This is a phase-I, 10 person trial which started in September 2022, and is expected to finish in January 2024. This trial is for adults (18-50 years old, within 3 years of diagnosis). Half the people will be treated with a standard level of Extracorporeal Photopheresis (ECP) and half will get a double dose. There is no placebo (untreated group). The trial is randomized but open label, meaning that each person will be randomly assigned to standard or double dose, but that everyone will know which group a person is in.
The standard dose is basically one treatment every two weeks for a six month period. The treatment takes about 3 hours and is done in a clinic. I discuss it in detail below, but it is basically: blood is removed, processed "off line" and then injected back into the person. The double dose is basically twice as often.
This trial has five primary end points. For me, the one that matters is C-peptide, but they are also measuring adverse effects, A1c, and insulin use, and the number of people who drop out of the trial. There are a bunch of secondary end points which measure changes in the immune system. Data will be collected for a year after treatment.
Note that different sources have different information for this clinical trial. The US FDA clinical trial registry lists 10 people within 3 years of T1D diagnosis, but the literature at ASDCC says 40 people will be enrolled, and an earlier interview on Facebook says within 6 months of diagnosis. If you have any doubts about eligibility, the treatment, or the trial in general, I recommend you get in touch with ASDCC. This study is enrolling at one site:
Abu Dhabi Stem Cells Center Abu Dhabi, United Arab Emirates, 4600
Contact: Yandy M Castillo-Aleman +971-26655155 ext 104 yandy.castillo@adscc.ae
Contact: Muhammad M Alam +971-26655155 ext 104 muhammad.alam@adscc.ae
Previous Research
There has been one clinical trial of ECP on people with T1D in the past, so it makes sense to look at those results.
In 2001 there was a 40 person study done on children (age 10 to 18) in their honeymoon phase. The indented text is paraphrased from the abstract:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1718876/
The actively treated children secreted significantly more C peptide in urine during follow up than control children. C peptide values in serum showed corresponding differences between the two groups. The insulin dose/kg body weight needed to achieve satisfactory HbA1c values was always lower in the photopheresis group; there was no difference between the groups regarding HbA1c values during follow up.
The first thing to notice about this summery is that there are no specific numbers reported. That is usually a bad sign. I looked at the results in the paper, and my opinion is that there was no strong signal of success. The treated group did do a little bit better, so I would describe the results as hopeful, but not strong. The treated group did use less insulin, however. About 25% less, which is another interesting taste of hope.
In the next few years, this same group published a couple of papers looking at what changed in kids who got ECP vs. kids who did not. However, they used blood samples from the original group of kids, so there was no additional data on effectiveness.
More Discussion
Differences from Previous Research
If previous research on ECP was not a strong success, and this research area has been dormant for about 20 years, it is reasonable to ask what is different about this clinical trial. Why do these researchers hope for better results?
The major difference I see is the number of treatments. The previous trial gave 5 treatments in 3 months. This trial is giving 7 treatments in 4 months to one group and about double that many to the other group. However, this treatment is more complex than just giving a drug, so it may be that there are other differences between the previous protocol and the current one.
Why so many primary end points?
Clinical trials usually have 1 primary end point. I've seen 2 on occasion as well, but this is the first time I can remember 5 different primary end points. Why design a trial like that? The first question is, why do most clinical trials have a single primary end point? That is pretty straight forward: especially for phase-III studies, both the FDA and the company funding the work, need a clear success or failure decision. Of course they could analyze a bunch of results and synthesize a single success or failure out of a bunch of different primary outcomes, but no one wants to do that. Therefore, clinical trials are usually designed from the beginning to have one primary outcome, and that one outcome feeds the rest of the experimental design.
However, if the FDA will not be using the study to approve a drug, and a company will not be using the study to raise more money for drug development, then there is much less pressure to have just one primary end point. These researchers seem to have taken that idea farther than others, but there is no rule saying they cannot.
Extracorporeal Photopheresis (ECP)
A person's blood is taken, white blood cells are separated out, and treated with a drug called 8-methoxypsoralen (8-MOP). The white blood cells are then injected back into the person. So this is a way of selectively treating just white blood cells and not any other part of the body. This treatment was FDA approved for one form of cancer in 1988, but is currently used for several other immune issues, especially graph vs. host disease and transplant rejections.
8-methoxypsoralen (8-MOP), also known as Methoxsalen, is an unusual drug in that it is activated by ultra violet light, as part of the treatment. This means that people getting this treatment must avoid sun light for 24 hours afterwards to avoid over-exposure. This link describes the treatment as used for transplantation issues by CHOP (great acronym for the Children's Hospital of Philadelphia):
https://www.chop.edu/services/extracorporeal-photopheresis-ecp
There are also pills and creams, which have been available for decades. These forms are used to treat psoriasis, eczema, vitiligo, and some cutaneous lymphomas. The skin is exposed to a very specific amount of ultraviolet (UVA) light from lamps or sunlight after taking the drug.
https://en.wikipedia.org/wiki/Methoxsalen
Abu Dhabi Stem Cells Center (ADSCC)
ADSCC is a private clinic in the Arab Emirates. It was founded in 2019, and is already involved in 5 clinical trials: 2 are completed, 2 are in progress, and 1 is waiting to start. Several of these involve applying ECP to different diseases or in combination with other treatments.
Note that although ADSCC has "stem cells" in its name, the Opera trial discussed here (and ECP in general) is not a stem cell treatment. I would describe it as a "cellular therapy".
Sources:
New Article: https://www.arnnewscentre.ae/news/uae/uae-explores-new-treatment-options-for-diabetes-multiple-sclerosis/
New Article: https://www.weqaya.ae/en/posts/adscc-conducts-clinical-trials-for-diabetes-ms-treatment
Video: https://www.facebook.com/watch/?v=1907192579465520
Clinic Web Site: https://www.adscc.ae/ (takes a long time to load)
Clinical Trial Registry: https://clinicaltrials.gov/ct2/show/NCT05413005
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