Clinical Trials for Fabry Disease

Did you know that there are 158 Fabry disease studies listed on the Clinical Trials website, two of these have locations including Ireland, both of these are recruiting applicants to determine the effectiveness of Lucerastat. To learn more about which clinical studies are happening for Fabry disease go to You can search by disease and check if any studies are happening in Ireland. Remember – there may be a study not going on in your particular location, but you can still contact the study investigator to find out more about the research they are conducting.

Apabetalone (RVX-208)

Apabetalone in clinical trials

In March 2017, Health Canada approved a clinical trial of apabetalone in patients with Fabry disease. This Phase 1/2 trial (NCT03228940) will evaluate the safety, tolerability, adverse effects, and changes in clinical laboratory parameters in patients taking apabetalone pills for up to 12 weeks. The trial is expected to start in April 2018 and aims to recruit 16 patients in Canada.

PRX-102 (Pegunigalsidase Alfa)

PRX-102 in clinical trials

An open-label, Phase 1/2 clinical trial (NCT01678898) found that 0.2 mg/kg, 1 mg/kg, and 2 mg/kg doses of PRX-102 given every two weeks was able to maintain consistent alpha-galactosidase A enzyme levels in the blood. Patients were given PRX-102 for three months and were also monitored for side effects, kidney function, Gb3 levels, and pain.

An extension study (NCT01769001) where patients continued their allocated dose of PRX-102 for another nine months, produced the same results. Both the Phase 1/2 trial and its first extension ended in 2016.

Another open-label extension trial (NCT01981720) is still ongoing where patients who have completed the Phase 1/2 trial and its first extension trial receive 1 mg/kg of PRX-102 every two weeks for up to five years. The trial is enrolling participants by invitation only and is expected to be completed in 2021.

Two-year interim data that included 16 patients from the first two completed trials and 11 from the ongoing extension trial revealed that PRX-102 was well-tolerated, with most side effects being mild to moderate.

Patients had stable kidney and heart functions, improved gastrointestinal symptoms, and a 40% reduction in disease severity. Only 19% of the Fabry patients developed antibodies against PRX-102, but these disappeared after one year of treatment. Antibody formation is a problem while receiving enzyme replacement therapy and may hamper the effectiveness of the treatment.

Three Phase 3 clinical trials are currently underway to compare PRX-102 with existing enzyme replacement therapies for Fabry disease. Investigators are assessing various aspects of Fabry disease and PRX-102 in these trials.

The open-label Phase 3 BRIDGE study (NCT03018730) is recruiting up to 22 patients with Fabry disease have been taking Replagal (agalsidase alfa) for at least two years and had a stable dose for the last six months. After an initial three months of observation, patients will be switched to 1 mg/kg of PRX-102, which will be administered every two weeks for a year. The trial is currently recruiting in Australia, Canada, Europe, and the U.K.

The Phase 3 BALANCE trial (NCT02795676) will compare 1 mg/kg of Fabrazyme (agalsidase beta) with 1 mg/kg of PRX-102 taken twice a month for two years. Enrolled patients had to be already taking Fabrazyme for a year and on a stable dose for the last six months and will be randomized to one of the two medications. The trial is recruiting participants in various countries.

The open-label BRIGHT trial (NCT03180840) is another switchover study for patients who have been taking either Frabrazyme or Replagal for three years. It will switch them to 2 mg/kg of PRX-102 given once a month for one year. The trial is recruiting Fabry disease patients in the U.S., Canada, and Europe, including the U.K.

All three Phase 3 clinical trials are planned to end in 2019.

More details

PRX-102 was granted orphan drug designation by the European Commission in December 2017. In 2018, the U.S. Food and Drug Administration granted fast-track designation to PRX-102, a move that will speed up the development and review process of the drug.

In October 2017, Protalix licensed PRX-102 to Italy-based Chiesi Group for all markets outside the U.S.

AVR-RD-01 (Clinical Trials*)

AVR-RD-01 in clinical trials

AVR-RD-01 is currently being tested in two separate clinical trials that are still recruiting patients.

The first (NCT02800070) is a Phase 1 study in Canada aimed at determining whether AVR-RD-01 can safely increase alpha-galactosidase A levels in Farby patients. A six-month follow-up of the first patient to receive this therapy showed consistent and normal levels of alpha-galactosidase A starting at 45 days after treatment with no negative side effects. The study’s enrollment is estimated at six participants.

The second trial (NCT03454893) is a multinational Phase 1/2 study assessing the effectiveness and safety of AVR-RD-01 in patients with Fabry disease who have not received any other treatments. It is being conducted in Australia with the first results expected in 2020. The preparation, treatment, and initial follow-up process is expected to take about one year, after which patients will be monitored regularly. Enrollment is estimated at 12 participants.

Further information

Enzyme replacement therapy is the current standard of care for Fabry disease, requiring lifelong weekly infusions. AVR-RD-01 offers a potentially permanent cure for the disease with only one infusion.

Although AVR-RD-01 trials have not reported any side effects yet, gene therapy has some potential risks that can only be revealed in time. Some of these are toxicity, inflammation, and cancer.

Lucerastat (Clinical Trials*)

Lucerastat in clinical trials

Lucerastat has been tested in three Phase 1 clinical trials in healthy volunteers to assess its safety, tolerability, and pharmacokinetics (movement in the body) at various doses. These trials showed that the medication was well-tolerated at all doses and did not cause any serious adverse events.

Lucerastat was also tested in a Phase 1 clinical trial (NCT02930655) in Fabry patients who were being treated with enzyme replacement therapy (ERT). This small, open-label exploratory trial included 10 people who were given oral lucerastat in addition to ERT, and four  who received ERT only. Its results showed that levels of Gb3 and related fats in the blood decreased significantly in the lucerastat group. The medication was also well-tolerated by adults with Fabry disease.

A Phase 3 clinical trial (NCT03425539), called MODIFY, is now assessing the safety and effectiveness of lucerastat (1,000 mg total; taken as two capsules twice daily) against placebo in adults with Fabry disease. Effectiveness at six months will be measured by patient-reported neuropathic pain, gastrointestinal symptoms, and Gb3 levels in the blood. This trial is currently recruiting up to 108 patients at sites across the U.S., Australia, Canada, and Europe; information is available here. Study results are expected in June 2021, when the trial concludes.

Patients who complete MODIFY will have the open of rolling into a Phase 3 long-term, open-label extension study (NCT03737214). Here, all will be given lucerastat for 24 months and then followed after another month. The study will monitor treatment-emergent adverse events, along with physiological measures like changes in Gb3 blood levels. It is expected to conclude in May 2022.

Venglustat (Ibiglustat)

Venglustat in clinical trials

The first Phase 2 clinical trial (NCT02228460) of venglustat was conducted to assess the short-term safety and effects of the treatment in adult men with Fabry disease. It involved 11 patients treated with daily venglustat given by mouth for 26 weeks.

An extension study of the first trial (NCT02489344) is investigating the long-term effects of venglustat, where eight patients receive venglustat for 30 months. The aim of the study is to see whether venglustat decreases Gb3 levels in the blood vessel cells of the skin.

Additional information

The U.S. Food and Drug Administration granted venglustat fast-track designation in 2015 for the treatment of Fabry disease. With this designation from the FDA, venglustat’s clinical development is expected to speed up. Researchers hope that once-daily oral administration of this inhibitor will help prevent the extensive organ damage caused by Fabry disease.