CompletedNCT01340482Updated Jun 18, 2024Results posted

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

A Phase 1/2 interventional study of KRN23 in X-linked Hypophosphatemia, sponsored by Kyowa Kirin Co., Ltd.. Completed at 6 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-06-18.

Sponsored by Kyowa Kirin Co., Ltd. · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 29
Allocation: Not applicable
Ages: 18 Years and older
Sex: All

Study 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.

Conditions studied

X-linked Hypophosphatemia

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Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility 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

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 29 participants (actual)

Study arms

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

Interventions

DrugKRN23
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.

What researchers measure

Primary outcomes

Safety and Efficacy of Repeated SC Injections of KRN23
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.
Time frame: On-Treatment: 6.5 months, 27 total visits

Secondary outcomes

Evaluation of Effect of Repeated SC Injections of KRN23
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. Summary of serum phosphorus by visit/day is captured below.
Time frame: On-Treatment: 6.5 months, 27 total visits

Other outcomes

Evaluation of Effect of Repeated SC Injections of KRN23 in Bone Substudy
Evaluation of effect of repeated SC injections of KRN23, compared to Placebo on bone mineral density and bone quality.
Time frame: On-Treatment: 6.5 months, 27 total visits

Results

Posted Oct 26, 2020

Limitations and caveats

Only 2 subjects were randomized in and completed the bone substudy. Subsequently, the Sponsor terminated the bone substudy due to slow accrual.

Participant flow

Participant flow — Overall Study
Milestone	KRN23	Bone Substudy KRN23	Bone Substudy Placebo
Started	27	1	1
Completed	25	1	1
Not completed	2	0	0
Withdrew: Adverse event	2	0	0

Outcome measures

PrimarySafety and Efficacy of Repeated SC Injections of KRN23

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.

Time frame:: On-Treatment: 6.5 months, 27 total visits
Reported as:: Count of participants · Participants

Safety and Efficacy of Repeated SC Injections of KRN23
Participants	KRN23	Bone Substudy KRN23	Bone Substudy Placebo
Subjects reporting at least one TEAE	24	1	1
Subjects who died	0	0	0
Subjects reporting SAE other than death	0	0	0
Subjects reporting at least one DLT	0	0	0
Subjects reporting AE leading to discontinuation	1	0	0

SecondaryEvaluation of Effect of Repeated SC Injections of KRN23

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. Summary of serum phosphorus by visit/day is captured below.

Time frame:: On-Treatment: 6.5 months, 27 total visits
Reported as:: Mean · mg/dL

Evaluation of Effect of Repeated SC Injections of KRN23
mg/dL	KRN23
Visit 2 (D0)/0	1.89 (1.2 to 2.8)
Visit 3 (D3)/3	2.18 (1.5 to 2.9)
Visit 4 (D7)/7	2.20 (1.7 to 3.2)
Visit 5 (D12)/12	2.14 (1.7 to 2.7)
Visit 6 (D18)/18	2.15 (1.7 to 3.0)
Visit 7 (D26)/26	1.96 (1.4 to 2.7)
Visit 8 (D28)/0	1.93 (1.3 to 2.6)
Visit 9 (D31)/3	2.35 (1.5 to 3.3)
Visit 10 (D35)/7	2.45 (1.9 to 3.1)
Visit 11 (D40)/12	2.31 (1.6 to 3.2)
Visit 12 (D46)/18	2.28 (1.3 to 3.0)
Visit 13 (D54)/26	2.15 (1.7 to 3.0)
Visit 14 (D56)/0	2.12 (1.5 to 2.7)
Visit 15 (D59)/3	2.57 (1.7 to 3.8)
Visit 16 (D63)/7	2.85 (1.9 to 3.5)
Visit 17 (D68)/12	2.83 (1.9 to 3.9)
Visit 18 (D74)/18	2.60 (1.6 to 3.5)
Visit 19 (D82)/26	2.33 (1.7 to 3.0)
Visit 20 (D84)/0	2.26 (1.8 to 3.0)
Visit 21 (D87)/3	2.64 (1.9 to 3.6)
Visit 22 (D91)/7	3.03 (2.3 to 3.7)
Visit 23 (D96)/12	2.94 (2.2 to 3.5)
Visit 24 (D102)/18	2.82 (1.7 to 4.0)
Visit 25 (D110)/26	2.54 (1.9 to 3.3)
End of Study - Visit 26 (D120)	2.22 (1.6 to 2.9)
Early Withdrawal	1.30 (1.3 to 1.3)

Other pre-specifiedEvaluation of Effect of Repeated SC Injections of KRN23 in Bone Substudy

Evaluation of effect of repeated SC injections of KRN23, compared to Placebo on bone mineral density and bone quality.

Time frame:: On-Treatment: 6.5 months, 27 total visits
Reported as:: Number · units on a scale

Evaluation of Effect of Repeated SC Injections of KRN23 in Bone Substudy
units on a scale	Bone Substudy KRN23	Bone Substudy Placebo
Evaluation of Effect of Repeated SC Injections of KRN23 in Bone Substudy	NA	NA

Adverse events

Collected over Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
KRN23	0/27 (0%)	0/27 (0%)	24/27 (88.9%)
Bone Substudy KRN23	0/1 (0%)	0/1 (0%)	1/1 (100%)
Bone Substudy Placebo	0/1 (0%)	0/1 (0%)	1/1 (100%)

Most frequent other events

Showing 10 of 87

Most frequent other events
Event	KRN23	Bone Substudy KRN23	Bone Substudy Placebo
Ear painEar and labyrinth disorders	0/27	1/1	0/1
DyspepsiaGastrointestinal disorders	2/27	1/1	0/1
Mouth ulcerationGastrointestinal disorders	0/27	1/1	0/1
Lip ulcerationGastrointestinal disorders	0/27	1/1	0/1
PyrexiaGeneral disorders	0/27	0/1	1/1
Injection site painGeneral disorders	0/27	1/1	0/1
Influenza like illnessGeneral disorders	0/27	1/1	0/1
InfluenzaInfections and infestations	1/27	0/1	1/1
Urinary tract infectionInfections and infestations	2/27	1/1	0/1
NasopharyngitisInfections and infestations	7/27	1/1	1/1

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	KRN23	Bone Substudy KRN23	Bone Substudy Placebo	Total
<=18 years	0	0	0	0
Between 18 and 65 years	26	1	1	28
>=65 years	1	0	0	1

Age, Continuous
Age, Continuous(years)	KRN23	Bone Substudy KRN23	Bone Substudy Placebo	Total
Median	42 (19 to 66)	21 (21 to 21)	28 (28 to 28)	41 (19 to 66)

Sex: Female, Male
Sex: Female, Male(Participants)	KRN23	Bone Substudy KRN23	Bone Substudy Placebo	Total
Female	18	1	1	20
Male	9	0	0	9

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	KRN23	Bone Substudy KRN23	Bone Substudy Placebo	Total
White/Caucasian	26	1	1	28
Black/African American/African Caribbean	1	0	0	1

Region of Enrollment
Region of Enrollment(participants)	KRN23	Bone Substudy KRN23	Bone Substudy Placebo	Total
Canada	0	1	1	2
United States	27	0	0	27

Study locations

6 sites

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

References and documents

Publications

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. PubMed 26073451 ↗
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. Erratum In: J Clin Endocrinol Metab. 2017 Jan 1;102(1):336. doi: 10.1210/jc.2016-3665. PubMed 25919461 ↗

Registry details

Key details

Study ID: NCT01340482
Lead sponsor: Kyowa Kirin Co., Ltd.
Responsible party: Sponsor
First posted: Apr 22, 2011
Start date: Apr 2011
Primary completion: May 2013
Completion: Oct 2013
Results posted: Oct 26, 2020
Last update: Jun 18, 2024

Study contacts

Amy Zhang, PhD

study director · Kyowa Hakko Kirin Pharma, Inc.

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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