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

NCT04842019 | Completed Phase 4

• 2 other identifiers: KRN23-CN005CTR20210506
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to assess the safety, pharmacokinetics and efficacy of KRN23 in adult 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 4, 8, 12, 16, 20, 24, 36, and 48

Secondary Outcomes (13)

• Change in Brief Pain Inventory (BPI) Worst Pain score over time

  Weeks 0, 12, 24, 36, and 48

• Change in BPI Pain Severity score and Pain Interference score over time

  Weeks 0, 12, 24, 36, and 48

• Change in BPI Pain Interference score over time

  Weeks 0, 12, 24, 36, and 48

• Change in the Stiffness and Physical Function domains of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) over time

  Weeks 0, 12, 24, 36, and 48

• Change in the health related QOL assessment by Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function over time

  Weeks 0, 12, 24, 36, and 48

Other Outcomes (18)

• Radiologic healing or resolution of pre-existing fractures and/or pseudofractures, as defined by skeletal survey at Baseline and subsequent targeted radiography

  Weeks 0, 12, 24, 36, and 48

• Change in enthesopathy spur at the calcaneus measured by lateral foot X-rays

  Weeks 0, 24 and 48

• Change in 6-minute walking test (6MWT) over time

  Weeks 0, 12, 24, 36, and 48

Study Arms (1)

KRN23

EXPERIMENTAL

KRN23 1 mg/kg administered subcutaneously (SC) every 4 weeks for 48 weeks. 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: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female Chinese patients, aged 18 to 65 years (inclusive) at the time of signing the ICF
• Diagnosis of XLH supported by classic clinical features of adult XLH (such as short stature or bowed legs) and at least either of the following at screening:
• Confirmed PHEX mutation (prior to the study with historic record) in the patient or a directly related family member with appropriate X linked inheritance
• Serum iFGF23 level ≥30 pg/mL by the Kainos assay at Screening
• Biochemical findings consistent with XLH following overnight fasting (≥8 hours) at Screening:
• Serum phosphorus \<2.5 mg/dL (0.81 mmol/L). Serum phosphorus level may be re tested (once only) at least 7 days after discontinuation of therapy, if applicable.
• TmP/GFR of \<2.5 mg/dL
• Presence of skeletal pain attributed to XLH/osteomalacia, as defined by a score of ≥4 on the BPI Worst Pain question at Screening (Skeletal pain that, in the opinion of the investigator or subinvestigator, is attributed solely to causes other than XLH/osteomalacia \[e.g., back pain or joint pain in the presence of severe osteoarthritis by radiograph in that anatomical location\] in the absence of any skeletal pain likely attributed to XLH/osteomalacia should not be considered for eligibility)
• Patients who are taking chronic pain medications (including narcotic pain medications/opioids) must be on a stable regimen for at least 21 days before signing the ICF and be willing to maintain the medications at the same stable dose(s) and schedule throughout the study. The dose must not exceed 60 mg oral morphine equivalents/day
• Able to receive conventional therapy (oral phosphate and pharmacologic vitamin D \[or metabolites/analogs\])
• Written informed consent provided 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
• Have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study (female patients of child-bearing potential only)
• Be willing to use an effective method of contraception while participating in the study (sexually active patients of child bearing potential) and for 12 weeks after last dose of study drug. Women of non child bearing potential are defined as permanently sterile (i.e. due to hysterectomy or bilateral oophorectomy) or postmenopausal (defined as at least 12 months postcessation of menses without an alternative medical cause). Postmenopausal status of female patients will be confirmed with a Screening serum follicle stimulating hormone (FSH) level \>40 mIU/mL
• 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

You may not qualify if:

• Use of a pharmacologic vitamin D, its metabolites, or analogs, and oral phosphate for treatment of XLH within 14 days prior to Screening.
• Use of aluminum hydroxide antacids, acetazolamide, thiazide diuretics and/or systemic corticosteroids within 14 days prior to Week -14
• Corrected serum calcium level ≥10.8 mg/dL (2.69 mmol/L) at Screening
• Plasma iPTH ≥2.5 times the upper limit of normal at Screening
• Uncontrolled diabetes mellitus, defined as HbA1c \>7.5% at Screening
• Use of medication to suppress PTH (e.g., Sensipar®, cinacalcet, calcimimetics) within 60 days before signing the ICF
• Use of oral bisphosphonates in the 2 years before signing the ICF
• Planned or recommended orthopedic surgery within the clinical trial period
• History of traumatic fracture or orthopedic surgery within 6 months before signing the ICF
• Use of KRN23, or any other therapeutic mAb within 90 days before signing the ICF
• Use of any investigational product or investigational medical device within 30 days before signing the ICF, or requirement for any investigational agent prior to completion of all scheduled study assessments
• Pregnant or breastfeeding at Screening or Week -14, or intention to become pregnant (the patient or partner) at any time during the study
• Unable or unwilling to withhold prohibited medications throughout the study
• Presence or history of any hypersensitivity, or allergic or anaphylactic reactions to any mAb or KRN23 excipients that, in the judgment of the investigator or subinvestigator, places the patient at increased risk for adverse effects
• Positive for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibody at Screening, or prior history of positive test

Sponsors & Collaborators

• Kyowa Kirin Co., Ltd.: lead

Study Sites (5)

Peking Union Medical College Hospital

Beijing, China

Location

The First Medical Center of Chinese People's Liberation Army General Hospital

Beijing, China

Location

Nanfang Hospital

Guangzhou, China

Location

The Second Affiliated Hospital of Zhejiang University

Hangzhou, China

Location

Shanghai 6th Hospital

Shanghai, 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 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: September 28, 2021
• Primary Completion: August 17, 2023
• Study Completion: August 17, 2023
• Last Updated: July 9, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)