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

Study Overview
=================
Brief 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.

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

Conditions
-----------------
Wilson's Disease

Intervention / Treatment
-----------------
* Genetic: VTX-801


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: Dose escalation study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VTX-801<br> | Genetic: VTX-801<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 |