Cu & Mo balance in patients with Wilson disease treated with ALXN1840

  • Research type

    Research Study

  • Full title

    A Phase 2, open-label study to assess copper and molybdenum balance in participants with Wilson disease treated with ALXN1840

  • IRAS ID

    281823

  • Contact name

    Ulrike Lorch

  • Contact email

    u.lorch@richmondpharmacology.com

  • Sponsor organisation

    Alexion Pharmaceuticals, Inc.

  • Eudract number

    2020-001104-41

  • Clinicaltrials.gov Identifier

    119006, Investigational New Drug (IND)

  • Duration of Study in the UK

    0 years, 11 months, 30 days

  • Research summary

    We are conducting a trial with the investigational drug bis-choline tetrathiomolybdate (ALXN1840), being developed by Alexion Pharmaceuticals, Inc. for the treatment of Wilson’s Disease (WD).

    WD is a genetic disorder causing abnormally high copper levels in the body. Increased copper levels can be toxic and cause damage to the liver, brain and other organs. Currently there are few treatment options available for individuals with WD.

    This study assesses changes in copper and molybdenum levels seen with repeat and escalating doses of ALXN1840 over 39 days in patients with WD. Specifically, whether a net negative copper balance occurs through faecal elimination of copper. Molybdenum measurements are used as a surrogate measure for ALXN1840.
    ALXN1840 is a novel, first-in-class, protein binding agent that rapidly forms virtually irreversible, stable copper-protein complexes. These complexes are then removed by biliary excretion into faeces. It also acts directly on the liver to remove excess copper. We believe 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 mean serum 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.

    Up to ten patients will participate in the study in two cohorts lasting 96 days ;34 days for screening and 62 days for admission, dosing and follow up. The proposed starting dose is 15mg/day for 28 days, increased to 30mg/day for 11 days.

    These doses have been chosen as they have shown acceptable safety profiles in previous trials in WD patients. Cohort one of this study will contain non-naïve patients who have tolerated ALXN1840 successfully for over 28 days in a previous study.

    We will assess safety parameters including physical examination, vital signs, laboratory evaluations, electrocardiogram and monitor adverse events.

  • REC name

    London - London Bridge Research Ethics Committee

  • REC reference

    20/LO/0588

  • Date of REC Opinion

    22 Jul 2020

  • REC opinion

    Further Information Favourable Opinion