NurOwn stem cell phase 3 study

[KarenNWendyn]

I have looked into this study and had a fairly extensive discussion with the study coordinator at the San Francisco site. I am posting information about this study here in case anyone is interested.

Enrollment is still open for this phase 3 study. The study is sponsored by Brainstorm Cell Therapeutics. A previous phase 2 study of a small group of ALS patients in Israel showed very promising results that this treatment could markedly slow down or perhaps even halt ALS progression. That study involved one intrathecal (into spinal fluid) injection of patient’s stem cells that had been treated to produce neuroprotective factors.

Six sites in the US are participating in the phase 3 trial. Three in CA (SF, UC Irvine, LA-Cedar Sinai), two in MA, and one in MN (Mayo). They plan to enroll a total of 200 patients. One half get active treatment and the other half get placebo. Only the people processing the stem cells know who gets what.

Participants must have ALS symptoms less than 2 years, be age 18-60, no use of BiPAP or feeding tube, no history of malignancy (other than noninvasive skin cancer) or autoimmune disease (excluding thyroid disease). No recent Edaravone is permitted. A stable dose of Riluzole or no Riluzole is permitted.

Participants undergo 14 visits over 11 months at the treatment center. The first 3 months are monitoring of disease progression (pretreatment), and they will exclude people who progress too fast or too slow. At about 3-4 months, they harvest bone marrow (a 3 hour procedure). Then a month later, treated bone marrow neurotrophic factors (or placebo) are injected intrathecally and the patient stays over night in the hospital for 24-72 hours for monitoring. This injection is repeated two more times over the next several months, each time requiring an inpatient hospital stay. Monitoring visits are required in between transplantations and after for a total of 14 visits.

I found out that no open label extension is planned. So if you are in the placebo group, you never get active treatment. Also, the bone marrows of the placebo group patients are thrown away — not saved. Bone marrows of the treatment group are thrown away at the end of the study.

Brainstorm Therapeutics may pay for lodging for a spouse when PALS is hospitalized following the three transplantations, but otherwise there is no financial compensation for transportation or lodging.

The study coordinator I spoke with emphasized to me that this treatment is not a cure but rather a stop-gap therapy that will hopefully keep PALS functional until a real cure is available. There is no data to suggest how often one must be treated once (and if) this therapy is approved. She thought it would be at least 2020 or maybe 2021 before approval. Also there is no data to suggest how this may compare with Edaravone.

I’m still considering enrolling. However, I live 7 hours from the closest treatment site (SF) or would have to fly. It’s a huge time and energy commitment that I could see making if I lived much closer. I have to decide if it’s worth the commitment considering there’s a 50% chance I could get placebo, no promise of getting active treatment at the conclusion of the study, no access to my frozen bone marrow at the conclusion of the study (for future use if the treatment were approved), and it’s not yet the cure we all seek.

Obviously, anyone who meets study criteria will have to make this choice for themselves.

 

[Nikki J]

Thank you for sharing this Karen. It seems as if one could make several trips only to be told progression does not match their needs? Were you given information about what they are basing the decision on ? ALSFRS scores? ATLIS testing? HHD testing?

Good luck in deciding. I am not sure what I would do in your place

 

[affected]

Karen thank you so much for such a detailed explanation of what this trial would actually mean for PALS. The commitment is huge, even if you live close that is a lot of visits.

I don't know what I would decide, but I'm grateful there is another trial running and people can make a choice.

 

[KarenNWendyn]

They monitor ALSFRS-R, slow vital capacity, and also a Columbia Suicide Severity Rating Questionnaire (apparently required by the FDA for neurological studies).

True, one could conceivably have 4 visits and then be terminated from the study if rate of disease progression doesn’t fall into their parameters.

I also have concerns about the 3 inpatient stays. People get sick from hospitals!

 

[KimT]

My hope is that if the Phase 3 trial is successful, they can somehow fast track approval.

That's a lot to think about, Karen.

Thanks for describing it to us so thoroughly.

 

[Vincent]

They are risking all the complications that come with intrathecal injections to give half the participants a placebo? Sounds scary to me.
Vincent

 

[Nikki J]

It is essentially a spinal tap which lots of us have for research. I suspect they extract the volume they infuse. Might be less side effects than a tap where they take volume away.

 

[KarenNWendyn]

Yes, they do a spinal tap and evaluate the spinal fluid for neuroprotective factors and inflammatory markers. They then inject neuroprotective factors grown from patient’s own stem cells (or placebo) back into the spinal fluid.

 

[Firefighter58]

I have had no progression for a year and a half just by following the ALS society's program
Al

 

[Nikki J]

I think the spinal tap issue highlights a really important point. The consents always say this may not benefit you but may help others in the future. Of course everyone hopes to get the real treatment not placebo and have it help but that is not the point of the trial really.

There is some research that says those in clinical trials whether they get placebo or not do better. There also are data that people who attend clinic do better. I do wonder how much of this is chicken and how much egg. Maybe people choose those things because they are more able/ slower progressing. Still, having been in observational studies, I do think there is some benefit. When you are being studied it means extra visits and tests so problems might be picked up earlier. You also form relationships with the study team.

 

[KarenNWendyn]

Nikki makes some good points.

I have come to the conclusion that participation in this (and really in any) study is best approached with the attitude of doing it to advance scientific/ medical research and to potentially help others rather than seeing it as an opportunity to help oneself. Certainly that could be an outcome.

Given the rigors of this particular study, potential participants must consider the time and energy (and financial) commitment and decide if that expenditure is worth it to them.

One additional correction regarding the spinal taps — I carefully reread the consent form. In addition to the three separate intrathecal injections of either neurotrophic factors or placebo, a lumbar puncture is performed at four additional visits checking for presence in the CSF of neuroprotective factors and inflammatory markers. So participants get their spinal sac punctured a on 7 separate occasions.

 

[Nikki J]

I will add do not be too freaked out by multiple spinal taps. I have more than the number in the study and on track for more. They are not fun but usually pretty ok.

They have learned a lot from spinal fluid and are close to having reliable biomarkers that will make trials more efficient. They are working on translating this to blood and urine which would obviously be easier on everyone.

They don’t know where the data from the samples will lead. Sometimes they unexpectedly get results that open new pathways.

As Karen says you have to weigh pros and cons. Your quality of life matters a lot.

On a somewhat lighter note there was a recent thread in my FALS groups. Someone was having a research tap and they were nervous. As well as well wishes, the thread contained reviews of the neurologist who was doing the tap and recommendations of the optimal position to have it. I thought it was sad and funny that a group of non medical people were discussing this

 

[Firefighter58]

Let's all remember that about a year ago we were all saying that stem cell treatment in Mexico and Japan was a waste of time and money, what makes this treatment so much better?
Al

 

[Nikki J]

This is controlled trial, approved by the FDA and IRBs for the institutions and administered by ALS specialists. They make no promises and charge nothing ( though there are expenses). It is a different technique than is used at the for pay clinics.

Ultimately it may not help at all. Finding out is the point of the trial

There are risks to being in the trial but There are more safeguards by far than an unregulated clinic where the doctor is usually not even a neurologist

 

[Gorby]

Al - I wonder if your plateau might qualify as an "ALS Reversal"? Have you thought about contacting Dr. Bedlack?