Triferic IRIDA (Iron-Refractory Iron-Deficiency Anemia) Protocol
Condition: Iron-Refractory Iron-Deficiency Anemia
MeSH terms: Anemia; Anemia, Iron-Deficiency; Iron Deficiencies; Deficiency Diseases
Intervention: Fer-In-Sol; Shohl's solution; Triferic
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.; 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.; 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.
Intervention MeSH terms: Citric Acid; Sodium Citrate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: IRIDA; Triferic; soluble ferric pyrophosphate; Shohl's solution

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).
    

Eligibility criteria:

        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.