CHELATE STUDY GMPO-131-002
Research type
Research Study
Full title
CHELATE STUDY: Trientine tetrahydrochloride (TETA 4HCl) for the treatment of Wilson’s disease.
IRAS ID
219812
Contact name
Aftab Ala
Contact email
Sponsor organisation
gmp-orphan SA
Eudract number
2016-003876-29
Duration of Study in the UK
2 years, 6 months, 8 days
Research summary
Research Summary
CHELATE STUDY: Trientine tetrahydrocloride (TETA 4 HCl) for the treatment of Wilson’s disease
In this trial a new drug named TETA 4HCl (trientine tetrahydrochloride or TETA 4HCl) will be studied, which is still being clinically investigated, i.e., it has not yet been approved for marketing.
A total of approximately 55 clinical trial participants with Wilson’s disease between the ages of 18 and 75 years will participate.
TETA 4HCl is used to help the body clear itself of excess copper. Taking TETA 4HCl works by binding to copper throughout the body and allowing the body to rid itself of the excess copper through urination.
The active ingredient, trientine, is identical to the active ingredient in marketed products (Syprine® in the USA and Trientine dihydrochloride in the UK).In this trial TETA 4HCl is being developed to be taken in a tablet form which is stable at room temperature.
The efficacy (whether a drug works) of TETA 4HCl will be compared to penicillamine. Penicillamine is the only approved chelator for first line treatment of Wilson's Disease, so there is a need for an effective, well tolerated additional chelator that is also convenient to be used throughout the patient’s lifetime need. TETA 4HCl is being developed as a treatment to demonstrate it is as effective as the existing first line treatment, penicillamine, in stable patients.
The safety of TETA 4HCl compared to penicillamine will also be evaluated.Participation could last up to 108 weeks as each patient will participate in the initial part of the study for approximately 9 months, which is followed by an extension phase of up to 18 months.
Participants will need to attend up to 14 visits for the total duration of the trial.
Summary of Results
: Research title:
CHELATE STUDY: Trientine tetrahydrochloride (TETA 4HCl) for the treatment of Wilson’s disease.The research was funded by Orphalan SA, previously known as GMP-Orphan SA, a French pharmaceutical company active in identifying, developing, and providing access to innovative treatments to patients with rare disease. Orphalan commercializes trientine tetrahydrochloride (TETA 4HCl) product in Europe under the name of Cuprior®. Cuprior® is used in Europe to treat Wilson Disease (WD) patients who cannot take D-penicillamine (DPA).
Before the research commenced, the protocol of this study was reviewed and approved by national and local health and ethics authorities, as required by law.
The study was performed at 15 research sites in 10 countries, 7 in Europe (Poland, Germany, France, Belgium, Denmark, Italy), United Kingdom; 11 sites), United States (1 site) and Brazil (3 sites).
Although WD patients have been treated with chelating agents like DPA and trientine (TETA) for decades, very limited research has been done to directly compare both products. The study was aimed at testing whether TETA 4HCl with DPA were similarly effective in reducing levels of non-bound copper in blood serum.
The WD patients participating in this study were selected to be at least:
- stable on their DPA chelation therapy for at a year or more,
- aged between 18 and 75,
- without evidence of uncontrolled liver disease and
- willingness to comply with all study requirements.The study started with a 12-week DPA baseline period, in which all screened and eligible patients continued their DPA chelation therapy with the same daily dose, split as twice daily. At the end of this period patients were assessed as being stable and adequately controlled by an adjudication committee consisting of three independent WD experts. When confirmed as stable, the patients were randomly assigned to continue with DPA or to switch to TETA 4HCl treatment in a 1:1 ratio over a 24-week post-randomization period (week 12-36). During the 24-week post-randomization period, patients were frequently (every 4 weeks) medically assessed, and laboratory samples taken.
Patients who successfully completed the 24-week post-randomization period were given the opportunity to continue with their allocated treatment for another 24 weeks in an extension period (week 36-60). At week 60, patients on DPA and on TETA 4HCl could either finish the study or continue the extension period up to week 108, with TETA 4HCl treatment only.
During the study the number of patients reporting medical problems were similar for both treatment arms across all treatment periods. The most common problems during the randomisation phase were headaches. These were reported in 5 patients on DPA and 2 patients on TETA 4HCl. Abdominal pain was also reported for 1 patient on TETA4HCl vs. 4 for DPA. The medical issues reported in both treatment arms were mild to moderate and resolved. One patient developed a rash with TETA 4HCl that resolved after stopping therapy.
During the study 8 patients experienced serious medical problems which were all considered unrelated to the study medication, except for one case of leukopenia (a decrease in the disease-fighting cells or leukocytes found in your blood) that was considered and known to be related to DPA. One subject passed away during the study for reasons unrelated to study medication.
The primary objective of the study was the monitoring of the ability of patients to maintain their levels of unbound Copper in their blood. Maintaining a correct copper balance below certain ranges is essential for minimizing the harmful effects of Wilson disease in the longer term, whereas overtreatment could lead to copper depletion which may cause other issues. The enrolled patients were selected to be well controlled for their copper levels when treated with DPA. After the 24-week post randomization period we could conclude that the patients that switched to TETA were equally well treated when put on TETA 4 HCl. Extended treatment, up to 48 weeks also show the same results.
Next to the unbound copper levels, patients were examined for their health with special attention for neurologic signals and liver health. The safety signals in both treatment arms were similar at 24 weeks and 48 weeks after randomization, although a liver enzyme (alanine transaminase) showed some increase in the TETA arm compared to DPA, but was not considered important from a clinical perspective.
These study results will inform doctors that for patients not intolerable to DPA, TETA 4HCl might be an equally suitable alternative to DPA. This is important because long-term treatment with DPA has been associated with significant side effects for patients. The study results have been shared with the medical community through a publication in The Lancet Gastroenterology and Hepatology. Furthermore, the study results have been used for a New Drug Application in the US, for which a Marketing Authorisation was obtained in April 2022. The plan is to launch TETA 4 HCl in the US in the course of first half of 2023 and make it available to patients in the United States under the name CuvriorTM.REC name
London - London Bridge Research Ethics Committee
REC reference
17/LO/0092
Date of REC Opinion
15 Mar 2017
REC opinion
Further Information Favourable Opinion