Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of Burosumab in Patients Less Than 1 Year of Age

NCT04188964 | Completed Phase 1 DMC

• 1 other identifier: BUR-CL207
• Study Type: interventional
• Target: 16
• Locations: 6 countries
• Sites: 9

Brief Summary

A Phase 1/2, Open-label, Multicenter, Non-randomized Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of Burosumab in Paediatric Patients from Birth to Less than 1 Year of Age with X-linked Hypophosphatemia (XLH)

Conditions

X-linked Hypophosphatemia (XLH)

Outcome Measures

Primary Outcomes (1)

• To assess the safety and tolerability of Burosumab in paediatric subjects with X-linked Hypophosphatemia (XLH) starting treatment below 12 months of age

  Incidence, frequency, and severity of adverse events (AEs) and serious AEs (SAEs), including clinically significant changes in laboratory, physical examinations, vital signs, ECGs and imaging assessments

  From Baseline to scheduled time points (measured throughout the study up to Week 48).

Secondary Outcomes (7)

• To characterize the pharmacokinetics (PK) of Burosumab following subcutaneous (SC) injection in paediatric subjects with XLH below 12 months of age.

  Measured throughout the study up to Week 48

• To characterize the effect of Burosumab on serum phosphate and 1,25-dihydroxyvitamin D (1,25[OH]2D) in paediatric subjects with XLH starting treatment below 12 months of age

  Change from Baseline at Week 20, 26, 32, 40 and 48

• To assess the clinical effects of Burosumab on growth and prevention and/or healing of rickets and skeletal deformities

  Baseline and Week 48

• To assess the clinical effects of Burosumab on growth and prevention and/or healing of rickets and skeletal deformities

  At week 48

• To assess the clinical effects of burosumab on growth and prevention and/or healing of rickets and skeletal deformities

  At week 48

Study Arms (1)

Treatment

EXPERIMENTAL

Pediatric subjects \> = 6 months to \< 12 months will receive a starting dose of 0.4mg/kg administered subcutaneously (SC) every 2 weeks (Q2W) for 48 weeks with the option of the dose to be increased to 0.8mg/kg upon recommendation of the Data Safety Management Board (DSMB). The dose can be either increased up to a maximum of 2 mg/kg or decreased to 0.2 mg/kg depending on serum phosphate response. Upon recommendation of the DSMB subjects \< 6 months can then start at 0.4mg/kg starting dose administered subcutaneously (SC) every 2 weeks (Q2W) for 48 weeks with the option to be increased to 0.8mg/kg upon recommendation of the DSMB and can be either increased up to a maximum of 2 mg/kg or decreased to 0.2 mg/kg depending on serum phosphate response.

Drug: Burosumab

Interventions

Burosumab DRUG

Burosumab is a sterile clear colourless to slightly yellow and preservative free solution supplied in single use 5ml vials containing 1 mL of Burosumab at a concentration of 10mg/mL,20 mg/mL or 30mg/mL, administered by SC injections every 2 weeks.

Also known as: KRN23, Crysvita

Treatment

Eligibility Criteria

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

You may qualify if:

• Male or female pediatric subjects, aged \<12 months at burosumab treatment initiation.
• Pediatric subjects with PHEX mutation or variant of uncertain significance in either the subject or a directly related family member with appropriate X-linked inheritance.
• Presenting serum phosphate levels below the age-specific LLN at Screening.
• A legally authorized representative has provided written informed consent prior to any research-related procedures.
• A legally authorized representative 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 required by the study protocol, including providing access to prior medical records for the collection of historical growth, biochemical, and radiographic data and disease history.

You may not qualify if:

• The pediatric subject's legally authorized representative is unwilling or unable to stop the subject's treatment with oral phosphate and/or pharmacologic vitamin D metabolite or analogue (e.g. calcitriol, alfacalcidol) for at least 1 week before planned treatment start and for the duration of the study.
• Preterm pediatric patients (defined as born before 37 weeks of pregnancy) with a chronological age of \<6 months. Enrolment of preterm pediatric patients with a chronological age ≥6 months must be confirmed by the Study Medical Monitor before study entry.
• Impairment of renal function measured as serum creatinine above the age-adjusted normal range and estimated GFR (calculated using the Bedside Schwartz equation) below the age-adjusted normal range.
• Presence of nephrocalcinosis on renal ultrasound.
• Hypocalcemia or hypercalcemia, defined as serum calcium levels outside the age-adjusted normal limits.
• Presence of a concurrent disease or condition that would interfere with study participation or affect subject safety.
• Predisposition to infection or known immunodeficiency.
• Severe dermatological conditions over the available injection sites.
• Use of any investigational product or investigational medical device within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
• Metabolic bone disease, nutritional rickets and/or osteopenia of other origin than XLH at Screening and/or Baseline.
• Serum levels of 25-hydroxyvitamin D (25(OH)D) below the LLN that are clinically significant in the opinion of the Investigator.
• Evidence of any hyperparathyroidism not associated with XLH as determined by the Investigator.

Sponsors & Collaborators

• Kyowa Kirin Pharmaceutical Development Ltd: lead

Study Sites (9)

Kepler Universitaetsklinikum GmbH

Linz, Austria

Location

Centre de reference des maladies renales rares-Hospices Civils de Lyon-Hopital Femme Mere Enfant

Lyon, France

Location

Hopital Kremlin APHP

Paris, France

Location

Ospedale Pediatrico Bambino Gesù

Rome, Italy

Location

Hospital Virgen del Rocío

Seville, Spain

Location

Karolinska University Hospital

Stockholm, Sweden

Location

Evelina London Children's Hospital - Guy's & St Thomas' NHS Foundation Trust

London, United Kingdom

Location

Great Ormond Street Hospital

London, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, United Kingdom

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 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2019
• First Posted: December 6, 2019
• Study Start: February 26, 2020
• Primary Completion: October 4, 2023
• Study Completion: March 6, 2024
• Last Updated: November 7, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); FR (2); GB (3); SE (1); ES (1); IT (1)