Ferric Citrate for the Transition From CKD Stage 4/5 to CKD Stage 5D

This is an up to 50 week, phase 3, clinical trial in patients with estimated glomerular
filtration rate (eGFR) ≤ 20 ml/min/1.73m2. It will be comprised of an up to 36-week
non-dialysis period (NDP), or until such time as subjects require renal replacement therapy
(RRT) with dialysis when they will immediately roll into a 12-week dialysis period (DP). The
study will consist of up to 16 clinic visits over a maximum period of 50 weeks. There will be
a screening period of up to 14 days after which subjects will be randomized into the NDP in a
2:1 ratio to receive either FC (n=150) or SOC (n=75). Each eligible participant will be
randomized to either fixed dose open-label ferric citrate (FC) or standard of care (SOC)
treatment. Participants randomized to SOC will receive care directed by their primary
nephrologist throughout the study duration with the only restriction being that they cannot
receive treatment with FC during the NDP or DP. Participants randomized to FC will receive it
throughout the study duration.

220 participants were screened to randomize 200 subjects 2:1 (FC:SOC) into the NDP. It is
anticipated that 35-45% of participants will reach the dialysis period (DP) during the 36
week follow up. Participants who initiate RRT with dialysis will enter the Dialysis Period
(DP) during which those participants previously assigned to ferric citrate will continue to
receive open-label ferric citrate and those previously assigned to SOC will receive
open-label, non-FC phosphate binders at the discretion of their treating physician. During
this period all participants will be treated to standard of care guidelines which suggest
that if serum phosphate is above the upper limit of normal (4.5 mg/dL), it should be reduced.
During the DP, dose of P binders, use of ESA, intravenous iron and blood transfusions will be
at the discretion of the primary treating nephrologist. Participants assigned to the SOC
treatment arm may not receive FC at any point during the study.

Only participants that begin permanent RRT with dialysis will be eligible to enter the 12
week DP. Participants that do not begin RRT after 9 months participation in the NDP will be
deemed to have reach the end of study and have end of study procedures performed.

Inclusion Criteria:

1. Age >18 years at screening visit

2. Serum phosphate > or equal to 3.0 mg/dL obtained at screening

3. CKD with eGFR < or equal to 20 mL/min obtained at screening*

4. Hemoglobin (Hgb) >8.0 g/dL obtained at screening

5. TSAT <55% obtained at screening

6. Females of child bearing potential with negative serum pregnancy test obtained at
screening

7. Willing and able to give written informed consent

8. Anticipated to have > or equal to 8 weeks prior to need for initiating RRT in the
opinion of the investigator

Exclusion Criteria:

1. Liver enzymes (ALT/AST) >X3 times upper limit of normal at screening

2. Use of IV iron, blood transfusions or ESA agents within 2 weeks prior to the screening
visit and prior to the Day 1 visit.

3. Evidence of acute kidney injury (i.e., no CKD) or planned need for RRT within 12 weeks
of screening

4. Scheduled kidney transplant within 24 weeks of screening

5. Contra-indication to ferric citrate: iron overload syndrome, allergic reaction or
known intolerance to ferric citrate

6. Clinically significant medical condition felt to interfere with tolerance of oral
medication

7. Life expectancy < 6 months or confirmed conviction that subject does NOT want to
initiate RRT despite a decline in kidney function

8. Active drug or alcohol dependence or abuse (excluding tobacco use or marijuana use)
within the 12 months prior to screening (in the opinion of the PI)

9. Psychiatric disorder that interferes with the subject's ability to comply with the
study protocol in the opinion of the PI

10. Any other medical condition that, in the opinion of the PI, renders the subject unable
to or unlikely to complete the trial or that would interfere with optimal
participation in the trial or produce significant risk to the subject

11. Inability to cooperate with study personnel or study procedures

12. Females who are pregnant or breastfeeding

13. Receiving or has received any investigational drug with in the past 30 days prior to
the Day 1 visit