Study to Assess the Safety, Pharmacokinetics and Efficacy of KRN23 in Pediatric Chinese Patients With XLH

NCT04842032 | Completed Phase 4

• 2 other identifiers: KRN23-CN006CTR20210505
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to assess the safety, pharmacokinetics and efficacy of KRN23 in pediatric Chinese patients with XLH

Conditions

X-linked Hypophosphatemia (XLH)

Outcome Measures

Primary Outcomes (1)

• Change from Baseline (CFB) in mean serum phosphorus level at the end of the dose cycle

  Weeks 2, 4, 8, 12, 16, 24, 32, 40, 52, and 64

Secondary Outcomes (17)

• Change in rickets at Weeks 40 and 64 as examined by the Radiograph Global Impression of Change (RGI-C) global score

  Weeks 40 and 64

• Change in Rickets Severity Score (RSS) total score at Weeks 40 and 64

  Weeks 40 and 64

• Change in lower extremity skeletal abnormalities, including genu varum and genu valgus, as determined by the RGI-C long leg score at Weeks 40 and 64

  Weeks 40 and 64

• Change in serum phosphorus over time

  Weeks 0, 1, 2, 4, 8, 12, 16, 24, 32, 40, 52, 64, and 74

• Change in serum 1,25-dihydroxyvitamin D (1,25(OH)2D) over time

  Weeks 0, 1, 2, 4, 8, 12, 16, 24, 32, 40, 52, 64, and 74

Other Outcomes (9)

• Safety of KRN23 by studying the number, severity and relatedness of Adverse Events (including laboratory and imaging assessments)

  Week 0 to Week 76

• Pharmacokinetics (PK): KRN23 concentrations

  Weeks 0, 1, 2, 4, 8, 16, 24, 40, 64, and 74

• Change from Week -14 to Baseline in serum phosphorus over time during Run-in Period

  Week -14, -10 and -4

Study Arms (1)

KRN23

EXPERIMENTAL

KRN23 0.8 mg/kg starting dose, administered Q2W by SC injection up to Week 64. Before KRN23 treatment, all patients will receive oral phosphate and vitamin D analogs for 12 weeks of Run-in period.

Drug: KRN23

Interventions

KRN23 DRUG

KRN23 is a sterile clear colourless and preservative free solution supplied in single use 5 mL vials containing 1 mL of KRN23 at a concentration of 30mg/mL

Also known as: Burosumab, Crysvita

KRN23

Eligibility Criteria

• Age: 1 Year - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female Chinese patients, aged 1 to ≤12 years at ICF signature with radiographic evidence of rickets
• Diagnosis of XLH supported by either of the following:
• Confirmed PHEX mutation (prior to the study with historic record) in the patient or a directly related family member with approximate X linked inheritance
• Serum intact FGF23 level ≥30 pg/mL by Kainos assay at Screening
• Able to receive conventional therapy (oral phosphate and pharmacologic vitamin D)
• Biochemical findings associated with XLH: Serum phosphorus \<3.0 mg/dL (0.97 mmol/L). Serum phosphorus may be re tested (once only) at least 7 days after discontinuation of therapy, if applicable (\[see Section 3.1\])
• Serum creatinine within age-adjusted normal range (based on overnight fasting \[minimum 4 hours\] values collected at Screening)
• Serum 25(OH)D above or equal to the lower limit of normal (≥16 ng/mL) at Screening. If 25(OH)D levels are below the normal range, 25(OH)D supplementation will be prescribed. Assuming a patient meets all other eligibility requirements, the patient may be re tested for serum 25(OH)D after a minimum of 7 days of treatment
• Willing to provide access to prior medical records for the collection of historical growth and radiographic data and disease history
• Written or verbal assent (as appropriate for the patient and region) by the patient and written informed consent by legally authorized representatives provided after the nature of the study has been explained, and prior to any research-related procedures
• Be willing and able to complete all aspects of the study, adhere to the study visit schedule and comply with the assessments, as judged by the investigator or subinvestigator
• Female patients who have reached menarche must have a negative pregnancy test at Screening and be willing to have additional pregnancy testing during the study. If sexually active, male and female patients must be willing to use an effective method of contraception for the duration of the study and for 12 weeks after the last dose of IP

You may not qualify if:

• Positive for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibody at Screening
• Tanner stage 4 or higher through physical examination
• Height percentile \>50% based on country specific norms
• Use of a pharmacologic vitamin D, its metabolites, or analogs, oral phosphate for treatment of XLH, aluminum hydroxide antacids, acetazolamide, thiazide diuretics, and/or systemic corticosteroids within 7 days prior to Week -14
• Current or prior use of leuprorelin, triptorelin, goserelin, or other drugs known to delay puberty
• Use of growth hormone therapy within 12 months before ICF signature
• Have uncontrolled diabetes mellitus, defined as glycated hemoglobin (HbA1c) \>8.5% at Screening
• Presence of nephrocalcinosis on renal ultrasound Grade 4 based on the following scale:
• Planned or recommended orthopedic surgery (implantation or removal), including staples, 8 plates, or osteotomy, within the first 40 weeks of the study
• Hypocalcemia or hypercalcemia, defined as serum calcium levels outside the age adjusted normal limits (based on overnight fasting \[minimum 4 hours\] values collected at the Screening)
• Evidence of hyperparathyroidism (parathyroid hormone \[PTH\] levels 2.5 × ULN)
• Use of medication to suppress PTH (e.g., Sensipar®, cinacalcet, calcimimetics) within 2 months prior to ICF signature
• Presence or history of any condition that, in the view of the investigator or subinvestigator, places the subject at high risk of poor treatment compliance or of not completing the study
• Presence of a concurrent disease or condition that would interfere with study participation or affect safety
• History of recurrent infection or predisposition to infection, or of known immunodeficiency

Sponsors & Collaborators

• Kyowa Kirin Co., Ltd.: lead

Study Sites (5)

Peking Union Medical College Hospital

Beijing, China

Location

Guangzhou Women and Children Medical Center

Guangzhou, China

Location

Shanghai 6th Hospital

Shanghai, China

Location

Shanghai Xinhua Hopsital

Shanghai, China

Location

Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology

Wuhan, China

Location

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

Study Officials

• KRN23 Study Director

  Kyowa Kirin Co., Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2021
• First Posted: April 12, 2021
• Study Start: November 1, 2021
• Primary Completion: December 18, 2023
• Study Completion: December 18, 2023
• Last Updated: July 9, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)