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

• ClinicalTrials.gov Identifier: NCT04537377
• Recruitment Status: Recruiting
• First Posted: September 3, 2020
• Last Update Posted: November 7, 2023
• Sponsor: Vivet Therapeutics SAS
• Information provided by (Responsible Party): Vivet Therapeutics SAS

Tracking Information

• First Submitted Date: August 19, 2020
• First Posted Date: September 3, 2020
• Last Update Posted Date: November 7, 2023
• Actual Study Start Date: September 3, 2021
• Estimated Primary Completion Date: March 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 22, 2020)

Safety and tolerability profile (including treatment-emergent adverse events (TEAE)) [ Time Frame: at 1-Year post treatment ]

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.

Original Primary Outcome Measures (submitted: August 28, 2020)

Safety and tolerability profile (including treatment-emergent adverse events (TEAE) [ Time Frame: at 1-Year post treatment ]

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.

Current Secondary Outcome Measures (submitted: November 22, 2020)

• Free serum Cu [ Time Frame: at 1-Year post treatment ]
  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.
• Total serum Cu [ Time Frame: at 1-Year post treatment ]
  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.
• 24-hour urinary Cu [ Time Frame: at 1-Year post treatment ]
  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.
• Serum ceruloplasmin activity (enzymatic assay) [ Time Frame: at 1-Year post treatment ]
  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.
• VTX-801 Responder status [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: August 28, 2020)

• Free serum Cu [ Time Frame: at 1-Year post treatment ]
  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.
• Total serum Cu [ Time Frame: at 1-Year post treatment ]
  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.
• 24-hour urinary Cu [ Time Frame: at 1-Year post treatment ]
  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.
• Serum ceruloplasmin activity (enzymatic assay) [ Time Frame: at 1-Year post treatment ]
  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.
• VTX-801 Responder status [ Time Frame: 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.
• Radiocopper-related parameters (blood PK) [ Time Frame: Baseline, Week 12 and Week 36 ]
  Radiocopper concentrations in plasma will be listed and summarized by dose cohort, planned visit and timepoint, using descriptive statistics.
• Radiocopper-related parameters (fecal excretion) [ Time Frame: Baseline, Week 12 and Week 36 ]
  Fecal radiocopper excretion rate will be summarized across each of the 24 hour collection periods (i.e. 24h, 48h and 72h), by dose cohort and planned visit, using descriptive statistics.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase I/II Study of VTX-801 in Adult Patients With Wilson's Disease
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description:

Dose escalation study

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: 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.

Study Arms

Experimental: VTX-801

Intervention: Genetic: VTX-801

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 28, 2020): 16
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2029
• Estimated Primary Completion Date: March 2025 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Sonia Valero; +33 1 83 81 17 10; info@vivet-therapeutics.com

• Listed Location Countries: Denmark, Germany, United Kingdom, United States

Administrative Information

• NCT Number: NCT04537377
• Other Study ID Numbers: VTX-801_CLN_001; 2020-000963-22 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Vivet Therapeutics SAS
• Original Responsible Party: Same as current
• Current Study Sponsor: Vivet Therapeutics SAS
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Vivet Therapeutics SAS
• Verification Date: November 2023