Clinical trial NCT05126901: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anemia
Iron-deficiency
Keywords: Anemia
Iron-Deficiency
Lead sponsor: Shield Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-11-19
Enrollment: 65
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study will include 98 subjects in the 2 - 17 years age group, randomised 1:1 between ferric maltol and ferrous sulfate: 49 in each treatment group. The study will also include up to 12 subjects in the 1 month to less than 2 years age group. If less than 91 subjects in total have been randomized when 32 ferric maltol subjects have completed, then an interim analysis will be conducted. If significant, the study will stop recruitment. If not significant, the study will continue until 54 subjects have been recruited in the ferric maltol arm.
Primary purpose: TREATMENT

Brief summary: 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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 12 weeks
measure: Assess the effect on haemoglobin and iron markers in children and adolescents aged 1 month to 17 years after twice daily ferric maltol oral suspension administration for 12 weeks
timeFrame: 12 weeks
Secondary outcomes:
measure: Assess the PK in children and adolescents aged 2 to 17 years
timeFrame: 12 weeks
measure: Assess the PK, in children aged 1 month to less than 2 years of age
timeFrame: 12 weeks
measure: Assess the effect, in children aged 1 month to less than 2 years of age
timeFrame: 12 weeks
measure: Assess the effect, in children aged 2 to 17
timeFrame: 12 weeks
measure: To compare the palatability from age-appropriate scoring system of ferric maltol oral suspension and ferrous sulfate oral liquid
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Saraland
country: United States
facility: The Center for Clinical Trials
state: Alabama
city: Homestead
country: United States
facility: Homestead Research Institute
state: Florida
city: Kissimmee
country: United States
facility: Kissimmee Clinical Research Corp
state: Florida
city: Miami
country: United States
facility: Miami Clinical Research
state: Florida
city: Miami
country: United States
facility: Medical Research of Westcheste
state: Florida
city: N. Lauderdale
country: United States
facility: Eminent Clinical Research and Associates
state: Florida
city: Idaho Falls
country: United States
facility: Clinical Research Prime
state: Idaho
city: Las Vegas
country: United States
facility: Sierra Clinical Research
state: Nevada
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Hershey
country: United States
facility: Penn State Hershey Children's Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Hasbro Children's Hospital
state: Rhode Island
city: Edinburg
country: United States
facility: BRCR Global Texas
state: Texas
city: Katy
country: United States
facility: Zion Research
state: Texas
city: Tacoma
country: United States
facility: MultiCare Health System Institute for Research and Innovation
state: Washington
city: San Juan
country: Puerto Rico
facility: BRCR Global Puerto
city: Cardiff
country: United Kingdom
facility: Noah's Ark Children's Hospital for Wales
city: Edinburgh
country: United Kingdom
facility: Royal Hospital for Sick Children - Edinburgh
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: Liverpool
country: United Kingdom
facility: Alder Hey Children's NHS Foundation Trust
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: Newham University Hospital
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals
Study officials:
References: