Comparison of Zinc Acetate Dose Regimens Using 64Cu PET/CT to Assess Intestinal Copper Absorption in Healthy Volunteers for the Management of Wilson Disease

The primary objective is to evaluate the effect of zinc acetate dose regimens, specifically Galzin 50 mg three times daily and ET-700 75 mg twice daily, compared to a placebo, on intestinal copper absorption. This assessment is performed using 64Cu PET/CT imaging to quantify the accumulation of 64Cu chloride in the liver, which serves as a measure of systemic copper uptake in the context of Wilson disease.

The sponsor did not provide the total number of participants. The study population consists of healthy volunteers, including both males and females, within the age ranges categorized as 3 and 4. Participants must be at least 18 years of age and possess a body mass index below 30. Women of childbearing potential are required to utilize effective contraception from the time of inclusion until 14 days following the final scan, or remain sexually abstinent. On the day of tracer administration, fertile women must demonstrate a negative urine pregnancy test. All subjects must be capable of reading and understanding Danish to ensure compliance with study protocols.

This Phase 4, therapeutic exploratory clinical trial is designed to evaluate the effects of different zinc acetate dose regimens on intestinal copper absorption in healthy volunteers. The study utilizes a comparative methodology involving three groups: ET-700, Galzin, and placebo. To assess pharmacodynamics, 64Cu PET/CT imaging is employed to measure the hepatic uptake of copper (64cu) chloride. The primary endpoint is the change in mean hepatic 64Cu standard uptake value from pre- to post-intervention. Secondary endpoints include changes in plasma zinc, total copper, exchangeable copper, ceruloplasmin, metallothionein induction in peripheral blood mononuclear cells, and urinary zinc and copper levels. The study protocol involves an initial screening visit to assess eligibility, followed by intervention and imaging procedures, and an end-of-study assessment. Participants must maintain reliable contraception during the trial period. The estimated recruitment and study duration is from March 2026 to June 2027.

The experimental treatment consists of ET-700 75 mg, which is administered as 0.15 g of zinc in capsules. This medication is delivered via the oral route at a frequency of twice daily.

The comparator treatment is Galzin 50 mg, containing 0.15 g of zinc in capsules. This substance is administered through the oral route at a frequency of three times daily.

A placebo is utilized as a control in the study design.

For the assessment of intestinal copper absorption, copper (64cu) chloride is administered orally at a dose of 30 MBq.

The primary efficacy endpoint is the change in mean hepatic 64Cu standard uptake value (SUV) from pre-intervention to post-intervention across the study groups. This assessment of intestinal copper absorption is performed using 64Cu PET/CT scans to measure the quantity of 64Cu within the liver.

Secondary efficacy parameters include the following changes from pre- to post-intervention:

• Plasma zinc, total copper, exchangeable copper, and ceruloplasmin levels.
• Metallothionein induction in peripheral blood mononuclear cells.
• Urinary zinc and copper levels.