Study of KRN23 in Adult Subjects With Tumor-Induced Osteomalacia (TIO) or Epidermal Nevus Syndrome (ENS)
Status: | Active, not recruiting |
---|---|
Healthy: | No |
Age Range: | 18 - Any |
Updated: | 12/22/2018 |
Start Date: | March 24, 2015 |
End Date: | December 31, 2019 |
A Phase 2 Open-Label Trial to Assess the Efficacy and Safety of KRN23, an Antibody to FGF23, in Subjects With Tumor-Induced Osteomalacia (TIO) or Epidermal Nevus Syndrome (ENS)-Associated Osteomalacia
The primary objectives of this study are to evaluate the effect of KRN23 treatment on:
- Increasing serum phosphorus levels in adults with TIO or ENS-associated osteomalacia
- Improvement in TIO/ENS-associated osteomalacia as determined by osteoid thickness
(O.Th), osteoid surface/bone surface (OS/BS), osteoid volume/bone volume (OV/BV) and
mineralization lag time (MLt).
- Increasing serum phosphorus levels in adults with TIO or ENS-associated osteomalacia
- Improvement in TIO/ENS-associated osteomalacia as determined by osteoid thickness
(O.Th), osteoid surface/bone surface (OS/BS), osteoid volume/bone volume (OV/BV) and
mineralization lag time (MLt).
Inclusion Criteria:
1. Have a clinical diagnosis of TIO/ENS based on evidence of excessive FGF23 that is not
amenable to cure by surgical excision of the offending tumor/lesion (documented by
investigator)
2. Be ≥18 years of age
3. Have a fasting serum phosphorus level <2.5 mg/dL
4. Have an FGF23 level ≥ 100 pg/mL by Kainos assay
5. Have a ratio of renal tubular maximum reabsorption rate of phosphate to glomerular
filtration rate (TmP/GFR) <2.5 mg/dL
6. Have an estimated glomerular filtration rate (eGFR) ≥60 mL/min (using Cockcroft-Gault
formula). Subjects with eGFR ≥30 but <60 mL/min will be considered eligible as long as
in the opinion of the investigator the decline in renal function is not related to
nephrocalcinosis.
7. Have a corrected serum calcium level <10.8 mg/dL
8. Females of child-bearing potential must have a negative urine pregnancy test at
Screening and Baseline and be willing to have additional pregnancy tests during the
study. Females considered not to be of childbearing potential include those who have
not experienced menarche, are post-menopausal (defined as having no menses for at
least 12 months without an alternative medical cause) or are permanently sterile due
to total hysterectomy, bilateral salpingectomy, or bilateral oophorectomy.
9. Participants of child‐bearing potential or fertile males with partners of
child-bearing potential who are sexually active must consent to use a highly effective
method of contraception as determined by the site Investigator from the period
following the signing of the informed consent through the final Safety Follow-up TC.
10. Be willing to provide access to prior medical records to determine eligibility
including imaging, biochemical, and diagnostic, medical, and surgical history data
11. Provide written informed consent after the nature of the study has been explained, and
prior to any research-related procedures
12. Be willing and able to complete all aspects of the study, adhere to the study visit
schedule and comply with the assessments (in the opinion of the investigator)
Exclusion Criteria:
1. Have a prior diagnosis of human immunodeficiency virus (HIV), hepatitis B and/or
hepatitis C
2. Have a history of recurrent infection, a predisposition to infection, or a known
immunodeficiency
3. Are pregnant or breastfeeding at Screening or are planning to become pregnant (self or
partner) at any time during the study
4. Have participated in an investigational drug or device trial within 30 days prior to
Screening or are currently enrolled in another study of an investigational product or
device
5. Have used a therapeutic monoclonal antibody, including KRN23, within 90 days prior to
Screening or have a history of allergic or anaphylactic reactions to any mAb
6. Have or a have a history of any hypersensitivity to KRN23 excipients that, in the
judgment of the investigator, places the subject at increased risk for adverse effects
7. Have used a pharmacologic vitamin D metabolite or its analog (e.g., calcitriol,
doxercalciferol, and paricalcitol), phosphate, or aluminum hydroxide antacids (e.g.,
Maalox® and Mylanta®) within 2 weeks prior to Screening or during the study
8. Have used medication to suppress PTH (e.g., Sensipar®, cinacalcet, calcimimetics)
within 2 months prior to Screening
9. Have a history of malignancy within 5 years of study entry with the exception of
PMT-MCT (Phosphaturic mesenchymal tumors of the mixed connective tissue type) tumors
or non-melanoma skin cancers such as basal cell skin cancer
10. Have donated blood or blood products within 60 days prior to Screening
11. Have a history of allergic reaction to or have shown adverse reactions to a
tetracycline (e.g., tetracycline HCl and demeclocycline), benzodiazepines, fentanyl or
lidocaine
12. Have any condition, which in the opinion of the investigator and sponsor, could
present a concern for either subject safety or difficulty with data interpretation
We found this trial at
7
sites
Durham, North Carolina 27710
(919) 684-8111
Principal Investigator: Tomas Weber, MD
Phone: 919-684-1674
Duke University Younger than most other prestigious U.S. research universities, Duke University consistently ranks among...
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Johns Hopkins University The Johns Hopkins University opened in 1876, with the inauguration of its...
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550 University Boulevard
Indianapolis, Indiana 46202
Indianapolis, Indiana 46202
Principal Investigator: Munro Peacock, MD
Phone: 317-274-0948
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Lakewood, Colorado 80337
Principal Investigator: Paul Miller, MD
Phone: 303-980-9475
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333 Cedar St
New Haven, Connecticut 06504
New Haven, Connecticut 06504
(203) 432-4771
Principal Investigator: Thomas Carpenter, MD
Phone: 203-785-3759
Yale University School of Medicine Founded in 1810, the Yale School of Medicine is a...
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