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

Purpose

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	Intervention	Phase
X-linked Hypophosphatemia	Drug: KRN23	Phase 1 Phase 2


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

Genetics Home Reference related topics: hereditary hypophosphatemic rickets

Genetic and Rare Diseases Information Center resources: X-linked Hypophosphatemia Hypophosphatemic Rickets Rickets

U.S. FDA Resources

Further study details as provided by Kyowa Kirin Pharmaceutical Development, Inc.:

Primary Outcome Measures:

Safety and Efficacy of repeated SC injections of KRN23 [ Time Frame: On-Treatment: 6.5 months, 27 total visits ] [ Designated as safety issue: Yes ]
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:

Evaluation of effect of repeated SC injections of KRN23 [ Time Frame: On-Treatment: 6.5 months, 27 total visits ] [ Designated as safety issue: No ]
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:

Evaluation of effect of repeated SC injections of KRN23 in Bone Substudy [ Time Frame: On-Treatment: 6.5 months, 27 total visits ] [ Designated as safety issue: No ]
Evaluation of effect of repeated SC injections of KRN23, compared to Placebo on bone mineral density and bone quality.


Enrollment:	29
Study Start Date:	April 2011
Study Completion Date:	October 2013
Primary Completion Date:	May 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

Eligibility


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

Criteria

Main Inclusion Criteria:

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

Main Exclusion Criteria:

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01340482

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 Company, Limited

Investigators


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

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
Study First Received:	April 15, 2011
Last Updated:	June 10, 2016
Health Authority:	United States: Food and Drug Administration Canada: Health Canada

Keywords provided by Kyowa Kirin Pharmaceutical Development, 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

ClinicalTrials.gov processed this record on September 30, 2016