Study of KRN23 in Adult Subjects With Tumor-Induced Osteomalacia (TIO) or Epidermal Nevus Syndrome (ENS)

• Status: Active, not recruiting
• Trial end date: 0000-00-00
• Target enrollment: 15
• Participant gender: Both

Summary

UX023T-CL201 is an, open-label, Phase 2 study. The study will be conducted in adults aged 18 years or older with TIO or ENS whose tumor/skin lesion is inoperable to assess the efficacy and safety of KRN23 administered via subcutaneous injections monthly (every 4 weeks) for a total of 144 weeks. Subjects will need to discontinue oral phosphate and vitamin D metabolite therapy prior to randomization and throughout the duration of the study.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ultragenyx Pharmaceutical Inc
• Collaborator: Kyowa Hakko Kirin Korea Co., Ltd.
• Last Updated: 2016-04-21

Criteria

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 ≥2 times the upper limit of normal

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. Have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study (females of childbearing potential only). Females considered not of childbearing potential include those who have been in menopause for at least 2 years, have had tubal ligation at least 1 year prior to Screening, or have had a total hysterectomy

9. Be willing to use an acceptable method of contraception while participating in the study (sexually active subjects)

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 received chemotherapeutic pharmaceuticals for treatment of malignant tumors associated (or not associated) with TIO, within 4 months prior to Screening

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 tetracycline, 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