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An early-stage clinical trial evaluating CK0803, <a href="https://cellenkosinc.com/">Cellenkos</a>&#8216; regulatory T-cell-based therapy for people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), has completed dosing its first patient group, the company announced in a <a href="https://www.prnewswire.com/news-releases/michael-e-debakey-va-medical-center-va-hospital-announces-new-cell-therapy-clinical-trial-for-amyotrophic-lateral-sclerosis-302039441.html">press release</a>.
The six patients, all adults, were treated at the Columbia University Irving Medical Center, in New York City, in the Phase 1 run-in period of the <a href="https://clinicaltrials.gov/ct2/show/NCT05695521">REGALS Phase 1/1b clinical trial (NCT05695521)</a>, which focused on safety. The trial now will enroll another 60 adults with ALS in its randomized Phase 1b part to continue to examine the treatment’s safety and efficacy.
The participants to date have been recruited at the single New York study site, but a U.S. Department of Veteran Affairs (VA) hospital in Houston has <a href="https://www.va.gov/houston-health-care/stories/new-hope-for-als-veterans/#:~:text=DeBakey%20VA%20Medical%20Center%20in,treatment%20for%20the%20neurodegenerative%20disease.">announced it will recruit 10 patients</a> for the clinical trial, slated to span about six months.
The Michael E. DeBakey Veteran Affairs Medical Center is the first and only VA hospital in the U.S. to join REGALS — and provide military veterans the opportunity to receive the cell-based therapy, which is designed to reduce neuroinflammation and balance the activity of the immune system.
&#8220;We are thrilled that our veterans will get the opportunity to receive such a cutting edge therapeutic that could be life altering,&#8221; said James Orengo, MD, PhD, principal investigator of the study at the DeBakey VA Medical Center.
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<h3>VA hospital &#8216;excited&#8217; to be among first sites to test novel therapy</h3>
&#8220;The incidence of ALS is elevated in veterans and novel therapies are desperately needed,&#8221; Orengo said.
Indeed, it&#8217;s estimated that more than 16% of all ALS patients are veterans, who are <a href="https://alsnewstoday.com/causes-of-als/">twice as likely to develop the disease</a> as are individuals in the general population.
Scientists have suggested that this increased prevalence likely is related to increased exposure to chemicals, strenuous physical conditions, and trauma during military service.
&#8220;We made a conscious decision to make this novel cell therapy available to the veterans and remain committed to provide our continued support to those who have served our country,&#8221; said Tara Sadeghi, Cellenkos&#8217; chief operating officer, noting that &#8220;there is an urgent need for novel treatments for all forms of ALS.&#8221;
Altogether, the REGALS trial will involve a total of 66 ALS patients with disease onset in the previous five years. All will receive the cell-based therapy through intravenous or into-the-vein infusions. The first four treatment doses are given weekly, followed by monthly infusions for the next five months.
[quote=&#8221;center&#8221;]We made a conscious decision to make this novel cell therapy available to the veterans and remain committed to provide our continued support to those who have served our country.[/quote]
In the <a href="https://alsnewstoday.com/news/patient-dosed-trial-potential-als-cell-based-therapy-ck0803/">Phase 1 part of the trial</a>, which is now complete, researchers assessed the treatment&#8217;s safety and efficacy. The main goals of the Phase 1b part are to determine the incidence and severity of side effects as well as changes in a combined assessment of function and survival.
Secondary efficacy measures include changes in the rate of disease progression, quality of life, lung function, and muscle strength.
For its part, the Houston VA clinic is &#8220;excited to be one of the first sites [to test this] novel T regulatory cells therapy for ALS,&#8221; Barbara W. Trautner, the center&#8217;s deputy associate chief of staff for clinical research, said in the VA announcement.
&#8220;We hope this is the first of many trials that we can open to develop new therapies for veterans with neurodegenerative disorders,” Trautner said, noting that the center&#8217;s neurologists &#8220;jumped at the chance to offer this to our veterans.&#8221;
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<h3>Cell-based therapy aims to reduce inflammation in ALS</h3>
People with ALS generally have high levels of inflammatory T-cells, which aid in the progressive dysfunction and death of motor neurons, the nerve cells that control voluntary movements. Conversely, immunosuppressive regulatory T-cells, known as Tregs, usually are found at lower levels than are normal in these patients, and are also less effective.
Tregs are immune cells that help suppress excessive inflammation and maintain the immune system&#8217;s healthy functioning. As such, they&#8217;re believed to help reduce some of the inflammation that causes damage in ALS.
CK0803 is a cell-based therapy that uses Tregs isolated from healthy umbilical cord blood, without the need to match patient and donor. These cells are then enriched and differentiated to target a given condition using the company&#8217;s proprietary <a href="https://cellenkosinc.com/ourscience/index.html">CRANE technology</a>.
The technology enables the production of several CK0803 doses from a single umbilical cord blood unit, and the final product can be frozen and stored for long periods — making treatments readily available for patients when needed.
“We are very excited to open this first cell therapy trial for ALS in the VA,” Orengo, also a professor of neurology at Baylor College of Medicine, in Houston, said in the Veteran Affairs announcement.
“We know that neuroinflammation fuels the ALS disease process. We believe that this new treatment, which involves calming the immune system in the central nervous system, holds great promise in halting this disease,” Orengo said.

Trial of cell-based therapy CK08031 finishes dosing 1st patient group

<a href="https://www.ai-therapeutics.com/">AI Therapeutics</a>&#8216; experimental therapy AIT-101 led to reductions in levels of toxic proteins in people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) associated with mutations in the C9ORF72 gene, according to data from a clinical trial.
The Phase 2a clinical trial also met its main goals of showing that AIT-101 had an acceptable safety and tolerability profile, and that the therapy&#8217;s active ingredients were able to reach participants&#8217; brains.
&#8220;This study provides early clinical evidence of AIT-101’s ability to clear the toxic protein aggregates that may contribute to the adverse pathology of ALS and provides a strong rationale for further clinical studies,&#8221; Murat Gunel, MD, said in a <a href="https://www.globenewswire.com/news-release/2023/04/05/2641635/0/en/AI-Therapeutics-Announces-Positive-Results-from-Phase-2a-Biomarker-driven-Trial-of-AIT-101-in-Patients-with-C9ORF72-Amyotrophic-Lateral-Sclerosis-ALS.html">press release</a>. Gunel is a member of AI Therapeutics’ board of directors and chair of the company&#8217;s scientific advisory board.
&#8220;This is exciting progress toward a new treatment for ALS,&#8221; added Gunel, a professor at Yale University in Connecticut.
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Although the exact molecular mechanisms that cause ALS are not completely understood, abnormal clumps of proteins have been identified in nerve cells in virtually all cases of ALS. These clumps are thought to be toxic and contribute to nerve cell death and dysfunction in the disease.
AIT-101 is designed to activate the autophagy lysosomal pathway, a set of cellular recycling machinery that breaks down proteins and other complex molecules that are faulty or no longer needed.
The experimental therapy specifically acts by targeting a protein called PIKfyve, which activates the transcription factor TFEB and results in a <a href="https://alsnewstoday.com/news/phase-2-trial-oral-ait-101-enrolling-adults-c9orf72-mutations-us/">greater production of lysosomes</a> — the structures where the cellular recycling takes place. By activating this pathway, AIT-101 aims to help clear toxic disease-driving protein clumps.
AI Therapeutics recently announced new preclinical data showing that AIT-101 was effective in a mouse model of ALS driven by mutations in the gene coding for the TDP-43 protein. AIT-101 also is known as LAM-002A.
&#8220;AIT-101 belongs to a new class of experimental therapeutics that directly target the clearance of toxic protein aggregates in motor neurons, which is a hallmark of ALS,&#8221; said Suma Babu, a physician scientist at Massachusetts General Hospital and professor at Harvard Medical School.
AI Therapeutics sponsored a <a href="https://clinicaltrials.gov/ct2/show/NCT05163886?term=NCT05163886&amp;draw=2&amp;rank=1">Phase 2a clinical trial (NCT05163886)</a> to evaluate AIT-101 in people with ALS caused by mutations in the C9ORF72 gene, the most common type of ALS-associated mutation. Mutations in this gene normally result in a hexanucleotide repeat region, where a sequence of six nucleotides (the building blocks of DNA) is repeated an excessive number of times.
This causes the production of abnormally long proteins, including the poly(GP) protein, which may contribute to abnormal protein clumping in nerve cells.
<h3>Study design</h3>
The trial enrolled 15 adults with C9ORF72-associated ALS. For the first 12 weeks (about three months), participants were assigned randomly to take oral capsules of AIT-101 or a placebo twice daily. Then, for the next 12 weeks, all participants were treated with AIT-101.
Biomarker analyses showed that after 12 weeks of treatment with AIT-101  levels of toxic poly(GP) clumps decreased by 73%. There also was a significant increase in levels of a biomarker called sGPNMB in AIT-101-treated patients, which suggests the therapy is affecting the PIKfyve protein as expected, according to AI Therapeutics.
&#8220;The positive results of this trial are encouraging for further development of AIT-101 in ALS. &#8230; This data may have broad implications for all ALS individuals, not only for C9ORF72 ALS individuals tested in this trial,&#8221; said Babu, the trial&#8217;s principal investigator.
<h3>Encouraging results</h3>
&#8220;We are encouraged by the results of this initial study of AIT-101, our first-in-class PIKfyve kinase inhibitor. In particular, we are impressed with the speed and magnitude of reduction of toxic protein aggregates as measured by poly(GP),&#8221; added Brigette Roberts MD, CEO of AI Therapeutics.
After the 24-week study, participants had the option to continue into a long-term extension study where they can continue to receive the experimental treatment.
&#8220;This patient-centric, biomarker-driven, Phase 2a ALS clinical trial was able to efficiently inform us about the biological efficacy and [central nervous system] drug delivery of AIT-101 in C9ORF72 ALS individuals, using a relatively small sample size, short placebo exposure duration and short trial duration overall, while also providing trial completers with the option of long term expanded access to AIT-101,&#8221; Babu said.
&#8220;We thank all the patients and investigators who participated in this study; the dedication of so many towards this and other clinical studies offers inspiration and hope for patients suffering from this devastating disease,&#8221; Roberts said.

Tag: clinical trial for ALS

Trial of cell-based therapy CK08031 finishes dosing 1st patient group

AIT-101 clears toxic protein clumps, early data show