The trial, led by King's College London and King's College Hospital, is investigating the safety and tolerability of modified regulatory T cells - otherwise known as Tregs - in treating aplastic anaemia.
> The TIARA trial - the first to use high doses of Tregs in two doses, two weeks apart - is based on six years of pioneering work at King's College London in which it was discovered that Tregs were abnormal and reduced in numbers in patients with aplastic anaemia.”
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> Professor Ghulam Mufti, Chief Investigator of the TIARA trial, King's
Aplastic anaemia is a rare and life-threatening blood disorder that occurs when the bone marrow fails to produce enough red blood cells (responsible for carrying oxygen around the body), white blood cells (which help fight infection), and platelets (responsible for clotting after bleeding).
Tregs are white blood cells that have a role in regulating or modulating the body’s immune responses to prevent disease or ‘autoimmune hit’ where the cells of the immune system attack the bone marrow stem cells. Tregs are reduced in number and functionally abnormal in people with aplastic anaemia.
The trial aims to test the safety and effectiveness of a new treatment that involves collecting a patient’s own Tregs, expanding and modifying them outside of the body, and then putting them back in the patient in the form of two infusions.
In a presentation at the American Association of Haematologists (ASH) conference in San Diego, Dr Nazia Matto, the trial's lead GMP production scientist, revealed promising initial results from Phase 1 of the TIARA trial. Tregs were successfully expanded from all six patients, with only one patient developing a minor safety concern (an antibiotic-responsive low-grade fever).
A year on from one trial participant’s treatment, they have gone from being transfusion-dependent to no longer requiring transfusions. Another patient also showed improvements with red cell transfusion independence lasting 100 days.
People with aplastic anaemia often experience fatigue, shortness of breath, headaches and chest pains. They are also prone to infections and have a tendency to bleed easily, with the potential for serious bleeding in the brain or the gut, due to a reduction in platelets. The condition can affect anyone but is most common during the late teens, and in those aged over 60 years.
Currently, there are two standard first-line treatments for aplastic anaemia: immune-suppressive therapy, which uses drugs to dampen down abnormal immune responses but this will only work in two-thirds of patients; or a stem cell transplant, which is not a viable or safe treatment option for many people with the disease. Those who fail to respond to treatment experience significant worsening of their condition, and a reduction in quality of life as well as life expectancy.
This first-of-its-kind trial is funded by LifeArc and The Aplastic Anaemia Trust, and is managed by King’s Health Partners Haematology – a pioneering collaboration between three NHS Foundation Trusts in London with the academic expertise of King’s College London. Phase 2 of the TIARA trial is due to begin early next year.