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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02304367
First Posted: December 1, 2014
Last Update Posted: May 4, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc
  Purpose
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.

Condition Intervention Phase
Tumor Induced Osteomalacia (TIO) Epidermal Nevus Syndrome (ENS) Drug: KRN23 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Ultragenyx Pharmaceutical Inc:

Primary Outcome Measures:
  • 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 Outcome Measures:
  • 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 ]

Enrollment: 17
Actual Study Start Date: April 23, 2015
Estimated Study Completion Date: May 2019
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: All Subjects
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.
Drug: 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).

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 ≥ 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02304367


Locations
United States, Colorado
Colorado Center for Bone Research
Lakewood, Colorado, United States, 80227
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06520-8064
United States, Indiana
Indiana University Hospital
Indianapolis, Indiana, United States, 46202
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21224
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27705
United States, Texas
Houston Methodist University
Houston, Texas, United States, 77030
Sponsors and Collaborators
Ultragenyx Pharmaceutical Inc
  More Information

Responsible Party: Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier: NCT02304367     History of Changes
Other Study ID Numbers: UX023T-CL201
First Submitted: November 24, 2014
First Posted: December 1, 2014
Last Update Posted: May 4, 2017
Last Verified: May 2017

Keywords provided by Ultragenyx Pharmaceutical Inc:
TIO
ENS
FGF23
KRN23

Additional relevant MeSH terms:
Syndrome
Nevus
Osteomalacia
Neoplasms, Connective Tissue
Nevus, Sebaceous of Jadassohn
Disease
Pathologic Processes
Nevi and Melanomas
Neoplasms by Histologic Type
Neoplasms
Rickets
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Metabolic Diseases
Calcium Metabolism Disorders
Vitamin D Deficiency
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Neoplasms, Connective and Soft Tissue
Connective Tissue Diseases
Neurocutaneous Syndromes
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities