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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 65
- 试验地点
- 23
- 主要终点
- Change in Hemoglobin Concentration
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
12 weeks open label treatment
入排标准
- 年龄范围
- 1 Month 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •Age ≥1 month and ≤17 years at the time of informed consent
- •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%,
- •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.
排除标准
- •Subject with anaemia due to any cause other than iron deficiency, including, but not limited to,
- •a. Untreated or untreatable severe malabsorption syndrome
- •Subjects who have received prior to Screening:
- •Within 28 days intramuscular or intravenous (IV) injection or administration of depot iron preparation.
- •Within 7 days single agent iron preparations and during the study.
- •Within 12 weeks of blood transfusion or is scheduled to have blood transfusion or donation during the study period
- •Within 28 days erythropoiesis stimulating agents and during the study period
- •Within 14 days COVID-19 vaccination
- •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.
- •Has concomitant disease that would significantly compromise iron absorption or absorbed iron utilization such as swallowing disorders and/or extensive small bowel resection.
- •History of active peptic ulcer
- •Has chronic renal disease (eGFR <60 mL/min/m2), as assessed at Screening based on serum creatinine.
- •Known hypersensitivity or allergy to either the active substance or excipients of ferric maltol or ferrous sulfate.
- •Has a known contraindication for treatment with iron preparations, e.g. haemochromatosis, chronic haemolytic disease, sideroblastic anaemia, thalassemia, or lead intoxication induced anaemia.
- •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.
- •Active acute inflammatory disease, including IBD flare or disease exacerbation, which in the opinion of the Investigator, is clinically significant.
- •Active chronic or acute infectious diseases requiring antibiotic treatment.
- •Pregnant or breast feeding.
- •Concomitant medical conditions with extensive active bleeding, other than menstrual cycles; subjects who suffer from menorrhagia may be included at the Investigator's discretion.
- •Scheduled or expected hospitalisation and/or surgery during the course of the study
- •Participation in any other interventional clinical study within 28 days prior to Screening.
- •Diagnosed to be COVID-19 positive by (SARS-CoV-2-RT-PCR positive) within 28 days prior to screening.
- •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.
- •Any other unspecified reason that, in the opinion of the Investigator or the Sponsor make the subject unsuitable for enrolment.
研究组 & 干预措施
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.
干预措施: Ferric Maltol (Drug)
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.
干预措施: Ferric Maltol (Drug)
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.
干预措施: Ferrous sulfate (Drug)
结局指标
主要结局
Change in Hemoglobin Concentration
时间窗: From baseline to week 12.
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.
次要结局
- Changes in Ferritin Concentration(From baseline to week 12.)
- Change in Iron Concentration(From baseline to week 12.)
- Change in the Percentage of Transferrin Saturation(From baseline to week 12.)
- Cmax for Plasma Maltol Glucuronide(PK parameters assessed at Day 1 (Visit 2) and Day 7-10 (Visit 3).)
- Tmax for Plasma Maltol Glucuronide(PK parameters assessed at Day 1 (Visit 2) and Day 7-10 (Visit 3).)
- AUC0-t for Plasma Maltol Glucuronide(PK parameters assessed at Day 1 (Visit 2) and Day 7-10 (Visit 3).)
- Cmax for Baseline Corrected Serum Iron(PK parameters assessed at Day 1 (Visit 2) and Day 7-10 (Visit 3).)
- Tmax for Baseline Corrected Serum Iron(PK parameters assessed at Day 1 (Visit 2) and Day 7-10 (Visit 3).)
- AUC0-t for Baseline Corrected Serum Iron(PK parameters assessed at Day 1 (Visit 2) and Day 7-10 (Visit 3).)