Clinical trial NCT01340872: Safety and Efficacy Study of Oral Ferric Iron To Treat Iron Deficiency Anaemia in Quiescent Ulcerative Colitis (AEGIS-1)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Iron Deficiency Anaemia
Inflammatory Bowel Disease
Ulcerative Colitis
Keywords: iron deficiency
anaemia
inflammatory bowel disease
ulcerative colitis
Lead sponsor: Shield Therapeutics
Sponsor class: INDUSTRY
First posted: 2011-04-25
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in Haemoglobin (Hb) Concentration From Baseline to Week 12 (Full Analysis Set, FAS)
timeFrame: Baseline to Week 12 - double-blind phase
Secondary outcomes:
measure: Proportion of Subjects That Achieved ≥1 g/dL Change From Baseline in Hb Concentration at Week 12 (Full Analysis Set, FAS)
timeFrame: Subjects that achieved ≥1 g/dL change from baseline in Hb concentration at Week 12 - double-blind phase
measure: Proportion of Subjects That Achieved ≥2 g/dL Change From Baseline in Hb Concentration at Week 12 (Full Analysis Set, FAS)
timeFrame: Baseline to Week 12 - double-blind phase
measure: Proportion of Subjects That Achieved Hb Concentration Within Normal Range at Week 12 (Full Analysis Set, FAS)
timeFrame: Baseline to Week 12 - double-blind phase
measure: Change in Hb Concentration From Baseline to Week 4 (Full Analysis Set, FAS)
timeFrame: Baseline to Week 4 - double-blind phase
measure: Change in Hb Concentration From Baseline to Week 8 (Full Analysis Set, FAS)
timeFrame: Baseline to Week 8 - double-blind phase
measure: Change in Haemoglobin Concentration From Baseline to Week 16 (Full Analysis Set, FAS)
timeFrame: Baseline to Week 16 - open-label phase
measure: Change in Haemoglobin Concentration From Baseline to Week 20 (Full Analysis Set, FAS)
timeFrame: Baseline to Week 20 - open-label phase
measure: Change in Haemoglobin Concentration From Baseline to Week 24 (Full Analysis Set, FAS)
timeFrame: Baseline to Week 24 - open-label phase
measure: Change in Haemoglobin Concentration From Baseline to Week 36 (Full Analysis Set, FAS)
timeFrame: Baseline to Week 36 - open-label phase
measure: Change in Haemoglobin Concentration From Baseline to Week 48 (Full Analysis Set, FAS)
timeFrame: Baseline to Week 48 - open-label phase
measure: Change in Haemoglobin Concentration From Baseline to Week 64 (Full Analysis Set, FAS)
timeFrame: Baseline to Week 64 - open-label phase
measure: Change in Haemoglobin Concentration From Baseline to Week 64 EOS (Full Analysis Set, FAS)
timeFrame: Baseline to Week 64 EOS - open-label phase
measure: Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 16 (Full Analysis Set, FAS)
timeFrame: Baseline to Week 16 - open-label phase
measure: Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 36 (Full Analysis Set, FAS)
timeFrame: Baseline to Week 36 - open-label phase
measure: Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 64 (Full Analysis Set, FAS)
timeFrame: Baseline to Week 64 - open-label phase
Other outcomes:
measure: Change in Haemoglobin Concentration From Baseline to Week 12 (Per Protocol Analysis Set, PPAS)
timeFrame: Baseline to Week 12 - double-blind phase
measure: Change in Haemoglobin Concentration From Baseline to Week 12 (Full Analysis Set [FAS] LOCF)
timeFrame: Baseline to Week 12 - double-blind phase
measure: Change in Serum Ferritin Concentration From Baseline to Week 12 (Full Analysis Set, FAS)
timeFrame: Baseline to Week 12 - double-blind phase
measure: Change in Serum Ferritin Concentration From Baseline to Week 64 (Full Analysis Set, FAS)
timeFrame: Baseline to Week 64 - open-label phase
measure: Change in Serum TSAT% From Baseline to Week 12 (Full Analysis Set, FAS)
timeFrame: Baseline to Week 12 - double-blind phase
measure: Change in Serum TSAT% From Baseline to Week 64 (Full Analysis Set, FAS)
timeFrame: Baseline to Week 64 - open-label phase
measure: Irritable Bowel Disease Questionnaire (IBDQ) Score at Week 12 (Full Analysis Set, FAS)
timeFrame: Week 12 - double-blind phase
measure: Irritable Bowel Disease Questionnaire (IBDQ) Score at Week 64 (Full Analysis Set, FAS)
timeFrame: Week 64 - open-label phase
measure: Change From Baseline in Simple Clinical Colitis Activity Index (SCCAI) Score at Week 12 (Full Analysis Set, FAS)
timeFrame: Baseline to Week 12 - double-blind phase
measure: Change From Baseline in Simple Clinical Colitis Activity Index (SCCAI) Score at Week 64 (Full Analysis Set)
timeFrame: Baseline to Week 64 - open-label phase
Locations:
Study officials:
affiliation: Shield Therapeutics
name: Nicholas Mallard, PhD
role: STUDY_DIRECTOR
References:
citation: Gasche C, Ahmad T, Tulassay Z, Baumgart DC, Bokemeyer B, Buning C, Howaldt S, Stallmach A; AEGIS Study Group. Ferric maltol is effective in correcting iron deficiency anemia in patients with inflammatory bowel disease: results from a phase-3 clinical trial program. Inflamm Bowel Dis. 2015 Mar;21(3):579-88. doi: 10.1097/MIB.0000000000000314.
citation: Schmidt C, Ahmad T, Tulassay Z, Baumgart DC, Bokemeyer B, Howaldt S, Stallmach A, Buning C; AEGIS Study Group. Ferric maltol therapy for iron deficiency anaemia in patients with inflammatory bowel disease: long-term extension data from a Phase 3 study. Aliment Pharmacol Ther. 2016 Aug;44(3):259-70. doi: 10.1111/apt.13665. Epub 2016 May 29.