FDA clears Ultragenyx to test higher doses of GTX-102 in KIK-AS trial

Enrollment to begin 'as quickly as possible' at multiple sites in US

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

Share this article:

Share article via email
Illustration of bottle labelled

Ultragenyx Pharmaceutical has been cleared by the U.S. Food and Drug Administration to proceed to higher dosing of its investigational gene therapy GTX-102 in children and adolescents with Angelman syndrome in a Phase 1/2 clinical trial.

The amendment to the KIK-AS trial (NCT04259281) protocol in the U.S. follows similar decisions in the U.K., Canada, and Australia, and means that all locations will be testing a similar dose range.

“Agreement on the protocol amendment enables comparable dose ranges across all geographies and allows us to move forward rapidly to complete the study,” Scott Stromatt, MD, chief medical officer of neurology clinical development at Ultragenyx, said in a press release. “We have begun working urgently to activate multiple study sites in the U.S. and plan to begin enrollment as quickly as possible.”

Recruitment of children with Angelman, ages 4-17, to the higher dose groups is underway across all clinical sites in the U.K., Canada, and Australia.

Recommended Reading
A double helix strand of DNA undergoes

Angelman gene therapy is made for preclinical-clinical translation

KIK-AS trial results will inform treatment regimen for Phase 3 testing

“We are eager to expand the study in the U.S. to build on the encouraging data, which demonstrate important clinical activity across multiple functional domains impacted by Angelman syndrome with an acceptable safety profile,” Stromatt said.

The results will help inform the dosing and treatment regimen of GTX-102 to be used in Phase 3 testing, according to Ultragenyx, which is developing GTX-102 after acquiring GeneTx Biotherapeutics.

GTX-102, given into the spinal canal (intrathecally), is an antisense oligonucleotide that targets UBE3A-AS. Antisense oligonucleotides are short strings of genetic material (DNA or RNA) that can control how much of a protein is made in cells. UBE3A-AS normally binds to the paternal copy of UBE3A in brain cells and inactivates it.

By binding UBE3A-AS, GTX-102 is believed to reactivate the paternal copy of UBE3A in the brain as a way to compensate for the lack of a working maternal copy of the gene. Lack of functional UBE3A leads to symptoms such as developmental delays, speech impairments, movement disorders, and seizures.

The open-label KIK-AS trial, which began dosing in 2021, seeks to enroll approximately 40 participants to the expansion groups.

Overall, participants are patients with Angelman syndrome caused by a complete deletion of the maternal UBE3A gene. Those in the earlier groups are now on long-term maintenance dosing where they continue to receive GTX-102 every three months. As of May 4, 13 patients had been dosed for more than a year, with the longest dosing reaching more than 18 months (one and a half years).

The study’s primary goal is to assess the safety and tolerability of GTX-102. Secondary goals include assessing the therapy’s pharmacokinetics — how a medicine moves into, through, and out of the body.

Interim data showed GTX-102 improved sleep, and communication and motor skills, and also lessened disease severity.