Safety Seen in AMT-130 Gene Therapy Trial, Six More Patients to Enroll

No significant safety concerns were found in the first four patients participating in a Phase 1/2 trial assessing the safety and efficacy of uniQure’s AMT-130, an experimental gene therapy for Huntington’s disease.

This finding — the outcome of a second meeting with the independent Data Safety Monitoring Board (DSMB) overseeing the proof-of-concept trial (NCT04120493) — opens the way for enrolling and treating another six people.

uniQure expects to finish recruiting a full first group of study patients by mid-year, with a release of early results to follow.

In a first meeting, the DSMB reviewed three-month safety data from a first set of two patients, one who received AMT-130 and the other a control sham surgery, with no safety concerns reported. The second meeting reviewed six-month safety data on these two patients and 90-day safety data from the next two enrolled patients. Again, one was given the gene therapy and the other underwent a sham surgery, becoming part of the trial’s control group.

“We are encouraged with the positive recommendation to proceed with patient enrollment from this second DSMB meeting,” Ricardo Dolmetsch, uniQure’s president of research and development, said in a press release. “We will now focus on enrolling the last six additional patients in the first cohort and look forward to sharing initial biomarker and imaging data towards the end of the year.” 

Huntington’s disease is caused by mutations in the HTT gene, leading to the degeneration of two areas of the brain, the basal ganglia, responsible for movement coordination, and the cortex, which controls behavior, thought, and memory.

AMT-130’s active ingredient is a small piece of synthetic genetic material known as microRNA (miRNA) carried by a harmless adeno-associated virus (AAV) vector. Inside the cell, miRNA targets RNA that contains the instructions for the abnormal huntingtin protein, marking it for degradation and lowering its production.

The five-year trial, which is currently recruiting 26 patients at several sites across the U.S., consists of a blinded 12-month core study period followed by an unblinded four-year follow-up. It is exploring the therapy’s safety and efficacy against a sham procedure in people with early stage Huntington’s disease. Those in the control group will be given the option of treatment after one year and the unblinding of trial data.

A 10 patient, low-dose cohort will be followed by a 16 patient, higher-dose group, randomized to received AMT-130 or an imitation (sham) surgery. Treated participants will receive a single dose of AMT-130 through a surgical procedure known as MRI-guided convection-enhanced delivery directly into the striatum, the area of the brain responsible for movement control. 

The trial’s primary outcome is safety, assessed by adverse events related to clinical safety laboratory tests, vital signs, electrocardiograms, neurological and physical examinations, AAV viral shedding, immunological response, suicide risk, overall cognitive functioning, and MRI measures of swelling, volume loss, and structural changes.

Additional outcomes will be the duration of AMT-130 in the brain, along with its effects on disease biomarkers in the liquid that surrounds the brain and spinal cord (cerebrospinal fluid). Measures of disease severity, and motor and cognitive abilities also will be evaluated.

After the first 12-month blinded period, participants will be individually unblinded and data reviewed by the DSMB as well as the Food and Drug Administration, opening the way for eligible sham surgery patients to be given AMT-130.