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

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ClinicalTrials.gov Identifier: NCT02304367
Recruitment Status : Active, not recruiting
First Posted : December 1, 2014
Last Update Posted : July 20, 2018
Sponsor:
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc

Brief Summary:

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).

Condition or disease Intervention/treatment Phase
Tumor Induced Osteomalacia (TIO) Epidermal Nevus Syndrome (ENS) Biological: KRN23 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
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
Actual Study Start Date : March 24, 2015
Actual Primary Completion Date : July 27, 2017
Estimated Study Completion Date : December 31, 2019


Arm Intervention/treatment
Experimental: KRN23 0.3 mg/kg
KRN23 starting dose 0.3 mg/kg administered subcutaneously (SC) every 4 weeks (Q4W). Doses may be titrated up to a maximum of 2.0 mg/kg every 2 weeks (Q2W).
Biological: KRN23
Solution for SC injection
Other Names:
  • burosumab
  • Crysvita®
  • UX023




Primary Outcome Measures :
  1. Proportion of Participants Achieving Mean Serum Phosphorus Levels Above the Lower Limit of Normal (LLN) at the Mid-Point of the Dose Interval, as Averaged Across Dose Cycles Between Baseline and Week 24 [ Time Frame: Baseline, Week 24 ]
  2. Change From Baseline in Osteoid Thickness (O.Th) at Week 48 [ Time Frame: Baseline, Week 48 ]
  3. Change From Baseline in Osteoid Surface/Bone Surface (OS/BS) at Week 48 [ Time Frame: Baseline, Week 48 ]
  4. Change From Baseline in Osteoid Volume/Bone Volume (OV/BV) at Week 48 [ Time Frame: Baseline, Week 48 ]
  5. Change From Baseline in Mineralization Lag Time (MLt) at Week 48 [ Time Frame: Baseline, Week 48 ]

Secondary Outcome Measures :
  1. Proportion of Participants Achieving Mean Serum Phosphorus Levels Above the LLN at the End of the Dosing Cycle (4 Weeks After Dosing), as Averaged Across Dose Cycles Between Baseline and Week 24 [ Time Frame: Baseline, Week 24 ]
  2. Mean Change From Baseline in Serum Phosphorus Levels at the Mid-Point of the Dose Interval, as Averaged Across Dose Cycles Between Baseline and Week 24 [ Time Frame: Baseline, Week 24 ]
  3. Percent Change From Baseline in Serum Phosphorus Levels at the Mid-Point of the Dose Interval, as Averaged Across Dose Cycles Between Baseline and Week 24 [ Time Frame: Baseline, Week 24 ]
  4. Mean Change From Baseline in Serum Phosphorus Levels at the End of the Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24 [ Time Frame: Baseline, Week 24 ]
  5. Percent Change From Baseline in Serum Phosphorus Levels at the End of the Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24 [ Time Frame: Baseline, Week 24 ]
  6. Time-Adjusted Area Under the Curve (AUC) of Serum Phosphorus Levels Between Baseline and Week 24 [ Time Frame: Baseline, Week 24 ]
  7. Change From Baseline Over Time in Serum 1,25-dihydroxyvitamin D (1,25(OH)2D) [ Time Frame: Baseline, up to Week 244 (or 31 Dec 2019) ]
  8. Change From Baseline Over Time in Serum Fibroblast growth factor 23 (FGF23) [ Time Frame: Baseline, up to Week 244 (or 31 Dec 2019) ]
  9. Change From Baseline Over Time in Alkaline phosphatase (ALP) [ Time Frame: Baseline, up to Week 244 (or 31 Dec 2019) ]
  10. Change From Baseline Over Time in Urinary Phosphorus [ Time Frame: Baseline, up to Week 244 (or 31 Dec 2019) ]
  11. Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) [ Time Frame: Baseline, up to Week 244 (or 31 Dec 2019) ]
  12. Change From Baseline Over Time in Ratio of Renal Tubular Maximum Phosphate Reabsorption Rate to Glomerular Filtration Rate (TmP/GFR) [ Time Frame: Baseline, up to Week 244 (or 31 Dec 2019) ]
  13. Change From Baseline Over Time in Bone-Specific Alkaline Phosphatase (BALP) [ Time Frame: Baseline, up to Week 244 (or 31 Dec 2019) ]
  14. Percent Change From Baseline Over Time in BALP [ Time Frame: Baseline, up to Week 244 (or 31 Dec 2019) ]
  15. Change From Baseline Over Time in Carboxy Terminal Cross-Linked Telopeptide of Type 1 Collagen (CTx) [ Time Frame: Baseline, up to Week 244 (or 31 Dec 2019) ]
  16. Percent Change From Baseline Over Time in CTx [ Time Frame: Baseline, up to Week 244 (or 31 Dec 2019) ]
  17. Change From Baseline Over Time in Procollagen Type 1 N-Propeptide (P1NP) [ Time Frame: Baseline, up to Week 244 (or 31 Dec 2019) ]
  18. Percent Change From Baseline Over Time in P1NP [ Time Frame: Baseline, up to Week 244 (or 31 Dec 2019) ]
  19. Change From Baseline Over Time in Osteocalcin [ Time Frame: Baseline, up to Week 244 (or 31 Dec 2019) ]
  20. Percent Change From Baseline Over Time in Osteocalcin [ Time Frame: Baseline, up to Week 244 (or 31 Dec 2019) ]
  21. Change From Baseline Over Time in Hand-Held Dynamometry (HHD) [ Time Frame: Baseline, up to Week 244 (or 31 Dec 2019) ]
  22. Change From Baseline Over Time in Sit-to-Stand (STS) Test [ Time Frame: Baseline, up to Week 244 (or 31 Dec 2019) ]
  23. Change From Baseline Over Time in Weighted Arm Lift (WAL) Test [ Time Frame: Baseline, up to Week 244 (or 31 Dec 2019) ]
  24. Change From Baseline Over Time in Six-Minute Walk Test (6MWT) [ Time Frame: Baseline, up to Week 244 (or 31 Dec 2019) ]
  25. Change From Baseline Over Time in Brief Pain Inventory (BPI) [ Time Frame: Baseline, up to Week 244 (or 31 Dec 2019) ]
  26. Change From Baseline Over Time in Brief Fatigue Inventory (BFI) [ Time Frame: Baseline, up to Week 244 (or 31 Dec 2019) ]
  27. Change From Baseline Over Time in 36-Item Short Form Health Survey (SF-36) [ Time Frame: Baseline, up to Week 244 (or 31 Dec 2019) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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. 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

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 Research Institute
Houston, Texas, United States, 77030
Sponsors and Collaborators
Ultragenyx Pharmaceutical Inc
Investigators
Study Director: Medical Director Ultragenyx Pharmaceutical Inc

Responsible Party: Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier: NCT02304367     History of Changes
Other Study ID Numbers: UX023T-CL201
First Posted: December 1, 2014    Key Record Dates
Last Update Posted: July 20, 2018
Last Verified: July 2018

Keywords provided by Ultragenyx Pharmaceutical Inc:
TIO
ENS
FGF23
KRN23

Additional relevant MeSH terms:
Osteomalacia
Syndrome
Nevus
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