Phase 1/2 Trial Is Testing Cutting-edge Immunotherapy in MS Patients
A Phase 1/2 clinical trial is evaluating the safety and effectiveness of a cutting-edge immunotherapy called extracorporeal photopheresis in people with multiple sclerosis (MS).
The study, dubbed PHOMS (NCT05168384), is enrolling up to 45 adults with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) at a single site, the Abu Dhabi Stem Cells Center (ADSCC), in Dubai.
“Multiple sclerosis is a debilitating disease with a devastating impact on many patients’ lives in the Middle East and around the world; our world-leading research center has the chance to advance global biotechnology treatments to the next level,” Yendry Ventura, MD, ADSCC’s general manager and a specialist in immunology, said in a press release.
“Getting here is the result of years of tireless work and commitment from our fantastic team at ADSCC, and we are thrilled to be commencing phase 1/2 of the study,” Ventura said. “We anticipate providing life-changing remedies for people in the UAE [United Arab Emirates], the Middle East and beyond.”
MS is an autoimmune disease wherein the immune system wrongly recognizes myelin — the protective sheath around nerve fibers — as foreign and mounts immune responses against it. This leads to inflammation, myelin loss, and nerve cell death.
Extracorporeal photopheresis (ECP) is a cutting-edge, cell-based immunotherapy used for certain T-cell lymphomas, complications of bone marrow and stem cell transplants, organ transplant rejection, and other autoimmune conditions linked to abnormal immune T-cells, a type of white blood cell involved in the fight against infections and cancer.
T-cells also drive the abnormal immune responses that characterize autoimmune diseases such as MS.
ECP involves drawing blood from a patient and separating its white blood cells. These cells are then combined with a natural molecule called psoralen exposed to ultraviolet light to activate it, and then infused back into the patient.
When activated, psolaren becomes a highly reactive molecule that binds to DNA, cell membranes, and proteins that together lead to cell death and other toxic effects.
While its underlying mechanisms remain largely unclear, research suggests ECP promotes anti-inflammatory responses and reduces abnormal immune reactions through several processes, such as activation of regulatory T-cells (Tregs). Tregs are a subset of T-cells that dampen responses of other immune cells.
This approach does not result in a global immunosuppression, as seen with several immunosuppressive therapies, meaning the body may still be able to effectively fight infections and cancer.
Results from three ADSCC-based studies testing ECP were presented at the 2022 European Society for Blood and Marrow Transplantation (EBMT) Annual Meeting, held virtually, March 19–23.
The Phase 1/2 trial will test the therapy in 45 RRMS and SPMS patients who are able to walk, even if only with help. Participants will be randomly assigned to receive either 28 ECP sessions plus standard disease-modifying therapies (DMTs; 30 patients) or DMTs alone (15 patients) for 24 weeks (nearly six months).
ECP will be administered twice a week in the first eight weeks (16 sessions), once a week from weeks 9–16, and once every two weeks from weeks 17–24.
Allowed DMTs do not include B-cell depleting therapies, which work by promoting the death of B-cells, another type of immune cell involved in the abnormal responses against myelin in MS.
The study’s main goals are to assess the ECP’s safety and effectiveness, while secondary goals include assessing MS patients’ immune response profile.
Effectiveness measurements include changes in disability progression, walking ability, occurrence of clinical relapses, finger dexterity, and general health; all assessed with validated measures.
“The research has the potential to revolutionize global care for patients fighting the debilitating illness,” and is part of the directives of Abu Dhabi’s crown Prince and deputy supreme commander of the UAE Armed Forces to tackle the most prevalent diseases,” ADSCC stated in the release.
The trial is expected to conclude in April 2024, and should it produce positive results, the researchers plan to launch a Phase 3 trial to confirm the findings in a larger group of patients.
“The UAE is introducing unique and innovative treatments to the region in this ground-breaking clinical trial,” Ventura said.