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

Completed · Phase 3 · Has a placebo group

Conditions studied: X-linked Hypophosphatemia

In brief

The primary efficacy objective of this study is to establish the effect of burosumab treatment compared with placebo on increasing serum phosphorus levels in adults with XLH.

Key facts

Study ID

NCT02526160

Run by

Kyowa Kirin, Inc.

People needed

134

Starts

2015-10-22

Expected to finish

2018-12-06

Last updated by the study team

2024-06-18

Who can join

Age: 18 and older, up to 65. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Male or female, aged 18 - 65 years, inclusive
• 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
• 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
• 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)
• 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
• 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
• 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
• Willing to provide access to prior medical records for the collection of biochemical and radiographic data and disease history
• 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
• 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
• 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
• Must have completed at least 4 of 7 days of the patient diaries before the Baseline visit.

You may not qualify if…

• Use of a pharmacologic vitamin D metabolite or analog (calcitriol, doxercalciferol, and paricalcitol) within 14 days prior to Screening Visit 2
• Use of oral phosphate within 14 days prior to Screening Visit 2
• Use of aluminum hydroxide antacids, acetazolamides, and thiazides within 7 days prior to Screening Visit 2
• Chronic use of systemic corticosteroids defined as more than 10 days in the previous 2 months
• Corrected serum calcium level ≥ 10.8 mg/dL (2.7 mmol/L) at Screening Visit 2
• Serum intact parathyroid hormone (iPTH) ≥ 2.5 upper limit of normal (ULN) at Screening Visit 1
• Use of medication to suppress parathyroid hormone (PTH) (cinacalcet for example) within 60 days prior to Screening Visit 1
• Use of oral bisphosphonates for 6 months or more in the 2 years prior to Screening Visit 1
• Use of denosumab in the 6 months prior to Screening Visit 1
• Use of teriparatide in the 2 months prior to Screening Visit 1
• Planned or recommended orthopedic surgery within the first 24 weeks of the clinical trial period
• History of traumatic fracture or orthopedic surgery within 6 months prior to Screening Visit 1
• Use of KRN23, or any other therapeutic monoclonal antibody within 90 days prior to Screening Visit 1
• 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.
• Pregnant or breastfeeding at Screening /Baseline or planning to become pregnant (self or partner) at any time during the study
• Unable or unwilling to withhold prohibited medications throughout the study
• 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.
• Prior history of positive test for human immunodeficiency virus antibody, hepatitis B surface antigen, and/or hepatitis C antibody
• History of recurrent infection or predisposition to infection, or of known immunodeficiency
• Presence of malignant neoplasm (except basal cell carcinoma)
• Presence of a concurrent disease or condition that would interfere with study participation or affect safety
• 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

Where it is running

• Children's Hospital of Los Angeles — Los Angeles, California, United States
• University of California-San Francisco Medical Center — San Francisco, California, United States
• Yale University School of Medicine — New Haven, Connecticut, United States
• Indiana University Department of Medicine — Indianapolis, Indiana, United States
• Johns Hopkins University — Baltimore, Maryland, United States
• Duke University Medical Center — Durham, North Carolina, United States
• The Ohio State University Wexner Medical Center — Columbus, Ohio, United States
• Houston Methodist Hospital — Houston, Texas, United States
• CHU de Bicêtre, Service d'Endocrinologie et des Maladies de la Reproduction — Le Kremlin-Bicêtre, France
• Hôpital Lariboisière, Dept. of Rheumatology — Paris, France
• CHU Paris Centre-Hôpital Cochin — Paris, France
• St. Vincent's University Hospital — Dublin, Ireland
• Azienda Ospedaliero Universitaria Careggi - Neurofarba — Florence, Italy
• Okayama Saiseikai General Hospital — Okayama, Japan
• Osaka City University Hospital — Osaka, Japan
• Osaka University Hospital — Osaka, Japan
• Toranomon Hospital — Tokyo, Japan
• The University of Tokyo Hospital — Tokyo, Japan
• Seoul National University Hospital — Seoul, South Korea
• Asan Medical Center — Seoul, South Korea
• University of Edinburgh Edinburgh Clinical Trials Unit (ECTU) - Western General Hospital — Edinburgh, United Kingdom
• Univeristy College of London Hospital — London, United Kingdom
• University of Oxford — Oxford, United Kingdom
• Northern General Hospital, Metabolic Bone Centre (Sorby Wing) — Sheffield, United Kingdom
• Royal National Orthopaedic Hospital — Stanmore, United Kingdom

Full record on ClinicalTrials.gov

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