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

A Prospective, Multicentre, Randomised, Double-blind, Placebo Controlled Study With Oral ST10-021 for the Treatment of Iron Deficiency Anaemia in Subjects With Quiescent Crohn's Disease Where Oral Ferrous Preparations Have Failed or Cannot be Used (AEGIS 2)

Sponsors

Lead Sponsor: Shield Therapeutics

Source Shield Therapeutics
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 Crohn's Disease (CD).

Detailed Description

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.

Overall Status Completed
Start Date August 2011
Completion Date October 2014
Primary Completion Date October 2013
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Change in Haemoglobin (Hb) Concentration From Baseline to Week 12 (Full Analysis Set, FAS) Baseline to Week 12 - double-blind phase
Secondary Outcome
Measure Time Frame
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
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
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 16 (Full Analysis Set, FAS) Baseline to Week 16 - open-label 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
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
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
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 36 (Full Analysis Set, FAS) Baseline to Week 36 - 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
Change in Haemoglobin Concentration From Baseline to Week 12 (Per Protocol Analysis Set, PPAS) Baseline to Week 12 - double-blind phase
Change in Haemoglobin Concentration From Baseline to Week 12 (Full Analysis Set [FAS] LOCF) Baseline to Week 12 - double-blind phase
Enrollment 128
Condition
Intervention

Intervention Type: Drug

Intervention Name: ST10

Description: 30 mg capsules to be taken orally twice a day for 12 weeks in double-blind phase

Arm Group Label: ST10

Intervention Type: Drug

Intervention Name: Placebo oral capsule

Description: Matching placebo capsules for ST10 to be taken orally twice a day for 12 weeks in double-blind phase

Arm Group Label: Placebo

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 CD as defined by CDAI score of < 220

- 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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Nicholas Mallard, PhD Study Director Shield Therapeutics
Verification Date

October 2017

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: ST10

Type: Experimental

Description: ST10 (Ferric Maltol) 30mg capsules, taken orally twice a day

Label: Placebo

Type: Placebo Comparator

Description: Matching placebo capsules for ST10 (Ferric Maltol), taken orally twice a day

Acronym AEGIS-2
Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Double (Participant, Investigator)

Source: ClinicalTrials.gov