FRONTIER: Ferric Citrate for the Prevention of Renal Failure in Adults With Advanced Chronic Kidney Disease

• Sponsor: USRC Kidney Research (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05085275
• Collaborator: Akebia Therapeutics (Industry)
• Enrollment: 400
• Locations: 23
• Arms: 2
• Anticipated Duration (Months): 28.1
• Patients Per Site: 17.4
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

A 9-month randomized, double-blind, placebo-controlled study to compare the effect of fixed dose ferric citrate versus placebo in patients with advanced chronic kidney disease (eGFR ≤20 ml/min/1.73m2) on the composite endpoint of time to initiation of maintenance dialysis or all-cause mortality.

Condition or Disease	Intervention/Treatment	Phase
Anemia, Iron Deficiency; Hyperphosphatemia; Renal Insufficiency, Chronic; Renal Anemia; Disease Progression; Cardiovascular; Iron	Drug: Ferric Citrate 1 GM Oral Tablet [AURYXIA]; Drug: Placebo	Phase 3

Detailed Description

This multicenter, randomized, double-blind, placebo-controlled clinical trial is being conducted to determine the effect of ferric citrate on the time to a composite endpoint of initiation of maintenance dialysis or all-cause mortality in patients with non-dialysis dependent, advanced CKD. Up to 400 subjects will be randomized in 1:1 ratio to receive either ferric citrate or matching placebo. All subjects will initiate dosing at 2 tablets per meal or snacks, up to 3 times per day (maximum of 6 tablets per day). The dose of ferric citrate/placebo will only be adjusted based on safety and/or tolerability. Given the double-blind design of this trial, investigators will be instructed to not prescribe commercial Auryxia to either study arm. Study visits during the treatment period are to be conducted as part of routine scheduled clinical encounters. Standard of care local laboratory results will be collected however no study specific laboratory tests other than a pregnancy test in women of child-bearing potential will be required.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 400 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, placebo controlled, double-blind, parallel assignmentRandomized, placebo controlled, double-blind, parallel assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Determine the Effect of Ferric Citrate on Time to a Composite Endpoint of Initiation of Maintenance Dialysis or All-cause Mortality vs Placebo in Adults With Advanced CKD
• Actual Study Start Date: Mar 30, 2022
• Anticipated Primary Completion Date: Aug 1, 2024
• Anticipated Study Completion Date: Aug 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ferric citrate Supplied as tablets for oral administration containing 1 gram ferric citrate (210 milligrams of ferric iron). Administered orally with meals or snacks.	Drug: Ferric Citrate 1 GM Oral Tablet [AURYXIA]; All subjects will be instructed to take study drug (ferric citrate or placebo) at a fixed dose of 2 tablets per meal or snacks, up to three times per day. The maximum dose is 6 tablets per day. No additional tablets (beyond a total of 6 per day) should be taken. Tablets should not be crushed or chewed.; Other Names: Auryxia
Placebo Comparator: Placebo Tablets, matching in color and size to ferric citrate.	Drug: Placebo; All subjects will be instructed to take study drug (ferric citrate or placebo) at a fixed dose of 2 tablets per meal or snacks, up to three times per day. The maximum dose is 6 tablets per day. No additional tablets (beyond a total of 6 per day) should be taken. Tablets should not be crushed or chewed.

Outcome Measures

Primary Outcome Measures

1. Time to a composite endpoint of initiation of maintenance dialysis or all-cause mortality [9 months]

   Time to a composite endpoint of initiation of maintenance dialysis or all-cause mortality

Secondary Outcome Measures

1. Time to first hospitalization event reported as a serious adverse event (SAE) (excluding disease-related hospitalization [e.g., dialysis access placement, dialysis initiation, kidney transplant] and elective procedures) [9 months]

   Time to first hospitalization event reported as a serious adverse event (SAE) (excluding disease-related hospitalization [e.g., dialysis access placement, dialysis initiation, kidney transplant] and elective procedures)

2. Component of Primary - Time to Initiation of Maintenance Dialysis [9 months]

   Component of Primary - Time to Initiation of Maintenance Dialysis

3. Component of Primary - Time to All-Cause Mortality [9 months]

   Component of Primary - Time to All-Cause Mortality

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Adult patients greater or equal to 18 years old.

2. Diagnosis of NDD advanced CKD, regardless of etiology. Advanced CKD is defined as at least one local laboratory determined estimated glomerular filtration rate (eGFR) ≤20 ml/min/1.73m2 (calculated per any commonly used method or equation for estimating eGFR) within 90 days of Day 1.

3. Most recent transferrin saturation (TSAT) less than or equal to 45% within 45 days of Day 1.

4. Most recent serum phosphate is greater or equal to 3.0 mg per dL within 45 days of Day

6. Most recent ferritin is less than or equal to 500 ng per mL within 45 days of Day 1.

7. Women of child-bearing potential must have a negative serum or urine pregnancy test within 28 days prior to Day 1.

8. Understands the procedures and requirements of the study and provides written informed consent and authorization for protected health information disclosure.

Exclusion Criteria:

1. Patients who, in the opinion of the Investigator, have acute kidney injury rather than CKD.

2. Patients with planned/imminent maintenance dialysis, or that are anticipated to begin maintenance dialysis within 8 weeks from Screening, in the opinion of the Investigator.

3. A known allergy or intolerance to ferric citrate or any of its constituents.

4. Hypersensitivity reaction to previous oral iron therapy.

5. History of hemochromatosis or iron overload syndrome (e.g., hereditary sideroblastic anemia, thalassemia, polycythemia vera).

6. Active malignancy requiring current treatment except for non-melanoma skin cancer regardless of treatment.

7. Active drug or alcohol dependence or abuse (excluding tobacco use or use of medical or recreational marijuana) within the 12 months prior to Screening or evidence of such abuse, in the opinion of the Investigator.

8. Limited life expectancy (less than 6 months) in the opinion of the Investigator.

9. Females who are known to be pregnant or are breast-feeding during Screening or are planning to become pregnant and breastfeeding during the study period.

10. Evidence of a clinically active infection requiring antibiotics at Randomization.

11. Unable to comply with study requirements or in the opinion of the Investigator, not clinically stable to participate in the study.

12. Use of an investigational medication or participation in an investigational study within 30 days prior to Day 1.

13. Patients with a scheduled date for receipt of living donor kidney transplant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arkansas Nephrology & Hypertension Clinic	Pine Bluff	Arkansas	United States	71603
2	Balboa Research SMO	Chula Vista	California	United States	91910
3	Balboa Research SMO	El Centro	California	United States	92243
4	Balboa Research SMO	Escondido	California	United States	92025
5	Balboa Research SMO	La Mesa	California	United States	91942
6	Balboa Research SMO - Kearney Mesa	San Diego	California	United States	92111
7	Rocky Mountain Kidney Care	Lone Tree	Colorado	United States	80124
8	Associates in Nephrology	Fort Myers	Florida	United States	33908
9	Dialysis Clinic, Inc.	Albany	Georgia	United States	31701
10	Nephrology and Hypertension Specialists, PC	Dalton	Georgia	United States	30720
11	Major Health Partners	Shelbyville	Indiana	United States	46176
12	Kidney Associates of Kansas City	Kansas City	Missouri	United States	64131
13	Nephrology-Hypertension Associates of Central NJ	S. River	New Jersey	United States	08882
14	High Desert Nephrology Associates	Gallup	New Mexico	United States	87301
15	Nephrology Associates of Western NY	Amherst	New York	United States	14228
16	Spartanburg Nephrology Associates	Spartanburg	South Carolina	United States	29302
17	Dialysis Clinic, Inc.	Knoxville	Tennessee	United States	37920
18	South Texas Renal Care Group	Live Oak	Texas	United States	78233
19	South Texas Renal Care Group	San Antonio	Texas	United States	78202
20	South Texas Renal Care Group	San Antonio	Texas	United States	78211
21	Clinical Advancement Center, PLLC	San Antonio	Texas	United States	78212
22	South Texas Renal Care Group	San Antonio	Texas	United States	78221
23	South Texas Renal Care Group	San Antonio	Texas	United States	78251

Sponsors and Collaborators

• USRC Kidney Research
• Akebia Therapeutics

Investigators

• Principal Investigator: Geoff Block, MD, USRC Kidney Research

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: USRC Kidney Research
• ClinicalTrials.gov Identifier: NCT05085275
• Other Study ID Numbers: USRC-2021-002
• First Posted: Oct 20, 2021
• Last Update Posted: Aug 17, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by USRC Kidney Research: ferric citrate
• Additional relevant MeSH terms: Renal Insufficiency; Renal Insufficiency, Chronic; Anemia; Anemia, Iron-Deficiency; Hyperphosphatemia; Disease Progression

Study Results

No Results Posted as of Aug 17, 2022