Wilson's Disease
Conditions
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.
Interventions
GENETICVTX-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.
Sponsors
Vivet Therapeutics SAS
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose escalation study
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability Profile (Including Treatment-emergent Adverse Events (TEAE)) - Number of Participants | through primary completion visit, an average of 1 year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Free Serum Cu | through primary completion visit, an average of 1 year | Free serum Cu will be summarized descriptively for all patients by dose cohort and planned visit, for absolute values and changes from baseline. |
| Total Serum Cu | through primary completion visit, an average of 1 year | Total serum Cu will be summarized descriptively for all patients by dose cohort and planned visit, for absolute values and changes from baseline. |
| 24-hour Urinary Cu | through primary completion visit, an average of 1 year | 24-hour urinary Cu will be summarized descriptively for all patients by dose cohort and planned visit, for absolute values and changes from baseline. |
| Serum Ceruloplasmin Activity (Enzymatic Assay) | through primary completion visit, an average of 1 year | Serum ceruloplasmin will be summarized descriptively for all patients by dose cohort and planned visit, for absolute values and changes from baseline. |
| VTX-801 Responder Status | At Week 12 and Week 36 | The number of Responders and Insufficient-Responders will be summarized by dose cohort and planned visit, with response to treatment. Responder status was assessed using radiocopper blood PK results and other cold copper parameters if needed. |
Countries
Denmark, Germany, United Kingdom, United States
Participant flow
Pre-assignment details
The study was prematurely terminated by the Sponsor for futility reasons, after insufficient pharmacodynamic response in cohorts 1 and 2. No further patient enrollment occurred after this date. The 4 treated patients entered the long-term follow-up (LTFU) up to 5 years post injection, thus 2 sites remain active. An abbreviated CSR was issued including all data until early termination (an average of 1 year). The LTFU results will be provided in a separate addendum at the end of 2029.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 32.0 years STANDARD_DEVIATION 18.38 |
| Alcohol Consumption No | 2 Participants |
| Alcohol Consumption Yes current | 0 Participants |
| Alcohol Consumption Yes former | 0 Participants |
| BMI | 27.6 kg/m^2 STANDARD_DEVIATION 3.83 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 1 Participants |
| Smoking History No | 2 Participants |
| Smoking History Yes | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 |
| other Total, other adverse events | 2 / 2 | 2 / 2 |
| serious Total, serious adverse events | 0 / 2 | 1 / 2 |
Outcome results
None listed