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Completed

NCT Number: NCT02312687

Long-Term Extension Study of KRN23 in Adult Subjects With X-Linked Hypophosphatemia (XLH)

The primary objectives of this study are to:

* Assess the long-term safety of KRN23 subcutaneous (SC) administration in adult subjects with XLH * Assess the proportion of subjects achieving serum phosphorus levels in the normal range (2.5-4.5 mg/dL) with long-term administration of KRN23 * Assess long-term pharmacodynamics (PD) of KRN23 as measured by changes in the following: serum intact parathyroid hormone (iPTH); serum and urinary phosphorus; ratio of renal tubular maximum phosphate reabsorption rate to glomerular filtration rate (TmP/GFR) and tubular reabsorption of phosphate (TRP); serum 1,25-dihydroxy vitamin D (1,25[OH]2D); serum fibroblast growth factor 23 (FGF23); bone biomarkers: serum alkaline phosphatase (ALP), bone-specific ALP (BALP), carboxy terminal crosslinked telopeptide of type I collagen (CTx), and procollagen type 1 N-terminal propeptide (P1NP) * Assess long-term immunogenicity of KRN23 as measured by presence of anti-KRN23 antibody (ADA)

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Key information

Conditions

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

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University California San Francisco Hospital, San Francisco, California, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Have participated in Kyowa Hakko Kirin Pharma, Inc.'s KRN23-INT-001 (NCT01340482) or KRN23-INT-002 (NCT01571596) studies (received at least 2 doses of KRN23)
  • Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min or eGFR of 45 to < 60 mL/min at Screening with confirmation that the renal insufficiency was not due to nephrocalcinosis.
  • Sexually active subjects must be willing to use an acceptable method of contraception (e.g., double barrier method) while participating in the study and for 30 days after receiving the last dose of KRN23.

Exclusion criteria

  • Subject experienced a safety-related event in the KRN23-INT-001 or KRN23-INT-002 study that, in the opinion of the investigator and sponsor, precludes resuming KRN23 treatment.
  • Presence of nephrocalcinosis on renal ultrasound that, in the opinion of the investigator and sponsor, precludes resuming KRN23 treatment.
  • Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study.
  • Participation in an investigational drug or device trial within 30 days of enrollment (other than KRN23-INT-001 or KRN23-INT-002).
  • Use of a pharmacologic vitamin D metabolite or analog (e.g., calcitriol, doxercalciferol, and paricalcitol), phosphate, or aluminum hydroxide antacids (e.g., Maalox® and Mylanta®) within 21 days prior to Screening or during the study.
  • Use of medication to suppress parathyroid hormone (PTH) (e.g., Sensipar®, cinacalcet, calcimimetics) within 2 months prior to Screening.

Treatment and study plan

KRN23

Biological

solution for SC injection

Other names: burosumab, Crysvita®

Primary outcomes

  1. Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious AEs (SAEs), and AEs Leading to Discontinuation or Death

    Time frame: Screening through the end of study plus 4-8 weeks. The mean duration of burosumab exposure was 165.6 weeks (range: 68-184 weeks).

    An AE is defined as any untoward medical occurrence, whether or not considered drug related. An SAE or serious suspected adverse reaction is an AE or suspected adverse reaction that at any dose, in the view of either the investigator or sponsor, results in any of the following outcomes: death; a life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; a congenital anomaly/birth defect; an important medical event. A TEAE is an AE that occurred on or after the first burosumab dose. AEs were graded as 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). AEs were classified by the Investigator as possibly related, probably related, or definitely related.

  2. Number of Participants With Clinically Significant Changes From Baseline in Vital Signs

    Time frame: Through Week 184

    Clinically significant changes from baseline reported as adverse events are presented.

  3. Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category

    Time frame: Through Week 184

    Clinically significant changes from baseline reported as adverse events are presented.

  4. Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category

    Time frame: Through Week 184

    Clinically significant changes from baseline reported as adverse events are presented.

  5. Number of Participants With Clinically Significant Changes From Baseline in Echocardiogram (ECHO) Tests

    Time frame: Through Week 184

    Clinically significant changes from baseline reported as adverse events are presented.

  6. Number of Participants With Clinically Significant Changes From Baseline in ECGs

    Time frame: Through Week 184

    Clinically significant changes from baseline reported as adverse events are presented.

  7. Number of Participants With Clinically Significant Changes From Baseline in Renal Ultrasound, by Category

    Time frame: Through Week 184

    Clinically significant changes from baseline reported as adverse events are presented.

  8. Number of Participants Positive for Anti-KRN23 Antibodies and Neutralizing Antibodies at Baseline and Anytime Post-Baseline

    Time frame: Through Week 184

  9. Percentage of Participants Reaching Serum Phosphorus Normal Range at Baseline and Any Time After Dosing

    Time frame: Through Week 184

  10. Change From Baseline Over Time in Serum Phosphorus

    Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144

  11. Change From Baseline Over Time in Serum iPTH

    Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144

  12. Change From Baseline Over Time in Serum Total FGF23

    Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144

  13. Change From Baseline Over Time in Serum Free FGF23

    Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144

  14. Change From Baseline Over Time in Serum 1,25(OH)2D

    Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144

  15. Change From Baseline Ovr Time in 2-hour Urine TmP/GFR

    Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144

  16. Change From Baseline Over Time in in 2-hour Urine TRP

    Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144

  17. Change From Baseline Over Time in FEP

    Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144

  18. Change From Baseline Over Time in 24-hour Urine Phosphorus

    Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144

  19. Change From Baseline Over Time in 24-Hour Urine Calcium

    Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144

  20. Change From Baseline Over Time in 24-Hour Urine Creatinine

    Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144

  21. Change From Baseline Over Time in 24-Hour Urine Calcium/Creatinine Ratio

    Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144

  22. Change From Baseline Over Time in Total ALP

    Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144

  23. Change From Baseline Over Time in BALP

    Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144

  24. Change From Baseline Over Time in CTx

    Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144

  25. Change From Baseline Over Time in P1NP

    Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144

Sponsors and collaborators

Lead sponsor

Kyowa Kirin, Inc.

Industry

Collaborators

  • Kyowa Kirin Co., Ltd.

Registry information

Official study title

A Phase 2b, Open-Label, Long-Term Extension Study to Evaluate the Safety and Pharmacodynamics of KRN23 in Adult Subjects With X-Linked Hypophosphatemia (XLH)

Important dates

Study start
2015
Primary completion
2018
Study completion
2018
First posted
Dec 9, 2014
Registry last updated
May 6, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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