A Repeated Study of KRN23 in Adults With X-Linked Hypophosphatemia

Study Description

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Brief Summary:

The primary purpose of this study is to assess the safety and efficacy of repeated subcutaneous (SC) injections of KRN23 in adult subjects with X-Linked Hypophosphatemia (XLH). A Bone Substudy will evaluate the effects of single-blind KRN23 versus Placebo on bone mineral density and bone quality.

Condition or disease	Intervention/treatment	Phase
X-linked Hypophosphatemia	Drug: KRN23	Phase 1; Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	29 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase I/II, Open-Label, Repeat-Dose, Dose-Escalation Study of KRN23 in Adult Subjects With X-Linked Hypophosphatemia
Study Start Date :	April 2011
Actual Primary Completion Date :	May 2013
Actual Study Completion Date :	October 2013

Arms and Interventions

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Arm	Intervention/treatment
Experimental: KRN23; Escalating doses of KRN23 (0.05, 0.10, 0.30 and 0.60 mg/kg) will be administered SC every 28 days (up to 4 doses)	Drug: KRN23; Subjects will receive escalating doses of KRN23 administered by SC injections every 28-days (up to 4 doses) based on a dosing algorithm and discretion of the investigator and sponsor.

Outcome Measures

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Primary Outcome Measures :

1. Safety and Efficacy of repeated SC injections of KRN23 [ Time Frame: On-Treatment: 6.5 months, 27 total visits ]
   Safety and efficacy of repeated SC injections of KRN23 from baseline as assessed by serum phosphorus levels,immunogenicity, adverse events and clinically significant changes in vital signs and laboratory testing.

Secondary Outcome Measures :

1. Evaluation of effect of repeated SC injections of KRN23 [ Time Frame: On-Treatment: 6.5 months, 27 total visits ]
   Effect of repeated SC injections of KRN23, from baseline, on pharmacodynamic parameters including serum phosphorus, sex hormone, bone biomarkers, quality of life assessments and population pharmacokinetics of KRN23 dose levels from cumulative dosing.

Other Outcome Measures:

1. Evaluation of effect of repeated SC injections of KRN23 in Bone Substudy [ Time Frame: On-Treatment: 6.5 months, 27 total visits ]
   Evaluation of effect of repeated SC injections of KRN23, compared to Placebo on bone mineral density and bone quality.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Main Inclusion Criteria:

1. 18 years or older
2. Clinical diagnosis of XLH
3. TmP/GFR < 2.0 mg/dL
4. GFR ≥60 mL/min
5. Corrected Ca <10.8 mg/dL
6. A willingness to utilize adequate contraception and not become pregnant[or to have their partner(s) become pregnant] during the study
7. Additional inclusion criteria apply

Main Exclusion Criteria:

1. Have any sign of active infectious disease or have had an infection requiring treatment with antibiotics within 3-weeks of Screening
2. History of known immunodeficiency
3. Pregnant or lactating females subjects or female planning to be become pregnant during the study
4. Receipt of a live (attenuated) vaccine (except for influenza vaccines) within 3-months of Screening, and/or during the study
5. Use of pharmacologic vitamin D metabolite or its analog, phosphate, calcimimetics, and ingestion of aluminum hydroxide antacids within 10-days prior to Screening and/or dosing
6. Use of any supplement containing phosphate, calcium and/or vitamin D within 10-days prior to Screening and/or dosing
7. Condition which could present a concern for either the subject's safety or difficulty with data interpretation
8. Additional exclusion criteria apply

Contacts and Locations

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Locations

United States, California
University of California, San Francisco Medical Center
San Francisco, California, United States, 94143
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06520
United States, Indiana
Clinical Research Center, Indiana University School of Medicine
Indianapolis, Indiana, United States, 46202-5250
United States, North Carolina
Duke Clinical Research Unit
Durham, North Carolina, United States, 27710
United States, Texas
University of Texas Health Science Center at Houston
Houston, Texas, United States, 77030
Canada, Quebec
Shriners Hospital for Children - Canada
Montreal, Quebec, Canada, H3G 1A6

Sponsors and Collaborators

Kyowa Hakko Kirin Pharma, Inc.

Kyowa Hakko Kirin Co., Ltd

Investigators

Study Director:	Amy Zhang, PhD	Kyowa Hakko Kirin Pharma, Inc.

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Zhang X, Imel EA, Ruppe MD, Weber TJ, Klausner MA, Ito T, Vergeire M, Humphrey J, Glorieux FH, Portale AA, Insogna K, Carpenter TO, Peacock M. Pharmacokinetics and pharmacodynamics of a human monoclonal anti-FGF23 antibody (KRN23) in the first multiple ascending-dose trial treating adults with X-linked hypophosphatemia. J Clin Pharmacol. 2016 Feb;56(2):176-85. doi: 10.1002/jcph.570. Epub 2015 Aug 11.

Imel EA, Zhang X, Ruppe MD, Weber TJ, Klausner MA, Ito T, Vergeire M, Humphrey JS, Glorieux FH, Portale AA, Insogna K, Peacock M, Carpenter TO. Prolonged Correction of Serum Phosphorus in Adults With X-Linked Hypophosphatemia Using Monthly Doses of KRN23. J Clin Endocrinol Metab. 2015 Jul;100(7):2565-73. doi: 10.1210/jc.2015-1551. Epub 2015 Apr 28.

Responsible Party:	Kyowa Hakko Kirin Pharma, Inc.
ClinicalTrials.gov Identifier:	NCT01340482 History of Changes
Other Study ID Numbers:	KRN23-INT-001
First Posted:	April 22, 2011
Last Update Posted:	June 14, 2016
Last Verified:	January 2015

Keywords provided by Kyowa Kirin Pharmaceutical Development, Inc. ( Kyowa Hakko Kirin Pharma, Inc. ):

XLH

Additional relevant MeSH terms:

Hypophosphatemia; Familial Hypophosphatemic Rickets; Phosphorus Metabolism Disorders; Metabolic Diseases; Rickets, Hypophosphatemic; Rickets; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Hypophosphatemia, Familial; Renal Tubular Transport, Inborn Errors	Kidney Diseases; Urologic Diseases; Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Calcium Metabolism Disorders; Vitamin D Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders