E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Wilson’s Disease is a rare genetic disorder. It causes excess copper to build up in the body, particularly in the liver and brain. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047988 |
E.1.2 | Term | Wilson's disease |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Assessing, for up to 5 years, the safety and tolerability of single ascending doses of VTX-801 administered intravenously (IV) to adult patients with Wilson’s Disease prior to and following background WD therapy withdrawal. |
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E.2.2 | Secondary objectives of the trial |
•Exploring VTX-801 pharmacodynamics and efficacy •Assessing humoral and cellular immune responses to VTX-801 •Providing data to support VTX-801 dose level selection |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female aged 18-65 years old (inclusive) 2. Confirmed diagnosis of WD 3. Treated for WD according to international recommendations with no current evidence for inadequate treatment (EASL, 2012; Roberts et al, 2008) 4. 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 including 24-hour urinary copper, free serum copper such as NCC or CuEXC (when available), as well as liver enzymes, hemoglobin, and white blood cell count |
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E.4 | Principal exclusion criteria |
1. ALT level ≥ 2 x ULN that is not readily explained by extrinsic factors (e.g., strenuous exercise, medication use) 2. Total bilirubin > 1.5 x ULN in the absence of proven Gilbert's syndrome; in case of Gilbert's syndrome, direct bilirubin > ULN 3. Platelet count < 120.000 / µL 4. Any signs of liver cirrhosis decompensation, including gastrointestinal bleed within 6 months (24 weeks) prior to screening/enrolment visit 5. Patient has moderate or severe renal impairment or patient has nephritis or nephrotic syndrome 6. Any history or current evidence of HIV-1, HIV-2, HTLV 1, or HTLV-2 infection 7. Any history or current evidence of hepatitis B infection 8. Any history of hepatitis C infection, unless previous viral RNA assays in two samples, collected at least 6 months apart, are negative 9. Positive QuantiFERON®-TB Gold tuberculosis test result 10. Any concomitant disorder/condition - including hepatic disorders - or treatment possibly interfering with the conduct or evaluation of the study, according to the Investigator 11. Pregnancy or breastfeeding 12. Body Mass Index ≥ 35 kg/m2 |
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E.5 End points |
E.5.1 | Primary end point(s) |
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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The safety of the study intervention will be assessed through the recording, reporting and analyzing of baseline medical conditions, AEs, general physical examination, laboratory tests, and vital signs data.
End points will be assessed over the course of the study from baseline to Month 60. All SAEs and VTX-801-related AEs linked to copper deficiency and WD deterioration.
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E.5.2 | Secondary end point(s) |
1. Free serum Cu 2. Total serum Cu 3. 24-hour urinary Cu 4. Serum ceruloplasmin activity (enzymatic assay) 5. VTX-801 Responder status 6. Immune response to VTX-801
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Serum / urinary copper and ceruloplasmin activity will be assessed over the course of the study from baseline to Month 60.
The Responder status will be assessd at Week 12 and Week 36 following an IV administration.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United Kingdom |
United States |
Denmark |
Germany |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 12 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 12 |