While Rush University Medical Center in Chicago, Illinois, will be the first to enroll patients, additional trial sites will follow, and are planned for Boston, Cincinnati, Denver, Los Angeles, New York and Ottawa, Canada.
GTX-102 is an antisense oligonucleotide designed to target the molecule that causes Angelman syndrome (UBE3A antisense transcript, or UBE3A-AS) and prevent it from working. Antisense oligonucleotides (ASOs) are small molecules that can bind to RNA to change how it is spliced.
The compound was granted granted both orphan drug and rare pediatric disease designations by the U.S. Food and Drug Administration in September 2019 to help speed its advancement.
The KIK-AS (Knockdown of UBE3A-antisense in Kids with Angelman Syndrome, NCT04259281) is an open-label trial that will evaluate the safety and tolerability of multiple doses and dose escalations of GTX-102.
The trial expects to enroll approximately 20 patients (male and female) with Angelman, ages 4 to 17 years, and a confirmed genetic diagnosis of maternal UBE3A gene deletion. More informations on trial recruitment is available here.
In addition to safety and tolerability the trial also will assess GTX-102’s pharmacokinetics (how a medicine moves throughout the body) and its concentrations in patients’ blood and cerebrospinal fluid (the fluid around the brain and spinal cord).
GTX-102 will be administered via intrathecal injection (through the spinal canal) at the beginning of the study, followed by three subsequent intrathecal injections 30, 58 and 86 days after. The duration of study is expected to be approximately six months and patients can choose to continue into the trial’s open-label extension (OLE) study in which they will receive continued treatment with GTX-102.
“A tremendous amount of basic research over decades, and intense research and development over the last couple of years has now brought us to the cusp of testing a novel drug [GTX-102] in individuals with Angelman syndrome,” Scott Stromatt, MD, chief medical officer of GeneTx Biotherapeutics, said in a press release.
“We are extremely excited to begin the process of understanding the effects of GTX-102, which is directed at correcting the genetic defect and potentially improving the quality of life of our patients with Angelman syndrome,” said Elizabeth Berry-Kravis MD, PhD, principal investigator of the Rush University center, and co-director of the Angelman Syndrome Clinic at Rush.
“The GeneTx team continues to make significant progress in advancing the GTX-102 program for patients with Angelman Syndrome, and we look forward to continuing our work with the team to move this program into the clinic,” said Camille L Bedrosian, MD, chief medical officer of Ultragenyx.