Triferic Pediatric Pharmacokinetic Protocol

Phase 1

Completed

• Conditions: End Stage Renal Disease
• Interventions: Drug: Triferic

• Registration Number: NCT02595437
• Lead Sponsor: Rockwell Medical Technologies, Inc.

Brief Summary

The main purpose is to determine the pharmacokinetics (PK) of Triferic iron administered intravenously in pediatric patients with chronic kidney disease on chronic hemodialysis (CKD-5HD). It is an open-label, two-period sequential dosing study.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2015-10-30
• Study Start: 2015-11-01
• Study First Submitted QC: 2015-11-02
• Study First Posted: 2015-11-03
• Primary Completion: 2016-12
• Study Completion: 2017-01
• Results First Submitted: 2018-08-27
• Status Verified: 2018-09
• Results First Submitted QC: 2018-09-26
• Last Update Submitted: 2018-09-26
• Results First Posted: 2018-10-25
• Last Update Posted: 2018-10-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

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

1. 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.
2. Patient is <18 years of age at screening.
3. Patient has chronic kidney disease receiving in-center hemodialysis at least twice weekly for at least 1 month prior to screening.
4. Patient is receiving adequate hemodialysis as assessed by the investigator and based on a single pool Kt/V measurement >1.2.
5. Patient has a vascular access (tunneled catheter, AV fistula or AV graft) suitable to support blood flows for hemodialysis treatment.
6. Patient has a body mass of 11 lbs (5 kg).
7. Patient is iron-replete as measured by a TSAT 20% and a ferritin >100 micrograms/L at screening.
8. Patient has a whole blood Hgb concentration of 10.0 g/dL at screening.
9. If patient is receiving ESA, the dose has been stable (unchanged) for at least 3 weeks prior to Baseline admission.
10. Patient has appropriate laboratory values for their disease state at screening (per investigator judgment).
11. Patient has no significant abnormal findings on physical examination that would preclude participation in the study.
12. 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:

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Triferic via IV and Hemodialysate	Triferic	On study Day 1, patients will receive IV Triferic iron 0.07 mg/kg diluted in an appropriate amount of D5W administered as a 100 mL infusion into the venous return port of the blood lines during the time the patient is receiving dialysis.The rate of administration will be calculated as such that the entire amount will be administered over the course of the dialysis treatment. On study Day 3, Triferic will be mixed with the liquid bicarbonate concentrate used in the preparation of the hemodialysate solution. This will result in a final Triferic iron concentration in the dialysate of 2 µM (110 µg/L). The patients will receive Triferic via the hemodialysate over the course of the dialysis treatment.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK) of Triferic Iron Administered IV in Pediatric CKD-5HD Patients: Cmax.	0, 1, 2, 4, 4.5, 5, 6, 8, 10 hrs	The PK will be done by assessing the mean absolute and baseline-corrected Cmax of total iron with an IV infusion of Triferic at 0.07 mg iron/kg during a single dialysis session. The absolute Cmax includes the concentration of iron that was present in the serum prior to dosing as well the iron administered, while the baseline-corrected Cmax factors out the iron present in the serum prior to dosing and includes the administered iron only.
Pharmacokinetics (PK) of Triferic Iron Administered IV in Pediatric CKD-5HD Patients: AUC(Last).	0, 1, 2, 4, 4.5, 5, 6, 8, 10 hours	The PK will be done by assessing the mean absolute and baseline-corrected AUC(last) of total iron with an IV infusion of Triferic at 0.07 mg iron/kg during a single dialysis session. The absolute AUC(last) includes iron that was present in the serum prior to dosing as well the iron administered, while the baseline-corrected AUC(last) factors out the iron present in the serum prior to dosing and includes the administered iron only.
Pharmacokinetics (PK) of Triferic Iron Administered IV in Pediatric CKD-5HD Patients: AUC(0-end).	0, 1, 2, 4, 4.5, 5, 6, 8, 10 hours	The PK will be done by assessing the mean absolute and baseline-corrected AUC(0-end) of total iron with an IV infusion of Triferic at 0.07 mg iron/kg during a single dialysis session. The absolute AUC (0-end) includes iron that was present in the serum prior to dosing as well the iron administered, while the baseline-corrected AUC (0-end) factors out the iron present in the serum prior to dosing and includes the administered iron only.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK) of Triferic Iron Administered Via the Hemodialysate in Pediatric CKD-5HD Patients: Cmax.	0, 1, 2, 4, 4.5, 5, 6, 8, 10 hours	The PK will be done by assessing the mean absolute and baseline-corrected Cmax of total iron. The absolute Cmax includes the concentration of iron that was present in the serum prior to dosing as well the iron administered, while the baseline-corrected Cmax factors out the iron present in the serum prior to dosing and includes the administered iron only.
Pharmacokinetics (PK) of Triferic Iron Administered Via the Hemodialysate in Pediatric CKD-5HD Patients: AUC(Last).	0, 1, 2, 4, 4.5, 5, 6, 8, 10 hours	The PK will be done by assessing the mean absolute and baseline-corrected AUC(last) of total iron. The absolute AUC (last) includes the iron that was present in the serum prior to dosing as well the iron administered, while the baseline-corrected Cmax factors out the iron present in the serum prior to dosing and includes the administered iron only.
Pharmacokinetics (PK) of Triferic Iron Administered Via the Hemodialysate in Pediatric CKD-5HD Patients: AUC(0-end).	0, 1, 2, 4, 4.5, 5, 6, 8, 10 hours	The PK will be done by assessing the mean absolute and baseline-corrected AUC(0-end) of total iron. The absolute AUC (0-end) includes the of iron that was present in the serum prior to dosing as well the iron administered, while the baseline-corrected Cmax factors out the iron present in the serum prior to dosing and includes the administered iron only.

Trial Locations

Locations (9)

Lucile Packard Childrens Hospital; 🇺🇸 Stanford, California, United States

Nemours/A. I. DuPont Hospital for Children; 🇺🇸 Wilmington, Delaware, United States

Children's Hospital of Alabama; 🇺🇸 Birmingham, Alabama, United States

Joe DiMagggio Children's Hospital/Memorial Regional Hospital; 🇺🇸 Hollywood, Florida, United States

Loma Linda University Hospital; 🇺🇸 Loma Linda, California, United States

Jackson Memorial Hospital; 🇺🇸 Miami, Florida, United States

Childrens Mercy Hospital; 🇺🇸 Kansas City, Missouri, United States

Cincinnati Children's Hospital and Medical Center; 🇺🇸 Cincinnati, Ohio, United States

University of Texas Health Science Center at San Antonio; 🇺🇸 San Antonio, Texas, United States