In response to the COVID-19 pandemic, Atara Biotherapeutics has temporarily paused patient enrollment in the second and randomized part of its ongoing Phase 1 clinical trial investigating ATA188 in people with progressive forms of multiple sclerosis (MS).
People treated in the first, open-label part of this trial, however, will continue to be monitored as defined by trial protocol, and may enter an open-label extension period to continue with this immunotherapy candidate “in an appropriate setting.”
“While this is an unprecedented time in history, Atara is working hard to ensure operational continuity to serve patients whose lives are affected by severe diseases,” Pascal Touchon, president and CEO of Atara Biotherapeutics, said in a press release.
“The COVID-19 pandemic is evolving rapidly, and we are closely monitoring it to both ensure the safety and well-being of our employees, patients and communities, as well as assess the potential impacts to our business so we can continue delivering transformative medicines to patients in critical need,” Touchon added.
Infection with the Epstein-Barr virus (EBV, a common form of the herpes virus) is known to increase the risk of MS. This virus infects B-cells (immune cells involved in antibody production), making them more likely to produce antibodies that wrongly attack myelin — the protective coating of nerve fibers that is progressively damaged in MS.
T-cells, another type of immune cell, would normally be able to recognize the infected B-cells and eliminate them, but MS patients are thought to be deficient in these cells.
Atara designed ATA188 to overcome this deficiency, providing fully functional T-cells to patients to help rid their bodies of the faulty B-cells. The T-cells are isolated from partly matched donors, and cultured in the lab in a way that makes them highly specific to EBV-infected cells.
The Phase 1 trial (NCT03283826), taking place in the U.S. and Australia, is assessing the safety and effectiveness of ATA188 in 97 patients with either primary progressive MS (PPMS) or secondary progressive disease (SPMS).
The trial is being conducted in two parts. First, about 24 patients were given one of four ATA188 doses — 5 million (5 x 106), 10 million (1 x 107), 20 million (2 x 107), or 40 million (4 x 107) cells — to determine the safest and most effective dose for future studies.
Treatment was administered in two cycles, and patients were followed for one year after initiating treatment. They could then enter an extension part and receive once-a-year ATA188 intravenous (IV) injections for up to four years.
The second part is designed to randomly assign a new group of adult patients to an established dose of ATA188, or a placebo, to continue studying this dose’s safety and effectiveness. As in the escalating part, treatment will be given in two cycles and all enrolled will be monitored for one year.
At the start of year two, those in the placebo group will receive two cycles of ATA188, and those on ATA188 will be given one cycle of AT188 and another cycle of placebo. Patients who complete the two years of treatment may then enter the open-label extension part, and be treated with ATA188 for an additional three years.
Results from the first patients included in the escalating part showed that the treatment was well-tolerated across the four dose groups, with no evidence of cytokine release syndrome (a systemic inflammatory response), graft versus host disease (a situation in which healthy cells are attacked by transplanted T-cells), or dose-limiting toxicities.
Data also demonstrated that all six patients given the 10 million cell dose experienced clinical improvement at six months. At the time, only two of six in the 5 million dose showed at least partial clinical improvement at six months, and only one of those had stable disease at one year.
In the coming months, Atara plans to present six-month data from all four dose groups, as well as one-year data from the first three groups, the company said in the release.
Atara added that it will continue to monitor the COVID-19 pandemic, and assess the impact and timing of potential changes to its operations, and to clinical and preclinical studies.
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