Overview

This trial is active, not recruiting.

Conditions tumor induced osteomalacia (tio), epidermal nevus syndrome (ens)
Treatment krn23
Phase phase 2
Sponsor Ultragenyx Pharmaceutical Inc
Start date April 2015
End date July 2017
Trial size 17 participants
Trial identifier NCT02304367, UX023T-CL201

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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Intervention model single group assignment
Primary purpose treatment
Masking no masking
Arm
(Experimental)
Subjects will receive sub-cutaneous injections of KRN23 every 4 weeks from Week 0 through Week 44 during the Treatment Period and every 4 weeks from Week 48 through Week 140 during the Treatment Extension Period. All enrolled subjects will begin treatment with KRN23 at a starting dose of 0.3 mg/kg (Week 0). Doses may be titrated to achieve the target peak serum phosphorus range.
krn23
KRN23 is a recombinant fully human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to and inhibits the activity of fibroblast growth factor 23 (FGF23).

Primary Outcomes

Measure
The proportion of subjects achieving mean serum phosphorus levels above the lower limit of normal.
time frame: 48 Weeks
Percent change from baseline in excess osteoid based on analysis of iliac crest bone biopsies after 48 weeks of KRN23 treatment
time frame: 48 Weeks

Secondary Outcomes

Measure
Incidence, frequency, and severity of adverse events and serious adverse
time frame: 144 Weeks
PK profile of serum levels of KRN23 to assess KRN23 concentration and possible accumulation
time frame: Baseline (Weeks 0, 2, 4) and 6 months (Weeks 20, 22, 24)
Change from Baseline in serum FGF23
time frame: 144 weeks
Change from Baseline in serum ALP
time frame: 144 weeks
Change from Baseline in serum 1,25(OH)2D
time frame: 144 weeks
Change from Baseline in serum phosphorus
time frame: 144 weeks
Change from Baseline in TRP and TMP/GFR
time frame: 144 weeks
Change from Baseline in biomarkers of bone turnover biomarkers including BALP, CTx, P1NP, and osteocalcin
time frame: 144 weeks
Brief Fatigue Inventory (BFI)
time frame: 144 Weeks
Brief Pain Inventory (BPI)
time frame: 144 Weeks
Short Form Health Survey (SF36)
time frame: 144 Weeks
Western Ontario and McMaster Universities osteoarthritis index (WOMAC)
time frame: 48 Weeks
Sit to Stand (STS)
time frame: 48 Weeks
Hand Held Dynamometry (HHD)
time frame: 48 Weeks
Timed Up and Go (TUG)
time frame: 48 Weeks
Weighted Arm Lift (WAL) test
time frame: 48 weeks
6-Minute Walk Test
time frame: 48 Weeks

Eligibility Criteria

All participants at least 18 years old.

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. 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), and for 12 weeks after the last dose of study drug 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

Additional Information

Official title 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
Trial information was received from ClinicalTrials.gov and was last updated in February 2017.
Information provided to ClinicalTrials.gov by Ultragenyx Pharmaceutical Inc.