Study of the Safety, Pharmacodynamics (PD) and Efficacy of KRN23 in Children From 1 to 4 Years Old With X-linked Hypophosphatemia (XLH)

An Open-Label, Phase 2 Study to Assess the Safety, Pharmacodynamics, and Efficacy of KRN23 in Children From 1 to 4 Years Old With X-linked Hypophosphatemia (XLH)

The primary objectives of the study are to:

• Establish the safety profile of KRN23 for the treatment of XLH in children between 1 and 4 years old
• Determine the PD effects of KRN23 treatment on serum phosphorus and other PD markers that reflect the status of phosphate homeostasis in children between 1 and 4 years old with XLH

Inclusion Criteria:

1. Male or female, aged ≥1 year and <5 years

2. Diagnosis of XLH supported by ONE or more of the following

   • Confirmed phosphate regulating gene with homology to endopeptidases located on the X chromosome (PHEX) mutation in the patient or a directly related family member with appropriate X-linked inheritance
   • Serum fibroblast growth factor 23 (FGF23) level > 30 pg/mL by Kainos assay

3. Biochemical findings associated with XLH including:

   • Serum phosphorus < 3.0 mg/dL (0.97 mmol/L)
   • Serum creatinine within age-adjusted normal range

4. Radiographic evidence of rickets

5. Willing to provide access to prior medical records for the collection of historical growth, biochemical, and radiographic data and disease history

6. Provide written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures

7. Must, in the opinion of the investigator, be willing and able to complete all aspects of the study, adhere to the study visit schedule, and comply with the assessments

Exclusion Criteria:

1. Unwilling to stop treatment with oral phosphate and/or pharmacologic vitamin D metabolite or analog (e.g. calcitriol, alfacalcidol) during the screening period and for the duration of the study
2. Presence of nephrocalcinosis on renal ultrasound grade 4 based on the following scale: 0 = Normal, 1 = Faint hyperechogenic rim around the medullary pyramids, 2 = More intense echogenic rim with echoes faintly filling the entire pyramid, 3 = Uniformly intense echoes throughout the pyramid, 4 = Stone formation: solitary focus of echoes at the tip of the pyramid
3. Planned or recommended orthopedic surgery including staples, 8-plates or osteotomy, within the clinical trial period
4. Hypocalcemia or hypercalcemia, defined as serum calcium levels outside the age-adjusted normal limits
5. Presence or history of any condition that, in the view of the investigator, places the subject at high risk of poor treatment compliance or of not completing the study
6. Presence of a concurrent disease or condition that would interfere with study participation or affect safety
7. History of recurrent infection or predisposition to infection, or of known immunodeficiency
8. Use of any investigational product or investigational medical device within 30 days prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments