A Prospective, Multicentre, Randomised, Double-blind, Placebo Controlled Study With Oral ST10-021 for the Treatment of Iron Deficiency Anaemia in Subjects With Quiescent Ulcerative Colitis Where Oral Ferrous Preparations Have Failed or Cannot be Used (AEGIS 1)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 128
- 主要终点
- Change in Haemoglobin (Hb) Concentration From Baseline to Week 12 (Full Analysis Set, FAS)
研究概览
简要总结
The purpose of this study is to determine whether ST10-021, an oral ferric iron preparation, is safe and effective in the treatment of iron deficiency anaemia (IDA) in subjects with non-active ulcerative colitis (UC).
详细描述
As no curative treatment is currently available for ulcerative colitis (UC), treatment options are restricted to controlling symptoms, maintaining remission and preventing relapse. As such, treatment of iron deficiency anaemia (IDA), a key symptom of the disease, is integral to the medical management of UC. Iron deficiency anaemia in UC is a chronically debilitating disorder which has a significant impact on the quality of life of affected subjects. Characteristic symptoms of IDA include chronic fatigue, headache, and subtle impairment of cognitive function. Up to one third of subjects with UC suffer from recurrent anaemia, with hospitalization required in severe cases. First line standard therapy for mild to moderate IDA in UC is typically oral ferrous products (OFP), however this is often not successful. Many subjects are intolerant and suffer from continuously occurring side effects, occasional exacerbation of inflammatory lesions and failure to correct iron deficiency. Common adverse effects of OFP include nausea, epigastric discomfort and constipation, all of which are dose-related and appear especially evident in subjects with UC.
As compared to oral ferrous iron, oral ferric iron can be administered with improved tolerability and the total dose exposure of unabsorbed iron within the gastrointestinal tract is significantly reduced. In addition, the iron is retained in its chelated form if not absorbed and this may reduce the risk of irritation within the gastrointestinal tract. Clinical studies conducted to date provide preliminary evidence for the therapeutic potential of ST10-021 in patients with IDA in Inflammatory Bowel Disease, including UC.
The purpose of this study is to determine whether ST10-021 is safe and effective in the treatment of IDA in subjects with non-active UC. In an effort to target an underserved population, the study will include only those subjects who have failed OFP in the past, or where OFP cannot be used.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Competency to understand and sign the IEC/IRB approved informed consent form prior to any study mandated procedure, and willing/able to comply with study requirements
- •Age ≥ 18 years
- •Current diagnosis of quiescent UC as defined by SCCAI score of < 4
- •Current diagnosis of IDA as defined by Hb ≥ 9.5 g/dl and <12.0 g/dl for women and ≥ 9.5 g/dl and <13.0 g/dl for men; ferritin < 30 µg/l
- •Prior OFP failure as defined per protocol
- •If receiving protocol-allowed immunosuppressant must be on stable dose
- •Females of childbearing potential must agree to use a reliable method of contraception
排除标准
- •Anaemia due to any cause other than iron deficiency
- •Intramuscular or intravenous injection or administration of depot iron preparation, blood infusions, or erythropoietin within 3 months
- •Oral iron supplementation use within 1 month
- •Use of immunosuppressant with known effect of anaemia induction within 1 month
- •Vitamin B12 or Folic Acid injection/infusion within 4 weeks
- •Untreated Vitamin B-12 or Folic Acid deficiency
- •Known hypersensitivity or allergy to ST10-021 or components of the study medication, or contraindication for treatment with iron preparations
- •Other chronic or acute inflammatory or infectious diseases
- •Creatinine > 2.0 mg/dl
- •AST or ALT levels ≥ 5 times the upper limit of normal
- •Cardiovascular, liver, renal, hematologic, gastrointestinal, immunologic, endocrine, metabolic, or central nervous system disease that may adversely affect the safety of the subject and/or efficacy of the study drug or severely limit the lifespan of the subject
- •History of malignancy within the past 5 years (except in situ removal of basal cell carcinoma)
- •Significant neurologic or psychiatric symptoms resulting in disorientation, memory impairment, or inability to report accurately that might interfere with treatment compliance, study conduct or interpretation of the results
- •Participation in another interventional clinical study within 30 days or during the study
- •Inmates of a psychiatric ward, prison, or other state institution
- •Investigator or any other team member involved directly or indirectly in the conduct of the clinical study
- •Scheduled or expected hospitalization and/or surgery during the course of the study
- •Females who are pregnant or lactating
研究组 & 干预措施
ST10
ST10 (Ferric Maltol) 30mg capsules, taken orally twice a day
干预措施: ST10-021 (Drug)
Placebo
Matching placebo capsules for ST10 (Ferric Maltol), taken orally twice a day
干预措施: Placebo Comparator (Drug)
结局指标
主要结局
Change in Haemoglobin (Hb) Concentration From Baseline to Week 12 (Full Analysis Set, FAS)
时间窗: Baseline to Week 12 - double-blind phase
Primary efficacy endpoint, defined as the change in Hb concentration from Baseline to Week 12. Baseline was defined as the pre-dose Hb concentration measured at the Randomisation Visit (Week 0). Missing Randomisation Hb values were replaced by Screening Hb values, if the randomisation was within the protocol-specified window. Hb concentration (g/dL) was analysed by a central laboratory from blood samples collected at every clinic visit: Screening, Randomisation (Week 0), Weeks 4, 8, 12, 14, 16, 20, 24, 36, 48, 64, Weeks 14 to 64 were open-label. The baseline, absolute concentration and change from baseline in Hb at all post-randomisation visits were listed and summarised by week using descriptive statistics. An analysis of covariance (ANCOVA) was used to analyse the primary endpoint; this included treatment, gender and disease as factors and baseline Hb as a covariate.
次要结局
- Proportion of Subjects That Achieved ≥2 g/dL Change From Baseline in Hb Concentration at Week 12 (Full Analysis Set, FAS)(Baseline to Week 12 - double-blind phase)
- Proportion of Subjects That Achieved Hb Concentration Within Normal Range at Week 12 (Full Analysis Set, FAS)(Baseline to Week 12 - double-blind phase)
- Change in Hb Concentration From Baseline to Week 4 (Full Analysis Set, FAS)(Baseline to Week 4 - double-blind phase)
- Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 36 (Full Analysis Set, FAS)(Baseline to Week 36 - open-label phase)
- Change in Haemoglobin Concentration From Baseline to Week 36 (Full Analysis Set, FAS)(Baseline to Week 36 - open-label phase)
- Change in Haemoglobin Concentration From Baseline to Week 48 (Full Analysis Set, FAS)(Baseline to Week 48 - open-label phase)
- Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 16 (Full Analysis Set, FAS)(Baseline to Week 16 - open-label phase)
- Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 64 (Full Analysis Set, FAS)(Baseline to Week 64 - open-label phase)
- Proportion of Subjects That Achieved ≥1 g/dL Change From Baseline in Hb Concentration at Week 12 (Full Analysis Set, FAS)(Subjects that achieved ≥1 g/dL change from baseline in Hb concentration at Week 12 - double-blind phase)
- Change in Haemoglobin Concentration From Baseline to Week 16 (Full Analysis Set, FAS)(Baseline to Week 16 - open-label phase)
- Change in Haemoglobin Concentration From Baseline to Week 64 (Full Analysis Set, FAS)(Baseline to Week 64 - open-label phase)
- Change in Haemoglobin Concentration From Baseline to Week 64 EOS (Full Analysis Set, FAS)(Baseline to Week 64 EOS - open-label phase)
- Change in Hb Concentration From Baseline to Week 8 (Full Analysis Set, FAS)(Baseline to Week 8 - double-blind phase)
- Change in Haemoglobin Concentration From Baseline to Week 20 (Full Analysis Set, FAS)(Baseline to Week 20 - open-label phase)
- Change in Haemoglobin Concentration From Baseline to Week 24 (Full Analysis Set, FAS)(Baseline to Week 24 - open-label phase)