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FDA Clears Way for KIK-AS Phase 1/2 Trial to Resume

Margarida Maia avatar

by Margarida Maia |

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GTX-102 | Angelman Syndrome News | Clinical trials | Illustration of woman speaking through megaphone

The U.S. Food and Drug Administration (FDA) has lifted the clinical hold on a Phase 1/2 study testing GTX-102 — an investigational therapy by GeneTx Biotherapeutics and Ultragenyx Pharmaceutical — in children and adolescents with Angelman syndrome.

GeneTx is now cleared to begin dosing treatment-naïve patients — those who have never received GTX-102 — in the U.S.

The study (NCT04259281), known as KIK-AS, was placed on a clinical hold late last year after five patients in the U.S. experienced serious, but reversible, muscle weakness in their legs and feet after receiving the highest dose of GTX-102.

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Earlier this year, after a change to the study’s protocol that included narrowing the dose range and switching the mode of administration to intrathecal (into the spinal canal), the company got a green light to resume the study in the U.K. and in Canada.

“We are working with urgency to begin treating study participants in all three regions over the next several months recognizing that there is no approved therapy available for the Angelman community,” Scott Stromatt, MD, chief medical officer of GeneTx, said in a press release.

KIK-AS was designed to assess the safety, tolerability, and preliminary efficacy of multiple doses of GTX-102 in up to 20 children and adolescents, ages 4–17, with a genetically confirmed diagnosis of complete deletion of the maternal UBE3A gene.

“The dosing protocol across the three regions is designed to provide a broad picture on dose response to inform loading and maintenance regimens as we move to the next phase of development,” Stromatt said.

In the U.S., a dose-loading phase will include eight treatment-naïve patients, ages 4 to 7, who will be split into two groups: an active treatment group and an age-matched control group. The active group will receive 2 milligrams (mg) of GTX-102, given as four monthly doses. The control group will be assessed at the beginning and at day 128 of the study, and thereafter be eligible to receive the same dosing scheme as the active group. All patients who complete the dose-loading phase will then move to a maintenance phase during which they will receive 2 mg of GTX-102, given every three months.

In the U.K. and Canada, the study will include about 12 patients who will be split into two groups according to age: group 4 (ages 4 to 7) and group 5 (ages 8 to 17). Group 4 will receive 3.3 mg of GTX-102, given as three to four monthly doses. Group 5 will receive 5 mg of GTX-102, also given as three to four monthly doses. They will then move to a maintenance phase during which, if safety is maintained, they will receive GTX-102, given every three months, up to a maximum of 14 mg.

GTX-102 is an antisense oligonucleotide — a short piece of DNA or RNA that can bind to a specific RNA molecule — that is designed to block the UBE3A antisense transcript. This molecule normally silences the paternal copy of UBE3A. By blocking the UBE3A antisense transcript, GTX-102 is designed to reactivate the silent paternal copy of UBE3A in the brain, which in turn may compensate for the missing maternal copy of the gene that is known to cause Angelman.

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