CSL Begins Enrollment for Hizentra Study for POTS

CSL Ltd. has begun enrolling U.S. patients in a Phase III late-stage randomized control trial to assess whether Hizentra subcutaneous immune globulin (SCIG) can alleviate symptoms of postural orthostatic tachycardia syndrome (POTS) — a blood circulation disorder that is one of the most common and disabling symptoms of long COVID with no approved therapies. The U.S. Food and Drug Administration granted the trial a fast track designation, recognizing its potential to address a significant unmet need. One hundred seventy seven participants in the study will be randomized to receive infusions of Hizentra or a placebo for 24 weeks, followed by an open-label treatment phase. The primary goal is to measure the proportion of participants who no longer meet the diagnostic criteria for post-COVID POTS. The study is slated to conclude in September 2027.

POTS is marked by sudden increases in heart rate, dizziness, fatigue and other symptoms when moving from a seated or lying position to standing. As of the end of 2023, more than 400 million people globally are estimated to have developed long COVID, with studies indicating around two to 14 percent of COVID survivors develop POTS, and another nine to 61 percent experience POTS-like symptoms within six to eight months.

“Subcutaneous immune globulin is particularly interesting,” said Akiko Iwasaki, PhD, director of Yale’s Center for Infection and Immunity. Previous studies with intravenous IG have raised concerns that symptom improvements might be due to large saline infusions in the placebo group, but SCIG bypasses this issue. The CSL-sponsored trial also uses a control injection of the same volume to ensure accuracy.

Animal studies from Dr. Iwasaki’s lab have shown that IG from long COVID patients reporting new pain symptoms following infection can transfer that pain to recipient mice, suggesting that certain autoantibodies may target pain neurons. If true, healthy human IG could potentially block the receptors responsible for this pain.