Trial Outcomes & Findings for A Trial to Assess the Safety and Efficacy of KRN23 in Epidermal Nevus Syndrome (ENS) (NCT NCT04320316)
NCT ID: NCT04320316
Last Updated: 2022-10-07
Results Overview
Checking PO4 levels every two weeks and adjusting doses every 4 weeks in blood
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
1 participants
Primary outcome timeframe
every 2 week, from baseline to 52 weeks.
Results posted on
2022-10-07
Participant Flow
recruited 1 patient with Epidermal nevus and hypophosphatemia
Participant milestones
| Measure |
Crysvita (Burosumab-twza) Treatment
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.
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.
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|---|---|
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Overall Study
STARTED
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1
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Overall Study
COMPLETED
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1
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Trial to Assess the Safety and Efficacy of KRN23 in Epidermal Nevus Syndrome (ENS)
Baseline characteristics by cohort
| Measure |
Crysvita (Burosumab-twza) Treatment
n=1 Participants
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.
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.
The primary measure of the study is to see a rise of the phosphorus level to the normal range or as close as possible to the normal range.
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Age, Categorical
<=18 years
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1 Participants
n=5 Participants
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Age, Categorical
Between 18 and 65 years
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0 Participants
n=5 Participants
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Age, Categorical
>=65 years
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0 Participants
n=5 Participants
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Sex: Female, Male
Female
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0 Participants
n=5 Participants
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Sex: Female, Male
Male
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1 Participants
n=5 Participants
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Ethnicity (NIH/OMB)
Hispanic or Latino
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0 Participants
n=5 Participants
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Ethnicity (NIH/OMB)
Not Hispanic or Latino
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1 Participants
n=5 Participants
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Ethnicity (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
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Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Asian
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Black or African American
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0 Participants
n=5 Participants
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Race (NIH/OMB)
White
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1 Participants
n=5 Participants
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Race (NIH/OMB)
More than one race
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
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Region of Enrollment
United States
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1 participants
n=5 Participants
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PRIMARY outcome
Timeframe: every 2 week, from baseline to 52 weeks.Population: Same as above with only 1 patient
Checking PO4 levels every two weeks and adjusting doses every 4 weeks in blood
Outcome measures
| Measure |
Crysvita (Burosumab-twza) Treatment
n=1 Participants
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.
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.
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
baseline
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0.8 mg/dl
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
2 week
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1.2 mg/dl
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
4 week
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1.3 mg/dl
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
6 week
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1.1 mg/dl
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
8 week
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1.4 mg/dl
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
10 week
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1.7 mg/dl
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
12 week
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1.9 mg/dl
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
14 week
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1.3 mg/dl
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
16 week
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2 mg/dl
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
18 week
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2.3 mg/dl
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
20 week
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1.8 mg/dl
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
22 week
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2.1 mg/dl
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
24 week
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2.1 mg/dl
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
26 week
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2.3 mg/dl
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
28 week
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2.6 mg/dl
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
30 week
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2 mg/dl
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
32 week
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1.9 mg/dl
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
34 week
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1.8 mg/dl
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
36 week
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2.1 mg/dl
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
38 week
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2.5 mg/dl
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
40 week
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2.9 mg/dl
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
42 weeks
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2.7 mg/dl
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
44 weeks
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1.8 mg/dl
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
46 week
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2.4 mg/dl
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
48 weeks
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2.6 mg/dl
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
50
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2.5 mg/dl
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The Participant Will Achieve Normal Age-adjusted Phosphorous Levels as Tested by Fasting Serum Lab Values
52
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3.3 mg/dl
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SECONDARY outcome
Timeframe: 1 yearPopulation: one patient with Epidermal nevus and hypophosphatemia
check Vitamin D 1,25 in blood every 3 months
Outcome measures
| Measure |
Crysvita (Burosumab-twza) Treatment
n=1 Participants
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.
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.
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Participant Will Achieve Improving Vitamin D Levels as Measured by Serum Blood Tests.
Baseline Vit D 1,25
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15 pg/ml
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Participant Will Achieve Improving Vitamin D Levels as Measured by Serum Blood Tests.
2 months Vit D 1,25
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68 pg/ml
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Participant Will Achieve Improving Vitamin D Levels as Measured by Serum Blood Tests.
6 months Vit D 1,25
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105 pg/ml
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Participant Will Achieve Improving Vitamin D Levels as Measured by Serum Blood Tests.
9 months Vita D 1,25
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95 pg/ml
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Participant Will Achieve Improving Vitamin D Levels as Measured by Serum Blood Tests.
1 year Vit D 1,25
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115 pg/ml
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SECONDARY outcome
Timeframe: every 3 months, From Baseline to 52 weeksPopulation: same as above
measure PTH levels approximately every 3 months
Outcome measures
| Measure |
Crysvita (Burosumab-twza) Treatment
n=1 Participants
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.
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.
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Participant Will Achieve Improving iPTH Levels as Measured by Serum Blood Tests.
1 year
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330.4 pg/ml
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Participant Will Achieve Improving iPTH Levels as Measured by Serum Blood Tests.
baseline PTH
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334.5 pg/ml
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Participant Will Achieve Improving iPTH Levels as Measured by Serum Blood Tests.
3 months
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334.1 pg/ml
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Participant Will Achieve Improving iPTH Levels as Measured by Serum Blood Tests.
6 months
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317 pg/ml
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Participant Will Achieve Improving iPTH Levels as Measured by Serum Blood Tests.
9 months
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245.9 pg/ml
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SECONDARY outcome
Timeframe: every 3 months, From Baseline to 52 weeksPopulation: same as above
measure Calcium level every 3 months
Outcome measures
| Measure |
Crysvita (Burosumab-twza) Treatment
n=1 Participants
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.
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.
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Participant Will Achieve Improving Calcium Levels as Measured by Serum Blood Tests.
baseline Calcium
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10.5 mg/dl
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Participant Will Achieve Improving Calcium Levels as Measured by Serum Blood Tests.
3 months
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10.5 mg/dl
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Participant Will Achieve Improving Calcium Levels as Measured by Serum Blood Tests.
6 months
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11.2 mg/dl
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Participant Will Achieve Improving Calcium Levels as Measured by Serum Blood Tests.
9 months
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12 mg/dl
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Participant Will Achieve Improving Calcium Levels as Measured by Serum Blood Tests.
1 year
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13.4 mg/dl
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SECONDARY outcome
Timeframe: baseline scans prior to drug administrationPopulation: same as above
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.
Outcome measures
| Measure |
Crysvita (Burosumab-twza) Treatment
n=1 Participants
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.
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.
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Participant Will Achieve Improvement of Underlying Skeletal Disease/Rickets as Assessed by Standard Radiographs.
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-3.9 Z score
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SECONDARY outcome
Timeframe: every 3 months, From baseline to 52 weeksPopulation: same as above
obtain Alkaline phosphatase in blood every 3 months
Outcome measures
| Measure |
Crysvita (Burosumab-twza) Treatment
n=1 Participants
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.
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.
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Participant Will Achieve Improving Levels of Alkaline Phosphatase (ALP)
baseline
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672.4 U/L
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Participant Will Achieve Improving Levels of Alkaline Phosphatase (ALP)
3 months
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468.3 U/L
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Participant Will Achieve Improving Levels of Alkaline Phosphatase (ALP)
6 months
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313 U/L
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Participant Will Achieve Improving Levels of Alkaline Phosphatase (ALP)
9 months
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287 U/L
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Participant Will Achieve Improving Levels of Alkaline Phosphatase (ALP)
1 year
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185.2 U/L
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Adverse Events
Adverse Events
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place