Safety and Efficacy Study of Oral Ferric Iron To Treat Iron Deficiency Anaemia in Quiescent Crohn's Disease (AEGIS-2)

• Number of subjects that achieve an increase in Hb concentration by ≥1 g/dl over the trial period [ Time Frame: up to Week 12 ] [ Designated as safety issue: No ]
• Number of subjects that achieve an increase in Hb concentration by ≥2 g/dl over the trial period [ Time Frame: up to Week 12 ] [ Designated as safety issue: No ]
• Number of subjects that achieve Hb concentration within normal range over the trial period [ Time Frame: up to Week 12 ] [ Designated as safety issue: No ]
• Change in Hb concentration from baseline to Week 8 [ Time Frame: Week 8 ] [ Designated as safety issue: Yes ]
• Change in Hb concentration from baseline to Week 4 (early response) [ Time Frame: Week 4 ] [ Designated as safety issue: Yes ]
• Change in quality of life (QOL) based upon changes of the SF-36 QOL questionnaire from baseline to Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
• Treatment emergent Adverse Events, Serious Adverse Events, and clinically relevant laboratory abnormalities [ Time Frame: up to Week 14 ] [ Designated as safety issue: Yes ]
• Change from baseline to Week 12 of CDAI [ Time Frame: Week 12 ] [ Designated as safety issue: Yes ]
  The Crohn's Disease Activity Index (CDAI) is a measure of disease activity for Crohn's Disease(CD)
• Change from baseline to Week 12 in vital signs: blood pressure, heart rate and body weight [ Time Frame: Week 12 ] [ Designated as safety issue: Yes ]
• Adverse events leading to premature discontinuation of study drug [ Time Frame: up to Week 14 ] [ Designated as safety issue: Yes ]

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 Crohn's Disease (CD).

As no curative treatment is currently available for Crohn's Disease (CD), 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 CD. Iron deficiency anaemia in CD 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 CD suffer from recurrent anaemia, with hospitalization required in severe cases. First line standard therapy for mild to moderate IDA in CD 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 CD.

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 CD.

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 CD. 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.

• Iron Deficiency Anaemia
• Inflammatory Bowel Disease
• Crohn's Disease

• Drug: ST10-021
  30 mg capsules to be taken orally twice a day for 12 weeks
  Other Name: Ferric Trimaltol
• Drug: Placebo Comparator
  Matching sugar pill to be taken orally twice a day for 12 weeks

• Experimental: ST10-021
  oral ferric iron compound
  Intervention: Drug: ST10-021
• Placebo Comparator: Sugar pill
  Intervention: Drug: Placebo Comparator

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 CD as defined by CDAI score of < 220
• Current diagnosis of IDA as defined by Hb ≥ 10.0 g/dl and <12.0 g/dl for women and ≥ 10.0 g/dl and <13.0 g/dl for men; ferritin < 30 µg/l; TSAT < 16%; and MCV < 80 µm3
• 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 2 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

• AOP Orphan Pharmaceuticals AG
• Shield Holdings