Rifampin in CYP24A1-related Hypercalcemia and Hypercalciuria

NCT03301038 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 16-013429R01DK112955
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

hypercalcemia; nephrocalcinosis; CYP24A1; hypercalciuria

Outcome Measures

Primary Outcomes (3)

• Serum albumin-adjusted calcium

  Measured at baseline and every 4 weeks

  up to 32 weeks

• Serum parathyroid hormone

  Measured at baseline and every 4 weeks

  up to 32 weeks

• Urinary calcium excretion

  Measured at baseline and every 4 weeks

  up to 32 weeks

Secondary Outcomes (3)

• Intestinal calcium absorption

  baseline, 8, 16, 24 and 32 weeks post-dose

• Nephrocalcinosis

  Baseline and week 32

• Rifampin pharmacokinetics

  8, 16 and 24 weeks post-dose

Study Arms (1)

All Subjects

EXPERIMENTAL

SingleArm: Escalating doses of rifampin (5 and 10 mg/kg/day) (SingleArm)

Drug: Rifampin

Interventions

Rifampin DRUG

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

Also known as: Rifadin, Rifampicin

All Subjects

Eligibility Criteria

• Age: 6 Months - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females age 6 months to 65 years.
• at least one mutations of CYP24A1
• Serum and/or urinary calcium above the normal reference range for age
• Serum PTH concentration \<20 pg/ml
• Elevated or normal serum concentration of 1,25-dihydroxyvitamin D3.

You may not qualify if:

• Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
• Allergy to rifampin or related medications
• Pregnancy or breastfeeding
• Laboratory abnormalities that indicate clinically significant hepatic, or renal disease:
• Aspartate Aminotransferase (AST/SGOT) \> 2.0 times the upper limit of normal Alanine aminotransferase (ALT/SGPT) \> 2.0 times the upper limit of normal Total bilirubin \> 2.0 times the upper limit of normal Creatinine \> 2.0 times the upper limit of normal

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Related Publications (3)

• Hawkes CP, Li D, Hakonarson H, Meyers KE, Thummel KE, Levine MA. CYP3A4 Induction by Rifampin: An Alternative Pathway for Vitamin D Inactivation in Patients With CYP24A1 Mutations. J Clin Endocrinol Metab. 2017 May 1;102(5):1440-1446. doi: 10.1210/jc.2016-4048.

  PMID: 28324001 BACKGROUND

• Dauber A, Nguyen TT, Sochett E, Cole DE, Horst R, Abrams SA, Carpenter TO, Hirschhorn JN. Genetic defect in CYP24A1, the vitamin D 24-hydroxylase gene, in a patient with severe infantile hypercalcemia. J Clin Endocrinol Metab. 2012 Feb;97(2):E268-74. doi: 10.1210/jc.2011-1972. Epub 2011 Nov 23.

  PMID: 22112808 BACKGROUND

• Schlingmann KP, Kaufmann M, Weber S, Irwin A, Goos C, John U, Misselwitz J, Klaus G, Kuwertz-Broking E, Fehrenbach H, Wingen AM, Guran T, Hoenderop JG, Bindels RJ, Prosser DE, Jones G, Konrad M. Mutations in CYP24A1 and idiopathic infantile hypercalcemia. N Engl J Med. 2011 Aug 4;365(5):410-21. doi: 10.1056/NEJMoa1103864. Epub 2011 Jun 15.

  PMID: 21675912 BACKGROUND

MeSH Terms

Conditions

Genetic Diseases, Inborn; Hypercalcemia, Idiopathic, of Infancy; Hypercalciuric Hypercalcemia; Hypercalciuria; Hypercalcemia; Nephrocalcinosis

Interventions

Rifampin

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Calcium Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Water-Electrolyte Imbalance; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Calcinosis

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Michael A Levine, MD

  Children'sHospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael A Levine, MD

CONTACT

267-426-3907; levinem@chop.edu

Vashisht Arshanapally

CONTACT

267-426-7482; arshanapav@chop.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2017
• First Posted: October 4, 2017
• Study Start: July 25, 2018
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2030
• Last Updated: June 22, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)