Idiopathic Infantile Hypercalcaemia - Severe FormPhase 2RICHHNCT03301038
Rifampin in CYP24A1-related Hypercalcemia and Hypercalciuria
A Phase 2 study testing Rifampin in people with Idiopathic Infantile Hypercalcaemia - Severe Form and Genetic Disease, run by Children's Hospital of Philadelphia at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 months to 70 years
- Conditions the study is for
- Idiopathic Infantile Hypercalcaemia - Severe Form, Genetic Disease, Hypercalcemia, Idiopathic, of Infancy
- What is being tested?
- Rifampin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Jul 2018to 1 Dec 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Males or females age 6 months to 70 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.
Who cannot join
- 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
- Current therapies with medications that have significant drug-drug interactions with rifampin, defined as a medication considered to interact with CYP3A4 or CYP3A5 and either induce or inhibit expression or function of these P450 enzymes. By "drug-drug" interactions we are looking for medications that will affect metabolism or action of rifampin as exclusionary, not medications that will be affected by rifampin.
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Michael A Levine, MD, 267-426-3907, levinem@chop.edu
David Weber, MD, 203-843-0021, PINNEYS@chop.edu
About this study
Official title: Rifampin to Reduce Elevated Levels of Blood and Urine Calcium in Patients With Inactivating Mutations in the CYP24A1 Gene
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.
Read the 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
- Being tested
- Rifampin
- Keywords
- hypercalcemia, nephrocalcinosis, CYP24A1, hypercalciuria
- Medical subject headings
- Genetic Diseases, Inborn, Hypercalcemia, Idiopathic, of Infancy, Hypercalciuric Hypercalcemia, Hypercalciuria, Hypercalcemia, Nephrocalcinosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RifampinDrug
Also called Rifadin, Rifampicin
Rifampin 5 mg/kg (max 300 mg) daily for 8 weeks, followed by rifampin 10 mg/kg (max 600 mg) daily for 8 weeks.
| Study group | Role | What they receive |
|---|---|---|
| All Subjects | Experimental | SingleArm: Escalating doses of rifampin (5 and 10 mg/kg/day) (SingleArm) Receives: Drug: Rifampin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum albumin-adjusted calcium
Measured at baseline and every 4 weeks
Measured: up to 32 weeks
Serum parathyroid hormone
Measured at baseline and every 4 weeks
Measured: up to 32 weeks
Urinary calcium excretion
Measured at baseline and every 4 weeks
Measured: up to 32 weeks
Secondary outcomes (3)
Intestinal calcium absorption
Measured using stable calcium isotopes five times during the study
Measured: baseline, 8, 16, 24 and 32 weeks post-dose
Nephrocalcinosis
Renal ultrasound performed before and after treatment
Measured: Baseline and week 32
Rifampin pharmacokinetics
Measured three times during the study
Measured: 8, 16 and 24 weeks post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2017
- Study start25 Jul 2018
- Primary completion1 Dec 2027 (estimated)
- Study completion1 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Idiopathic Infantile Hypercalcaemia - Severe FormStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael A Levine, MD, Principal investigator, Children'sHospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03301038
- Sponsor's protocol ID
- 16-013429
- Other IDs
- R01DK112955
- Acronym
- RICHH
- Status last verified
- Oct 2026
- First submitted
- 1 Sep 2017
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 28324001Dauber 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.
PubMed 22112808Schlingmann 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.
PubMed 21675912
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rifampin to Reduce Elevated Levels of Blood and Urine Calcium in Patients With Inactivating Mutations in the CYP24A1 Gene
- ClinicalTrials.gov ID
- NCT03301038
- Acronym / sponsor ID
- RICHH / 16-013429
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 25 Jul 2018 (actual)
- Primary completion
- 1 Dec 2027 (estimated)
- Study completion
- 1 Dec 2030 (estimated)
- First posted
- 4 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All Subjects | Experimental | Drug: RifampinSingleArm: Escalating doses of rifampin (5 and 10 mg/kg/day) (SingleArm) |
Who may qualify
- Ages
- 6 months to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Males or females age 6 months to 70 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.
Key exclusion criteria (6 listed)
- 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
- Current therapies with medications that have significant drug-drug interactions with rifampin, defined as a medication considered to interact with CYP3A4 or CYP3A5 and either induce or inhibit expression or function of these P450 enzymes. By "drug-drug" interactions we are looking for medications that will affect metabolism or action of rifampin as exclusionary, not medications that will be affected by rifampin.
- Pregnancy or breastfeeding
- Laboratory abnormalities that indicate clinically significant hepatic, or renal disease:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RifampinAlso: Rifadin, RifampicinRifampin 5 mg/kg (max 300 mg) daily for 8 weeks, followed by rifampin 10 mg/kg (max 600 mg) daily for 8 weeks. | Drug | All Subjects |
Primary outcome
Serum albumin-adjusted calcium
Time frame: up to 32 weeks
Measured at baseline and every 4 weeks
Serum parathyroid hormone
Time frame: up to 32 weeks
Measured at baseline and every 4 weeks
Urinary calcium excretion
Time frame: up to 32 weeks
Measured at baseline and every 4 weeks
3 secondary outcomes
Intestinal calcium absorption
Time frame: baseline, 8, 16, 24 and 32 weeks post-dose
Nephrocalcinosis
Time frame: Baseline and week 32
Rifampin pharmacokinetics
Time frame: 8, 16 and 24 weeks post-dose
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2026.
- Background: PubMed 28324001Hawkes 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.
- Background: PubMed 22112808Dauber 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.
- Background: PubMed 21675912Schlingmann 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Michael A Levine, MD principal investigator
Children'sHospital of Philadelphia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rifampin in people with Idiopathic Infantile Hypercalcaemia - Severe Form and Genetic Disease, run by Children's Hospital of Philadelphia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Michael A Levine, MD (267-426-3907, levinem@chop.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum albumin-adjusted calcium (time frame: up to 32 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03301038, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2026.