We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov Menu

Study of KRN23 in Adults With X-linked Hypophosphatemia (XLH)

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.
ClinicalTrials.gov Identifier: NCT02526160
Recruitment Status : Active, not recruiting
First Posted : August 18, 2015
Last Update Posted : February 15, 2018
Kyowa Hakko Kirin Co., Ltd
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc

Brief Summary:
UX023-CL303 is a phase 3 multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of KRN23 in adult subjects with XLH. Approximately 120 subjects with a diagnosis of XLH supported by clinical and biochemical features consistent with XLH and/or a confirmed PHEX mutation (self or family member consistent with X-linked inheritance) and with bone or joint pain at baseline will be enrolled. Subjects not receiving supplementation therapy with oral phosphate and active vitamin D metabolites or those willing to discontinue supplementation therapy are eligible.

Condition or disease Intervention/treatment Phase
X-linked Hypophosphatemia Biological: KRN23 Other: Placebo Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 134 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Assess the Efficacy and Safety of KRN23 in Adults With X-linked Hypophosphatemia (XLH)
Study Start Date : October 2015
Primary Completion Date : December 22, 2016
Estimated Study Completion Date : September 30, 2018

Arm Intervention/treatment
Experimental: KRN23 1 mg/kg
KRN23 1 mg/kg administered subcutaneously (SC) every 4 weeks, for the duration of the study.
Biological: KRN23
solution for SC injection
Other Name: UX023
Placebo Comparator: Placebo
Placebo administered SC every 4 weeks through Week 24, followed by KRN23 1 mg/kg, for the duration of the study.
Biological: KRN23
solution for SC injection
Other Name: UX023
Other: Placebo
saline solution for SC injection

Primary Outcome Measures :
  1. Proportion of subjects achieving mean serum phosphorus levels above the lower limit of normal [ Time Frame: 24 weeks ]

Secondary Outcome Measures :
  1. Brief Pain Inventory (BPI) Q3 pain [ Time Frame: 24 weeks ]
  2. Serum 1,25-dihydroxyvitamin D (1,25(OH)2D) [ Time Frame: 24 weeks ]
  3. Proportion of subjects achieving mean serum phosphorus levels above the Lower Limit of Normal (LLN) at the end of the dosing cycle, mid-point of dosing cycle,end of dosing cycle and cumulative exposure [ Time Frame: 24 weeks ]
  4. Procollagen type 1 N-propeptide (P1NP) [ Time Frame: 24 weeks ]
  5. BPI Pain Severity [ Time Frame: 24 weeks ]
  6. Stiffness and Physical Function domains of the Western Ontario and McMaster University Osteoarthritis Index (WOMAC®) [ Time Frame: 24 weeks ]
  7. Urinary phosphorus [ Time Frame: 24 weeks ]
  8. Tubular reabsorption of phosphate (TRP) [ Time Frame: 24 weeks ]
  9. Ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) [ Time Frame: 24 weeks ]
  10. Carboxy-terminal cross-linked telopeptide of type I collagen (CTx) [ Time Frame: 24 weeks ]
  11. Bone-specific alkaline phosphatase (BALP) [ Time Frame: 24 weeks ]
  12. Brief Fatigue Inventory (BFI) Severity [ Time Frame: 24 weeks ]

Other Outcome Measures:
  1. Time to radiologic healing or resolution of pre-existing pseudofractures and/or Looser zones [ Time Frame: 24 weeks ]
  2. Patient global impression of improvement (PGI-I) [ Time Frame: 24 weeks ]
  3. Six Minute Walk Test (6MWT) total distance walked (meters) [ Time Frame: 24 weeks ]
  4. Six Minute Walk Test (6MWT) percent predicted distance [ Time Frame: 24 weeks ]
  5. Incidence, frequency and severity of Adverse Events (AEs) and serious adverse events (SAEs) [ Time Frame: 24 weeks ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  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 phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) mutation in the patient or 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 at Screening Visit 2 following overnight fasting (min. 8 hours):

    • Serum phosphorus < 2.5 mg/dL
    • TmP/GFR of < 2.5 mg/dL
  4. Presence of skeletal pain attributed to XLH/osteomalacia, as defined by a score of ≥ 4 on Brief Pain Inventory (BPI) Questions 3 (Worst Pain) at Screening Visit 1. (Skeletal pain that, in the opinion of the investigator, is attributed solely to causes other than XLH/osteomalacia—for example, back 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 60 mL/min at Screening Visit 2 with confirmation that the renal insufficiency is not due to nephrocalcinosis
  6. If taking chronic pain medications (including narcotic pain medications/opioids), must be on a stable regimen for at least 21 days prior to Screening Visit 1, and be willing to maintain medications at the same stable dose(s) and schedule throughout the Placebo-controlled Treatment Period of the study. The dose must not exceed 60 mg oral morphine equivalents/day
  7. Provide written informed consent or if a minor, provide written consent 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
  8. Willing to provide access to prior medical records for the collection of biochemical and radiographic data and disease history
  9. 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
  10. Participants of child‐bearing potential or with partners of child-bearing potential who have not undergone a bilateral salpingo‐oophorectomy and are sexually active must consent to use an effective method 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
  11. 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
  12. Must have completed at least 4 of 7 days of the patient diaries before the Baseline visit.

Exclusion Criteria:

  1. Use of a pharmacologic vitamin D metabolite or analog (calcitriol, doxercalciferol, and paricalcitol) within 14 days prior to Screening Visit 2
  2. Use of oral phosphate within 14 days prior to Screening Visit 2
  3. Use of aluminum hydroxide antacids, acetazolamides, and thiazides within 7 days prior to Screening Visit 2
  4. Chronic use of systemic corticosteroids defined as more than 10 days in the previous 2 months
  5. Corrected serum calcium level ≥ 10.8 mg/dL (2.7 mmol/L) at Screening Visit 2
  6. Serum intact parathyroid hormone (iPTH) ≥ 2.5 upper limit of normal (ULN) at Screening Visit 1
  7. Use of medication to suppress parathyroid hormone (PTH) (cinacalcet for example) within 60 days prior to Screening Visit 1
  8. Use of oral bisphosphonates for 6 months or more in the 2 years prior to Screening Visit 1
  9. Planned or recommended orthopedic surgery within the first 24 weeks of the clinical trial period
  10. History of traumatic fracture or orthopedic surgery within 6 months prior to Screening Visit 1
  11. Use of KRN23, or any other therapeutic monoclonal antibody within 90 days prior to Screening Visit 1
  12. Use of any investigational product or investigational medical device within 30 days prior to Screening Visit 1, 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.

  13. Pregnant or breastfeeding at Screening /Baseline 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. 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.
  16. Prior history of positive test for human immunodeficiency virus antibody, hepatitis B surface antigen, and/or hepatitis C antibody
  17. History of recurrent infection or predisposition to infection, or of known immunodeficiency
  18. Presence of malignant neoplasm (except basal cell carcinoma)
  19. Presence of a concurrent disease or condition that would interfere with study participation or affect safety
  20. 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

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): NCT02526160

  Show 25 Study Locations
Sponsors and Collaborators
Ultragenyx Pharmaceutical Inc
Kyowa Hakko Kirin Co., Ltd

Responsible Party: Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier: NCT02526160     History of Changes
Other Study ID Numbers: UX023-CL303
First Posted: August 18, 2015    Key Record Dates
Last Update Posted: February 15, 2018
Last Verified: February 2018

Keywords provided by Ultragenyx Pharmaceutical Inc:
Fibroblast growth factor 23 (FGF23)
X-linked hypophosphatemia

Additional relevant MeSH terms:
Familial Hypophosphatemic Rickets
Phosphorus Metabolism Disorders
Metabolic Diseases
Rickets, Hypophosphatemic
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Hypophosphatemia, Familial
Renal Tubular Transport, Inborn Errors
Kidney Diseases
Urologic Diseases
Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Calcium Metabolism Disorders
Vitamin D Deficiency
Deficiency Diseases
Nutrition Disorders