Title

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

    Phase 3
  • Study Type

    Interventional
  • Intervention/Treatment

    ferric maltol ...
  • Study Participants

    128
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).
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.
Study Started
Aug 31
2011
Primary Completion
Oct 31
2013
Study Completion
Oct 31
2014
Results Posted
Aug 03
2018
Last Update
Oct 30
2020

Drug ST10-021

30 mg capsules to be taken orally twice a day for 12 weeks

  • Other names: Ferric Trimaltol, Ferric maltol, Feraccru

Drug Placebo Comparator

Matching sugar pill to be taken orally twice a day for 12 weeks

ST10 Experimental

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

Placebo Placebo Comparator

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

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

Summary

ST10 - Safety Set, Double-blind Phase

Placebo - Safety Set, Double-blind Phase

ST10 Continuation - Safety Set, Open-label Phase

Placebo Switch to ST10 Treatment-Safety Set, Open-label Phase

All Events

Event Type Organ System Event Term ST10 - Safety Set, Double-blind Phase Placebo - Safety Set, Double-blind Phase ST10 Continuation - Safety Set, Open-label Phase Placebo Switch to ST10 Treatment-Safety Set, Open-label Phase

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.

ST10

2.26
g/dL (Mean)
Standard Deviation: 1.184

Placebo

0.01
g/dL (Mean)
Standard Deviation: 0.764

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

ST10 - Open-label Continuation From Active Arm in Double-blind

Placebo Switch to Open-label Extension ST10 Treatment

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

ST10 - Open-label Continuation From Active Arm in Double-blind

Placebo Switch to Open-label Extension ST10 Treatment

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

ST10

1.08
g/dL (Mean)
Standard Deviation: 0.676

Placebo

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

ST10

1.79
g/dL (Mean)
Standard Deviation: 1.037

Placebo

0.04
g/dL (Mean)
Standard Deviation: 0.722

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.

ST10 - Open-label Continuation From Active Arm in Double-blind

2.34
g/dL (Mean)
Standard Deviation: 1.281

Placebo Switch to Open-label Extension ST10 Treatment

1.04
g/dL (Mean)
Standard Deviation: 1.023

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

ST10 - Open-label Continuation From Active Arm in Double-blind

2.45
g/dL (Mean)
Standard Deviation: 1.213

Placebo Switch to Open-label Extension ST10 Treatment

1.46
g/dL (Mean)
Standard Deviation: 1.056

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

ST10 - Open-label Continuation From Active Arm in Double-blind

2.68
g/dL (Mean)
Standard Deviation: 1.127

Placebo Switch to Open-label Extension ST10 Treatment

1.87
g/dL (Mean)
Standard Deviation: 1.195

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

ST10 - Open-label Continuation From Active Arm in Double-blind

2.85
g/dL (Mean)
Standard Deviation: 1.227

Placebo Switch to Open-label Extension ST10 Treatment

2.17
g/dL (Mean)
Standard Deviation: 1.048

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

ST10 - Open-label Continuation From Active Arm in Double-blind

3.09
g/dL (Mean)
Standard Deviation: 1.339

Placebo Switch to Open-label Extension ST10 Treatment

2.0
g/dL (Mean)
Standard Deviation: 1.191

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

ST10 - Open-label Continuation From Active Arm in Double-blind

3.07
g/dL (Mean)
Standard Deviation: 1.457

Placebo Switch to Open-label Extension ST10 Treatment

2.19
g/dL (Mean)
Standard Deviation: 1.605

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

ST10 - Open-label Continuation From Active Arm in Double-blind

1.32
g/dL (Mean)
Standard Deviation: 1.713

Placebo Switch to Open-label Extension ST10 Treatment

0.52
g/dL (Mean)
Standard Deviation: 1.417

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

ST10 - Open-label Continuation From Active Arm in Double-blind

Placebo Switch to Open-label Extension ST10 Treatment

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

ST10

Placebo

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

ST10

Placebo

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

ST10

Placebo

Change in Haemoglobin Concentration From Baseline to Week 12 (Per Protocol Analysis Set, PPAS)

ANCOVA sensitivity analysis of the Primary efficacy endpoint analysis on the PPAS - Change in Haemoglobin Concentration from Baseline to Week 12

ST10

2.23
g/dL (Least Squares Mean)
Standard Error: 0.13

Placebo

0.05
g/dL (Least Squares Mean)
Standard Error: 0.13

Irritable Bowel Disease Questionnaire (IBDQ) Score at Week 12 (Full Analysis Set, FAS)

Irritable Bowel Disease Questionnaire (IBDQ) score at Week 12 (FAS), end of double-blind phase. The IBDQ was developed as an activity index for determining the effect of Ulcerative Colitis symptoms on perceived quality of life. It is a 32-item questionnaire with four dimensions: bowel function, emotional status, systemic symptoms and social function. Total IBDQ score ranges from 32 to 224, with higher scores indicating better quality of life. The score of patients in remission usually is between 170 and 190.

ST10

178.3
score on a scale (Mean)
Standard Deviation: 32.36

Placebo

176.3
score on a scale (Mean)
Standard Deviation: 31.5

Irritable Bowel Disease Questionnaire (IBDQ) Score at Week 64 (Full Analysis Set, FAS)

Irritable Bowel Disease Questionnaire (IBDQ) score at Week 64 (FAS), after 12-week double-blind phase and 52 weeks of open-label ST10 treatment. The IBDQ was developed as an activity index for determining the effect of Ulcerative Colitis symptoms on perceived quality of life. It is a 32-item questionnaire with four dimensions: bowel function, emotional status, systemic symptoms and social function. Total IBDQ score ranges from 32 to 224, with higher scores indicating better quality of life. The score of patients in remission usually is between 170 and 190.

ST10 - Open-label Continuation From Active Arm in Double-blind

180.7
score on a scale (Mean)
Standard Deviation: 30.14

Placebo Switch to Open-label Extension ST10 Treatment

177.2
score on a scale (Mean)
Standard Deviation: 36.97

Change From Baseline in Simple Clinical Colitis Activity Index (SCCAI) Score at Week 12 (Full Analysis Set, FAS)

Change from baseline in Simple Clinical Colitis Activity Index (SCCAI) score at Week 12 (FAS), end of double-blind phase (in subjects with UC). The SCCAI is a diagnostic and research questionnaire used to assess the severity of symptoms in people who suffer from UC. The calculated score ranges from 0 to 19, where active disease is a score of 5 or higher. The score is determined by asking the person with UC questions regarding: bowel frequency at day/night urgency of defecation blood in stool general health extracolonic manifestations

ST10

Placebo

Change From Baseline in Simple Clinical Colitis Activity Index (SCCAI) Score at Week 64 (Full Analysis Set)

Change from baseline in Simple Clinical Colitis Activity Index (SCCAI) score at Week 64 (FAS), after 12-week double-blind phase and 52 weeks open-label ST10 treatment (in participants with UC only). The SCCAI is a diagnostic and research questionnaire used to assess the severity of symptoms in people who suffer from UC. The calculated score ranges from 0 to 19, where active disease is a score of 5 or higher. The score is determined by asking the person with UC questions regarding: bowel frequency at day/night urgency of defecation blood in stool general health extracolonic manifestations

ST10 - Open-label Continuation From Active Arm in Double-blind

Placebo Switch to Open-label Extension ST10 Treatment

Change in Haemoglobin Concentration From Baseline to Week 12 (Full Analysis Set [FAS] LOCF)

ANCOVA sensitivity analysis of the Primary efficacy endpoint analysis on the FAS LOCF - Change in Haemoglobin Concentration from Baseline to Week 12

ST10

2.11
g/dL (Least Squares Mean)
Standard Error: 0.12

Placebo

-0.03
g/dL (Least Squares Mean)
Standard Error: 0.12

Change in Serum Ferritin Concentration From Baseline to Week 12 (Full Analysis Set, FAS)

Change in serum Ferritin concentration from Baseline to Week 12 (Full Analysis Set), after 12-week double-blind phase

ST10

17.3
μg/dL (Mean)
Standard Deviation: 28.3

Placebo

1.2
μg/dL (Mean)
Standard Deviation: 7.85

Change in Serum Ferritin Concentration From Baseline to Week 64 (Full Analysis Set, FAS)

Change in serum Ferritin concentration from Baseline to Week 64 (FAS), after 12-week double-blind phase and 52 weeks open-label ST10 treatment

ST10 - Open-label Continuation From Active Arm in Double-blind

60.4
μg/dL (Mean)
Standard Deviation: 93.35

Placebo Switch to Open-label Extension ST10 Treatment

36.6
μg/dL (Mean)
Standard Deviation: 46.8

Change in Serum TSAT% From Baseline to Week 12 (Full Analysis Set, FAS)

Change in serum TSAT% from Baseline to Week 12 (FAS), after 12-week double-blind phase

ST10

18.0
% serum TSAT (Mean)
Standard Deviation: 20.17

Placebo

-0.4
% serum TSAT (Mean)
Standard Deviation: 7.82

Change in Serum TSAT% From Baseline to Week 64 (Full Analysis Set, FAS)

Change in serum TSAT% from Baseline to Week 64 (Full Analysis Set), after 12-week double-blind phase and 52 weeks open-label ST10 treatment

ST10 - Open-label Continuation From Active Arm in Double-blind

18.8
% serum TSAT (Mean)
Standard Deviation: 12.46

Placebo Switch to Open-label Extension ST10 Treatment

17.7
% serum TSAT (Mean)
Standard Deviation: 16.2

Total

128
Participants

Age, Continuous

39.2
years (Mean)
Standard Deviation: 12.9

Duration of ulcerative colitis (years)

9.99
years (Mean)
Standard Deviation: 9.8

Haemoglobin concentration at baseline

11.05
g/dL (Mean)
Standard Deviation: 0.93

Irritable Bowel Disease Questionnaire (IBDQ) score at baseline

173.02
score on a scale (Mean)
Standard Deviation: 32.23

Serum Ferritin concentration at baseline

8.4
μg/L (Mean)
Standard Deviation: 6.6

Simple Clinical Colitis Activity Index (SCCAI) score at baseline

1.6
score on a scale (Mean)
Full Range: 0.0 to 3.0

Time since last IBD flare-up (months)

23.2
months (Mean)
Standard Deviation: 48.4

Time since last OFP dose (months)

34.76
months (Mean)
Standard Deviation: 41.7

TSAT% at baseline

10.05
percentage (Mean)
Standard Deviation: 9.6

Age, Categorical

Region of Enrollment

Sex: Female, Male

Double-blind Phase

ST10

Placebo

Open-label Phase

ST10 - Open-label Continuation From Active Arm in Double-blind

Placebo Switch to Open-label Extension ST10 Treatment

Drop/Withdrawal Reasons

ST10

Placebo

ST10 - Open-label Continuation From Active Arm in Double-blind

Placebo Switch to Open-label Extension ST10 Treatment