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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 12 December 2020
Main ID:  NCT03539952
Date of registration: 04/05/2018
Prospective Registration: Yes
Primary sponsor: GMP-Orphan SAS
Public title: Trientine Tetrahydrochloride (TETA 4HCL) for the Treatment of Wilson's Disease
Scientific title: CHELATE STUDY: Trientine Tetrahydrochloride (TETA 4HCL) for the Treatment of Wilson's Disease
Date of first enrolment: June 4, 2018
Target sample size: 55
Recruitment status: Active, not recruiting
URL:  https://clinicaltrials.gov/show/NCT03539952
Study type:  Interventional
Study design:  Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).  
Phase:  Phase 3
Countries of recruitment
Belgium Brazil Denmark France Germany Italy Poland Sweden
United Kingdom United States
Contacts
Key inclusion & exclusion criteria

Inclusion Criteria:

1. Patient is able to provide, and has provided, written informed consent

2. Written documentation has been obtained in accordance with the relevant country and
local privacy requirements, where applicable, including: For US sites: Authorization
for Use and Release of Health Research Study Information and for EU sites: Data
Protection Consent

3. Male or female, aged = 18 and = 75 years of age at time of consent

4. Patient has a diagnosis of Wilson's disease, as defined by a prior or current Leipzig
score of = 4

5. Patient's Wilson's disease is clinically stable, in the opinion of the investigator,
and being treated with penicillamine for at least 1 year (52 weeks) prior to the
screening/enrolment visit

6. Patient is on a stable dose and regimen of penicillamine for at least 4 months (16
weeks) prior to the screening/enrolment visit (other prescribed treatments for
Wilson's disease not permitted during this study)

7. No anticipated need that patient will require additional pharmacological therapies
other than study medication, including prescribed zinc therapy, for the management of
copper levels during the study

8. Patient must be willing to maintain stable diet throughout the study, and avoid foods
with high copper content, including the Penicillamine Baseline Period

9. Patient considered suitable to receive therapy with both TETA 4HCl and penicillamine
administered twice a day

10. Negative central laboratory tests for HIV and viral hepatitis (results will be
available after start of run-in period)

11. For female patients of childbearing potential, negative urine pregnancy test (at
screening/enrolment visit and prior to randomization)

12. For females of childbearing potential, use of a reliable form of contraceptive

13. Patient is considered as able to complete study requirements and attend the study
visits, in the opinion of the investigator

Additional inclusion criteria following receipt of Screening laboratory results

14. Patient is adequately controlled and tolerating penicillamine therapy as defined by
fulfilment of all of the following: a. Serum non-ceruloplasmin bound copper (NCC)
level between = 25 and = 150 µg/L* b. 24-hour urinary copper excretion of between =
100 and = 900 µg/24 hours* c. Alanine transaminase (ALT) < 2 times upper limit of
normal* d. No other laboratory or clinical findings that would prevent continuation of
maintenance therapy, in the opinion of the investigator

* Based on results from screening/enrolment visit samples for which can be taken
within ± 7 days of visit. Result should be within the assay limits of quantification
for the sample. The ranges in µmol of copper are 0.40 to 2.38 µmol/L for NCC and 1.59
to 14.29 for 24-hour urinary copper excretion (using division by 63 of value in µg per
Walshe, 2011). In the event that one or more of the above lab values fall outside the
specified range, it can be repeated, including at the Week 4 and Week 8 visits.

Additional inclusion criteria at Week 12 visit (end of Penicillamine Baseline Period)
and prior to randomization

15. Patient is adequately controlled and tolerating penicillamine therapy as defined by
fulfilment of all of the following criteria:

1. Serum non-ceruloplasmin bound copper (NCC) level between = 25 and = 150 µg/L*

2. 24-hour urinary copper excretion of between = 100 and = 900 µg/24 hours**

3. Alanine transaminase (ALT) < 2 times upper limit of normal*

4. No other laboratory or clinical findings that would prevent continuation of
maintenance therapy, in the opinion of the investigator

- Based on lab values from Week 8 visit; ** Based on lab value from Week 4
visit as routinely not performed at Week 8 visit, however can also be based
on value at Week 8 visit if a repeat (unscheduled) urinary copper excretion
was performed at this visit. Result should be within the assay limits of
quantification for the sample. The ranges in µmol of copper are 0.40 to 2.38
µmol/L for NCC and 1.59 to 14.29 for 24-hour urinary copper excretion (using
division by 63 of value in µg per Walshe, 2011). In the event that one or
more of the above lab values fall outside the specified range, it can be
repeated. The repeat value(s) must be available prior to randomization at
Week 12 and, if within specified range, the patient can continue to
randomization. If a patient fails this additional criterion at the end of
the Penicillamine Baseline Period, the patient can return to the start of
the run-in period i.e. Day 1 (but only once). A negative urinary pregnancy
test is also required prior to randomization for females of childbearing
potential.

Exclusion Criteria:

1. Patient is in 'de-coppering' phase of treatment for Wilson's disease, in the opinion
of the investigator

2. Patient evidence of uncontrolled liver disease, including but not limited to:

1. Modified Nazer score of > 4 (result may not be available until after start of run
in period since based on lab results*)

2. decompensated cirrhosis

3. acute hemolytic anemia

4. acute hepatitis

5. hepatic malignancy

6. evidence of acute liver failure

3. Cause of patient's liver disease is due to another condition, in the investigator's
opinion

4. Patient has severe anemia defined as hemoglobin of = 9 g/dL (result will be available
after start of run-in period*)

5. Patient has experienced a gastrointestinal bleed within 6 months (24 weeks) prior to
screening/enrolment visit

6. Patient has renal impairment defined as creatinine clearance of = 30 mL/min (result
may not be available until after start of run-in period*), or patient has nephritis or
nephrotic syndrome, in the opinion of the investigator

7. Patient has neurological disease that prevents swallowing of study medication (e.g.,
requires a nasogastric feeding tube) or requires intensive in-patient medical care

8. Patient is currently taking medication containing trientine for management of Wilson's
disease or has taken it within 4 months (16 weeks) of screening/enrolment visit

9. Patient is currently receiving prescribed zinc therapy for management of Wilson's
disease or has taken it within 4 months (16 weeks) of screening/enrolment visit




Age minimum: 18 Years
Age maximum: 75 Years
Gender: All
Health Condition(s) or Problem(s) studied
Wilson Disease
Intervention(s)
Drug: Penicillamine
Drug: TETA 4HCL
Primary Outcome(s)
Serum NCC concentration [Time Frame: Week 36]
Secondary Outcome(s)
24-hour urinary copper excretion [Time Frame: Week 36]
Clinical Global Impression of Change (CGIC) rating scale [Time Frame: Week 36]
Secondary ID(s)
GMPO-131-002
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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