A Clinical Study on the Treatment of Wilson Disease With ATP7B mRNA/LNP (DSL101)

This study adopted an open, single-arm, non-randomized, dose-escalation research design, aiming to evaluate the safety, tolerability, preliminary efficacy, pharmacokinetic and immunogenicity characteristics of single and multiple intravenous infusions of DSL101 in patients with Wilson's disease.

Study Overview

• Status: Recruiting
• Conditions: Wilsons Disease
• Intervention / Treatment: Drug: Group 1: DSL101 Low dose; Drug: Group 2: DSL101 Medium dose; Drug: Group 3: DSL101 High dose

Detailed Description

In this study, low, medium and high dose groups were preset, the low dose group was accelerated titration group, and the medium and high dose groups used the traditional "3+3" method combined with Sentinel method for dose escalation.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230000
      • Recruiting
      • The First Affiliated Hospital of Anhui Medical University
      • Contact: Huan Zhou; Phone Number: 0551-62922017; Email: zhouhuanbest@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years old, gender not limited.
2. Meet the diagnostic criteria f Wilson's Disease in "Guidelines for Diagnosis and Treatment of Wilson's Disease (2022 Edition)", with a Leipzig score ≥4, at least one year between diagnosis and screening; ceruloplasmin level <0.1g/L.
3. Patinets with Wilson's disease confirmed by laboratory tests to have double-chromosome mutations in the ATP7B gene.
4. Low copper diet for at least six months befoer screening and willing to continue low copper diet during study.
5. Fertile subjects agreed to adopt reliable contrraceptive methods from the screening until 6 months after the last administration.
6. The subjects are atable patients with WD who have been trasted for at least six months without drug or dose changes for at least 6 momths at the time of screening , and have continuously used standard treatments [SOC, such as D-penicillamine, sodiu dihydroxypropane sulfonate, dimercaptosuccinic acid, trientine, and zinc preparations (zinc acetate, zinc gluconate, zinc sulfate)] for at least 6 months screening, and allowed subjects to continue with their prior SOC treatment.

7. The subject's condition was fully controlled after treatment, and its definition must meet all of the following conditions:

   1. Serum NCC level ≥ 25 μg/L and ≤ 150 μg/L;
   2. Urinary copper ≥100 μg/24 hours and ≤900 μg/24 hours;;
   3. ALT < 2 times of upper limit of normal value (ULN);
   4. The investigator believes that no other laboratory values or clinical symptoms would stop current standard therapy;
8. Subjects with good compliance, who can understand and cooperate to complete the requirements of protocol.
9. The subjects voluntarily participated in the trial and signed the informed consent form.

Exclusion Criteria:

1. Allergy or intolerance to the investigational drug.
2. Wilson's disease is accompanied by severe complications such as neurological and mental disorders.
3. History of liver transplantation.
4. Other liver-related diseases and clinical symptoms that can cause liver injury, such as acute and chronic hepatitis, alcoholic liver disease, autoimmune liver disease, drug-induced liver injury, liver cirrhosis, liver ascites, esophageal varices, hepatic encephalopathy, hepatorenal syndrome, liver failure, liver malignancy, etc.; Subjects with Model for end-stage liver disease score (MELD)>13.
5. Other diseases that can cause hemolysis or anemia, such as erythrocytosis, Mediterranean anemia, hemolytic anemia, various causes of infection, large area burns, etc.
6. Other diseases that can cause dysfunction of the nervous system, such as Parkinson's disease, Parkinson syndrome, various causes of dystonia, chorea, primary tremor, epilepsy, mental abnormalities (such as history of schizophrenia or suicide attempts), etc.

7. Screening period laboratory examination indicators:

   1. Hemoglobin < 90 g/L;
   2. Creatinine clearance ≤30 mL/min, or glomerular filtration rate <45 mL/min/1.73 m²;
   3. TBil≥2×ULN，ALP/TBil<4，AST/ALT>2.2;
   4. Platelets < 70 ×10^9/L;
   5. Neutrophils < 1.0 × 10^9 /L.
8. History of gastrointestinal bleeding within six months before screening.
9. Subjects with history of moderate to severe depression, suicidal thoughts or behaviors and serious psychiatric within 6 months prior to screening.
10. Subjects who have uncontrolled diseases of thr heart, liver, kidneys, endocrine system, digestive tract, metabolism, blood, or malignant tumors.
11. Active hepatitis B virus infection or active hepatitis C virus infection, or human immunodeficiency virus antibody positive.
12. Pregnant women or lactating women.
13. Subjects who have participated other clinical trial within 3 months prior to screening or plan to participate during the clinical trial.
14. Investigators evaluate other subjects who are not suitable to participate in this clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: DSL101; Subjects will receive intravenous infusions of DSL101 once every four weeks.	Drug: Group 1: DSL101 Low dose; Subjects will receive intravenous infusions of DSL101 once every four weeks.
Experimental: Group 2: DSL101; Subjects will receive intravenous infusions of DSL101 once every four weeks.	Drug: Group 2: DSL101 Medium dose; Subjects will receive intravenous infusions of DSL101 once every four weeks.
Experimental: Group 3: DSL101; Subjects will receive intravenous infusions of DSL101 once every four weeks.	Drug: Group 3: DSL101 High dose; Subjects will receive intravenous infusions of DSL101 once every four weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of adverse events and serious adverse events	up to 56 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK: Average steady-state concentration (Cav,ss)		up to week 6
Change in 24 hour urine copper		up to week 20
Change in sum total cpper [ serum copper bound by ceruloplasmin (NCC) ]		up to week 20
Change in serum free copper		up to week 20
Change from baseline in serum ceruloplasmin		up to week20
Change in serum iron concentration and serum ferritin concentration		up to week 20
Clinical laboratory test: Biochemistry - alanine aminotransferase (ALT)	The physician will judge whether an abnormality is clinically significant	up to week 20
Change in the total score of the Unified Wilson Disease Rating Scale (UWDRS )	The UWDRS scale consists of three parts: neurological, liver function and mental symptom. The higher scores mean a worse outcome.	up to week 20
Number of subjects and percentage decrease in standard of care (SOC) medication euse within 20 weeks of administration		up to week 20
Change from baseline in seurm ceruloplasmin activity		up to week20
Clinical laboratory test: Biochemistry - aspartate aminotransferase (AST)		up to week 20
Clinical laboratory test: Biochemistry - alkaline phosphatase (ALP)		up to week 20
Clinical laboratory test: Biochemistry - gamma-glutamyltransferase (γ-GGT)		up to week 20
Clinical laboratory test: Biochemistry - total bilirubin (TBIL)		up to week 20

Other Outcome Measures

Outcome Measure	Time Frame
PK: Cmax	up to week 6
PK: Time to reach peak plasma concentration (Tmax)	up to week 6
PK: Area under the plasma concentration-time curve (AUC)	up to week 6
Immunogenicity: Positive rate of anti-drug antibody (ADA)	up to week 20

Collaborators and Investigators

• Sponsor: DSciLab Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 31, 2025
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2029

Study Registration Dates

• First Submitted: September 25, 2025
• First Submitted That Met QC Criteria: November 16, 2025
• First Posted (Estimated): November 21, 2025

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: January 15, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Digestive System Diseases; Neurodegenerative Diseases; Liver Diseases; Movement Disorders; Heredodegenerative Disorders, Nervous System; Basal Ganglia Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Metal Metabolism, Inborn Errors; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Hepatolenticular Degeneration
• Other Study ID Numbers: DSLIIT101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The study is in early stages and will consider releasing related information when sufficient data is available in subjects.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No