Clinical trial NCT05917327: Performance and Safety of MEX-CD1 Low-volume Continuous Veno-venous Haemodialysis Medical Device for Copper-extraction in Patients With Wilson's Disease
Official title: MEXWILS - Performance and Safety of MEX-CD1 Low-volume Continuous Veno-venous Haemodialysis Medical Device for Copper-extraction in Patients With Wilson's Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Hepatolenticular Degeneration; Wilson
Keywords: Wilson's Disease
Low-volume continuous veno-venous hemodialysis
Copper
Lead sponsor: Mexbrain
Sponsor class: INDUSTRY
Collaborators: name: Integrated Scientific Services (ISS) AG
First posted: 2023-06-23
Enrollment: 17
Sex: ALL
Minimum age (years): 10
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective, multinational, multicentric, single-arm, open label, pivotal/registration clinical trial.
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to test the MEX-CD1 hemodialysis medical device in patients suffering from Wilson's Disease. The main questions it aims to answer are:

* Does the device work as expected by removing the excess of free copper from the blood?
* Is the device safe when used according to the instructions for use?

Depending on the severity of their symptoms, patients will receive either 5 or 10 treatments on consecutive days with the MEX-CD1 hemodialysis medical device.

Detailed description: This study investigates the performance and safety of the MEX-CD1 hemodialysis device in patients suffering from Wilson's Disease. Wilson's Disease is a rare genetic disease (1'000 to 2'000 patients in France) linked to a problem in copper homeostasis. The direct consequence is a progressive accumulation of copper, first in the liver and then in the whole body with two major implications: (i) at the hepatic level and (ii) at the neurological level.

The disease is globally well known and managed in developed countries. It can present itself in several manners:

An acute decompensation of the disease is possible. This concerns mainly big children or young adults, presenting themselves with an acute hepatic deficiency that may need intensive care and a liver transplant.

In most cases, the clinical picture is one of chronic hepatic and/or neurological disease. Treatment must be adapted to the clinical situation. Two phases can be distinguished:

* A primary treatment phase, whose goal it is to eliminate the excess copper deposited in the body. This phase generally takes 1 to 2 years with chelating treatments;
* A maintenance phase, corresponding to the treatment which will allow the copper balance to be maintained and equilibrated.

This lifelong treatment is to be taken daily (with doses of chelators and/or zinc salts).

Finally, during the maintenance phase, periods of lesser observance or escape phases can be observed, those are responsible for severe aggravation of the liver (fulminant hepatitis) or of neurological symptoms that can lead to death.

The proposed medical device allows, by combining dialysis to a hyper-chelating colloidal dialysate (MEX-CD1) to specifically extract copper from the blood (and particularly the exchangeable copper). All patients enrolled in this study will, depending on the severity of their symptoms, receive 4-hour long treatments with MEX-CD1:

* Patients with moderate liver injury not requiring extracorporeal blood epuration therapies as standard of care: 5 treatments with MEX-CD1 on consecutive days
* Patients requiring extracorporeal blood epuration therapies as standard of care: 10 treatments with MEX-CD1 on consecutive days During the MEX-CD1 treatment, the patient's condition will be closely monitored. Additionally, enrolled patients will have a thorough assessment of their Wilson's Disease at the screening visit and at the last visit. Between the last day of treatment and the last visit, enrolled patients will have two rest days.

Eligibility criteria: Inclusion Criteria:

* Males and females aged between 10 years and 80 years and weighing 30 kg and more
* Established diagnosis of Wilson disease (current Leipzig score ≥ 4). (For patients to whom Leipzig score can't be calculated at time of screening (while waiting for the genetic results), we assume a score of 4 (mutation detected on 2 chromosomes by default) if the two parents are Wilsonian.
* Adequate venous access to allow the setting up of recirculated low-volume continuous veno-venous hemodialysis (dialysis catheter ≥11.5 F, medium blood flow rate 100-200 mL/min) and the collection of blood samples.
* Both the patients already under Standard Of Care (SOC) or not under SOC.
* Patients must present at least one moderate hepatic or Neuropsychiatric symptom(s). (please refer 3.4 for the severity criteria)
* Patient, or parent or guardian in the case of minor, must have been informed about the nature of the clinical investigation, and must have agreed to participate in the clinical investigation, and signed the Informed Consent Form (ICF) prior to participation in any clinical investigation-related activities. Minors under the age of 14 must provide oral consent to participate in the clinical investigation.

Exclusion Criteria:

* Males and females weighing less than 30 kg
* Patients suffering from copper deficiency
* Patients who are unwilling or unable to comply with clinical investigation procedures
* Seafood allergy and prior allergy to one of the MEX-CD1 product components
* Allergy or contraindication to heparin or citrate
* Inadequate venous access
* Participation in another investigation with an investigational drug or another Medical Device (MD) within 30 days preceding, and during the present investigation
* Pregnant or breastfeeding women according to Article 66 of the Regulations (EU) 2017/745 on Medical Devices

Primary outcomes:
measure: Performance of MEX-CD1
timeFrame: 4 hours; from treatment start (0 hours) to treatment end (4 hours)
Secondary outcomes:
measure: Pulse measurement for safety purposes
timeFrame: From the start of the first MEX-CD1 treatment until the last visit, assessed up to 2 weeks.
measure: Temperature measurement for safety purposes
timeFrame: From the start of the first MEX-CD1 treatment until the last visit, assessed up to 2 weeks.
measure: Arterial blood pressure measurement every hour during treatment phase for safety purposes
timeFrame: Once at screening and last visit and every hour during treatment phase, assessed up to 2 weeks.
measure: Weight measurement for Safety purposes
timeFrame: From the start of the first MEX-CD1 treatment until the last visit, assessed up to 2 weeks.
measure: AE recording
timeFrame: From the start of the first MEX-CD1 treatment until the last visit, assessed up to 2 weeks.
measure: Number of participants with abnormal laboratory test results
timeFrame: From the start of the first MEX-CD1 treatment until the last visit, assessed up to 2 weeks.
measure: Responder rate
timeFrame: 4 hours; from treatment start (0 hours) to treatment end (4 hours)
measure: Copper kinetics
timeFrame: 4 hours; from treatment start (0 hours) to treatment end (4 hours)
measure: Changes in copper concentration between screening visit and last visit
timeFrame: Between the screening visit and the last visit, assessed up to 2 weeks.
measure: Hepatic function evolution
timeFrame: Between the screening visit and the last visit, assessed up to 2 weeks.
measure: Neurologic and psychiatric status evolution
timeFrame: Between the screening visit and the last visit, assessed up to 2 weeks.
measure: Wilson's Disease evolution
timeFrame: Between the screening visit and the last visit, assessed up to 2 weeks.
Other outcomes:
measure: non-ceruloplasmin-bound copper elimination and restoration during the treatment
timeFrame: 4 hours; from treatment start (0 hours) to treatment end (4 hours)
measure: non-ceruloplasmin-bound copper restoration between treatment
timeFrame: End of treatment session (n) to beginning of next treatment session (n+1), assessed up to 2 weeks.
Locations:
city: Bron
country: France
facility: Hôpital Femme Mère Enfant, Service des urgences et la réanimation pédiatriques
state: Rhône-Alpes
city: Lyon
country: France
facility: Hôpital Croix Rousse, Service d'hépatologie et gastroentérologie
state: Rhône-Alpes
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron, Unitat de Trasplantament Hepàtic Pediàtric
state: Catalonia
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona, Liver ICU
state: Catalonia
Study officials:
affiliation: Hôpital Femme Mère Enfant, Service Hépato-Gastroentérologie et Nutrition Pédiatrique
name: Edouardo COUCHONNAL-BEDOYA
role: PRINCIPAL_INVESTIGATOR
References: