PBF-1681 (Ferric Citrate) for the Treatment of IDA in Patients With NDD-CKD

Sponsor
Panion & BF Biotech Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04543812
Collaborator
(none)
200
8
2
26.6
25
0.9

Study Details

Study Description

Brief Summary

To assess the safety and effectiveness of PBF-1681 for the treatment of Iron Deficiency Anemia in patients with Non-Dialysis Dependent Chronic Kidney Disease.

Condition or Disease Intervention/Treatment Phase
  • Drug: Ferric citrate
  • Drug: Placebo
Phase 3

Detailed Description

This is a Phase 3, 24-week, multicenter study in Taiwan, comprising a 16-week, randomized, double-blind, placebo-controlled period ("Randomized Period"), followed by an 8-week open-label extension period, where all subjects receive PBF-1681 (ferric citrate) ("Extension Period"). The study will consist of 10 visits over a period of 24 weeks. There will be a screening period of up to 14 days. Approximately 200 subjects will be randomized into the Randomized Period in a 1:1 ratio to receive either PBF-1681 or matching placebo, at baseline.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
200 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 3 Study of PBF-1681 Comprising a 16-week, Placebo-controlled, Double-blind Randomized Period and an 8-week, Open-label Extension Period for the Treatment of Iron Deficiency Anemia in Patients With Non-Dialysis Dependent CKD
Actual Study Start Date :
Oct 14, 2020
Anticipated Primary Completion Date :
Jan 1, 2023
Anticipated Study Completion Date :
Jan 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: PBF-1681 (ferric citrate)

PBF-1681 (ferric citrate) will be dosed two times a day with the 2 largest meals (preferred) or three times a day with meals.

Drug: Ferric citrate
Ferric citrate will be provided as a 1g tablet. All intervention doses will be based on hemoglobin levels.

Placebo Comparator: Placebo

Matching placebo will be dosed two times a day with the 2 largest meals (preferred) or three times a day with meals.

Drug: Placebo
Matching placebo will be provided as a 1g tablet. All intervention doses will be based on hemoglobin levels.

Outcome Measures

Primary Outcome Measures

  1. The proportion of subjects achieving an increase in Hgb of ≥1.0 g/dL at any time point between baseline and the end of the 16-week Randomized Period. [16 weeks]

    Efficacy analyses were performed for the population consisted of all subjects who were randomized, had a baseline laboratory value, took at least 1 dose of study drug or placebo, and had at least 1 post-baseline laboratory assessment during the randomized period.

Secondary Outcome Measures

  1. Hemoglobin (Hgb) [16 weeks]

    The mean change from baseline to the end of the Randomized Period in Hgb.

  2. Transferring saturation (TSAT) [16 weeks]

    The mean change from baseline to the end of the Randomized Period in TSAT.

  3. Ferritin [16 weeks]

    The mean change from baseline to the end of the Randomized Period in ferritin.

  4. Serum Phosphate [16 weeks]

    The mean change from baseline to the end of the Randomized Period in serum phosphate.

  5. Sustained increase in Hgb of ≥0.75 g/dL [16 weeks]

    The proportion of subjects achieving a sustained increase in Hgb of ≥0.75 g/dL from baseline over any 4-week interval during the Randomization Period.

Other Outcome Measures

  1. Serum calcium [16 weeks]

    The mean change from baseline to the end of the Randomized Period in serum calcium.

  2. Serum bicarbonate [16 weeks]

    The mean change from baseline to the end of the Randomized Period in serum bicarbonate.

  3. Serum iron [16 weeks]

    The mean change from baseline to the end of the Randomized Period in serum iron.

  4. Unsaturated iron binding capacity (UIBC) [16 weeks]

    The mean change from baseline to the end of the Randomized Period in UIBC.

  5. Total iron binding capacity (TIBC) [16 weeks]

    The mean change from baseline to the end of the Randomized Period in TIBC.

  6. Hematocrit [16 weeks]

    The mean change from baseline to the end of the Randomized Period in hematocrit.

  7. Intact parathyroid hormone (iPTH) [16 weeks]

    The mean change from baseline to the end of the Randomized Period in iPTH.

  8. Fibroblast growth factor 23 (intact and C-terminal) [16 weeks]

    The mean change from baseline to the end of the Randomized Period in FGF23 (intact and C-terminal).

  9. Serum aluminum [16 weeks]

    The mean change from baseline to the end of the Randomized Period in serum aluminum.

  10. Sustained increase in Hgb [16 weeks]

    The proportion of subjects achieving a sustained increase in Hgb of ≥0.75 g/dL from baseline over any 4-week interval during the Randomized Period, provided that an increase in Hgb of ≥1.0 g/dL had occurred during that 4-week interval

  11. Increase in Hgb of ≥1.0 g/dL [16 weeks]

    Time (in days) to first increase in Hgb of ≥1.0 g/dL from baseline.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  1. Men or women ≥18 years of age at screening.

  2. CKD with eGFR <60 mL/min at screening using the 4-variable Modification of Diet in Renal Disease equation, where up to 20% of subjects with eGFR <15 mL/min are allowed.

  3. Hgb ≥9.0 g/dL and ≤11.5 g/dL at screening.

  4. Serum ferritin <300 ng/mL and TSAT <30% at screening.

  5. Serum iPTH ≤600 pg/mL at screening.

  6. Must consume minimally 2 meals per day.

  7. Willing to give written informed consent.

  8. Women may be enrolled if they are:

  9. Documented to be surgically sterile or postmenopausal (amenorrhea >1 year and follicle-stimulating hormone ≥30 mU/mL), or

  10. Practicing true abstinence for at least 28 days prior to study drug administration until 30 days after study drug administration and having a negative serum pregnancy test at screening, or

  11. Using 2 forms of highly effective contraception, out of which 1 should be a physical barrier (condom or diaphragm), and another method such as adequate hormonal method (eg, contraceptive implants, injectables, oral contraceptives) or non-hormonal methods (eg, intrauterine device, spermicidals) from screening or at least 2 weeks prior to study drug administration (whichever is earlier) until 30 days after the study drug administration and having a negative serum pregnancy test at screening.

Exclusion Criteria:
  1. Cause of anemia other than iron deficiency.

  2. Serum phosphate <3.5 mg/dL at screening.

  3. IV iron administered within 4 weeks of the start of screening.

  4. ESA administered within 4 weeks of the start of screening.

  5. Blood transfusion within 4 weeks of the start of screening.

  6. Liver enzymes (alanine aminotransferase [ALT]/aspartate aminotransferase [AST]) >3 times upper limit of normal (ULN) at screening.

  7. Symptomatic GI bleeding or symptomatic inflammatory bowel disease within 12 weeks of the start of screening.

  8. Concurrent GI diseases assessed by Investigators to be inappropriate for the study, eg, acute peptic ulcer, chronic ulcerative colitis, and regional enteritis.

  9. Active infection requiring systemic antimicrobial treatment such as antibiotics, antiviral, or antifungals at screening.

  10. Concomitant or prior malignancy, except non-melanoma skin cancer or disease-free for ≥2 years after curative therapy.

  11. Subjects with known allergic reaction to previous oral iron therapy.

  12. Subjects who were intolerant to oral iron therapy.

  13. History of hemochromatosis.

  14. Scheduled kidney transplant or initiation of dialysis planned within 24 weeks of the start of screening.

  15. Planned surgery or hospitalization (anticipated to last >72 hours) during the Randomized Period of the study other than dialysis access-related surgery.

  16. Any other medical condition that, in the Investigators' opinion, may disturb subject's completion or optimal participation of the study, act as a significant confounding variable, or carry significant risks to a subject.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital Kaohsiung Taiwan 80756
2 Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang-Gung Memorial Hospital Kaohsiung Taiwan 83301
3 Division of Nephrology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital Keelung Taiwan 20401
4 Division of Nephrology, Department of Internal Medicine, Far East Memorial Hospital New Taipei City Taiwan 22060
5 Division of Nephrology, Department of Internal Medicine, China Medical University Hospital Taichung Taiwan 40433
6 Division of Nephrology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital Taipei county Taiwan 23561
7 Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital Taipei Taiwan 10002
8 Division of Nephrology, Department of Internal Medicine, Taipei Veterans General Hospital Taipei Taiwan 11217

Sponsors and Collaborators

  • Panion & BF Biotech Inc.

Investigators

  • Principal Investigator: Der-Cherng Tarng, MD, PhD, Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Panion & BF Biotech Inc.
ClinicalTrials.gov Identifier:
NCT04543812
Other Study ID Numbers:
  • PBB00601
First Posted:
Sep 10, 2020
Last Update Posted:
Mar 8, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Panion & BF Biotech Inc.
Additional relevant MeSH terms:

Study Results

No Results Posted as of Mar 8, 2022