A Phase I/II Study of VTX-801 in Adult Patients With Wilson's Disease

Wilson's Disease Clinical Trial

— GATEWAY  

Official title:

A Phase I/II, Multicenter, Non-randomized, Open Label, Adaptive Design, 5-year Follow-up, Single Dose-escalation Study of VTX-801 in Adult Patients With Wilson's Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04537377
• Other study ID #: VTX-801_CLN_001
• Secondary ID: 2020-000963-22
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 3, 2021
• Est. completion date: March 2029

Study information

• Verified date: November 2023
• Source: Vivet Therapeutics SAS
• Contact: Sonia Valero
• Phone: +33 1 83 81 17 10
• Email: info[@]vivet-therapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objectives of this clinical trial are to assess, for up to 5 years, the safety, tolerability and pharmacological activity of a single ascending doses of VTX-801, a gene therapy, administered intravenously (IV) to adult patients with Wilson's Disease prior to and following background WD therapy withdrawal.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: March 2029
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Main Inclusion Criteria:

• Male or female aged 18 and 65 years inclusive
• Confirmed diagnosis of WD
• Treated for WD according to international recommendations with no current evidence for inadequate treatment
• Stable WD for = 1 year, defined as: (i) No significant change in neurologic examination and in status of mood disorder and (ii) Stable laboratory parameters used to assess copper metabolism

Main Exclusion Criteria:

• ALT level = 2 ULN that is not readily explained by extrinsic factors
• Total bilirubin > 1.5 x ULN in the absence of proven Gilbert's syndrome; in case of Gilbert's syndrome, direct bilirubin > ULN
• INR > 1.2
• Any signs of liver cirrhosis decompensation, including gastrointestinal bleed within 6 months (24 weeks) prior to screening/enrollment visit
• Patient has moderate or severe renal impairment defined as eGFR CKD-EPI < 60 mL/min/1.73 m2, or patient has nephritis or nephrotic syndrome
• Any history or current evidence of HIV-1, HIV-2, HTLV 1, or HTLV-2 infection
• Any history or current evidence of hepatitis B infection
• Any history of hepatitis C infection, unless previous viral RNA assays in two samples, collected at least 6 months apart, are negative
• Positive QuantiFERON®-TB Gold tuberculosis test result
• Any concomitant disorder/condition - including hepatic disorders - or treatment possibly interfering with the conduct or evaluation of the study
• Any history of diabetes
• Pregnancy or breastfeeding
• Body Mass Index = 35 kg/m2 Other protocol defined Inclusion/ Exclusion criteria may apply

Related Conditions & MeSH terms

• Wilson's Disease

Intervention

Genetic:
• VTX-801
The investigational medicinal product (VTX-801) is a replication-deficient recombinant adeno-associated viral vector (rAAV) consisting of an AAV liver tropic capsid containing a single-stranded DNA genome carrying a shortened version of the ATP7B gene (ATP7B-minigene). After reconstitution VTX-801 will be administered as a single dose intravenous (IV) administration per patient, at up to 3 different dose levels.

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus
Germany	University Hospital Essen	Essen
Germany	Universitätsklinikum Tübingen (UKT)	Tübingen
United Kingdom	Royal Surrey County Hospital	Guildford	Surrey
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Yale University School of Medecine	New Haven	Connecticut
United States	Advent Health	Orlando	Florida
United States	UC Davis Medical Center	Sacramento	California
United States	Wake Forest School of Medicine	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Vivet Therapeutics SAS

Countries where clinical trial is conducted

United States,  Denmark,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability profile (including treatment-emergent adverse events (TEAE))	AEs will be summarized based on the date of onset for the event. Number of treatment-emergent AEs will be provided by SOC and PT, by dose cohort and overall.	at 1-Year post treatment
Secondary	Free serum Cu	Free serum Cu will be summarized descriptively for all patients by dose cohort and planned visit, for absolute values, changes from baseline and percent change from baseline.	at 1-Year post treatment
Secondary	Total serum Cu	Total serum Cu will be summarized descriptively for all patients by dose cohort and planned visit, for absolute values, changes from baseline and percent change from baseline.	at 1-Year post treatment
Secondary	24-hour urinary Cu	24-hour urinary Cu will be summarized descriptively for all patients by dose cohort and planned visit, for absolute values, changes from baseline and percent change from baseline.	at 1-Year post treatment
Secondary	Serum ceruloplasmin activity (enzymatic assay)	Serum ceruloplasmin will be summarized descriptively for all patients by dose cohort and planned visit, for absolute values, changes from baseline and percent change from baseline.	at 1-Year post treatment
Secondary	VTX-801 Responder status	The number of Responders and Insufficient-Responders will be summarized by dose cohort and planned visit, with response to treatment.	At Week 12 and Week 36