A Phase 4 interventional study of Crysvita (burosumab-twza) Treatment in Epidermal Nevus Syndrome, sponsored by University of Alabama at Birmingham. Completed at 1 site in United States. Open to male participants aged 6 Months and older. Per ClinicalTrials.gov, last updated 2022-10-07.
Sponsored by University of Alabama at Birmingham · Phase 4, Interventional, and Treatment
KRN23 is a fully human immunoglobulin monoclonal antibody (mAb) that binds to and inhibits the activity of fibroblast growth factor 23 (FGF23), leading to an increase in serum phosphorus levels. There are multiple disorders that result in unusually high circulating levels of FGF23, which in turn result in renal phosphate wasting and reduced levels of 1,25-dihydroxy vitamin D (1,25[OH]2D). Across these disorders the clinical symptoms are similar and often include osteomalacia (and, in children, rickets), muscle weakness, fatigue, bone pain, and fractures. KRN23 has been studied in one of these disorders, X-linked hypophosphatemia (XLH). In single- and repeat-dose clinical studies in subjects with XLH, subcutaneous (SC) administration of KRN23 consistently increased and sustained serum phosphorus levels and tubular reabsorption of phosphate (TRP) without a major impact on urine calcium levels or vitamin D metabolism. Positive results were also observed in a nonclinical pharmacology model of XLH. It is hypothesized that KRN23 may provide clinical benefit in this patient due to the common underlying feature in this patient and in patients with XLH - abnormally elevated FGF23 in the context of low age -adjusted serum phosphorous levels. The primary objective is to study the effect of KRN23 treatment on normalizing age-adjusted fasting serum phosphorous levels in a single pediatric patient with Epidermal Nevus Syndrome associated hypophosphatemic rickets.
KRN23 is a fully human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to and inhibits the activity of fibroblast growth factor 23 (FGF23), leading to an increase in serum phosphorus levels. There are multiple disorders (each with a unique underlying cause) that result in unusually high circulating levels of FGF23, which in turn result in renal phosphate wasting and reduced (or aberrantly normal in relationship to elevated FGF23) levels of 1,25-dihydroxy vitamin D (1,25[OH]2D). Across these disorders the clinical symptoms are similar and often include osteomalacia (and, in children, rickets), muscle weakness, fatigue, bone pain, and fractures. KRN23 has been studied in one of these disorders, X-linked hypophosphatemia (XLH). In single- and repeat-dose clinical studies in subjects with XLH, subcutaneous (SC) administration of KRN23 consistently increased and sustained serum phosphorus levels and tubular reabsorption of phosphate (TRP) without a major impact on urine calcium levels or vitamin D metabolism. Positive results were also observed in a nonclinical pharmacology model of XLH. It is hypothesized that KRN23 may provide clinical benefit in this patient due to the common underlying feature in this patient and in patients with XLH - abnormally elevated FGF23 in the context of low age -adjusted serum phosphorous levels.
University of Alabama at Birmingham is the lead sponsor of 1,421 studies on the registry; 277 are open to participants now.
Of its 164 completed or terminated interventional studies of FDA-regulated products, 130 (79%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The starting dose will be 0.3 mg/kg to be given every 2 weeks. If required dose may be titrated with increments of 0.1 mg/kg/dose every 4 weeks up to a maximum of dose of 2.0mg/kg (not to exceed 90mg per dose) until phosphorus level is WNL. Patient will receive study drug via SC injection to the abdomen, upper arms, thighs, or buttocks; the injection site will be rotated with each injection. If the dose level exceeds 1.5 mL in volume, the dose should be administered at two injection sites. Duration of treatment is 52 weeks. Subjects that complete treatment through week 52 may have the option to continue KRN23 treatment. If this is warranted based on preliminary efficacy, the current protocol will be amended to allow for an extension.
Drug: Crysvita (burosumab-twza) Treatment
KRN23 is a fully human IgG1monoclonal antibody that binds to and inhibits the activity of FGF23, leading to an increase in serum phosphorus levels. It is a potential therapeutic candidate for the treatment of XLH, Tumor-Induced Osteomalacia (TIO), and the rickets/osteomalacia resulting from Epidermal Nevus Syndrome (ENS). All of these conditions are diseases of bone hypomineralization, caused by urinary phosphate wasting due to elevated levels of FGF23.
Also known as: no other names available
The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
Checking PO4 levels every two weeks and adjusting doses every 4 weeks in blood
Time frame: every 2 week, from baseline to 52 weeks.
Participant Will Achieve Improving Vitamin D Levels as Measured by Serum Blood Tests.
check Vitamin D 1,25 in blood every 3 months
Time frame: 1 year
Participant Will Achieve Improving iPTH Levels as Measured by Serum Blood Tests.
measure PTH levels approximately every 3 months
Time frame: every 3 months, From Baseline to 52 weeks
Participant Will Achieve Improving Calcium Levels as Measured by Serum Blood Tests.
measure Calcium level every 3 months
Time frame: every 3 months, From Baseline to 52 weeks
Participant Will Achieve Improvement of Underlying Skeletal Disease/Rickets as Assessed by Standard Radiographs.
DEXA (dual energy X-ray Absorbometry) scans and whole body x-rays will be taken at baseline. A lower Z score is indicative of poor results. Z score compares the standard deviations of the reading with matched aged persons. The normal range is +2 to - 2 Standard deviations and those are what we call Z scores. A Z score of 0 is the population mean.
Time frame: baseline scans prior to drug administration
Participant Will Achieve Improving Levels of Alkaline Phosphatase (ALP)
obtain Alkaline phosphatase in blood every 3 months
Time frame: every 3 months, From baseline to 52 weeks
recruited 1 patient with Epidermal nevus and hypophosphatemia
| Milestone | Crysvita (Burosumab-twza) Treatment |
|---|---|
| Started | 1 |
| Completed | 1 |
| Not completed | 0 |
Checking PO4 levels every two weeks and adjusting doses every 4 weeks in blood
| mg/dl | Crysvita (Burosumab-twza) Treatment |
|---|---|
| baseline | 0.8 |
| 2 week | 1.2 |
| 4 week | 1.3 |
| 6 week | 1.1 |
| 8 week | 1.4 |
| 10 week | 1.7 |
| 12 week | 1.9 |
| 14 week | 1.3 |
| 16 week | 2 |
| 18 week | 2.3 |
| 20 week | 1.8 |
| 22 week | 2.1 |
| 24 week | 2.1 |
| 26 week | 2.3 |
| 28 week | 2.6 |
| 30 week | 2 |
| 32 week | 1.9 |
| 34 week | 1.8 |
| 36 week | 2.1 |
| 38 week | 2.5 |
| 40 week | 2.9 |
| 42 weeks | 2.7 |
| 44 weeks | 1.8 |
| 46 week | 2.4 |
| 48 weeks | 2.6 |
| 50 | 2.5 |
| 52 | 3.3 |
check Vitamin D 1,25 in blood every 3 months
| pg/ml | Vitamin D Level on Treatment |
|---|---|
| Baseline Vit D 1,25 | 15 |
| 2 months Vit D 1,25 | 68 |
| 6 months Vit D 1,25 | 105 |
| 9 months Vita D 1,25 | 95 |
| 1 year Vit D 1,25 | 115 |
measure PTH levels approximately every 3 months
| pg/ml | PTH Levels |
|---|---|
| baseline PTH | 334.5 |
| 3 months | 334.1 |
| 6 months | 317 |
| 9 months | 245.9 |
| 1 year | 330.4 |
measure Calcium level every 3 months
| mg/dl | Calcium Levels |
|---|---|
| baseline Calcium | 10.5 |
| 3 months | 10.5 |
| 6 months | 11.2 |
| 9 months | 12 |
| 1 year | 13.4 |
DEXA (dual energy X-ray Absorbometry) scans and whole body x-rays will be taken at baseline. A lower Z score is indicative of poor results. Z score compares the standard deviations of the reading with matched aged persons. The normal range is +2 to - 2 Standard deviations and those are what we call Z scores. A Z score of 0 is the population mean.
| Z score | DEXA Scan |
|---|---|
| Participant Will Achieve Improvement of Underlying Skeletal Disease/Rickets as Assessed by Standard Radiographs. | -3.9 |
obtain Alkaline phosphatase in blood every 3 months
| U/L | Alkaline Phosphatase |
|---|---|
| baseline | 672.4 |
| 3 months | 468.3 |
| 6 months | 313 |
| 9 months | 287 |
| 1 year | 185.2 |
Collected over 1 year. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Adverse Events | 0/1 (0%) | 0/1 (0%) | 0/1 (0%) |
people with Epidermal nevus and also hypophopshatemia.
| Age, Categorical(Participants) | Crysvita (Burosumab-twza) Treatment |
|---|---|
| <=18 years | 1 |
| Between 18 and 65 years | 0 |
| >=65 years | 0 |
| Sex: Female, Male(Participants) | Crysvita (Burosumab-twza) Treatment |
|---|---|
| Female | 0 |
| Male | 1 |
| Ethnicity (NIH/OMB)(Participants) | Crysvita (Burosumab-twza) Treatment |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 1 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Crysvita (Burosumab-twza) Treatment |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 1 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(participants) | Crysvita (Burosumab-twza) Treatment |
|---|---|
| United States | 1 |
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Plan to share: No — To be determined
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Studies of the drug tested here: Burosumab
Nevus, Sebaceous of Jadassohn
University of Alabama at Birmingham →