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

NCT02312687 | Completed Phase 2 Results

• 1 other identifier: UX023-CL203
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 5

Brief Summary

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)

Conditions

X-Linked Hypophosphatemia

Keywords

XLH; FGF23; KRN23

Outcome Measures

Primary Outcomes (25)

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

  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.

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

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

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

  Through Week 184

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

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

  Through Week 184

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

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

  Through Week 184

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

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

  Through Week 184

• Number of Participants With Clinically Significant Changes From Baseline in ECGs

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

  Through Week 184

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

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

  Through Week 184

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

  Through Week 184

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

  Through Week 184

• Change From Baseline Over Time in Serum Phosphorus

  Baseline, Weeks 24, 48, 72, 96, 120, 144

• Change From Baseline Over Time in Serum iPTH

  Baseline, Weeks 24, 48, 72, 96, 120, 144

• Change From Baseline Over Time in Serum Total FGF23

  Baseline, Weeks 24, 48, 72, 96, 120, 144

• Change From Baseline Over Time in Serum Free FGF23

  Baseline, Weeks 24, 48, 72, 96, 120, 144

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

  Baseline, Weeks 24, 48, 72, 96, 120, 144

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

  Baseline, Weeks 24, 48, 72, 96, 120, 144

• Change From Baseline Over Time in in 2-hour Urine TRP

  Baseline, Weeks 24, 48, 72, 96, 120, 144

• Change From Baseline Over Time in FEP

  Baseline, Weeks 24, 48, 72, 96, 120, 144

• Change From Baseline Over Time in 24-hour Urine Phosphorus

  Baseline, Weeks 24, 48, 72, 96, 120, 144

• Change From Baseline Over Time in 24-Hour Urine Calcium

  Baseline, Weeks 24, 48, 72, 96, 120, 144

• Change From Baseline Over Time in 24-Hour Urine Creatinine

  Baseline, Weeks 24, 48, 72, 96, 120, 144

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

  Baseline, Weeks 24, 48, 72, 96, 120, 144

• Change From Baseline Over Time in Total ALP

  Baseline, Weeks 24, 48, 72, 96, 120, 144

• Change From Baseline Over Time in BALP

  Baseline, Weeks 24, 48, 72, 96, 120, 144

• Change From Baseline Over Time in CTx

  Baseline, Weeks 24, 48, 72, 96, 120, 144

• Change From Baseline Over Time in P1NP

  Baseline, Weeks 24, 48, 72, 96, 120, 144

Study Arms (1)

KRN23

EXPERIMENTAL

KRN23 subcutaneous (SC) injections every 4 weeks. Starting doses will be based on the subject's last dose in study KRN23-INT-001 (NCT02312687) or KRN23-INT-002 (NCT01571596). Doses may be titrated to achieve the target peak serum phosphorus range.

Biological: KRN23

Interventions

KRN23 BIOLOGICAL

solution for SC injection

Also known as: burosumab, Crysvita®

KRN23

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (5)

University California San Francisco Hospital

San Francisco, California, 94143, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

Location

Indiana University Hospital

Indianapolis, Indiana, 46202, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Houston Methodist Reasearch Institute

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Weber TJ, Imel EA, Carpenter TO, Peacock M, Portale AA, Hetzer J, Merritt JL, Insogna K. Long-term Burosumab Administration Is Safe and Effective in Adults With X-linked Hypophosphatemia. J Clin Endocrinol Metab. 2022 Dec 17;108(1):155-165. doi: 10.1210/clinem/dgac518.

  PMID: 36072994 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

1-888-756-8567

Study Officials

• Medical Director

  Ultragenyx Pharmaceutical Inc

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: December 3, 2014
• First Posted: December 9, 2014
• Study Start: January 30, 2015
• Primary Completion: November 30, 2018
• Study Completion: November 30, 2018
• Last Updated: May 6, 2024
• Results First Posted: December 16, 2019

Record last verified: 2024-05

Locations

US (5)