A medication that appeared to stabilize the function and shape of red blood cells in an earlier study for patients with sickle cell disease is now part of a Phase III clinical trial that is open for enrollment at UTHealth Houston.
The trial, led locally by Modupe Idowu, MD, professor of hematology with McGovern Medical School at UTHealth Houston, will enroll patients at the UT Physicians Comprehensive Adult Sickle Cell Center, which is one of the first sites open for recruitment in the global study.
Sickle cell disease is an inherited blood disorder that causes red blood cells to become misshapen, or sickle-shaped. The cells clump together and stick to vessel walls, preventing oxygen flow. The loss of the cell’s normal shape and ability to carry hemoglobin, an oxygen-carrying protein, in blood vessels results in severe pain episodes called vaso-occlusive crises and damage to organs in the body. The disease affects millions of people worldwide and an estimated 100,000 in the United States.
The trial, called RISE UP, will compare the efficacy and safety of two dose levels of the drug mitapivat, that activates an enzyme called pyruvate kinase, versus placebo. Pyruvate kinase helps improves energy conversion to maintain the energy and shape of red blood cells. Mitapivat works by attaching to and activating pyruvate kinase, causing it to generate more energy and reduce or prevent red blood cells from sickling.
“Disease-modifying therapies are important,” said Idowu, who is medical director of the center. “They don’t mask certain symptoms and cover up the pain. We want to change this disease to maintain the normal shape of red blood cells in patients.”
A total of 198 participants will be randomized into three groups and receive a medication dose level of 50 milligrams, 100 milligrams, or a placebo in pill form. After the initial 52-week clinical trial, all participants — including the placebo group — will be able to enroll in a five-year, open-label study extension period where they will receive a 100-milligram dose level of mitapivat. They will follow patients over the years to measure the increase in the amount of hemoglobin and reduction in the occurrence of sickle cell pain crises.
The new study builds on results from a Phase II trial which was led and presented at the American Society of Hematology annual conference in December 2023 by Idowu. The Phase II study revealed an increase of hemoglobin in 50% of the 79 patients who participated. Of the 26 patients who received 50 milligrams, overall occurrence of sickle cell pain crises was reduced by 50%, while the 26 patients who received 100 milligrams experienced a 70% reduction in sickle cell crises during the trial period.
“Our hope is that the results of this Phase III study confirm the decrease in the pain episodes and improvement in quality of life for patients who are taking mitapivat long-term,” Idowu said.
Idowu is looking to recruit 20 patients at the UT Physicians Comprehensive Adult Sickle Cell Center site. Participants must be at least 16 years old, diagnosed with sickle cell disease, and have had at least two pain crises in the past 12 months.
For more information on the RISE UP trial, visit clinicaltrials.gov
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