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NCT02750618

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

Completed Phase 2 Results posted Last updated 6 May 2024
What this trial tests

Phase 2 trial testing Burosumab in X-Linked Hypophosphatemia in 13 participants. Completed in 10 September 2019.

Timeline
5 May 2016
Primary endpoint
20 April 2017
10 September 2019

Quick facts

Lead sponsorKyowa Kirin, Inc.
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment13
Start date5 May 2016
Primary completion20 April 2017
Estimated completion10 September 2019
Sites3 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Kyowa Kirin, Inc. — full company profile →

Who can join

Adults 1 to 4, any sex, with X-Linked Hypophosphatemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline at Week 40 in Serum Phosphorus Primary · Baseline, Week 40

The Generalized Estimation Equation (GEE) model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with exchangeable covariance structure.

GroupValue95% CI
Burosumab Q2W0.96± 0.117
Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation Primary · From first dose of study drug through the end of the study (Week 160). Maximum duration of exposure to study drug was 160 weeks.

An AE was defined as any untoward medical occurrence associated with the use of a drug, whether or not considered drug related. A serious AE was defined as an AE 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 disability, a congenital anomaly/birth defect, or other important medical events (according to the investigator). An AE was considered a TEAE if it occurred on or after the first dose an

Adverse Event Starting during Screening Period
GroupValue95% CI
Burosumab Q2W5
TEAEs
GroupValue95% CI
Burosumab Q2W13
Related TEAEs
GroupValue95% CI
Burosumab Q2W5
Serious TEAEs
GroupValue95% CI
Burosumab Q2W1
Serious Related TEAEs
GroupValue95% CI
Burosumab Q2W0
Grade 3 or 4 TEAE
GroupValue95% CI
Burosumab Q2W2
TEAE Leading to Study Discontinuation
GroupValue95% CI
Burosumab Q2W0
TEAE Leading to Treatment Discontinuation
GroupValue95% CI
Burosumab Q2W0
Radiographic Global Impression of Change (RGI-C) Score at Week 40 Secondary · Week 40

Changes in the severity of rickets and bowing were assessed centrally by three independent pediatric radiologists contracted by a central imaging facility using a disease specific qualitative RGI-C scoring system. The RGI-C is a seven point ordinal scale with possible values: +3 = very much better (complete or near complete healing of rickets), +2 = much better (substantial healing of rickets), +1 = minimally better (i.e., minimal healing of rickets), 0 = unchanged, -1 = minimally worse (minimal worsening of rickets), -2 = much worse (moderate worsening of rickets), -3 = very much worse (sever

GroupValue95% CI
Burosumab Q2W2.21± 0.071
RGI-C Score at Week 64 Secondary · Week 64

Changes in the severity of rickets and bowing were assessed centrally by three independent pediatric radiologists contracted by a central imaging facility using a disease specific qualitative RGI-C scoring system. The RGI-C is a seven point ordinal scale with possible values: +3 = very much better (complete or near complete healing of rickets), +2 = much better (substantial healing of rickets), +1 = minimally better (i.e., minimal healing of rickets), 0 = unchanged, -1 = minimally worse (minimal worsening of rickets), -2 = much worse (moderate worsening of rickets), -3 = very much worse (sever

GroupValue95% CI
Burosumab Q2W2.23± 0.111
Change From Baseline in Rickets at Week 40 as Assessed by the RSS Total Score Secondary · Baseline, Week 40

The RSS system is a 10-point radiographic scoring method that was developed to assess the severity of nutritional rickets in the wrists and knees based on the degree of metaphyseal fraying, cupping, and the proportion of the growth plate affected. Scores are assigned for the unilateral wrist and knee X-rays deemed by the rater to be the more severe of the bilateral images. The maximum total score on the RSS is 10 points and the minimum score is 0, with a total possible score of 4 points for the wrists and 6 points for the knees. Higher scores indicate greater rickets severity.The ANCOVA model

GroupValue95% CI
Burosumab Q2W-1.75± 0.116
Change From Baseline in Rickets at Week 64 as Assessed by the RSS Total Score Secondary · Baseline, Week 64

The RSS system is a 10-point radiographic scoring method that was developed to assess the severity of nutritional rickets in the wrists and knees based on the degree of metaphyseal fraying, cupping, and the proportion of the growth plate affected. Scores are assigned for the unilateral wrist and knee X-rays deemed by the rater to be the more severe of the bilateral images. The maximum total score on the RSS is 10 points, with a total possible score of 4 points for the wrists and 6 points for the knees. Higher scores indicate greater rickets severity. The GEE model includes the change from base

GroupValue95% CI
Burosumab Q2W-2.02± 0.115
RGI-C Lower Limb Deformity Score at Week 40 Secondary · Week 40

Changes in the severity of lower extremity skeletal abnormalities were assessed centrally by three independent pediatric radiologists contracted by a central imaging facility using a disease specific qualitative RGI-C scoring system. The RGI-C is a seven point ordinal scale with possible values: +3 = very much better (complete or near complete healing of rickets), +2 = much better (substantial healing of rickets), +1 = minimally better (i.e., minimal healing of rickets), 0 = unchanged, -1 = minimally worse (minimal worsening of rickets), -2 = much worse (moderate worsening of rickets), -3 = ve

GroupValue95% CI
Burosumab Q2W1.21± 0.155
RGI-C Lower Limb Deformity Score at Week 64 Secondary · Week 64

Changes in the severity of lower extremity skeletal abnormalities were assessed centrally by three independent pediatric radiologists contracted by a central imaging facility using a disease specific qualitative RGI-C scoring system. The RGI-C is a seven point ordinal scale with possible values: +3 = very much better (complete or near complete healing of rickets), +2 = much better (substantial healing of rickets), +1 = minimally better (i.e., minimal healing of rickets), 0 = unchanged, -1 = minimally worse (minimal worsening of rickets), -2 = much worse (moderate worsening of rickets), -3 = ve

GroupValue95% CI
Burosumab Q2W1.51± 0.123
Change From Baseline Over Time in Recumbent Length/Standing Height Secondary · Baseline, Weeks 12, 24, 40, 64, 88, 112, 136, 160
Week 12
GroupValue95% CI
Burosumab Q2W1.44± 2.009
Week 24
GroupValue95% CI
Burosumab Q2W2.52± 1.518
Week 40
GroupValue95% CI
Burosumab Q2W4.29± 2.451
Week 64
GroupValue95% CI
Burosumab Q2W7.22± 3.157
Week 88
GroupValue95% CI
Burosumab Q2W10.30± 3.400
Week 112
GroupValue95% CI
Burosumab Q2W13.25± 3.724
Week 136
GroupValue95% CI
Burosumab Q2W15.41± 3.699
Week 160
GroupValue95% CI
Burosumab Q2W18.96± 4.206
Change From Baseline Over Time in Recumbent Length/Standing Height as Assessed by Height-for-Age Z-Scores Secondary · Baseline, Weeks 12, 24, 40, 64, 88, 112, 136, 160

Recumbent length/Standing height z scores are measures of height adjusted for a child's age and sex. The Z-score indicates the number of standard deviations away from a reference population (from the CDC growth charts) in the same age range and with the same sex. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z-scores indicate a better outcome.

Week 12
GroupValue95% CI
Burosumab Q2W-0.082± 0.4964
Week 24
GroupValue95% CI
Burosumab Q2W-0.208± 0.4540
Week 40
GroupValue95% CI
Burosumab Q2W-0.276± 0.6647
Week 64
GroupValue95% CI
Burosumab Q2W-0.264± 0.8755
Week 88
GroupValue95% CI
Burosumab Q2W-0.212± 0.9115
Week 112
GroupValue95% CI
Burosumab Q2W-0.174± 0.9273
Week 136
GroupValue95% CI
Burosumab Q2W-0.321± 0.9123
Week 160
GroupValue95% CI
Burosumab Q2W-0.172± 0.9048
Change From Baseline Over Time in Recumbent Length/Standing Height as Assessed by Percentiles Secondary · Baseline, Weeks 12, 24, 40, 64, 88, 112, 136, 160
Week 12
GroupValue95% CI
Burosumab Q2W-0.006± 11.6149
Week 24
GroupValue95% CI
Burosumab Q2W-4.940± 13.1323
Week 40
GroupValue95% CI
Burosumab Q2W-5.283± 20.1675
Week 64
GroupValue95% CI
Burosumab Q2W-4.980± 23.4412
Week 88
GroupValue95% CI
Burosumab Q2W-4.155± 23.9126
Week 112
GroupValue95% CI
Burosumab Q2W-3.000± 24.7569
Week 136
GroupValue95% CI
Burosumab Q2W-7.026± 24.8583
Week 160
GroupValue95% CI
Burosumab Q2W-3.628± 25.5113
Change From Baseline Over Time in Serum Alkaline Phosphatase (ALP) Secondary · Baseline, Weeks 4, 12, 20, 40, 48, 56, 64, 76, 88, 100, 112, 124, 136, 148, 160

The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with exchangeable covariance structure.

Week 4
GroupValue95% CI
Burosumab Q2W-82.91± 23.348
Week 12
GroupValue95% CI
Burosumab Q2W-83.84± 45.263
Week 20
GroupValue95% CI
Burosumab Q2W-161.38± 12.924
Week 40
GroupValue95% CI
Burosumab Q2W-214.99± 13.628
Week 48
GroupValue95% CI
Burosumab Q2W-226.58± 11.491
Week 56
GroupValue95% CI
Burosumab Q2W-216.45± 16.165
Week 64
GroupValue95% CI
Burosumab Q2W-216.76± 12.705
Week 76
GroupValue95% CI
Burosumab Q2W-231.22± 15.964

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug through the end of the study (at Week 160). Maximum duration of exposure to study drug was 160 weeks.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Burosumab Q2W
Serious: 1/13 (8%)
Deaths: 0/13

Serious adverse events (1 terms)

ReactionSystemBurosumab Q2W
Tooth AbscessInfections and infestations
Other adverse events (131 terms — click to expand)

ReactionSystemBurosumab Q2W
PyrexiaGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
Tooth AbscessInfections and infestations
Upper Respiratory Tract InfectionInfections and infestations
Pain In ExtremityMusculoskeletal and connective tissue disorders
Pharyngitis StreptococcalInfections and infestations
Nasal CongestionRespiratory, thoracic and mediastinal disorders
VomitingGastrointestinal disorders
RhinorrhoeaRespiratory, thoracic and mediastinal disorders
DiarrhoeaGastrointestinal disorders
Ear InfectionInfections and infestations
HeadacheNervous system disorders
Abdominal Pain UpperGastrointestinal disorders
Ear PainEar and labyrinth disorders
Oral PainGastrointestinal disorders
FallInjury, poisoning and procedural complications
Skin AbrasionInjury, poisoning and procedural complications
ArthralgiaMusculoskeletal and connective tissue disorders
UrticariaSkin and subcutaneous tissue disorders
Abdominal DiscomfortGastrointestinal disorders
ToothacheGastrointestinal disorders
HypersensitivityImmune system disorders
InfluenzaInfections and infestations
Molluscum ContagiosumInfections and infestations
NasopharyngitisInfections and infestations
Viral Upper Respiratory Tract InfectionInfections and infestations
Arthropod BiteInjury, poisoning and procedural complications
Bone PainMusculoskeletal and connective tissue disorders
Knee DeformityMusculoskeletal and connective tissue disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Oropharyngeal PainRespiratory, thoracic and mediastinal disorders
Productive CoughRespiratory, thoracic and mediastinal disorders
Aphthous UlcerGastrointestinal disorders
ConstipationGastrointestinal disorders
FatigueGeneral disorders
Injection Site ErythemaGeneral disorders
Injection Site PruritusGeneral disorders
ImpetigoInfections and infestations
PneumoniaInfections and infestations
Viral InfectionInfections and infestations

Most-reported serious reactions: Tooth Abscess.

Data from ClinicalTrials.gov NCT02750618 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Burosumab versus conventional therapy in children with X-linked hypophosphataemia: a randomised, active-controlled, open-label, phase 3 trial.
    Imel EA, Glorieux FH, Whyte MP, Munns CF, et al · · 2019 · cited 247× · PMID 31104833 · DOI 10.1016/s0140-6736(19)30654-3
  2. Efficacy and safety of burosumab in children aged 1-4 years with X-linked hypophosphataemia: a multicentre, open-label, phase 2 trial.
    Whyte MP, Carpenter TO, Gottesman GS, Mao M, et al · · 2019 · cited 122× · PMID 30638856 · DOI 10.1016/s2213-8587(18)30338-3
  3. Sustained Efficacy and Safety of Burosumab, a Monoclonal Antibody to FGF23, in Children With X-Linked Hypophosphatemia.
    Linglart A, Imel EA, Whyte MP, Portale AA, et al · · 2022 · cited 63× · PMID 34636899 · DOI 10.1210/clinem/dgab729
  4. The Saga of Endocrine FGFs.
    Phan P, Saikia BB, Sonnaila S, Agrawal S, et al · · 2021 · cited 48× · PMID 34572066 · DOI 10.3390/cells10092418
  5. Patient-Reported Outcomes from a Randomized, Active-Controlled, Open-Label, Phase 3 Trial of Burosumab Versus Conventional Therapy in Children with X-Linked Hypophosphatemia.
    Padidela R, Whyte MP, Glorieux FH, Munns CF, et al · · 2021 · cited 36× · PMID 33484279 · DOI 10.1007/s00223-020-00797-x
  6. Growth Curves for Children with X-linked Hypophosphatemia.
    Mao M, Carpenter TO, Whyte MP, Skrinar A, et al · · 2020 · cited 23× · PMID 32721016 · DOI 10.1210/clinem/dgaa495
  7. Nephrocalcinosis and kidney function in children and adults with X-linked hypophosphatemia: baseline results from a large longitudinal study.
    Portale AA, Ward L, Dahir K, Florenzano P, et al · · 2024 · cited 15× · PMID 39151033 · DOI 10.1093/jbmr/zjae127
  8. Population Pharmacokinetics and Pharmacodynamics of Burosumab in Adult and Pediatric Patients With X-linked Hypophosphatemia.
    Lee SK, Gosselin NH, Taylor J, Roberts MS, et al · · 2022 · cited 8× · PMID 34352114 · DOI 10.1002/jcph.1950

Verify or expand the search:

Other trials of Burosumab

Trials testing the same drug.

Other recruiting trials for X-Linked Hypophosphatemia

Currently open trials in the same condition.

Other Kyowa Kirin, Inc. trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02750618.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing