Phase 3, open-label study of ALXN1840 versus standard of care in pediatric participants with Wilson disease

Phase 1

• Conditions: Wilson Disease; MedDRA version: 20.0Level: LLTClassification code 10047988Term: Wilson's diseaseSystem Organ Class: 100000004850; Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]

• Registration Number: EUCTR2021-001015-82-ES
• Lead Sponsor: Alexion Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-08-23
• Last Update Posted: 6 December 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

Participants are eligible to be included in the study only if all of the following criteria apply:
Age
1. Participants must be aged 3 to <18 years at time of signing the informed consent/assent.
Type of Participants and Disease Characteristics
2. Established diagnosis of WD by Leipzig-Score = 4 documented by testing as outlined in the 2012 European Association for the Study of Liver WD Clinical Practice Guidelines (Ferenci, 2003; EASL, 2012). Note: Historical test results for WD, including some or all of the following: presence of KF rings, neurologic symptoms, serum ceruloplasmin below the reference range, Coombs-negative hemolytic anemia, elevated liver or urinary copper, presence of mutations in the ATP7B gene, or other, as considered appropriate, may be used instead to confirm the diagnosis of Wilson disease.
3. Participant's parent/proxy must be willing and able to give written informed consent and the participant must be willing to give written informed assent (if applicable as determined by the central or local Institutional Review Board [IRB]/Institutional [or Independent] Ethics Committee [IEC]). If allowable per local regulations, a participant’s Legally Acceptable Representative (LAR) may provide informed consent if a participant is unable to do so.
4. Adequate venous access to allow collection of required blood samples.
5. Able to swallow intact ALXN1840 tablets or mini-tablets. Participants who require gastrostomy devices for feeding or medications may be enrolled upon agreement by the Medical Monitor.
6. Willing to avoid intake of foods and drinks with high contents of copper throughout the study duration
Sex
7. Female participants of childbearing potential and male participants must follow protocol-specified contraception guidance as described in Section 10.4 of the protocol.
Informed Consent
8. Capable of giving signed informed consent or assent as described in Section 10.1.3 of the protocol, which includes compliance with the requirements and restrictions listed in the informed consent or assent form and in this protocol.
Are the trial subjects under 18? yes
Number of subjects for this age range: 48
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1. Decompensated hepatic cirrhosis.
2. MELD score > 13 (ages 12 to <18) or PELD score > 13 (ages 3 to < 12).
3. Modified Nazer score > 7.
4. Clinically significant gastrointestinal (GI) bleed within past 3 months
5. Alanine aminotransferase (ALT) > 2 × upper limit of normal (ULN) for participants treated for > 28 days with WD therapy (Cohort 1).
6. ALT > 5 × ULN for treatment naïve participants or participants who have been treated for = 28 days (Cohort 2)
7. Marked neurological disease requiring either nasogastric feeding tube or intensive inpatient medical care.
8. Hemoglobin less than lower limit of the reference range for age and sex.
9. History of seizure activity within 6 months prior to informed consent/assent.
Prior/Concomitant Therapy
10. Previous use of ALXN1840 or ammonium tetrathiomolybdate; concomitant use of penicillamine, trientine, or zinc (for participants randomized to ALXN1840).
Prior/Concurrent Clinical Study Experience
11. The use of an investigational drug within 30 days before initiation of the first dose of study intervention.
Diagnostic assessments
12. Participants in renal failure, defined as in end-stage renal disease on dialysis (chronic kidney disease stage 5 [CKD 5]) or estimated glomerular filtration rate < 30 mL/min/1.73m2.
13. Active infection with hepatitis B virus (positive hepatitis B surface antigen) or C virus (participants with positive hepatitis C antibody result would require confirmation of active disease with a positive hepatitis C polymerase chain reaction test), or seropositivity for HIV.
14. Any disability acquired from trauma or another illness that, in the opinion of the Investigator, could interfere with evaluation of disability due to WD.
15. Systemic disease or other illness, or any deviation in laboratory values that are confirmed on re-examination to be clinically significant by the Investigator that would, in the opinion of the Investigator, compromise participant safety or interfere with the collection or interpretation of study results.
Other Exclusions
16. Pregnant (or females who are planning to become pregnant) or breastfeeding females.
17. Known sensitivity to ALXN1840, ALXN1840 excipients (anhydrous di-calcium phosphate, anhydrous sodium carbonate), or any of the ingredients contained in ALXN1840 or related compounds.
18. Regular alcohol consumption within 6 months prior to the study defined as > 14 units for males or > 7 units for females per week. One unit is equivalent to 14 g of alcohol: a half pint (approx. 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
19. Abuse of illicit or prescribed drugs.
20. In the opinion of the Investigator, the participant and/or their parent/proxy is likely to be non-compliant or uncooperative during the study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified