UX701 Gene Therapy for Wilson Disease

Recruiting at 24 trial locations

Overseen By Patients Contact: Trial Recruitment

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Ultragenyx Pharmaceutical Inc

Must be taking: Copper chelators, Zinc

Disqualifiers: Liver transplant, Advanced liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

82 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new gene therapy called UX701 for individuals with Wilson disease, a condition that prevents the body from properly removing copper, leading to dangerous copper buildup. The study aims to determine the safety of UX701 and its effectiveness in controlling copper levels. Participants will receive different doses of UX701 through a single IV infusion, while some will continue their current treatments before trying UX701. Individuals with a confirmed diagnosis of Wilson disease who have been on stable copper-related treatment for at least two months may be suitable for this trial. As a Phase 1/Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to be among the first to benefit from this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications. However, it requires that your Wilson disease treatment with copper chelator or zinc therapy has been stable for at least 6 months, with no changes in medication or dose during that time.

Is there any evidence suggesting that UX701 is likely to be safe for humans?

Research shows that UX701, a potential gene therapy for Wilson disease, is still undergoing safety testing in humans. Although direct safety data for humans is not yet available, the trial is in its early stages, with a primary focus on safety. During these initial phases, researchers closely monitor any side effects and how well participants tolerate the treatment. Previous studies in animals, such as mice with Wilson disease, have suggested that UX701 might be safe, but animal results do not always predict human outcomes. Currently, there is no solid evidence of harmful effects in humans, but ongoing studies will provide more information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Wilson disease?

Researchers are excited about UX701 for Wilson Disease because it represents a cutting-edge approach to treatment with its use of gene therapy. Unlike traditional treatments that often involve ongoing medication to manage copper levels in the body, UX701 targets the root cause by introducing a functional copy of the ATP7B gene, which is defective in Wilson Disease patients. This potentially offers a one-time treatment option through a peripheral IV infusion, which could significantly reduce the burden of daily medication and long-term side effects. With the possibility of addressing the disease at a genetic level, UX701 aims to provide a more lasting and comprehensive solution compared to the current standard of care.

What evidence suggests that this trial's treatments could be effective for Wilson disease?

Research has shown that UX701 could be a promising treatment for Wilson disease, a condition where the body cannot manage copper properly, leading to organ damage. UX701 is a gene therapy designed to provide a working version of the ATP7B gene, which helps control copper levels. Early studies have demonstrated improvements in how patients process copper, suggesting the treatment might effectively address the root problem. This trial will evaluate UX701 at various dose levels. Some participants will receive a single, peripheral IV infusion at different doses, while others will continue their standard care before receiving UX701. The therapy uses a harmless virus to deliver the gene directly, aiming for stable and long-lasting effects. Although initial results are encouraging, further research is needed to confirm its full effectiveness. ^{1 2 3 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Ultragenyx Pharmaceutical Inc

Are You a Good Fit for This Trial?

This trial is for individuals with confirmed Wilson disease who have been avoiding high copper foods and taking copper chelators or zinc therapy consistently for at least 6 months. They should be able to follow the study's procedures, including blood and urine tests. People with significant liver inflammation, pre-existing antibodies to AAV9 capsid, severe neurological issues, a MELD score over 13, or history of liver transplant cannot participate.

Inclusion Criteria

I have been on a stable Wilson disease treatment for at least 6 months.

I am willing and able to follow all study requirements, including frequent tests and long-term follow-up.

I have been diagnosed with Wilson disease.

Exclusion Criteria

Participation in another gene transfer study or use of another gene transfer product before or during study participation

Your MELD score is higher than 13.

History of copper chelator or zinc therapy noncompliance, in the Investigator's judgment, within 6 months prior to Screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stage 1: Safety and Dose-Finding

Nonrandomized, open-label safety and dose-finding stage to evaluate the safety and efficacy of 3 dose levels of UX701

Varies

Stage 2: Randomized Treatment

Randomized, double-blind, placebo-controlled stage to evaluate the safety and efficacy of UX701 using the dose selected in Stage 1

Varies

Stage 3: Long-term Follow-up

Evaluation of long-term safety, efficacy, and clinical benefit of UX701. All participants will be followed for at least 5 years from the time of UX701 administration

5 years

What Are the Treatments Tested in This Trial?

Interventions

• UX701

Trial Overview The study is testing UX701 gene transfer against a placebo in patients with Wilson disease. It aims to assess the safety of single IV doses of UX701 and its effectiveness on regulating copper levels in the body. The best dose will be chosen based on safety and efficacy data collected during the trial.

How Is the Trial Designed?

Group I: Stage 2: UX701 at Selected Dose Experimental Treatment 1 Intervention

Participants randomized to UX701 receive a single, peripheral IV infusion of UX701 at the selected dose.

Group II: Stage 2: Standard of Care (SOC) to UX701 Experimental Treatment 2 Interventions

Participants randomized to SOC will continue their baseline SOC medications for 52 weeks, followed by a single, peripheral IV infusion of UX701 at the selected dose. Following UX701 administration, participants will be evaluated for modification of their SOC medications.

Group III: Stage 1: UX701 Dose Level 4 Experimental Treatment 1 Intervention

Participants receive a single, peripheral IV infusion of UX701 at dose level 4.

Group IV: Stage 1: UX701 Dose Level 3 Experimental Treatment 1 Intervention

Participants receive a single, peripheral IV infusion of UX701 at dose level 3.

Group V: Stage 1: UX701 Dose Level 2 Experimental Treatment 1 Intervention

Participants receive a single, peripheral IV infusion of UX701 at dose level 2.

Group VI: Stage 1: UX701 Dose Level 1 Experimental Treatment 1 Intervention

Participants receive a single, peripheral intravenous (IV) infusion of UX701 at dose level 1.

Who Is Running the Clinical Trial?

Ultragenyx Pharmaceutical Inc

Lead Sponsor

Trials

94

Recruited

104,000+

Dr. Emil D. Kakkis

Ultragenyx Pharmaceutical Inc

Chief Executive Officer since 2010

MD/PhD in Biological Chemistry from UCLA

Dr. Eric Crombez

Ultragenyx Pharmaceutical Inc

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04884815

NCT04884815 | A Phase 1/2/3 Study of UX701 Gene ... The primary objectives of this study are to evaluate the safety of single IV doses of UX701 in patients with Wilson disease.

2. ultragenyx.com ultragenyx.com/our-research/pipeline/ux701-for-wilson-disease/

UX701 for Wilson Disease UX701 (rivunatpagene miziparvovec) is an investigational AAV9 gene therapy designed to deliver stable expression of the ATP7B copper transporter following a ...

3. withpower.com withpower.com/trial/phase-3-hepatolenticular-degeneration-8-2021-a44b8

UX701 Gene Therapy for Wilson Disease UX701 is a gene therapy that uses a viral vector to deliver a modified version of the ATP7B gene, which helps correct copper metabolism in Wilson Disease.

4. ir.ultragenyx.com ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-provides-update-stage-1-cohorts-pivotal-phase-123

Ultragenyx Provides Update on Stage 1 Cohorts in Pivotal ... The Phase 1/2/3 Cyprus 2+ study of its UX701 gene therapy has demonstrated meaningful clinical activity as well as improvements in copper metabolism in Stage 1.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0168365925009186

Hepatocyte-targeted lipid nanoparticle for full-length ... This study establishes a translatable WD gene therapy platform using a hepatocyte-targeted, low immunoreactivity LNP for full-length ATP7B mRNA ...

6. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-and-effects-of-ux701-gene-therapy-for-adults-with-wilson-disease/

Study on the Safety and Effects of UX701 Gene Therapy for ... This clinical trial studies the safety and effects of UX701, a gene therapy, in treating adults with Wilson disease, a genetic disorder affecting copper ...

7. clinicaltrials.ucbraid.org clinicaltrials.ucbraid.org/trial/NCT04884815

Phase 1/2/3 Study of UX701 Gene Therapy in Adults With ... The primary objectives of this study are to evaluate the safety of single IV doses of UX701 in patients with Wilson disease, to select the ...