Phase 2 N=13 Treatment

Study of the Safety, Pharmacodynamics (PD) and Efficacy of KRN23 in Children From 1 to 4 Years Old With X-linked Hypophosphatemia (XLH)

X-Linked Hypophosphatemia

Bottom Line

View on ClinicalTrials.gov: NCT02750618 ↗

Enrolled (actual)

Serious AEs

7.7%

Results posted

Jun 2018

Primary outcome: Primary: Change From Baseline at Week 40 in Serum Phosphorus — 0.96 mg/dL — p=< 0.0001

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Burosumab (Biological)
Age: Pediatric · 1+ yrs
Sex: All
Sponsor: Kyowa Kirin, Inc.
Primary completion: Apr 2017

Outcome Measures

Outcome	Result	p-value
PRIMARY Change From Baseline at Week 40 in Serum Phosphorus	0.96	< 0.0001 sig
PRIMARY Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation	5; 13; 5; 1; 0; 2	—
SECONDARY Radiographic Global Impression of Change (RGI-C) Score at Week 40	2.21	< 0.0001 sig
SECONDARY RGI-C Score at Week 64	2.23	< 0.0001 sig
SECONDARY Change From Baseline in Rickets at Week 40 as Assessed by the RSS Total Score	-1.75	< 0.0001 sig
SECONDARY Change From Baseline in Rickets at Week 64 as Assessed by the RSS Total Score	-2.02	< 0.0001 sig
SECONDARY RGI-C Lower Limb Deformity Score at Week 40	1.21	< 0.0001 sig
SECONDARY RGI-C Lower Limb Deformity Score at Week 64	1.51	< 0.0001 sig
SECONDARY Change From Baseline Over Time in Recumbent Length/Standing Height	1.44; 2.52; 4.29; 7.22; 10.30; 13.25	—
SECONDARY Change From Baseline Over Time in Recumbent Length/Standing Height as Assessed by Height-for-Age Z-Scores	-0.082; -0.208; -0.276; -0.264; -0.212; -0.174	—
SECONDARY Change From Baseline Over Time in Recumbent Length/Standing Height as Assessed by Percentiles	-0.006; -4.940; -5.283; -4.980; -4.155; -3.000	—
SECONDARY Change From Baseline Over Time in Serum Alkaline Phosphatase (ALP)	-82.91; -83.84; -161.38; -214.99; -226.58; -216.45	0.0004 sig
SECONDARY Percent Change From Baseline Over Time in Serum ALP	-12.47; -5.00; -24.76; -36.25; -37.29; -35.80	—

Summary

The primary objectives of the study are to: * Establish the safety profile of KRN23 for the treatment of XLH in children between 1 and 4 years old * Determine the PD effects of KRN23 treatment on serum phosphorus and other PD markers that reflect the status of phosphate homeostasis in children between 1 and 4 years old with XLH

Eligibility Criteria

Inclusion Criteria

Male or female, aged ≥1 year and 30 pg/mL by Kainos assay
Biochemical findings associated with XLH including:
Serum phosphorus < 3.0 mg/dL (0.97 mmol/L)
Serum creatinine within age-adjusted normal range
Radiographic evidence of rickets
Willing to provide access to prior medical records for the collection of historical growth, biochemical, and radiographic data and disease history
Provide written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures
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

Exclusion Criteria

Unwilling to stop treatment with oral phosphate and/or pharmacologic vitamin D metabolite or analog (e.g. calcitriol, alfacalcidol) during the screening period and for the duration of the study
Presence of nephrocalcinosis on renal ultrasound grade 4 based on the following scale: 0 = Normal, 1 = Faint hyperechogenic rim around the medullary pyramids, 2 = More intense echogenic rim with echoes faintly filling the entire pyramid, 3 = Uniformly intense echoes throughout the pyramid, 4 = Stone formation: solitary focus of echoes at the tip of the pyramid
Planned or recommended orthopedic surgery including staples, 8-plates or osteotomy, within the clinical trial period
Hypocalcemia or hypercalcemia, defined as serum calcium levels outside the age-adjusted normal limits
Presence or history of any condition that, in the view of the investigator, 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
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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02750618). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.