Evidence map›Paper›PMID 25919461›Full record

Trial reportThe Journal of clinical endocrinology and metabolism2015

Prolonged Correction of Serum Phosphorus in Adults With X-Linked Hypophosphatemia Using Monthly Doses of KRN23.

Erik A Imel, Xiaoping Zhang, Mary D Ruppe, Thomas J Weber, Mark A Klausner, Takahiro Ito, Maria Vergeire, Jeffrey S Humphrey, Francis H Glorieux, Anthony A Portale and 3 more

Erratum issuedOpen access · bronzeAbstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Journal of clinical endocrinology and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 85 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed, 3 pooled it
13.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

85 citing papers in PubMed, 3 syntheses or guidelines pooled it, 166 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. Trial
  7. Trial
  8. Trial
  9. Trial
  10. Interim Analysis of a Phase 2 Open-Label Trial Assessing Burosumab Efficacy and Safety in Patients With Tumor-Induced Osteomalacia.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021
    Trial
  11. Trial
  12. Article
  13. Article
  14. FGF23　- A hormone produced by bone and has many faces.Reviews in endocrine & metabolic disorders · 2026
    Review
  15. Real-world impact of treatment on growth in children with X-linked hypophosphatemia.The Journal of clinical endocrinology and metabolism · 2026
    Observational
  16. Review
  17. Article
  18. Diagnosis and Management of Hypophosphatemic Disorders.Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2025
    Review
  19. Article
  20. Real-world effectiveness of burosumab vs oral phosphate and active vitamin D in adults with X-linked hypophosphatemia.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025
    Observational

25 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 7 institutions in 2 countries.

Erik A ImelIndiana University School of Medicine (E.A.I., M.P.), Indianapolis, Indiana 46202; Kyowa Hakko Kirin Pharma Inc (X.Z., M.A.K., T.I., M.V., J.S.H.), Princeton, New Jersey 08540; Houston Methodist Hospital (M.D.R.), Houston, Texas 77030; Duke University Medical Center (T.J.W.), Durham, North Carolina 27710; Shriners Hospital for Children (F.H.G.), Montreal, Quebec H3G 1A6, Canada; University of California (A.A.P.), San Francisco, California 94143; and Yale Center for X-Linked Hypophosphatemia (K.I., T.O.C.), Yale University School of Medicine, New Haven, Connecticut 06520.
Xiaoping ZhangIndiana University School of Medicine (E.A.I., M.P.), Indianapolis, Indiana 46202; Kyowa Hakko Kirin Pharma Inc (X.Z., M.A.K., T.I., M.V., J.S.H.), Princeton, New Jersey 08540; Houston Methodist Hospital (M.D.R.), Houston, Texas 77030; Duke University Medical Center (T.J.W.), Durham, North Carolina 27710; Shriners Hospital for Children (F.H.G.), Montreal, Quebec H3G 1A6, Canada; University of California (A.A.P.), San Francisco, California 94143; and Yale Center for X-Linked Hypophosphatemia (K.I., T.O.C.), Yale University School of Medicine, New Haven, Connecticut 06520.
Mary D RuppeIndiana University School of Medicine (E.A.I., M.P.), Indianapolis, Indiana 46202; Kyowa Hakko Kirin Pharma Inc (X.Z., M.A.K., T.I., M.V., J.S.H.), Princeton, New Jersey 08540; Houston Methodist Hospital (M.D.R.), Houston, Texas 77030; Duke University Medical Center (T.J.W.), Durham, North Carolina 27710; Shriners Hospital for Children (F.H.G.), Montreal, Quebec H3G 1A6, Canada; University of California (A.A.P.), San Francisco, California 94143; and Yale Center for X-Linked Hypophosphatemia (K.I., T.O.C.), Yale University School of Medicine, New Haven, Connecticut 06520.
Thomas J WeberIndiana University School of Medicine (E.A.I., M.P.), Indianapolis, Indiana 46202; Kyowa Hakko Kirin Pharma Inc (X.Z., M.A.K., T.I., M.V., J.S.H.), Princeton, New Jersey 08540; Houston Methodist Hospital (M.D.R.), Houston, Texas 77030; Duke University Medical Center (T.J.W.), Durham, North Carolina 27710; Shriners Hospital for Children (F.H.G.), Montreal, Quebec H3G 1A6, Canada; University of California (A.A.P.), San Francisco, California 94143; and Yale Center for X-Linked Hypophosphatemia (K.I., T.O.C.), Yale University School of Medicine, New Haven, Connecticut 06520.
Mark A KlausnerIndiana University School of Medicine (E.A.I., M.P.), Indianapolis, Indiana 46202; Kyowa Hakko Kirin Pharma Inc (X.Z., M.A.K., T.I., M.V., J.S.H.), Princeton, New Jersey 08540; Houston Methodist Hospital (M.D.R.), Houston, Texas 77030; Duke University Medical Center (T.J.W.), Durham, North Carolina 27710; Shriners Hospital for Children (F.H.G.), Montreal, Quebec H3G 1A6, Canada; University of California (A.A.P.), San Francisco, California 94143; and Yale Center for X-Linked Hypophosphatemia (K.I., T.O.C.), Yale University School of Medicine, New Haven, Connecticut 06520.
Takahiro ItoIndiana University School of Medicine (E.A.I., M.P.), Indianapolis, Indiana 46202; Kyowa Hakko Kirin Pharma Inc (X.Z., M.A.K., T.I., M.V., J.S.H.), Princeton, New Jersey 08540; Houston Methodist Hospital (M.D.R.), Houston, Texas 77030; Duke University Medical Center (T.J.W.), Durham, North Carolina 27710; Shriners Hospital for Children (F.H.G.), Montreal, Quebec H3G 1A6, Canada; University of California (A.A.P.), San Francisco, California 94143; and Yale Center for X-Linked Hypophosphatemia (K.I., T.O.C.), Yale University School of Medicine, New Haven, Connecticut 06520.
Maria VergeireIndiana University School of Medicine (E.A.I., M.P.), Indianapolis, Indiana 46202; Kyowa Hakko Kirin Pharma Inc (X.Z., M.A.K., T.I., M.V., J.S.H.), Princeton, New Jersey 08540; Houston Methodist Hospital (M.D.R.), Houston, Texas 77030; Duke University Medical Center (T.J.W.), Durham, North Carolina 27710; Shriners Hospital for Children (F.H.G.), Montreal, Quebec H3G 1A6, Canada; University of California (A.A.P.), San Francisco, California 94143; and Yale Center for X-Linked Hypophosphatemia (K.I., T.O.C.), Yale University School of Medicine, New Haven, Connecticut 06520.
Jeffrey S HumphreyIndiana University School of Medicine (E.A.I., M.P.), Indianapolis, Indiana 46202; Kyowa Hakko Kirin Pharma Inc (X.Z., M.A.K., T.I., M.V., J.S.H.), Princeton, New Jersey 08540; Houston Methodist Hospital (M.D.R.), Houston, Texas 77030; Duke University Medical Center (T.J.W.), Durham, North Carolina 27710; Shriners Hospital for Children (F.H.G.), Montreal, Quebec H3G 1A6, Canada; University of California (A.A.P.), San Francisco, California 94143; and Yale Center for X-Linked Hypophosphatemia (K.I., T.O.C.), Yale University School of Medicine, New Haven, Connecticut 06520.
Francis H GlorieuxIndiana University School of Medicine (E.A.I., M.P.), Indianapolis, Indiana 46202; Kyowa Hakko Kirin Pharma Inc (X.Z., M.A.K., T.I., M.V., J.S.H.), Princeton, New Jersey 08540; Houston Methodist Hospital (M.D.R.), Houston, Texas 77030; Duke University Medical Center (T.J.W.), Durham, North Carolina 27710; Shriners Hospital for Children (F.H.G.), Montreal, Quebec H3G 1A6, Canada; University of California (A.A.P.), San Francisco, California 94143; and Yale Center for X-Linked Hypophosphatemia (K.I., T.O.C.), Yale University School of Medicine, New Haven, Connecticut 06520.
Anthony A PortaleIndiana University School of Medicine (E.A.I., M.P.), Indianapolis, Indiana 46202; Kyowa Hakko Kirin Pharma Inc (X.Z., M.A.K., T.I., M.V., J.S.H.), Princeton, New Jersey 08540; Houston Methodist Hospital (M.D.R.), Houston, Texas 77030; Duke University Medical Center (T.J.W.), Durham, North Carolina 27710; Shriners Hospital for Children (F.H.G.), Montreal, Quebec H3G 1A6, Canada; University of California (A.A.P.), San Francisco, California 94143; and Yale Center for X-Linked Hypophosphatemia (K.I., T.O.C.), Yale University School of Medicine, New Haven, Connecticut 06520.
Karl InsognaIndiana University School of Medicine (E.A.I., M.P.), Indianapolis, Indiana 46202; Kyowa Hakko Kirin Pharma Inc (X.Z., M.A.K., T.I., M.V., J.S.H.), Princeton, New Jersey 08540; Houston Methodist Hospital (M.D.R.), Houston, Texas 77030; Duke University Medical Center (T.J.W.), Durham, North Carolina 27710; Shriners Hospital for Children (F.H.G.), Montreal, Quebec H3G 1A6, Canada; University of California (A.A.P.), San Francisco, California 94143; and Yale Center for X-Linked Hypophosphatemia (K.I., T.O.C.), Yale University School of Medicine, New Haven, Connecticut 06520.
Munro PeacockIndiana University School of Medicine (E.A.I., M.P.), Indianapolis, Indiana 46202; Kyowa Hakko Kirin Pharma Inc (X.Z., M.A.K., T.I., M.V., J.S.H.), Princeton, New Jersey 08540; Houston Methodist Hospital (M.D.R.), Houston, Texas 77030; Duke University Medical Center (T.J.W.), Durham, North Carolina 27710; Shriners Hospital for Children (F.H.G.), Montreal, Quebec H3G 1A6, Canada; University of California (A.A.P.), San Francisco, California 94143; and Yale Center for X-Linked Hypophosphatemia (K.I., T.O.C.), Yale University School of Medicine, New Haven, Connecticut 06520.
Thomas O CarpenterIndiana University School of Medicine (E.A.I., M.P.), Indianapolis, Indiana 46202; Kyowa Hakko Kirin Pharma Inc (X.Z., M.A.K., T.I., M.V., J.S.H.), Princeton, New Jersey 08540; Houston Methodist Hospital (M.D.R.), Houston, Texas 77030; Duke University Medical Center (T.J.W.), Durham, North Carolina 27710; Shriners Hospital for Children (F.H.G.), Montreal, Quebec H3G 1A6, Canada; University of California (A.A.P.), San Francisco, California 94143; and Yale Center for X-Linked Hypophosphatemia (K.I., T.O.C.), Yale University School of Medicine, New Haven, Connecticut 06520.
Yale University · USDuke Medical Center · USIndiana University – Purdue University Indianapolis · USIndiana University School of MedicineMethodist Hospital · USShriners Hospitals for Children - Canada · CAUniversity of California, San Francisco · US

Funding

Quality Assurance and Quality Control Project Management: Improving Submissions and Study Conduct in the Human Subjects Research Prior Approval ProcessUL1TR002529 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI MOE, SHARON M, WIEHE, SARAH ELIZABETH · 2018 to 2022
$27.2M
Indiana Clinical and Translational Sciences InstituteUL1TR001108 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI DENNE, SCOTT C., SHEKHAR, ANANTHA · 2013 to 2017
$23.3M
NCATS NIH HHS UL1 TR001108
6 · The paper itself

Abstract

contextIn X-linked hypophosphatemia (XLH), elevated fibroblast growth factor 23 (FGF23) decreases the renal tubular maximum reabsorption rate of phosphate/glomerular filtration rate (TmP/GFR) and serum inorganic phosphorus (Pi), resulting in rickets and/or osteomalacia.

objectiveThe objective was to test the hypothesis that monthly KRN23 (anti-FGF23 antibody) would safely improve serum Pi in adults with XLH.

designTwo sequential open-label phase 1/2 studies were done.

settingSix academic medical centers were used.

participantsTwenty-eight adults with XLH participated in a 4-month dose-escalation study (0.05-0.6 mg/kg); 22 entered a 12-month extension study (0.1-1 mg/kg).

interventionKRN23 was injected sc every 28 days.

main outcome measureThe main outcome measure was the proportion of subjects attaining normal serum Pi and safety.

resultsAt baseline, mean TmP/GFR, serum Pi, and 1,25-dihydroxyvitamin D [1,25(OH)2D] were 1.6 ± 0.4 mg/dL, 1.9 ± 0.3 mg/dL, and 36.6 ± 14.3 pg/mL, respectively. During dose escalation, TmP/GFR, Pi, and 1,25(OH)2D increased, peaking at 7 days for TmP/GFR and Pi and at 3-7 days for 1,25(OH)2D, remaining above (TmP/GFR, Pi) or near [1,25(OH)2D] pre-dose levels at trough. After each of the four escalating doses, peak Pi was between 2.5 and 4.5 mg/dL in 14.8, 37.0, 74.1, and 88.5% of subjects, respectively. During the 12-month extension, peak Pi was in the normal range for 57.9-85.0% of subjects, and ≥25% maintained trough Pi levels within the normal range. Serum Pi did not exceed 4.5 mg/dL in any subject. Although 1,25(OH)2D levels increased transiently, mean serum and urinary calcium remained normal. KRN23 treatment increased biomarkers of skeletal turnover and had a favorable safety profile.

conclusionsMonthly KRN23 significantly increased serum Pi, TmP/GFR, and 1,25(OH)2D in all subjects. KRN23 has potential for effectively treating XLH.

Indexed as

AdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedDose-Response Relationship, DrugDrug Administration ScheduleFamilial Hypophosphatemic RicketsFemaleFibroblast Growth Factor-23Fibroblast Growth FactorsGlomerular Filtration RateHumansImmunoglobulin GMaleMiddle AgedPhosphorusAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedburosumabFGF23 protein, humanFibroblast Growth Factor-23Fibroblast Growth FactorsImmunoglobulin GPhosphorusRecombinant Proteins

Identifiers

PMID25919461
PMCPMC4495171
OpenAlexW1964204750

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.