Safety and Efficacy Study of Oral Ferric Iron To Treat Iron Deficiency Anaemia in Quiescent Ulcerative Colitis (AEGIS-1)

Study Overview
=================
Brief Summary
-----------------
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).

Detailed Description
-----------------
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.

Official Title
-----------------
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)

Conditions
-----------------
Iron Deficiency Anaemia, Inflammatory Bowel Disease, Ulcerative Colitis

Intervention / Treatment
-----------------
* Drug: ST10-021
* Drug: Placebo Comparator


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ST10<br>ST10 (Ferric Maltol) 30mg capsules, taken orally twice a day | Drug: ST10-021<br>* 30 mg capsules to be taken orally twice a day for 12 weeks<br>* Other names: Feraccru;|
| Placebo Comparator: Placebo<br>Matching placebo capsules for ST10 (Ferric Maltol), taken orally twice a day | Drug: Placebo Comparator<br>* Matching sugar pill to be taken orally twice a day for 12 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Haemoglobin (Hb) Concentration From Baseline to Week 12 (Full Analysis Set, FAS) | 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. | Baseline to Week 12 - double-blind phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects That Achieved ≥1 g/dL Change From Baseline in Hb Concentration at Week 12 (Full Analysis Set, FAS) | Logistic regression analysis of proportion of subjects that achieved ≥1 g/dL change from baseline in Hb concentration at Week 12 in the double-blind phase | Subjects that achieved ≥1 g/dL change from baseline in Hb concentration at Week 12 - double-blind phase | 
| Proportion of Subjects That Achieved ≥2 g/dL Change From Baseline in Hb Concentration at Week 12 (Full Analysis Set, FAS) | Logistic regression analysis of proportion of subjects that achieved ≥2 g/dL change from baseline in Hb concentration at Week 12 in the double-blind phase | Baseline to Week 12 - double-blind phase | 
| Proportion of Subjects That Achieved Hb Concentration Within Normal Range at Week 12 (Full Analysis Set, FAS) | Logistic regression analysis of proportion of subjects that achieved Hb concentration within normal range at Week 12 - end of double-blind phase | Baseline to Week 12 - double-blind phase | 
| Change in Hb Concentration From Baseline to Week 4 (Full Analysis Set, FAS) | ANCOVA analysis of the change in Hb concentration from Baseline to Week 4 of the double-blind phase - Full Analysis Set, multiple imputation | Baseline to Week 4 - double-blind phase | 
| Change in Hb Concentration From Baseline to Week 8 (Full Analysis Set, FAS) | ANCOVA analysis of Change in Hb concentration from Baseline to Week 8 of double-blind phase - FAS, multiple imputation | Baseline to Week 8 - double-blind phase | 
| Change in Haemoglobin Concentration From Baseline to Week 16 (Full Analysis Set, FAS) | Change in Haemoglobin Concentration from Baseline to Week 16 (FAS), after 12-week double-blind phase and first 4 weeks of open-label ST10 treatment. | Baseline to Week 16 - open-label phase | 
| Change in Haemoglobin Concentration From Baseline to Week 20 (Full Analysis Set, FAS) | Change in Haemoglobin Concentration from Baseline to Week 20 (FAS), after 12-week double-blind phase and then 8 weeks of open-label ST10 treatment | Baseline to Week 20 - open-label phase | 
| Change in Haemoglobin Concentration From Baseline to Week 24 (Full Analysis Set, FAS) | Change in Haemoglobin Concentration from Baseline to Week 24 (FAS), after 12-week double-blind phase and then 12 weeks of open-label ST10 treatment | Baseline to Week 24 - open-label phase | 
| Change in Haemoglobin Concentration From Baseline to Week 36 (Full Analysis Set, FAS) | Change in Haemoglobin Concentration from Baseline to Week 36 (FAS), after 12-week double-blind phase and then 24 weeks of open-label ST10 treatment | Baseline to Week 36 - open-label phase | 
| Change in Haemoglobin Concentration From Baseline to Week 48 (Full Analysis Set, FAS) | Change in Haemoglobin Concentration from Baseline to Week 48 (FAS), after 12-week double-blind phase and then 36 weeks of open-label ST10 treatment | Baseline to Week 48 - open-label phase | 
| Change in Haemoglobin Concentration From Baseline to Week 64 (Full Analysis Set, FAS) | Change in Haemoglobin Concentration from Baseline to Week 64 (FAS), after 12-week double-blind phase and then 52 weeks of open-label ST10 treatment | Baseline to Week 64 - open-label phase | 
| Change in Haemoglobin Concentration From Baseline to Week 64 EOS (Full Analysis Set, FAS) | Change in Haemoglobin Concentration from Baseline to Week 64 EOS (FAS) - Week 64 was re-categorised as Week 64 EOS for those subjects who withdrew from the study early and the 'Week 64' visit was outside the visit window of 64 weeks ± 2 days | Baseline to Week 64 EOS - open-label phase | 
| Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 16 (Full Analysis Set, FAS) | Proportion of subjects that achieved Haemoglobin Concentration within normal range at Week 16 (Full Analysis Set), after 12-week double-blind phase and first 4 weeks of open-label ST10 treatment | Baseline to Week 16 - open-label phase | 
| Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 36 (Full Analysis Set, FAS) | Proportion of subjects that achieved Haemoglobin Concentration within normal range at Week 36 (Full Analysis Set), after 12-week double-blind phase and 24 weeks of open-label ST10 treatment | Baseline to Week 36 - open-label phase | 
| Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 64 (Full Analysis Set, FAS) | Proportion of subjects that achieved Haemoglobin Concentration within normal range at Week 64 (Full Analysis Set), after 12-week double-blind phase and 52 weeks of open-label ST10 treatment | Baseline to Week 64 - open-label phase | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
iron deficiency, anaemia, inflammatory bowel disease, ulcerative colitis