, if they would give me another crack at it and placebo was a part of it, I would sign up in a heartbeat!!!

By the way, I have no idea why anyone believes that Mirapex can cause compulsive gambling, eating and hypersexual behavior. I haven't experienced anything like that. Wait a minute!!! I'll be right back!!! I think that prostitute stole some of my gambling chips at the casino buffett!!!

Tom and Dottie, I hope we soon know the changes they are making for phase III. If they can't use the changes without first testing it in a clinical trial, could they keep you out of the statistics and do it all during phase III?

I'm thinking that you couldn't be fully in phase III, because it would be open label for you. It seems logical [this is all speculation] to keep you separate but give you the newer version being used in phase III. Does this leave more to actually observe and work with? 3 groups, two blnded- one placebo and one with new treatment- and one group open label with new treatment?

But then sometimes procedures defy logic from our perspective.

hope that makes sense,
paula