US Trial of Gene Therapy AMT-130 Enrolling High-dose Patient Group

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by Patricia Inácio, PhD |

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A Phase 1/2 clinical trial testing uniQure’s potential gene therapy AMT-130 in people with Huntington’s disease can continue enrollment, according to a positive review by the study’s independent data safety monitoring board (DSMB).

The DSMB reviewed safety data from four patients given the higher dose of the therapy, which is delivered directly into the brain. Data from these patients will be shared before the end of the year, according to uniQure’s press release.

Enrollment for the final 12 patients in the high-dose group is now open across 11 of the 12 U.S. clinical sites and is expected to be completed by June. More information is available here.

At this point, eight patients have been treated with AMT-130, and six patients serving as controls have received a sham brain surgery. 

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“The AMT-130 program continues to advance at a steady pace, and with this positive recommendation from the DSMB, we are eager to enroll the final 12 patients in the higher-dose cohort,” said David Cooper, MD, vice president of uniQure’s clinical development.

uniQure is also preparing an open-label Phase 1b/2 study of AMT-130 to be conducted in Europe. In total, 15 patients with early-stage Huntington’s disease will be enrolled across two dose groups.

Data from both the U.S. and European studies are expected to establish the gene therapy’s safety and optimal dose. This might allow AMT-130 to move into Phase 3 or confirmatory trials, the company announced.

AMT-130 is a gene therapy that uses a modified and harmless adeno-associated virus to deliver to cells a small RNA molecule, called microRNA, designed to lower the production of the disease-causing, mutated huntingtin protein.

As such, AMT-130 is thought to target Huntington’s underlying cause, rather than treating its symptoms. The gene therapy is administered once directly into the striatum — a brain region involved in movement control — through a surgical procedure known as MRI-guided, convection-enhanced delivery.

The Phase 1/2 trial (NCT04120493) is evaluating AMT-130’s safety, tolerability, and effectiveness against a sham procedure in up to 26 adults, ages 25–65, with early stage Huntington’s disease.

Participants are divided into two groups: one low-dose (10 patients) and one high-dose (16 patients).

In the low-dose group, already completed, six were treated with AMT-130, and four underwent the sham surgery.

Following a review of nine months of safety data from these 10 patients and DSMB approval, the trial began enrolling and dosing a high-dose group.

With a target goal of 16 patients, 10 will be assigned to AMT-130 and four will undergo a sham surgery.

One year after surgery, participants will be informed whether they received AMT-130 or the sham procedure. Patients in the sham surgery group may be eligible to receive the gene therapy, pending a data review by the monitoring board and the U.S. Food and Drug Administration.

The study’s main goal is to assess the therapy’s safety. Additional goals include assessing how long AMT-130 remains in the brain, as well as changes in patients’ motor and cognitive functions, brain features, levels of disease biomarkers, depression and anxiety, and quality of life.

Top-line data are expected by the end of 2022, and the study is estimated to end in May 2026.