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Triferic IRIDA (Iron-Refractory Iron-Deficiency Anemia) Protocol

Primary Purpose

Iron-Refractory Iron-Deficiency Anemia

Status
Terminated
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Fer-In-Sol
Shohl's solution
Triferic
Sponsored by
Rockwell Medical Technologies, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Iron-Refractory Iron-Deficiency Anemia focused on measuring IRIDA, Triferic, soluble ferric pyrophosphate, Shohl's solution

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Adult patients have provided informed consent and have signed the informed consent form. For pediatric patients, 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 the informed consent form. Where applicable, assent of the pediatric patient has also been obtained for all study procedures prior to any study-related activities.
  2. Patient has a history of congenital hypochromic microcytic anemia.
  3. Patient has a mean corpuscular volume (MCV) ≤75 fluid ounce (fL) at screening.
  4. Patient has a serum transferrin saturation ≤15% at screening.
  5. Patient has a history of no or incomplete response to oral iron therapy.
  6. Patient has a history of no or incomplete response to intravenous iron administration.
  7. Patient has a history of hepcidin concentration ≥10 nanograms per milliliter (ng/mL) (3.58 nanometer (nM)) off iron supplements, adjusted for the specific hepcidin assay used to be at least 1 standard deviation (SD) greater than the mean for patients with iron-deficiency anemia.
  8. Patient is documented to have homozygous or compound heterozygous pathogenic mutations in Transmembrane Serine Protease 6 (TMPRSS6) in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.
  9. Patient has appropriate laboratory values for their disease state at screening (per investigator judgment).
  10. Patient has no significant abnormal findings on physical examination at screening that would preclude participation in the study (per investigator judgment).
  11. If the patient is female, she must be pre-pubertal, have had documented surgical sterilization ≥2 years prior to screening, 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:

  1. Patient has had intravenous (IV) or oral iron supplements within 2 weeks prior to Visit 2.
  2. Patient has had a blood transfusion within 3 months prior to Visit 2.
  3. Patient is receiving intravenous or oral antibiotics or antifungals for any infectious process. Prophylactic antibiotics administered on a regular basis are allowed. Otherwise-eligible patients may be rescreened when they have recovered from any acute illnesses.
  4. Patient has a body weight of <11 lbs (5 kg) at screening.
  5. Patient has participated in an investigational drug study within the 30 days prior to Visit 2.
  6. Patient has any condition that, in the opinion of the investigator, is likely to prevent the patient from complying with or successfully completing the protocol.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Experimental

    Arm Label

    Period 1: Iron Absorption Tests

    Period 2: Dose Titration

    Period 3: Hemoglobin Maintenance

    Arm Description

    During 3 consecutive weekly study visits, patients will receive Fer-In- Sol orally 3 milligram iron per kilogram (mg Fe/kg) body weight, Shohl's solution 0.67 millimoles per kilogram (mmol/kg) followed 5 - 15 minutes later by Fer-In- Sol orally 3 mg Fe/kg body weight, and Shohl's solution 0.67 mmol/kg followed 5 - 15 minutes later by Triferic orally 3 mg Fe/kg body weight (respectively). All oral doses will be administered by study personnel at the research center. Blood tests will be conducted following each administration in order to measure iron absorption to see if patients qualify for Period 2.

    Patients who qualified as 'Triferic responders' in Period 1 will participate in Period 2. Patients will be given oral Shohl's solution and Triferic to administer at home 3 times per day, with the dose being titrated higher or lower based on lab results. The initial dose will be the same as Period 1 (Shohl's solution 0.67 mmol/kg followed 5 - 15 minutes later by Triferic orally 3 mg Fe/kg body weight) but may be adjusted during Period 2 based on lab results. Period 2 will involve 5 study visits, scheduled every 4 weeks. At the end of Period 2, blood tests will be performed to determine if patients qualify for Period 3.

    Patients who qualified as 'hemoglobin responders' in Period 2 will participate in Period 3. Patients will continue to take Shohl's solution and Triferic at their titrated dose for an additional six months to confirm that their hemoglobin can be maintained over an extended period of time. The period will be comprised of 3 study visits, scheduled every 8 weeks.

    Outcomes

    Primary Outcome Measures

    The Efficacy of Triferic Delivered to IRIDA Patients:Change in Hemoglobin (Hgb)
    The efficacy will be done by assessing the change from baseline in hemoglobin concentration

    Secondary Outcome Measures

    The Efficacy of Triferic Being Delivered to Iron-refractory Iron Deficiency Anemia (IRIDA) Patients:Change in Serum Iron
    The efficacy will be done by assessing the change from baseline in serum iron
    The Efficacy of Triferic Being Delivered to IRIDA Patients:Change From Baseline in Transferrin Saturation (TSAT)
    The efficacy will be done by assessing the change from baseline in TSAT

    Full Information

    First Posted
    September 14, 2016
    Last Updated
    September 2, 2020
    Sponsor
    Rockwell Medical Technologies, Inc.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02905981
    Brief Title
    Triferic IRIDA (Iron-Refractory Iron-Deficiency Anemia) Protocol
    Official Title
    Triferic (Ferric Pyrophosphate Citrate) Administered Orally With Shohl's Solution for the Treatment of Iron-Refractory Iron-Deficiency Anemia
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2020
    Overall Recruitment Status
    Terminated
    Why Stopped
    Limited subjects, patient compliance
    Study Start Date
    January 17, 2017 (undefined)
    Primary Completion Date
    March 15, 2018 (Actual)
    Study Completion Date
    March 15, 2018 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Rockwell Medical Technologies, Inc.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The main purpose is to determine whether Triferic, administered orally with Shohl's solution, is safe and effective for the treatment of iron-refractory iron-deficiency anemia (IRIDA).
    Detailed Description
    This is an open label, 3-period study assessing the safety, efficacy, and pharmacokinetics of Triferic and Shohl's solution administered orally to patients with IRIDA. A total of 28 patients stratified by 4 age groups (age 0 to <6 years, age 6 to <12 years, age 12 to <18 years, and age >=18 years) will be studied. Total participation in the study is between 4 weeks (Period 1) and 12 months (Periods 1, 2, and 3), depending upon how many Periods each patient participates in. Following screening, in Period 1 (iron absorption testing) patients undergo oral iron absorption testing during 3 visits to confirm that they adequately absorb iron from Triferic when it is administered with Shohl's solution ('Triferic responders': patients with a maximal increase from baseline in serum iron concentration >100 micrograms per deciliter (μg/dL) following an oral Shohl's solution and Triferic dose). The 'Triferic responders' from Period 1 are then invited to participate in Period 2 (dose titration). The patients will receive Shohl's solution and Triferic orally up to 3 times per day for 4 months, titrated as needed based on laboratory results and patient tolerance, to determine whether their hemoglobin levels respond to this treatment. Period 2 'hemoglobin responders' (patients with an increase from baseline in hemoglobin (Hgb) concentration ≥1.0 grams per deciliter (g/dL) at Visit 9) will be invited to participate in period 3. In Period 3 patients will receive Shohl's solution and Triferic orally up to 3 times per day for an additional 6 months to determine whether the hemoglobin response observed in Period 2 is sustainable. During Period 3, Shohl's solution and Triferic dose and frequency may continue to be titrated as needed based on laboratory results and patient tolerance. A follow-up visit will occur approximately 1 week after the last completed Period study visit, regardless of the Period that the patient completes the study.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Iron-Refractory Iron-Deficiency Anemia
    Keywords
    IRIDA, Triferic, soluble ferric pyrophosphate, Shohl's solution

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Crossover Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    1 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Period 1: Iron Absorption Tests
    Arm Type
    Experimental
    Arm Description
    During 3 consecutive weekly study visits, patients will receive Fer-In- Sol orally 3 milligram iron per kilogram (mg Fe/kg) body weight, Shohl's solution 0.67 millimoles per kilogram (mmol/kg) followed 5 - 15 minutes later by Fer-In- Sol orally 3 mg Fe/kg body weight, and Shohl's solution 0.67 mmol/kg followed 5 - 15 minutes later by Triferic orally 3 mg Fe/kg body weight (respectively). All oral doses will be administered by study personnel at the research center. Blood tests will be conducted following each administration in order to measure iron absorption to see if patients qualify for Period 2.
    Arm Title
    Period 2: Dose Titration
    Arm Type
    Experimental
    Arm Description
    Patients who qualified as 'Triferic responders' in Period 1 will participate in Period 2. Patients will be given oral Shohl's solution and Triferic to administer at home 3 times per day, with the dose being titrated higher or lower based on lab results. The initial dose will be the same as Period 1 (Shohl's solution 0.67 mmol/kg followed 5 - 15 minutes later by Triferic orally 3 mg Fe/kg body weight) but may be adjusted during Period 2 based on lab results. Period 2 will involve 5 study visits, scheduled every 4 weeks. At the end of Period 2, blood tests will be performed to determine if patients qualify for Period 3.
    Arm Title
    Period 3: Hemoglobin Maintenance
    Arm Type
    Experimental
    Arm Description
    Patients who qualified as 'hemoglobin responders' in Period 2 will participate in Period 3. Patients will continue to take Shohl's solution and Triferic at their titrated dose for an additional six months to confirm that their hemoglobin can be maintained over an extended period of time. The period will be comprised of 3 study visits, scheduled every 8 weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    Fer-In-Sol
    Other Intervention Name(s)
    FeSO4
    Intervention Description
    Fer-In-Sol is an over-the-counter oral iron supplement. It will be administered during Period 1 at a dose of 3 mg/kg body weight.
    Intervention Type
    Drug
    Intervention Name(s)
    Shohl's solution
    Other Intervention Name(s)
    Citrate, Oracit
    Intervention Description
    Shohl's solution will be supplied as 500-milliliter (mL) bottles containing citric acid United States Pharmacopeia (USP) 640 milligrams per 5 milliliters (mg/5 mL) and hydrous sodium citrate USP 490 mg/5 mL. It will be administered during all Periods at a dose of 0.67 mmol/kg body weight.
    Intervention Type
    Drug
    Intervention Name(s)
    Triferic
    Other Intervention Name(s)
    ferric pyrophosphate citrate (FPC)
    Intervention Description
    Triferic is an iron salt that is approved by the Food and Drug Administration (FDA) for the maintenance of hemoglobin in patients with end stage kidney disease on hemodialysis. It is experimental in this study because it has not yet been approved for patients with IRIDA. It will be administered during Period 1 at a dose of 3 mg/kg body weight. In Periods 2 and 3 the dose may be adjusted based on lab results.
    Primary Outcome Measure Information:
    Title
    The Efficacy of Triferic Delivered to IRIDA Patients:Change in Hemoglobin (Hgb)
    Description
    The efficacy will be done by assessing the change from baseline in hemoglobin concentration
    Time Frame
    4 months
    Secondary Outcome Measure Information:
    Title
    The Efficacy of Triferic Being Delivered to Iron-refractory Iron Deficiency Anemia (IRIDA) Patients:Change in Serum Iron
    Description
    The efficacy will be done by assessing the change from baseline in serum iron
    Time Frame
    4 months
    Title
    The Efficacy of Triferic Being Delivered to IRIDA Patients:Change From Baseline in Transferrin Saturation (TSAT)
    Description
    The efficacy will be done by assessing the change from baseline in TSAT
    Time Frame
    4 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Adult patients have provided informed consent and have signed the informed consent form. For pediatric patients, 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 the informed consent form. Where applicable, assent of the pediatric patient has also been obtained for all study procedures prior to any study-related activities. Patient has a history of congenital hypochromic microcytic anemia. Patient has a mean corpuscular volume (MCV) ≤75 fluid ounce (fL) at screening. Patient has a serum transferrin saturation ≤15% at screening. Patient has a history of no or incomplete response to oral iron therapy. Patient has a history of no or incomplete response to intravenous iron administration. Patient has a history of hepcidin concentration ≥10 nanograms per milliliter (ng/mL) (3.58 nanometer (nM)) off iron supplements, adjusted for the specific hepcidin assay used to be at least 1 standard deviation (SD) greater than the mean for patients with iron-deficiency anemia. Patient is documented to have homozygous or compound heterozygous pathogenic mutations in Transmembrane Serine Protease 6 (TMPRSS6) in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. Patient has appropriate laboratory values for their disease state at screening (per investigator judgment). Patient has no significant abnormal findings on physical examination at screening that would preclude participation in the study (per investigator judgment). If the patient is female, she must be pre-pubertal, have had documented surgical sterilization ≥2 years prior to screening, 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: Patient has had intravenous (IV) or oral iron supplements within 2 weeks prior to Visit 2. Patient has had a blood transfusion within 3 months prior to Visit 2. Patient is receiving intravenous or oral antibiotics or antifungals for any infectious process. Prophylactic antibiotics administered on a regular basis are allowed. Otherwise-eligible patients may be rescreened when they have recovered from any acute illnesses. Patient has a body weight of <11 lbs (5 kg) at screening. Patient has participated in an investigational drug study within the 30 days prior to Visit 2. Patient has any condition that, in the opinion of the investigator, is likely to prevent the patient from complying with or successfully completing the protocol.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Raymond D Pratt, MD, FACP
    Organizational Affiliation
    Rockwell Medical, Inc
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes

    Learn more about this trial

    Triferic IRIDA (Iron-Refractory Iron-Deficiency Anemia) Protocol

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