Copper Concentration & Histopathologic Changes in Liver Biopsy in Participants With Wilson Disease Treated With ALXN1840

Recruiting at 34 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alexion Pharmaceuticals, Inc.

Must be taking: Trientine, Penicillamine, Zinc

Disqualifiers: Decompensated cirrhosis, Renal failure, Malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

31 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it mentions that participants must have been on standard treatments like trientine, penicillamine, or zinc for at least a year before joining. It seems likely you will continue these medications during the trial.

What evidence supports the effectiveness of the drug Bis-Choline Tetrathiomolybdate?

Research on choline, a component of Bis-Choline Tetrathiomolybdate, shows it can improve cognitive function in Alzheimer's patients when combined with other treatments. This suggests potential benefits for brain health, although direct evidence for Bis-Choline Tetrathiomolybdate is not available. ^{1 2 3 4 5}

How is the drug Bis-Choline Tetrathiomolybdate different from other treatments?

Bis-Choline Tetrathiomolybdate is unique because it acts as a copper chelator, meaning it binds to copper in the body to prevent its harmful effects, which is particularly useful in conditions like Wilson Disease and certain cancers. This drug may have a lower risk of causing neurological side effects compared to traditional treatments for Wilson Disease. ^{6 7 8 9 10}

What is the purpose of this trial?

This trial is testing a new medication called ALXN1840 to help reduce liver copper levels in adults with Wilson Disease who have already been on standard treatments for a significant period. The medication works by binding to excess copper and helping the body remove it.

Research Team

Eugene S. Swenson, MD, PhD

Principal Investigator

Alexion Pharmaceuticals, Inc.

Eligibility Criteria

Inclusion Criteria

Diagnosis of WD by Leipzig Criteria ≥ 4 or by historical test results.

Continuous treatment for WD with penicillamine, trientine or zinc for at least 1 year prior to screening.

Capable of giving signed informed consent.

Exclusion Criteria

Decompensated cirrhosis or Model for End Stage Liver Disease score > 13.

Modified Nazer score > 7.

Alanine aminotransferase > 2 × upper limit of normal.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ALXN1840 for 48 weeks to evaluate the change in liver copper concentration and other histopathologic changes

48 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants may continue treatment with ALXN1840 for an additional 48 weeks to evaluate long-term efficacy and safety

48 weeks

Treatment Details

Interventions

• Bis-Choline Tetrathiomolybdate

Participant Groups

Group I: ALXN1840 Experimental Treatment 1 Intervention

Participants will receive ALXN1840.

Who Is Running the Clinical Trial?

Alexion Pharmaceuticals, Inc.

Lead Sponsor

Trials

267

Recruited

141,000+

Dr. Alberto R. Martinez

Alexion Pharmaceuticals, Inc.

Chief Medical Officer since 2010

MD from University of Sao Paulo

Marc Dunoyer

Alexion Pharmaceuticals, Inc.

Chief Executive Officer since 2021

PhD in Molecular Biology

Alexion

Lead Sponsor

Trials

247

Recruited

38,600+

Marc Dunoyer

Alexion

Chief Executive Officer since 2021

PhD in Molecular Biology, University of Brussels

Christophe Hotermans

Alexion

Chief Medical Officer since 2021

MD, University of Leuven

Alexion Pharmaceuticals

Lead Sponsor

Trials

231

Recruited

36,700+

Marc Dunoyer

Alexion Pharmaceuticals

Chief Executive Officer since 2021

B.A. in Psychology from the University of New Hampshire

Christophe Hotermans

Alexion Pharmaceuticals

Chief Medical Officer since 2023

MD

Findings from Research

Tetrahydroaminoacridine (THA) combined with highly concentrated lecithin showed promising improvements in cognition and functional autonomy in Alzheimer's patients, as measured by the Mini Mental State and Rapid Disability Rating Scale-2.

Current studies are underway to further evaluate the efficacy of this combination treatment through double-blind cross-over trials, indicating a structured approach to testing new therapies for Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress report on the Canadian Multicentre Trial of tetrahydroaminoacridine with lecithin in Alzheimer's disease. Gauthier, S., Bouchard, R., Bacher, Y., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Increasing dietary choline attenuates spatial memory deficits resulting from exposure to the chemotherapeutic agents cyclophosphamide and doxorubicin. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

The ASCOMALVA (Association between the Cholinesterase Inhibitor Donepezil and the Cholinergic Precursor Choline Alphoscerate in Alzheimer's Disease) Trial: interim results after two years of treatment. [2018]

3. Netherlands pubmed.ncbi.nlm.nih.gov

The ASCOMALVA trial: association between the cholinesterase inhibitor donepezil and the cholinergic precursor choline alphoscerate in Alzheimer's disease with cerebrovascular injury: interim results. [2018]

4. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Analysis of choline alfoscerate effectiveness in chronic ocular ischemic syndrome]. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Progress report on the Canadian Multicentre Trial of tetrahydroaminoacridine with lecithin in Alzheimer's disease. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Copper binding by tetrathiomolybdate attenuates angiogenesis and tumor cell proliferation through the inhibition of superoxide dismutase 1. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Inhibition of the growth of squamous cell carcinoma by tetrathiomolybdate-induced copper suppression in a murine model. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Copper chelation in cancer therapy using tetrathiomolybdate: an evolving paradigm. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of tetrathiomolybdate on copper metabolism in healthy volunteers and in patients with Wilson disease. [2023]

10. Germany pubmed.ncbi.nlm.nih.gov

Neuroprotective effects of ammonium tetrathiomolybdate, a slow-release sulfide donor, in a rodent model of regional stroke. [2021]