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Eligibility
for people ages 18 years to 65 years
Location
at San Francisco, California and other locations
Dates
study started
estimated completion:
Principal Investigator

Description

Summary

UX023-CL304 is a Phase 3 open-label, single-arm, multicenter study to establish the effects of KRN23 on bone quality and osteomalacia associated with XLH. Approximately 14 adult subjects with a diagnosis of XLH supported by typical clinical and biochemical features and who have not received oral phosphate and vitamin D therapy in the past two years will be enrolled. Iliac crest bone biopsies will be performed at baseline and end of study. Baseline histologic and histomorphometric assessments of the bone biopsy specimens will be performed as each biopsy is completed to assess sample quality and confirm the presence of osteomalacia in at least 8 subjects.

Official Title

An Open-Label, Single-Arm, Phase 3 Study to Evaluate the Effects of KRN23 on Osteomalacia in Adults With X-linked Hypophosphatemia (XLH)

Keywords

X-linked Hypophosphatemia KRN23 Fibroblast growth factor 23 (FGF23) XLH

Eligibility

You can join if…

Open to people ages 18 years to 65 years

  1. Male or female, aged 18 - 65 years, inclusive
  2. Diagnosis of XLH supported by classic clinical features of adult XLH (such as short stature or bowed legs), and at least ONE of the following at Screening:

    • Documented PHEX mutation in either the patient or in a directly related family member with appropriate X-linked inheritance
    • Serum intact FGF23 (iFGF23) level> 30 pg/mL by Kainos assay
  3. Biochemical findings consistent with XLH based on overnight fasting (min. 8 hours):

    • Serum phosphorus < 2.5 mg/dL at Screening
    • TmP/GFR < 2.5 mg/dL at Screening
  4. Presence of skeletal pain attributed to XLH/osteomalacia, as defined by a score of ≥4 on the Brief Pain Inventory question 3 (BPI-Q3, Worst Pain) at Screening. (Skeletal pain that, in the opinion of the investigator, is attributed solely to causes other than XLH/osteomalacia—for example, back pain or joint pain in the presence of severe osteoarthritis by radiograph in that anatomical location—in the absence of any skeletal pain likely attributed to XLH/osteomalacia should not be considered for eligibility)
  5. Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min (using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) or eGFR of 45 to <60 mL/min at Screening with confirmation that the renal insufficiency is not due to nephrocalcinosis
  6. Provide written informed consent after the nature of the study has been explained,and prior to any research-related procedures. If the subject in a minor, provide written assent and have a legally authorized representative willing and able to provide written informed consent, after the nature of the study has been explained,and prior to any research-related procedures
  7. Willing to provide access to prior medical records for the collection of biochemical and radiographic data and disease history
  8. Females of child-bearing potential must have a negative urine pregnancy test at Screening and be willing to have additional pregnancy tests during the study. Females considered not to be of childbearing potential include those who have been in menopause for at least two years prior to Screening, or have had tubal ligation at least one year prior to Screening, or have had a total hysterectomy or bilateral salpingo-oophorectomy.
  9. Participants of child‐bearing potential or with partners of child-bearing potential who have not undergone a total hysterectomy or a bilateral salpingo‐oophorectomy and are sexually active must consent to use two effective methods of contraception as determined by the site investigator (i.e. oral hormonal contraceptives, patch hormonal contraceptives, vaginal ring, intrauterine device, physical double-barrier methods, surgical hysterectomy, vasectomy, tubal ligation, or true abstinence) from the period following the signing of the informed consent through 12 weeks after last dose of study drug
  10. Must, in the opinion of the investigator, be willing and able to complete all aspects of the study, adhere to the study visit schedule and comply with the assessments

You CAN'T join if...

  1. Use of any pharmacologic vitamin D metabolite or analog (e.g. calcitriol,doxercalciferol, and paricalcitol) within the 2 years before Screening
  2. Use of oral phosphate within 2 years before Screening
  3. Use of aluminum hydroxide antacids, acetazolamides, and thiazides within 7 days prior to Screening
  4. Use of bisphosphonates in the 2 years prior to Screening
  5. Use of denosumab in the 6 months prior to Screening
  6. Use of teriparatide in the 2 months prior to Screening
  7. Chronic use of systemic corticosteroids defined as more than 10 days in the 2 months prior to Screening
  8. Corrected serum calcium level ≥ 10.8 mg/dL (2.7 mmol/L) at Screening
  9. Serum intact parathyroid hormone (iPTH) ≥ 2.5 times the upper limit of normal (ULN)at Screening
  10. Use of medication to suppress parathyroid hormone (PTH) (cinacalcet for example)within 60 days prior to Screening
  11. Prothrombin time/Partial thromboplastin time (PT/PTT) outside the normal range at Screening
  12. Evidence of any disease or use of anticoagulant medication (such as warfarin,heparin, direct thrombin inhibitors, or xabans that, in the opinion of the investigator, cannot be discontinued) that may increase the risk of bleeding during the biopsy procedure
  13. Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study
  14. Unable or unwilling to withhold prohibited medications throughout the study
  15. Documented dependence on narcotics
  16. Use of KRN23, or any other therapeutic monoclonal antibody within 90 days prior to Screening
  17. Use of investigational product or investigational medical device within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.

    OR, in Japan, use of any investigational product or investigational medical device within 4 months prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.

  18. Presence or history of any hypersensitivity, allergic or anaphylactic reactions to any monoclonal antibody or KRN23 excipients that, in the judgment of the investigator, places the subject at increased risk for adverse effects
  19. History of allergic reaction or adverse reactions to tetracycline or demeclocycline
  20. Prior history of positive test for human immunodeficiency virus antibody, hepatitis B surface antigen, and/or hepatitis C antibody
  21. History of recurrent infection (other than dental abscesses, which are known to be associated with XLH) or predisposition to infection, or of known immunodeficiency
  22. Presence of malignant neoplasm (except basal cell carcinoma)
  23. Presence of a concurrent disease or condition that would interfere with study participation or affect safety
  24. Presence or history of any condition that, in the view of the investigator, places the subject at high risk of poor treatment compliance or of not completing the study

Locations

  • Yale University School of Medicine - Yale New-Haven Hospital/Yale Center for Clinical Investigation
    New Haven, Connecticut, 06510, USA
  • Indiana University Department of Medicine University Hospital
    Indianapolis, Indiana, 46202, USA
  • Duke University Medical Center
    Durham, North Carolina, 27710, USA
  • Houston Methodist Hospital
    Houston, Texas, 77030, USA
  • Children's Hospital of Eastern Ontario
    Ottawa, Ontario, K1H 8L1, Canada
  • Shriners Hospital for Children
    Montreal, Quebec, H3G 1A6, Canada
  • Aarhus University Hospital-Dept of Endocrinology and Internal Medicine
    Aarhus, 8000, Denmark
  • CHU de Bicêtre, Service d'Endocrinologie et des Maladies de la Reproduction
    Le Kremlin-Bicêtre, 94275, France
  • CHU Paris Centre - Hôpital Cochin
    Paris, 75014, France
  • Osaka University Hospital
    Osaka, 565-0871, Japan
  • Hokkaido University Hospital
    Sapporo, 060-8648, Japan
  • The University of Tokyo Hospital
    Tokyo, 113-8655, Japan
  • Seoul National University Hospital
    Seoul, 110-744, Korea, Republic of

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Ultragenyx Pharmaceutical Inc
ID
NCT02537431
Phase
Phase 3
Lead Scientist
Anthony Portale
Study Type
Interventional
Last Updated
May 2016