NCT03301038

Rifampin in CYP24A1-related Hypercalcemia and Hypercalciuria

Rifampin to Reduce Elevated Levels of Blood and Urine Calcium in Patients With Inactivating Mutations in the CYP24A1 Gene

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Children's Hospital of Philadelphia · Academic / Other
• Sex: All
• Age: 6 Months – 65 Years
• Healthy volunteers: Not accepted

Summary

This study evaluates the efficacy of rifampin in the treatment of hypercalcemia and/or hypercalciuria in participants with at least one inactivating mutation of the CYP24A1 gene. Eligible subjects will receive rifampin for a total of 16 weeks during this study.

Detailed description

Idiopathic infantile hypercalcemia (IIH; omim 143880) is a genetic disorder of mineral metabolism characterized by severe hypercalcemia and/or hypercalciuria, suppressed serum levels of parathyroid hormone (PTH) and elevated levels of the active vitamin D metabolite, 1,25(OH)2D. Biallelic inactivating mutations of CYP24A1, the gene encoding the 24-hydroxylase enzyme that represents the principal pathway for inactivation of vitamin D metabolites, cause the most common and severe form of IIH. Investigators have preliminary data supporting a novel therapeutic approach to repurpose rifampin as an agent to induce over-expression of CYP3A4 and CYP3A5, enzymes that are expressed in the liver and intestine. When these enzymes are induced, the increased enzyme activity provides an alternative catabolic pathway for inactivation of vitamin D metabolites. The purpose of this study is to obtain support for an open label, escalating dose study to assess the effect, safety, and tolerability of once daily oral rifampin in participants with IIH due to inactivating mutations in CYP24A1. In this study, Investigators will recruit 60 patients with at least one inactivating mutation of CYP24A1. Participants will be observed for 8-weeks before a 16-week treatment phase of rifampin and 8 further weeks of observation. In addition to following the effect of treatment on calcium homeostasis, Investigators will also study the pharmacokinetics of rifampin in this condition and the effect on intestinal calcium absorption.

Conditions

• Idiopathic Infantile Hypercalcaemia - Severe Form
• Genetic Disease
• Hypercalcemia, Idiopathic, of Infancy
• Hypercalciuric Hypercalcemia
• Idiopathic Infantile Hypercalcemia - Mild Form
• Hypercalciuria

Interventions

Type	Name	Description
DRUG	Rifampin	Rifampin 5 mg/kg (max 300 mg) daily for 8 weeks, followed by rifampin 10 mg/kg (max 600 mg) daily for 8 weeks.

Timeline

• Start date: 2018-07-25
• Primary completion: 2026-12-01
• Completion: 2030-12-01
• First posted: 2017-10-04
• Last updated: 2025-07-28

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study