OsteomalaciaPhase 1NCT01748812

Cinacalcet for Fibroblast Growth Factor 23 (FGF23)-Mediated Hypophosphatemia (Hypophosphatemic Rickets)

A Phase 1 study testing Osteomalacia in people with Osteomalacia, run by National Institute of Dental and Craniofacial Research (NIDCR) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Background: Hypophosphatemia is a condition where a person has low levels of phosphorus in the blood. Low blood phosphorus can cause muscle and bone weakness (such as rickets) and teeth problems. One cause of the condition is having too much fibroblast growth factor 23 (FGF23). Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Osteomalacia
What is being tested?: Osteomalacia
How many people: 1 participants
Where: 1 siteUnited States
Study dates: 16 Nov 2012to 31 Dec 2016
Phase: Phase 1
Are there results?: None posted in the registry

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 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

<TAB>Chronological age: 18-70 years
<TAB>Diagnosis of a genetic form of FGF23-mediated hypophosphatemia:
<TAB>X-linked hypophosphatemic rickets (XLH)
<TAB>Autosomal dominant hypophosphatemic rickets (ADHR)
<TAB>Autosomal recessive hypophosphatemic rickets (ARHR)
Or, diagnosis of a non-genetic form of FGF23-mediated hypophosphatemia, i.e. tumor-induced osteomalacia (TIO)

Show all 9Show fewer

<TAB>Ability to understand and provide informed consent
<TAB>Ability to complete the protocol scheduled assessments and medication regimen
<TAB>Women of child-bearing potential (not surgically sterile via tubal ligation, bilateral oophorectomy or hysterectomy, or who are not postmenopausal for greater than or equal to 1 year) must agree to practice adequate contraception that may include, but is not limited to, abstinence, monogamous relationship with vasectomized partner, barrier methods such as condoms, diaphragms, spermicides, intrauterine devices, and licensed hormonal methods for the duration of the treatment portion of the study.

Who cannot join

<TAB>Chronic or recurrent hypocalcemia defined by a serum calcium < 8.4 mg/dL (2.1 mmol/L)
<TAB>Tertiary hyperparathyroidism as evidenced by concurrent PTH and calcium levels above the upper limit of normal
<TAB>History of parathyroid surgery and/or hypoparathyroidism
<TAB>Hypercalciuria as defined as > 4 mg/kg/day (0.1 mmol/kg/day) on optimized conventional therapy (as determined during SOC optimization phase)
<TAB>Moderate to severe hepatic insufficiency as defined by total bilirubin > 2 mg/dL and serum albumin < 3 g/dL and International Normalized Ratio (INR) >2 OR presence of ascites or hepatic encephalopathy.
<TAB>A calculated eGFR < 50 mL/min/1.73 m(2), using the CKD-EPI equation

Show all 13Show fewer

<TAB>History of a non-febrile seizure disorder
<TAB>History of a clinically significant cardiac arrhythmia
<TAB>History of chronic gastrointestinal disease
<TAB>Current therapy (at the time of informed consent) bisphosphonates, calcitonin, diuretics or medications that may have a significant drug interaction with cinacalcet
<TAB>Known hypersensitivity to cinacalcet or any of its constituents
<TAB>Positive pregnancy test or lactation
<TAB>Use of another investigational agent (i.e., in the context of a clinical trial, use of an investigational product that may have impact on the study) within the last 3 months

Trial locations and contacts

1 site in 1 country.

United States1 site

National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Open-label Dose-titration Study of the Tolerability and Efficacy of Cinacalcet to Treat Fibroblast Growth Factor 23 (FGF23)-Mediated Hypophosphatemia

Background:

Hypophosphatemia is a condition where a person has low levels of phosphorus in the blood. Low blood phosphorus can cause muscle and bone weakness (such as rickets) and teeth problems. One cause of the condition is having too much fibroblast growth factor 23 (FGF23). FGF23 is a hormone that causes the kidney to get rid of phosphorus in the urine. It can also prevent the body from making vitamin D, which helps the body absorb phosphorus in food.
Many people with low blood phosphorus take high doses of phosphorus and calcium medications. However, one side effect of these drugs is increased blood levels of parathyroid hormone (PTH). The drug cinacalcet can help lower PTH levels, which may decrease the amount of phosphorus lost in the urine and increase the phosphorus levels in the blood. Researchers want to see if cinacalcet can help blood phosphorus and decrease the amount of phosphorus supplements that people need to take.

Objectives:

To see if cinacalcet can be a safe and effective treatment for people with low phosphorus conditions due to high FGF23.

Eligibility:

Individuals between 18 and 70 years of age who have different forms of hypophosphatemic rickets and tumor-induced hypophosphatemia

Design:

Participants will have up to 25 study visits over about 28 weeks.
Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
Up to three more lab visits for blood and urine tests will be required before treatment. Imaging studies of the bones, spine, and kidneys will be performed.
Participants will have a 3-night hospital stay to start treatment. They will take cinacalcet once a day. Treatment will be monitored with frequent blood tests and imaging studies.
Participants will continue to take cinacalcet once a day for 3 weeks. They will have regular study visits to monitor the treatment.
There will be up to two other overnight hospital stays (1 to 3 nights) to adjust cinacalcet doses. The dose will increase until the maximum dose is reached, or side effects develop.
After the end of the cinacalcet study, participants will have several more followup visits to monitor the effects of treatment.

Read the detailed description

OBJECTIVES:

The primary objective of this protocol is to evaluate the tolerability of cinacalcet in individuals with fibroblast growth factor 23 (FGF23)-mediated hypophosphatemia, using an open-label, dose-titration study of once-daily dosing. Secondary objectives are to evaluate the pharmacodynamics of cinacalcet in this subject population and to explore the efficacy of cinacalcet by comparing a) level of oral phosphate required at baseline to the level required at maximum tolerated dose (MTD) and b) change in renal phosphate handling from baseline to MTD. Tertiary objectives are to evaluate tolerability, pharmacodynamics, and efficacy of twice daily dosing of each subject s MTD of cinacalcet after completion of the once-daily dose-titration phase. A final objective is to determine the length of time it takes for subjects to return to their pre-treatment steady state once treatment is complete.

STUDY POPULATION:

Up to 17 subjects with FGF23-mediated hypophosphatemia will be treated.

DESIGN:

This study is an open-label, dose-titration study of once-daily dosing of cinacalcet, with up to 4 escalating doses given at approximately 3 week intervals. After an initial standard of care optimization period of 2-9 weeks, subjects will proceed to the cinacalcet dose-titration period. Subjects who experience extended toxicity or study drug related serious adverse events or other related, intolerable adverse events will be down titrated to a lower dose of study medication. After subjects have achieved their own maximum tolerated dose (MTD) and completed the once-daily dosing phase, they will continue the study medication for approximately 3 additional weeks with twice daily dosing at their MTD. At the end of the cinacalcet treatment phase of the study, cinacalcet will be discontinued and standard of care (SOC) medications will be adjusted/restarted on an individualized basis. Subjects will continue in this final SOC safety follow-up period for up to 4 weeks until their SOC medications have been re-equilibrated.

OUTCOME MEASURES:

Primary safety:

Whether or not a subject discontinued the study due to a toxicity, related serious adverse event (SAE), or related intolerable adverse event (AE).

Secondary safety:

<TAB>Maximum tolerated dose of cinacalcet
<TAB>Serum calcium levels
<TAB>Urine calcium levels
<TAB>Adverse events
<TAB>Time from cinacalcet discontinuation to return to pre-treatment standard of care dosage levels

Secondary efficacy:

<TAB>Pharmacodynamic assessments
<TAB>Serum: FGF23, intact parathyroid hormone, calcium, creatinine, phosphorus
<TAB>Urine: phosphorus, creatinine, calcium.
<TAB>Tubular maximum reabsorption of phosphate/glomerular filtration rate
<TAB>Tubular reabsorption of phosphate
<TAB>Other
<TAB>Change in oral phosphate and calcitriol intake required to maintain adequate phosphorus and calcium serum levels
<TAB>Serum osteocalcin and alkaline phosphatase
<TAB>Serum intact parathyroid hormone (PTH)

Tertiary efficacy:

<TAB>Twice-Daily Dosing at MTD
<TAB>Time from cinacalcet discontinuation of twice-daily dosing to return to pre-treatment standard of care dosage levels
<TAB>Dental Evaluation
<TAB>Visible Plaque Index (VPI)
<TAB>Gingival Bleeding Index (GBI)
<TAB>Position of Gingival Margin (PGM)
<TAB>Relative Attachment Level (RAL)
<TAB>Periodontal Probing Pocket Depth (PPD)
<TAB>Gingival Crevicular Fluid (GCF) Biomarkers

Conditions: Osteomalacia
Being tested: Osteomalacia
Keywords: Tumor Induced Osteomalacia, Hypophosphatemic Rickets
Medical subject headings: Osteomalacia, Oncogenic osteomalacia, Rickets, Hypophosphatemic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

OsteomalaciaDrug

What is being measured

The primary outcome is the main question the study is designed to answer.

Evaluate the tolerability of cinacalcet in individuals with FGF23-mediated hypophosphatemia
Measured: 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Nov 201231 Dec 2016

First posted13 Dec 2012 (estimated)
Study start16 Nov 2012
Primary completion31 Dec 2016
Study completion31 Dec 2016

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 OsteomalaciaStudies of the same condition, open and under way.
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 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 1 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01748812
Sponsor's protocol ID: 130025
Other IDs: 13-D-0025
Status last verified: 7 Jul 2015
First submitted: 11 Dec 2012
Last updated: 5 Jul 2018
Results posted: No

Publications

Chen L, Liu H, Sun W, Bai X, Karaplis AC, Goltzman D, Miao D. Fibroblast growth factor 23 overexpression impacts negatively on dentin mineralization and dentinogenesis in mice. Clin Exp Pharmacol Physiol. 2011 Jun;38(6):395-402. doi: 10.1111/j.1440-1681.2011.05526.x.
PubMed 21488937
Makitie O, Doria A, Kooh SW, Cole WG, Daneman A, Sochett E. Early treatment improves growth and biochemical and radiographic outcome in X-linked hypophosphatemic rickets. J Clin Endocrinol Metab. 2003 Aug;88(8):3591-7. doi: 10.1210/jc.2003-030036.
PubMed 12915641
Bastepe M, Juppner H. Inherited hypophosphatemic disorders in children and the evolving mechanisms of phosphate regulation. Rev Endocr Metab Disord. 2008 Jun;9(2):171-80. doi: 10.1007/s11154-008-9075-3. Epub 2008 Mar 26.
PubMed 18365315

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Tumor-induced Osteomalacia Disease Monitoring Program
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Post Marketing Surveillance Study to Observe Safety and Effectiveness of CRYSVITA® in S. Korean Patients
FGF23-related Hypophosphataemic Rickets and Osteomalacia
RecruitingObservational study
A Natural History Study of Bone and Mineral Disorders
Tumor Induced Osteomalcia, Osteomalacia
Recruiting
Al18F-NOTA-LM3 PET/CT in Patients With TIO
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Active, not recruitingObservational study
Study of Longitudinal Observation for Patient With X-linked Hypophosphatemic Rickets/Osteomalacia in Collaboration With Asian Partners
X-Linked Hypophosphatemia

All Osteomalacia trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Open-label Dose-titration Study of the Tolerability and Efficacy of Cinacalcet to Treat Fibroblast Growth Factor 23 (FGF23)-Mediated Hypophosphatemia
ClinicalTrials.gov ID: NCT01748812
Acronym / sponsor ID: 130025
Conditions: Osteomalacia
Keywords: Tumor Induced Osteomalacia, Hypophosphatemic Rickets
Phase: Phase 1
Study type: Interventional
Recruitment status: Terminated
Enrolment: 1 participants (actual)
Lead sponsor: National Institute of Dental and Craniofacial Research (NIDCR)US National Institutes of Health
Study start: 16 Nov 2012
Primary completion: 31 Dec 2016 (actual)
Study completion: 31 Dec 2016 (actual)
First posted: 13 Dec 2012 (estimated)
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.

Background:

Hypophosphatemia is a condition where a person has low levels of phosphorus in the blood. Low blood phosphorus can cause muscle and bone weakness (such as rickets) and teeth problems. One cause of the condition is having too much fibroblast growth factor 23 (FGF23). FGF23 is a hormone that causes the kidney to get rid of phosphorus in the urine. It can also prevent the body from making vitamin D, which helps the body absorb phosphorus in food.
Many people with low blood phosphorus take high doses of phosphorus and calcium medications. However, one side effect of these drugs is increased blood levels of parathyroid hormone (PTH). The drug cinacalcet can help lower PTH levels, which may decrease the amount of phosphorus lost in the urine and increase the phosphorus levels in the blood. Researchers want to see if cinacalcet can help blood phosphorus and decrease the amount of phosphorus supplements that people need to take.

Objectives:

To see if cinacalcet can be a safe and effective treatment for people with low phosphorus conditions due to high FGF23.

Eligibility:

Individuals between 18 and 70 years of age who have different forms of hypophosphatemic rickets and tumor-induced hypophosphatemia

Design:

Participants will have up to 25 study visits over about 28 weeks.
Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
Up to three more lab visits for blood and urine tests will be required before treatment. Imaging studies of the bones, spine, and kidneys will be performed.
Participants will have a 3-night hospital stay to start treatment. They will take cinacalcet once a day. Treatment will be monitored with frequent blood tests and imaging studies.
Participants will continue to take cinacalcet once a day for 3 weeks. They will have regular study visits to monitor the treatment.
There will be up to two other overnight hospital stays (1 to 3 nights) to adjust cinacalcet doses. The dose will increase until the maximum dose is reached, or side effects develop.
After the end of the cinacalcet study, participants will have several more followup visits to monitor the effects of treatment.

Detailed description

OBJECTIVES:

STUDY POPULATION:

Up to 17 subjects with FGF23-mediated hypophosphatemia will be treated.

DESIGN:

OUTCOME MEASURES:

Primary safety:

Whether or not a subject discontinued the study due to a toxicity, related serious adverse event (SAE), or related intolerable adverse event (AE).

Secondary safety:

<TAB>Maximum tolerated dose of cinacalcet
<TAB>Serum calcium levels
<TAB>Urine calcium levels
<TAB>Adverse events
<TAB>Time from cinacalcet discontinuation to return to pre-treatment standard of care dosage levels

Secondary efficacy:

<TAB>Pharmacodynamic assessments
<TAB>Serum: FGF23, intact parathyroid hormone, calcium, creatinine, phosphorus
<TAB>Urine: phosphorus, creatinine, calcium.
<TAB>Tubular maximum reabsorption of phosphate/glomerular filtration rate
<TAB>Tubular reabsorption of phosphate
<TAB>Other
<TAB>Change in oral phosphate and calcitriol intake required to maintain adequate phosphorus and calcium serum levels
<TAB>Serum osteocalcin and alkaline phosphatase
<TAB>Serum intact parathyroid hormone (PTH)

Tertiary efficacy:

<TAB>Twice-Daily Dosing at MTD
<TAB>Time from cinacalcet discontinuation of twice-daily dosing to return to pre-treatment standard of care dosage levels
<TAB>Dental Evaluation
<TAB>Visible Plaque Index (VPI)
<TAB>Gingival Bleeding Index (GBI)
<TAB>Position of Gingival Margin (PGM)
<TAB>Relative Attachment Level (RAL)
<TAB>Periodontal Probing Pocket Depth (PPD)
<TAB>Gingival Crevicular Fluid (GCF) Biomarkers

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

Or, diagnosis of a non-genetic form of FGF23-mediated hypophosphatemia, i.e. tumor-induced osteomalacia (TIO)

Key exclusion criteria (13 listed)

<TAB>Chronic or recurrent hypocalcemia defined by a serum calcium < 8.4 mg/dL (2.1 mmol/L)
<TAB>Tertiary hyperparathyroidism as evidenced by concurrent PTH and calcium levels above the upper limit of normal
<TAB>History of parathyroid surgery and/or hypoparathyroidism
<TAB>Hypercalciuria as defined as > 4 mg/kg/day (0.1 mmol/kg/day) on optimized conventional therapy (as determined during SOC optimization phase)
<TAB>Moderate to severe hepatic insufficiency as defined by total bilirubin > 2 mg/dL and serum albumin < 3 g/dL and International Normalized Ratio (INR) >2 OR presence of ascites or hepatic encephalopathy.

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
Osteomalacia	Drug	–

Primary outcome

Evaluate the tolerability of cinacalcet in individuals with FGF23-mediated hypophosphatemia
Time frame: 4 years

Results and safety

The study was stopped early. Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2018.
Background: PubMed 21488937Chen L, Liu H, Sun W, Bai X, Karaplis AC, Goltzman D, Miao D. Fibroblast growth factor 23 overexpression impacts negatively on dentin mineralization and dentinogenesis in mice. Clin Exp Pharmacol Physiol. 2011 Jun;38(6):395-402. doi: 10.1111/j.1440-1681.2011.05526.x.
Background: PubMed 12915641Makitie O, Doria A, Kooh SW, Cole WG, Daneman A, Sochett E. Early treatment improves growth and biochemical and radiographic outcome in X-linked hypophosphatemic rickets. J Clin Endocrinol Metab. 2003 Aug;88(8):3591-7. doi: 10.1210/jc.2003-030036.
Background: PubMed 18365315Bastepe M, Juppner H. Inherited hypophosphatemic disorders in children and the evolving mechanisms of phosphate regulation. Rev Endocr Metab Disord. 2008 Jun;9(2):171-80. doi: 10.1007/s11154-008-9075-3. Epub 2008 Mar 26.

Related trials for Osteomalacia

Active, not recruitingObservational study
Tumor-induced Osteomalacia Disease Monitoring Program
Tumor-induced Osteomalacia (TIO)
RecruitingObservational study
Post Marketing Surveillance Study to Observe Safety and Effectiveness of CRYSVITA® in S. Korean Patients
FGF23-related Hypophosphataemic Rickets and Osteomalacia
RecruitingObservational study
A Natural History Study of Bone and Mineral Disorders
Tumor Induced Osteomalcia, Osteomalacia
Recruiting
Al18F-NOTA-LM3 PET/CT in Patients With TIO
Tumor-Induced Osteomalacia
Active, not recruitingObservational study
Study of Longitudinal Observation for Patient With X-linked Hypophosphatemic Rickets/Osteomalacia in Collaboration With Asian Partners
X-Linked Hypophosphatemia

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. This study is not recruiting at the moment.

Rachel I Gafni, M.D. principal investigator

National Institute of Dental and Craniofacial Research (NIDCR)

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Osteomalacia in people with Osteomalacia, run by National Institute of Dental and Craniofacial Research (NIDCR) 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 9 inclusion and 13 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: stopped early, as of the sponsor's last update on 5 Jul 2018. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early. Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Evaluate the tolerability of cinacalcet in individuals with FGF23-mediated hypophosphatemia (time frame: 4 years). 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 NCT01748812, 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 5 Jul 2018.