Evaluate the Safety and Efficacy of Ferric Maltol Oral Suspension vs. Ferrous Sulfate Oral Liquid in Children and Adolescents Aged 2 to 17 Years With Iron-deficiency Anaemia, With a Single Arm Study in Infants Aged 1 Month to Less Than 2 Years (FORTIS)

Randomised, Open-label, Active-controlled, Multicentre, Comparative Study to Evaluate the Safety and Efficacy of Ferric Maltol (Iron (III)-Maltol Complex) (ST10) Oral Suspension Compared to Ferrous Sulfate Oral Liquid in Children and Adolescents Aged 2 to 17 Years With Iron-deficiency Anaemia, Incorporating a Single Arm Study in Infants Aged 1 Month to Less Than 2 Years

The objective of the study is to compare the safety and gastrointestinal tolerability of ferric maltol oral suspension and ferrous sulfate oral liquid in children and adolescents aged 2 years to 17 years, and assess the safety and tolerability of ferric maltol oral suspension in children 1 month to less than 2 years, in the treatment of iron deficiency anaemia during the 12 weeks treatment period.

Study Overview

• Status: Completed
• Conditions: Iron-deficiency; Anemia
• Intervention / Treatment: Drug: Ferric Maltol; Drug: Ferrous sulfate

Detailed Description

The study is a randomised, Open-label, Active-controlled, Multicentre, Comparative Study to Evaluate the Safety and Efficacy of Ferric Maltol (Iron (III)-Maltol Complex) (ST10) Oral Suspension Compared to Ferrous Sulfate Oral Liquid in Children and Adolescents Aged 2 to 17 Years With Iron-deficiency Anaemia, Incorporating a Single Arm Study in Infants Aged 1 Month to Less Than 2 Years.

Approximately 110 male and female children from 1 month to 17 years of age, with iron deficiency anaemia. If less than 91 subjects in total have been randomized when 32 ferric maltol subjects have completed, then an interim analysis will be conducted.

Subjects aged 2 to 17 years will be 1:1 randomised to ferric maltol and ferrous sulfate, with 49 subjects in each arm. Subjects then will be further divided into 2 age groups: 2 yrs - 9 yrs and 10 yrs -17 yrs. A minimum of 18 subjects must be recruited into the 2 yrs - 9 yrs and 10 yrs - 17 yrs age groups and a minimum of 25% of either sex must be recruited.

A maximum of 12 subjects will be recruited in the 1 month to less than 2 years age group. They will only be assigned to the ferric maltol group, once there is evidence of absorption, of serum iron and elimination of maltol from the Pre-assignment PK samples by showing urine maltol return to baseline, or to a low level, confirming no accumulation of maltol or maltol glucuronide, they will continue on to the 12 weeks treatment phase.

Design: The study will comprise of the following stages:

• Screening: within 14 days prior to randomisation for each subject
• Pre-assignment PK phase: only applicable for subjects aged 1 month to less than 2 years. Up to 21 days from Screening.
• Randomised treatment: 12 weeks open label treatment
• Assigned treatment phase 12 weeks open label treatment for ferric maltol children aged 1 month to less than 2 years
• End of study: Week 12 visit
• Post-treatment safety follow-up: 10-14 days following study completion of the treatment period or premature discontinuation

Investigational Product Product: Ferric maltol oral suspension: oral suspension containing 30 mg elemental iron, in the form of 231.5 mg ferric maltol, in 5 ml suspension.

Ferric maltol oral suspension will be taken every morning and evening at least 30 minutes after a meal. Dosing will be supervised by the parent/legal guardian for children/adolescents throughout the treatment period and recorded on a dosing diary.

Ferric maltol bottles will be labelled for clinical trials use and each bottle will have a unique bottle number which will be utilised in the randomisation procedure.

A final eligibility evaluation must be conducted immediately prior to randomisation.

Reference safety information will be the Investigator Brochure.

Comparator therapy: Ferrous sulfate 125 mg/ml (25 mg/ml elemental iron) oral liquid or equivalent dose will be administered under this protocol. Dosing will be supervised by the parent/legal guardian for children/adolescents throughout the treatment period and recorded on a dosing diary.

Reference safety information will be the currently approved summary of product characteristics.

Statistical methods:

Safety and gastrointestinal tolerability will be compared between ferric maltol oral suspension and ferrous sulfate oral liquid via summaries of treatment emergent adverse events (TEAEs), treatment emergent serious AEs (TESAEs) and treatment-emergent AEs (TEAEs) leading to premature discontinuation of study drug.

Efficacy of ferric maltol will be assessed via the change in Hb concentration from baseline to week 12. If no interim analysis is conducted it will be based on a 95% two-sided confidence interval; If an interim analysis is conducted, a Pocock spending function will be used; the interim analysis will be based on a (100 - 3.45)% two sided confidence interval; if the study does not stop after the interim analysis, the final analysis will be based on a (100 - 2.57)% two sided confidence interval.

For the PK analysis, all analytes in serum will be summarised per PK day, for children and adolescents aged 1 month to 17 years receiving ferric maltol.

In addition, all analytes in urine will be summarised per PK day, for children aged 1 month to less than 2 years.

Full details of the statistical analysis, including the analysis of PK endpoints, will be specified in the statistical analysis plan (SAP).

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00907
    • BRCR Global Puerto
• United Kingdom
  • Cardiff, United Kingdom, CF14 4XW
    • Noah's Ark Children's Hospital for Wales
  • Edinburgh, United Kingdom, EH16 4TJ
    • Royal Hospital for Sick Children - Edinburgh
  • Leicester, United Kingdom, LE1 5WW
    • Leicester Royal Infirmary
  • Liverpool, United Kingdom
    • Alder Hey Children's NHS Foundation Trust
  • London, United Kingdom, SE5 9RS
    • King's College Hospital
  • London, United Kingdom
    • Newham University Hospital
  • Manchester, United Kingdom, M13 9WL
    • Royal Manchester Children's Hospital
  • Nottingham, United Kingdom, NG7 2UH
    • Nottingham University Hospitals
• United States
  • Alabama
    • Saraland, Alabama, United States, 36571
      • The Center for Clinical Trials
  • Florida
    • Homestead, Florida, United States, 33030
      • Homestead Research Institute
    • Kissimmee, Florida, United States, 34743
      • Kissimmee Clinical Research Corp
    • Miami, Florida, United States, 33155
      • Miami Clinical Research
    • Miami, Florida, United States, 33165
      • Medical Research of Westcheste
    • North Lauderdale, Florida, United States, 33068
      • Eminent Clinical Research and Associates
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Clinical Research Prime
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Sierra Clinical Research
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Hershey Children's Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Hasbro Children's Hospital
  • Texas
    • Edinburg, Texas, United States, 78539
      • BRCR Global Texas
    • Katy, Texas, United States, 77494
      • Zion Research
  • Washington
    • Tacoma, Washington, United States, 98405
      • MultiCare Health System Institute for Research and Innovation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patient is willing and able to comply with the study requirements and to provide written informed consent. In the case of patients under the age of legal consent, the legal guardian(s) must provide informed consent and the patient should provide assent per local and national requirements.
2. Age ≥1 month and ≤17 years at the time of informed consent
3. Subjects must have iron deficiency anaemia defined by the following criteria, as measured by the central laboratory at the screening visit

Haemoglobin thresholds define anaemia by age and gender:

Children (1 m - < 5 yrs) <11.0 g/dl Children (5 yrs - < 12 yrs) <11.5 g/dl Children (12 yrs) <12.0 g/dl Female child (≥13 yrs) <12.0 g/dl Male child (≥13 yrs) <13.0 g/dl and

Ferritin thresholds define anaemia by:

ferritin <30 µg/L, or ferritin <50 µg/L with transferrin saturation (TSAT) <20%, 4. Female subjects of childbearing potential must agree to use a highly effective method of contraception (which includes complete abstinence) until study completion and for at least 4 weeks following their final study visit. Highly effective contraception is defined as a method which results in a low failure rate, i.e., less than 1% per year when used consistently and correctly, such as implants, injectables, some intrauterine contraceptive devices (IUDs), a vasectomised partner and oral contraceptive medications.

The need for contraception and compliance with contraception requirements will be assessed at every visit for adolescent patients, and urine pregnancy testing will be performed at each visit for female subjects of childbearing potential.

Exclusion Criteria:

1. Subject with anaemia due to any cause other than iron deficiency, including, but not limited to,

   a. Untreated or untreatable severe malabsorption syndrome

2. Subjects who have received prior to Screening:

   1. Within 28 days intramuscular or intravenous (IV) injection or administration of depot iron preparation.
   2. Within 7 days single agent iron preparations and during the study.
   3. Within 12 weeks of blood transfusion or is scheduled to have blood transfusion or donation during the study period
   4. Within 28 days erythropoiesis stimulating agents and during the study period
   5. Within 14 days COVID-19 vaccination
3. Subjects with vitamin B12 or folic acid deficiency as determined by the central laboratory screening results. Subjects may start vitamin B12 or folate replacement and rescreen after at least 2 weeks.
4. Has concomitant disease that would significantly compromise iron absorption or absorbed iron utilization such as swallowing disorders and/or extensive small bowel resection.
5. History of active peptic ulcer
6. Has chronic renal disease (eGFR <60 mL/min/m2), as assessed at Screening based on serum creatinine.
7. Known hypersensitivity or allergy to either the active substance or excipients of ferric maltol or ferrous sulfate.
8. Has a known contraindication for treatment with iron preparations, e.g. haemochromatosis, chronic haemolytic disease, sideroblastic anaemia, thalassemia, or lead intoxication induced anaemia.
9. Impaired liver function as indicated by alanine aminotransferase (ALT) or aspartate transaminase (AST)>2.0 times upper normal limit as measured at the Screening visit.
10. Active acute inflammatory disease, including IBD flare or disease exacerbation, which in the opinion of the Investigator, is clinically significant.
11. Active chronic or acute infectious diseases requiring antibiotic treatment.
12. Pregnant or breast feeding.
13. Concomitant medical conditions with extensive active bleeding, other than menstrual cycles; subjects who suffer from menorrhagia may be included at the Investigator's discretion.
14. Scheduled or expected hospitalisation and/or surgery during the course of the study
15. Participation in any other interventional clinical study within 28 days prior to Screening.
16. Diagnosed to be COVID-19 positive by (SARS-CoV-2-RT-PCR positive) within 28 days prior to screening.
17. Cardiovascular, liver, renal, hematologic, psychiatric, neurologic, gastrointestinal, immunologic, endocrine, metabolic, respiratory or central nervous system disease that, in the opinion of the Investigator, may adversely affect the safety of the subject and/or objectives of the study drug or severely limit the lifespan of the subject.
18. Any other unspecified reason that, in the opinion of the Investigator or the Sponsor make the subject unsuitable for enrolment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1 month to 2 year old subjects (infants); Subjects aged 1 month to less than 2 years will enter a Pre-assignment phase: baseline urine samples are collected and subjects will take a single dose of 0.1 ml/kg ferric maltol suspension. Further 3 samples up to 12h will be taken. Subjects showing evidence of absorption, metabolism and elimination of maltol will enter the treatment phase and be assigned to the ferric maltol arm. The first 6 subjects screened will perform the pre-assignment PK phase. After review by the investigator, and medical monitors , if Maltol Glucuronide is shown to be adequately eliminated, timepoint 20-24 hrs (+ 4hrs) will not be performed on subsequent subjects. Subjects will be assigned to receive ferric maltol oral suspension and start the 0.1 ml/kg BID dose on V2 and continue for 7-10 days. On V3 they will perform the same PK assessments as on Pre-assignment PK visit.	Drug: Ferric Maltol; Ferric maltol oral suspension: 150 ml amber glass bottle with graduated syringe and adaptor. Oral suspension containing 30 mg elemental iron, in the form of 231.5 mg ferric maltol, in 5 ml suspension Study dosage: The dose of ferric maltol oral suspension that will be administered for children aged 1 month to < 2 yrs: 0.1 ml/kg BID, 2 to - 11 yrs: 2.5 ml BID, 12-17 yrs: 5 ml BID.; Other Names: Feraccru; Ferric Trimaltol; ST10; ST10-01
Experimental: 2 to 17 year old subjects - Ferric Maltol; Subjects aged 2-17 will be randomised 1:1 to receive ferric maltol oral suspension or ferrous sulfate oral liquid. The first 12 subjects randomised to ferric maltol in each age sub-group (2 - 9 yrs, 10 - 17 yrs respectively) will enter a PK phase with 2 PK days. Following PK Day 2 subjects will continue until Week 12. Once the 18 subjects in each age subgroup have finished their PK visits, they will continue until week 12. Ferrous sulfate 125 mg/ml (25 mg elemental iron) or equivalent dose will be used for all children/adolescents. To maximise the iron replenishment for subjects within this group as well; aged 2 - 17 yrs will be dosed 6 mg/kg to the maximum of 4 ml BID. Subjects randomised to ferrous sulfate oral liquid will not need to complete the PK period.	Drug: Ferric Maltol; Ferric maltol oral suspension: 150 ml amber glass bottle with graduated syringe and adaptor. Oral suspension containing 30 mg elemental iron, in the form of 231.5 mg ferric maltol, in 5 ml suspension Study dosage: The dose of ferric maltol oral suspension that will be administered for children aged 1 month to < 2 yrs: 0.1 ml/kg BID, 2 to - 11 yrs: 2.5 ml BID, 12-17 yrs: 5 ml BID.; Other Names: Feraccru; Ferric Trimaltol; ST10; ST10-01
Active Comparator: 2 to 17 year old subjects - Ferrous Sulfate; Subjects aged 2-17 will be randomised 1:1 to receive ferric maltol oral suspension or ferrous sulfate oral liquid. Ferrous sulfate 125 mg/ml (25 mg elemental iron) or equivalent dose will be used for all children/adolescents. To maximise the iron replenishment for subjects within this group as well; aged 2 - 17 yrs will be dosed 6 mg/kg to the maximum of 4 ml BID. Subjects randomised to ferrous sulfate oral liquid will not need to complete the PK period.	Drug: Ferrous sulfate; Ferrous sulfate 125 mg/ml (25 mg/ml elemental iron) oral liquid : 15 ml glass bottle. Study dosage: For ferrous sulfate oral liquid, the dose administered will be for children and adolescents aged 2 years to 17 yrs: 6 mg/kg to the maximum of 4 ml BID.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hemoglobin Concentration	The change in Hb concentration from baseline to Week 12 is summarized based on the mITT Population for each treatment group using descriptive statistics summarized by mean, standard deviation, median, and range (minimum and maximum). The Randomized/ITT Population is defined as all patients who were randomized/assigned to treatment arms. The mITT Population is defined as all patients in the ITT Population who received at least 1 treatment dose.	From baseline to week 12.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Ferritin Concentration	Changes in ferritin concentration from baseline to week 12 summarised based on the mITT Population for each treatment group. The Randomized/ITT Population is defined as all patients who were randomized/assigned to treatment arms. The mITT Population is defined as all patients in the ITT Population who received at least 1 treatment dose.	From baseline to week 12.
Change in Iron Concentration	Change in iron concentration from baseline to week 12 summarized based on the mITT Population for each treatment group. The Randomized/ITT Population is defined as all patients who were randomized/assigned to treatment arms. The mITT Population is defined as all patients in the ITT Population who received at least 1 treatment dose.	From baseline to week 12.
Change in the Percentage of Transferrin Saturation	Change from baseline to Day 84 summarized based on the mITT Population for each treatment group. The Randomized/ITT Population is defined as all patients who were randomized/assigned to treatment arms. The mITT Population is defined as all patients in the ITT Population who received at least 1 treatment dose.	From baseline to week 12.
Cmax for Plasma Maltol Glucuronide	Measured maximum plasma concentration (Cmax) (ng/mL) for plasma maltol glucuronide after a single dose of ferric maltol oral suspension on Visit 2 (PK Day 1) and after twice daily administrations for at least 6 days, on Visit 3 (PK Day 2) after a single morning dose. Because of the limitations of PK sampling in the pediatric patient population, data from multiple patients in the same treatment and age group had to be combined, using the naïve pooled approach, to achieve a complete set of observations over time for PK analysis. The data did not support PK parameters generation using noncompartmental analysis (NCA) without combining patients. Using validated PK software WinNonlin, the 'sparse sampling' option was utilized to treat the data as one virtual subject and thus the resulting data did not support reliable error estimates of the PK parameters.	PK parameters assessed at Day 1 (Visit 2) and Day 7-10 (Visit 3).
Tmax for Plasma Maltol Glucuronide	Time to maximum plasma concentration (Tmax) (h) for plasma maltol glucuronide after a single dose of ferric maltol oral suspension on Visit 2 (PK Day 1) and after twice daily administrations for at least 6 days, on Visit 3 (PK Day 2) after a single morning dose. Because of the limitations of PK sampling in the pediatric patient population, data from multiple patients in the same treatment and age group had to be combined, using the naïve pooled approach, to achieve a complete set of observations over time for PK analysis. The data did not support PK parameters generation using noncompartmental analysis (NCA) without combining patients. Using validated PK software WinNonlin, the 'sparse sampling' option was utilized to treat the data as one virtual subject and thus the resulting data did not support reliable error estimates of the PK parameters.	PK parameters assessed at Day 1 (Visit 2) and Day 7-10 (Visit 3).
AUC0-t for Plasma Maltol Glucuronide	Area under the plasma concentration-time curve from pre-dose (time 0) to the time of last quantifiable plasma concentration for plasma maltol glucuronide (AUC0-t) (hxng/mL) after a single dose of ferric maltol oral suspension on Visit 2 (PK Day 1) and after twice daily administrations for at least 6 days, on Visit 3 (PK Day 2) after a single morning dose. Because of the limitations of PK sampling in the pediatric patient population, data from multiple patients in the same treatment and age group had to be combined, using the naïve pooled approach, to achieve a complete set of observations over time for PK analysis. The data did not support PK parameters generation using noncompartmental analysis (NCA) without combining patients. Using validated PK software WinNonlin, the 'sparse sampling' option was utilized to treat the data as one virtual subject and thus the resulting data did not support reliable error estimates of the PK parameters.	PK parameters assessed at Day 1 (Visit 2) and Day 7-10 (Visit 3).
Cmax for Baseline Corrected Serum Iron	Measured maximum plasma concentration (Cmax) (μg/dL) for baseline corrected serum iron after a single dose of ferric maltol oral suspension on Visit 2 (PK Day 1) and after twice daily administrations for at least 6 days, on Visit 3 (PK Day 2) after a single morning dose. Because of the limitations of PK sampling in the pediatric patient population, data from multiple patients in the same treatment and age group had to be combined, using the naïve pooled approach, to achieve a complete set of observations over time for PK analysis. The data did not support PK parameters generation using noncompartmental analysis (NCA) without combining patients. Using validated PK software WinNonlin, the 'sparse sampling' option was utilized to treat the data as one virtual subject and thus the resulting data did not support reliable error estimates of the PK parameters.	PK parameters assessed at Day 1 (Visit 2) and Day 7-10 (Visit 3).
Tmax for Baseline Corrected Serum Iron	Time to maximum plasma concentration (Tmax) (h) for baseline corrected serum iron after a single dose of ferric maltol oral suspension on Visit 2 (PK Day 1) and after twice daily administrations for at least 6 days, on Visit 3 (PK Day 2) after a single morning dose. Because of the limitations of PK sampling in the pediatric patient population, data from multiple patients in the same treatment and age group had to be combined, using the naïve pooled approach, to achieve a complete set of observations over time for PK analysis. The data did not support PK parameters generation using noncompartmental analysis (NCA) without combining patients. Using validated PK software WinNonlin, the 'sparse sampling' option was utilized to treat the data as one virtual subject and thus the resulting data did not support reliable error estimates of the PK parameters.	PK parameters assessed at Day 1 (Visit 2) and Day 7-10 (Visit 3).
AUC0-t for Baseline Corrected Serum Iron	Area under the plasma concentration-time curve from pre-dose (time 0) to the time of last quantifiable plasma concentration for baseline corrected serum iron (AUC0-t) (hxng/mL) after a single dose of ferric maltol oral suspension on Visit 2 (PK Day 1) and after twice daily administrations for at least 6 days, on Visit 3 (PK Day 2) after a single morning dose. Because of the limitations of PK sampling in the pediatric patient population, data from multiple patients in the same treatment and age group had to be combined, using the naïve pooled approach, to achieve a complete set of observations over time for PK analysis. The data did not support PK parameters generation using noncompartmental analysis (NCA) without combining patients. Using validated PK software WinNonlin, the 'sparse sampling' option was utilized to treat the data as one virtual subject and thus the resulting data did not support reliable error estimates of the PK parameters.	PK parameters assessed at Day 1 (Visit 2) and Day 7-10 (Visit 3).

Collaborators and Investigators

• Sponsor: Shield Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2021
• Primary Completion (Actual): June 9, 2024
• Study Completion (Actual): June 9, 2024

Study Registration Dates

• First Submitted: October 27, 2021
• First Submitted That Met QC Criteria: November 8, 2021
• First Posted (Actual): November 19, 2021

Study Record Updates

• Last Update Posted (Estimated): November 10, 2025
• Last Update Submitted That Met QC Criteria: October 24, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Anemia; Iron-Deficiency
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Iron Metabolism Disorders; Anemia, Hypochromic; Nutritional and Metabolic Diseases; Hemic and Lymphatic Diseases; Iron Deficiencies; Anemia; Anemia, Iron-Deficiency; Hematinics; ferrous sulfate; ferric maltol; ferric trimaltol
• Other Study ID Numbers: ST10-01-305

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No