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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I/II, Open-Label, Repeat-Dose, Dose-Escalation Study of KRN23 in Adult Subjects With X-Linked Hypophosphatemia

Conditions
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X-linked Hypophosphatemia

Intervention / Treatment
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* Drug: KRN23


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KRN23<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | On-Treatment: 6.5 months, 27 total visits | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | On-Treatment: 6.5 months, 27 total visits | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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XLH