Limited subjects, patient compliance

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).

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.

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.

11 months

Study terminated after one patient was enrolled. Patient discontinued due to lack of improvement in hemoglobin levels and subject compliance issues. Termination after only one subject enrolled does not allow definitive conclusions to be reached.