Copper balance in healthy participants administered ALXN1840
Research type
Research Study
Full title
A Phase 1, Open-label Study to Assess Copper Balance in Healthy Participants Following Administration of ALXN1840
IRAS ID
279254
Contact name
Ulrike Lorch
Contact email
Sponsor organisation
Alexion Pharmaceuticals, Inc.
Eudract number
2019-003010-14
Clinicaltrials.gov Identifier
Duration of Study in the UK
0 years, 5 months, 12 days
Research summary
We are conducting a clinical trial with the investigational drug bis-choline tetrathiomolybdate (ALXN1840). This is being developed by Alexion Pharmaceuticals, Inc. for the treatment of Wilson’s Disease (WD).
This study will assess changes in copper and molybdenum levels that are seen with repeat dose administration of ALXN1840 over 2 weeks in healthy volunteers. Specifically, whether a net negative copper balance is achieved through fecal elimination of copper. Molybdenum measurements are used as a surrogate measure for ALXN1840.
WD is a genetic disorder that causes abnormally high levels of copper in the body. Increased levels of copper can be toxic and cause damage to the liver, brain and other organs. Currently there are few treatment options available for individuals with WD.
ALXN1840 is a novel first-in-class copper binding agent that rapidly forms virtually irreversible, stable copper-protein complexes. These complexes are then removed by biliary excretion into faeces. It acts directly on the liver to remove excess copper. It is hoped that ALXN1840 will yield greater compliance compared to current treatments, as it is administered once daily rather than in multiple daily doses.
ALXN1840 has previously been evaluated in patients with WD. Results showed that ALXN1840 monotherapy reduced free copper by 72% after 24 weeks compared to baseline. Liver status also improved in the majority of patients. ALXN1840 was generally well tolerated in WD patients and healthy volunteers.
We aim to recruit 17 volunteers to provide 13 evaluable subjects. These subjects will participate in the study in two cohorts lasting 78 days (26 days for screening and 52 days for dosing and follow up). Cohort one will consist of at least 6 and no more than 8 volunteers. The proposed dose is 30mg/day, which may be reduced to 15mg/day based on emerging safety data. The dose has been chosen as it had an acceptable safety profile in previous trials in WD patients.
We will assess safety parameters including physical examination, vital signs, laboratory evaluations, electrocardiogram and monitoring of adverse events.
REC name
London - London Bridge Research Ethics Committee
REC reference
20/LO/0224
Date of REC Opinion
9 Apr 2020
REC opinion
Favourable Opinion