ALXN1840 for Wilson's Disease

No longer recruiting at 36 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ALXN1840 (also known as Bis-Choline Tetrathiomolybdate) for individuals with Wilson Disease, a genetic disorder causing excess copper buildup in the body, particularly the liver. Researchers aim to determine if this treatment can reduce liver copper levels over 48 weeks and assess its safety and effectiveness. The trial includes adults who have managed their Wilson Disease with standard treatments like penicillamine, trientine, or zinc for at least a year and do not have severe liver damage. Participants must be able to undergo a liver biopsy and adhere to specific guidelines during the trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in Wilson Disease treatment.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that bis-choline tetrathiomolybdate, also called ALXN1840, is generally safe. Previous studies found that people with Wilson Disease, a condition where copper accumulates in the body, can take this treatment once a day without major side effects. Over six years, data presented at a major liver conference confirmed its safety and effectiveness. This suggests that ALXN1840 could be a promising option for patients, with a low risk of serious side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Wilson Disease?

Unlike the standard treatments for Wilson disease, which often include zinc or chelating agents like penicillamine and trientine, ALXN1840, also known as Bis-Choline Tetrathiomolybdate, offers a novel approach. This investigational drug works by uniquely binding copper and reducing its toxicity in the body, potentially offering a more direct and efficient way to manage copper accumulation compared to existing treatments. Researchers are excited about ALXN1840 because it could provide a more targeted mechanism of action, potentially leading to improved outcomes for patients with Wilson disease.

What evidence suggests that ALXN1840 might be an effective treatment for Wilson Disease?

Research has shown that ALXN1840, also known as bis-choline tetrathiomolybdate, might help treat Wilson Disease by controlling copper levels in the body. In one study, 71% of participants experienced a significant drop in harmful copper levels after 24 weeks of treatment. Another study found that ALXN1840 quickly improved copper balance without causing neurological issues. Participants generally tolerated it well, with most side effects being mild to moderate. These findings suggest that ALXN1840 could be a promising option for managing Wilson Disease by reducing excess copper. ^{1 4 5 6 7}

Who Is on the Research Team?

Eugene S. Swenson, MD, PhD

Principal Investigator

Alexion Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Bis-Choline Tetrathiomolybdate

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8698685/

Analyzing the Therapeutic Efficacy of Bis-Choline- ...

We found that ALXN1840 caused a massive increase of hepatic copper and molybdenum during early stages of therapy. Prolonged treatment with ...

2.

journal-of-hepatology.eu

journal-of-hepatology.eu/article/S0168-8278(25)02483-3/fulltext

Oral bis-choline tetrathiomolybdate rapidly improves ...

In this Letter to the Editor, we provide new evidence directly contradicting that conclusion – data showing that TTM rapidly improves copper ...

3.

monopartx.com

monopartx.com/pipeline/alxn1840

ALXN1840 :: Monopar Therapeutics Inc. (MNPR)

ALXN1840 was generally well-tolerated with most reported adverse events considered mild to moderate, and no neurological worsening upon initiation of treatment ...

4.

journals.lww.com

journals.lww.com/hep/fulltext/2019/02000/bis_choline_tetrathiomolybdate_as_old_drug_in_a.34.aspx

Bis‐choline Tetrathiomolybdate as Old Drug in ...

After 24 weeks of treatment, 71% of patients met the primary endpoint of normalized non‐ceruloplasmin‐bound copper (NCC) (57%) or a 25% or more reduction of NCC ...

5.

rarediseaseadvisor.com

rarediseaseadvisor.com/therapies/alxn1840/

ALXN1840

The potential therapy had a good safety profile, and it decreased plasma non-ceruloplasmin-bound copper levels and disease-related disability.7.

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/28988934/

Bis-choline tetrathiomolybdate in patients with Wilson's ...

In view of its once-daily dose and favourable safety profile, WTX101 could improve the treatment of patients with this debilitating condition.

7.

cdn.clinicaltrials.gov

cdn.clinicaltrials.gov/large-docs/09/NCT04573309/Prot_000.pdf

TITLE PAGE

Ammonium tetrathiomolybdate and bis-choline tetrathiomolybdate nonclinical and clinical data reported to date support the efficacy and safety of ...