Wilson Disease
Conditions
Keywords
Hepatolenticular Degeneration, Liver Diseases, Genetic Diseases, Inborn, Congenital, Hereditary, and Neonatal Diseases and Abnormalities, Metabolism, Inborn Errors, Metal Metabolism, Inborn Errors, Metabolic Diseases, Nutritional and Metabolic Diseases
Brief summary
The aim of this study is to inform and improve future clinical trials in Wilson Disease (WD) by better understanding how patients with WD are living with and managing the disease, and by identifying key factors that shape their decisions to participate in clinical research.
Detailed description
This will be a multi-region, multi-site, prescreening study for individuals with WD. Eligible participants must have a clinical history consistent with WD. p.H1069Q or p.R778L mutation are eligible for this study. Participants who do not have a known genotype at enrollment may have their ATP7B gene sequenced while on study, with the approval of the study Medical Monitor. Participants who have previously received liver transplant or gene therapy for WD are excluded. This study will enroll up to approximately 30 participants aged 18 and above, at least 15 of whom must have at least 1 ATP7B p.H1069Q allele. Participants must meet all inclusion criteria and none of the exclusion criteria to be eligible for the study. Each participant will have a blood sample collected to evaluate total serum ceruloplasmin and ceruloplasmin oxidase. For participants who have at least 1 ATP7B allele with the p.H1069Q or p.R778L mutation, chart review will be conducted to collect relevant medical history information, and the participant will be asked to complete a survey to evaluate their interest in and attitudes towards gene editing for WD. Study participants will receive no study mandated therapeutic interventions but will continue to receive standard of care (SOC) for the treatment of WD. The expected duration of participation for each participant is approximately 90 days.
Interventions
None listed
Sponsors
Prime Medicine, Inc.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed Wilson Disease (WD) as determined by the following criteria: 1. An established clinical diagnosis of WD 2. Genetic analysis confirming the presence of biallelic pathogenic variants at ATP7B, at least one of which is EITHER p.H1069Q OR p.R778L OR Participants without a confirmed genetic diagnosis may enroll only with explicit approval from the Medical Monitor
Exclusion criteria
1. Prior history of gene therapy, liver transplantation, hepatocyte (cellular) transplantation, or active listing for liver transplantation 2. For individuals with known ATP7B genotype: individual does not have at least 1 ATP7B allele with either the p.H1069Q or p.R778L mutation. 3. Significant neurological conditions within the prior 12 months which may impact participant safety or participation in the study, including ability to complete study requirements or procedures as outlined in the clinical study protocol. 4. In patients with psychiatric involvement, current or fluctuant clinical instability with new or changing diagnoses or substantial medication regimen changes in the past 12 months that could limit their participation, in the opinion of the Investigator. 5. History of cirrhotic decompensation within the past year. 6. Any other condition that, in the opinion of the Investigator, may compromise the safety or compliance of the participant or would preclude the participant from successful study completion, including participant unable or unwilling to comply with the protocol requirements. 7. Current participation in an investigational study for the treatment of WD. 8. Prior or active malignancy or myeloproliferative disorder (excluding Stage 1 or lower, fully treated/excised malignant and pre-malignant disease of the skin, cervix or colon. Additionally, any other malignant and pre-malignant disease that the Investigator in consultation with the treating oncologist and study Medical Monitor deem has been fully treated/excised for \> 5 years).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gene Editing Interest & Attitudes Survey | From enrollment to the end of study 90 days | This is a survey created by Prime Medicine. Survey answers are reported on both a scale and in open-ended response; the purpose of the survey is to better understand the patient's disease experience, current treatment and adherence, copper in diet and lifestyle, and gauge interest in a gene editing clinical study. No calculations with score values will be conducted. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Distribution of serum ceruloplasmin levels | From enrollment to end of study 90 days | The serum ceruloplasmin concentration will be measured once in all participants at a central laboratory using an oxidase activity-based assay. |
| Mutational landscape among adults with a clinically confirmed diagnosis of WD | From enrollment to end of study 90 days | Targeted sequencing of ATP7B will be performed in participants whose index diagnosis of WD did not require diagnostic genetic testing |
| WD-related health characteristics | From enrollment to the end of study 90 days | Targeted review of the available medical record will be performed and key health characteristics will be recorded and assessed in aggregate. A list of WD-related past medical history will be compiled. This will include all liver, neurological and psychiatric medical history categorized using MedDRA. |
Countries
United States
Outcome results
None listed