1st Group Enrolled in Trial of uniQure’s AMT-130 Gene Therapy

Patricia Inacio PhD avatar

by Patricia Inacio PhD |

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uniQure has completed patient enrollment for the first group participating in a Phase 1/2 trial assessing the safety and efficacy of AMT-130, its experimental gene therapy for Huntington’s disease.

“This is an important milestone in our ongoing clinical development of AMT-130,” David Cooper, MD, PhD, vice president of clinical development at uniQure, said in a press release.

“Completing enrollment of the first, 10-patient cohort ahead of schedule highlights the high level of interest among the Huntington’s disease patient and clinical community,” he added.

Enrollment of participants, ages 25 to 65, for the trial’s (NCT04120493) second group is expected to start in the third quarter of this year. Nine U.S. clinical sites are preparing for patient enrollment, which is expected to begin after a review by the independent Data Safety Monitoring Board, which is overseeing the proof-of-concept trial.

A new open-label clinical study of AMT-130 in Europe is expected to start later this year.

AMT-130 is a gene therapy designed to lower the production of the mutated form of the huntingtin protein, the underlying cause of Huntington’s disease.

The therapy is made of a small portion of synthetic genetic material — called microRNA (miRNA) — that is inserted into cells and carried using an adeno-associated virus, which has been modified to be harmless.

The miRNA targets the RNA molecule that has the instructions to produce the mutated form of huntingtin protein, and marks it for degradation. In this way, the therapy is thought to lower the production of abnormal huntingtin protein.

The five-year proof-of-concept Phase 1/2 trial consists of a blinded 12-month core study period followed by an unblinded four-year follow-up.

The trial’s main goal is to assess the gene therapy’s safety and efficacy against a sham procedure in people with early stage Huntington’s disease.

In the first group, six participants are assigned to a low dose of AMT-130 and four to an imitation (sham) surgery. Given as a single dose, AMT-130 is administered directly into the striatum — the area of the brain responsible for movement control — using a surgical procedure known as MRI-guided convection-enhanced delivery.

The second group will include 16 patients, out of which 10 will be assigned a high dose of AMT-130 and four the sham surgery.

After the first 12-month blinded period, participants will be individually unblinded and data reviewed by the independent safety board and the U.S. Food and Drug Administration, potentially opening the way for AMT-130 to be given to eligible patients who underwent the sham surgery.

The open-label study in Europe seeks to enroll 15 patients with early Huntington’s disease. The trial will also include two dose groups.

Results of the European study and the ongoing U.S. trial are expected to help uniQure determine the safety of its gene therapy, establish an optimal dose, and move forward into Phase 3 development, or to a confirmatory trial should AMT-130 earn accelerated approval by regulators.