Open Label Study of KRN23 on Osteomalacia in Adults With X-linked Hypophosphatemia (XLH)

NCT02537431 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: UX023-CL304
• Study Type: interventional
• Target: 14
• Locations: 6 countries
• Sites: 14

Brief Summary

The primary objective of this study is to establish the effect of KRN23 treatment on improvement in XLH-associated osteomalacia as determined by osteoid volume (osteoid volume/bone volume, OV/BV).

Conditions

X-linked Hypophosphatemia

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline in OV/BV at Week 48

  OV/BV: percent of a given volume of bone tissue that consists of unmineralized bone (osteoid).

  Baseline, 48 weeks

Secondary Outcomes (25)

• Percentage 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

  Baseline, up to 24 weeks

• Percent Change From Baseline in O.Th at Week 48

  Baseline, 48 weeks

• Percent Change From Baseline in OS/BS at Week 48

  Baseline, 48 weeks

• Percent Change From Baseline in MLt at Week 48

  Baseline, 48 weeks

• Change From Baseline in MAR at Week 48

  Baseline, 48 weeks

Study Arms (1)

Open-Label Burosumab Q4W

EXPERIMENTAL

1.0 mg/kg burosumab monthly (Q4W), calculated based on baseline weight and up to a maximum dose of 90 mg.

Biological: burosumab

Interventions

burosumab BIOLOGICAL

solution for subcutaneous injection

Also known as: KRN23, UX023, Crysvita

Open-Label Burosumab Q4W

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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 homology to endopeptidases located on the X chromosome (PHEX) 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
• Biochemical findings consistent with XLH based on overnight fasting (min. 8 hours):
• Serum phosphorus \< 2.5 mg/dL at Screening
• Ratio of renal tubular maximum phosphate reabsorption rate to glomerular filtration rate (TmP/GFR) \< 2.5 mg/dL at Screening
• 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)
• Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min (using the Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] equation) or estimated glomerular filtration rate (eGFR) eGFR of 45 to \<60 mL/min at Screening with confirmation that the renal insufficiency is not due to nephrocalcinosis
• 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
• 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 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
• 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 may not qualify if:

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

Sponsors & Collaborators

• Kyowa Kirin, Inc.: lead
• Kyowa Kirin Co., Ltd.: collaborator

Study Sites (14)

UCSF Medical Center at Mission

San Francisco, California, 94158, United States

Location

Yale University School of Medicine - Yale New-Haven Hospital/Yale Center for Clinical Investigation

New Haven, Connecticut, 06510, United States

Location

Indiana University Department of Medicine University Hospital

Indianapolis, Indiana, 46202, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

Shriners Hospital for Children

Montreal, Quebec, H3G 1A6, Canada

Location

Aarhus University Hospital-Dept of Endocrinology and Internal Medicine

Aarhus, 8000, Denmark

Location

CHU de Bicêtre, Service d'Endocrinologie et des Maladies de la Reproduction

Le Kremlin-Bicêtre, 94275, France

Location

CHU Paris Centre - Hôpital Cochin

Paris, 75014, France

Location

Osaka University Hospital

Osaka, 565-0871, Japan

Location

Hokkaido University Hospital

Sapporo, 060-8648, Japan

Location

The University of Tokyo Hospital

Tokyo, 113-8655, Japan

Location

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

Related Publications (1)

• Fratzl-Zelman N, Hartmann MA, Gamsjaeger S, Rokidi S, Paschalis EP, Blouin S, Zwerina J. Bone Matrix Mineralization and Response to Burosumab in Adult Patients With X-Linked Hypophosphatemia: Results From the Phase 3, Single-Arm International Trial. J Bone Miner Res. 2022 Sep;37(9):1665-1678. doi: 10.1002/jbmr.4641. Epub 2022 Aug 10.

  PMID: 35775373 DERIVED

MeSH Terms

Conditions

Familial Hypophosphatemic Rickets

Interventions

burosumab

Condition Hierarchy (Ancestors)

Rickets, Hypophosphatemic; Rickets; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Hypophosphatemia, Familial; Renal Tubular Transport, Inborn Errors; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Calcium Metabolism Disorders; Hypophosphatemia; Phosphorus Metabolism Disorders; Vitamin D Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders

Results Point of Contact

• Title: Medical Information
• Organization: Ultragenyx Pharmaceutical Inc

Medinfo@ultragenyx.com

1-888-756-8657

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: August 25, 2015
• First Posted: September 1, 2015
• Study Start: December 23, 2015
• Primary Completion: August 30, 2017
• Study Completion: December 13, 2018
• Last Updated: June 18, 2024
• Results First Posted: September 25, 2018

Record last verified: 2024-06

Locations

US (5); DK (1); JP (3); CA (2); KR (1); FR (2)