Triferic Pediatric Pharmacokinetic Protocol

This is a Phase 1/2, open-label, 2-period, single-dose study assessing the safety and pharmacokinetics (PK) of Triferic (ferric pyrophosphate citrate, or FPC) administered via dialysate and IV to pediatric patients (< 18 years of age) receiving chronic hemodialysis (CKD-5HD).

Total participation in the study is approximately three weeks and is comprised of a screening visit, two dosing (PK) visits, and a follow-up visit.

Each patient will receive a single dose of Triferic administered IV into the venous blood return line over the duration of the dialysis. At the next scheduled dialysis session each patient will receive a single dose of Triferic administered via dialysate during a single hemodialysis session.

Blood samples will be obtained at various times to analyze for serum iron parameters and for safety.

Inclusion criteria

A patient will be eligible for inclusion in the study only if all of the following criteria are met:

• Parents/legal guardians of the patient have the ability to understand the requirements of the study and have demonstrated a willingness to have their child comply with all study procedures by signing an institutional review board-approved informed consent form. Where applicable, assent of the patient has also been obtained for all study procedures prior to any study-related activities.
• Patient is <18 years of age at screening.
• Patient has chronic kidney disease receiving in-center hemodialysis at least twice weekly for at least 1 month prior to screening.
• Patient is receiving adequate hemodialysis as assessed by the investigator and based on a single pool Kt/V measurement >1.2.
• Patient has a vascular access (tunneled catheter, AV fistula or AV graft) suitable to support blood flows for hemodialysis treatment.
• Patient has a body mass of 11 lbs (5 kg).
• Patient is iron-replete as measured by a TSAT 20% and a ferritin >100 micrograms/L at screening.
• Patient has a whole blood Hgb concentration of 10.0 g/dL at screening.
• If patient is receiving ESA, the dose has been stable (unchanged) for at least 3 weeks prior to Baseline admission.
• Patient has appropriate laboratory values for their disease state at screening (per investigator judgment).
• Patient has no significant abnormal findings on physical examination that would preclude participation in the study.
• If the patient is female, she must be pre-pubertal, have had documented surgical sterilization prior to Baseline admission, or be practicing adequate birth control. All female patients 9 years of age and older, and also any who have reached menarche before age 9 years, must have a negative serum pregnancy test during screening. It is the investigator's responsibility to determine whether the patient has adequate birth control for study participation.

Exclusion criteria

A patient will not be eligible for inclusion in the study if any of the following criteria apply:

• Patient is positive for human immunodeficiency virus (HIV) or hepatitis B by history.
• Patient has an acute illness within 1 week of Baseline admission (patient may be screened again 2 weeks post resolution of the acute illness).
• Patient is receiving intravenous or oral antibiotics or antifungals for any infectious process. Prophylactic antibiotics administered on a regular basis are allowed.
• Patient has evidence of an ongoing active inflammatory process (e.g., systemic lupus erythematosus, acute or chronic active hepatitis, etc.).
• Patient has participated in an investigational drug study within the 30 days prior to Baseline admission.
• Administration of IV or oral iron supplements within 2 weeks prior to Baseline admission.