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

• ClinicalTrials.gov Identifier: NCT01340872
• Recruitment Status: Completed
• First Posted: April 25, 2011
• Results First Posted: August 3, 2018
• Last Update Posted: October 30, 2020
• Sponsor: Shield Therapeutics
• Information provided by (Responsible Party): Shield Therapeutics

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Conditions: Iron Deficiency Anaemia; Inflammatory Bowel Disease; Ulcerative Colitis
• Interventions: Drug: ST10-021; Drug: Placebo Comparator
• Enrollment: 128

Participant Flow

Recruitment Details	Potential subjects were selected from the general population attending each centre in UK, DE, AT or HU for routine care of their IBD and anaemia. Individuals interested in participating were invited for the Screening visit in order to assess eligibility. Written informed consent was obtained prior to conducting any study specific assessments.
Pre-assignment Details	Subjects were males or females aged ≥18 years with a confirmed diagnosis of UC, required to be in remission have a mild-to-moderate UC (defined by SCCAI score <4 at entry); mild-to-moderate IDA (Hb concentration ≥9.5 g/dL and <12.0 g/dL for females and ≥9.5 g/dL and <13.0 g/dL for males; serum ferritin levels <30 μg/L at Screening.

Arm/Group Title	ST10	Placebo	ST10 - Open-label Continuation From Active Arm in Double-blind	Placebo Switch to Open-label Extension ST10 Treatment
Arm/Group Description	30mg ST10 capsules BD - double-blind phase	Matching placebo for ST10 capsules - double-blind phase	Open-label extension of ST10 active treatment arm from double-blind phase	Open-label extension ST10 treatment arm for placebo subjects completing double-blind phase
Period Title: Double-blind Phase
Started	64	64	0 [1]	0 [1]
Completed	55	53	0 [1]	0 [1]
Not Completed	9	11	0	0
Reason Not Completed
Adverse Event	6	4	0	0
Withdrawal by Subject	3	5	0	0
Lost to Follow-up	0	1	0	0
Protocol Violation	0	1	0	0
[1] Not Applicable to double-blind phase
Period Title: Open-label Phase
Started	0 [1]	0 [1]	50 [2]	47 [2]
Completed	0 [1]	0 [1]	37	36
Not Completed	0	0	13	11
Reason Not Completed
Physician Decision	0	0	2	1
Pregnancy	0	0	1	0
Adverse Event	0	0	8	4
Withdrawal by Subject	0	0	1	6
Worsening of IBD	0	0	1	0
[1] Not Applicable to open-label phase; [2] Only subjects in DE, UK and HU could enter the open-label extension (OLE); OLE rejected by EC in AT

Baseline Characteristics

Arm/Group Title		ST10	Placebo	Total
Arm/Group Description		ST10: 30 mg Ferric Maltol capsules taken orally twice a day during a 12-week double-blind phase. For study participants in the UK, DE and HU only, the 12-week double-blind phase was followed by a 52-week open-label ST10 extension treatment phase.	Matching Placebo capsules taken orally twice a day during a 12-week double-blind phase. For study participants in the UK, DE and HU only, the 12-week double-blind phase was followed by a 52-week open-label ST10 extension treatment phase.	Total of all reporting groups
Overall Number of Baseline Participants		64	64	128
Baseline Analysis Population Description		Potential subjects were screened for eligibility to participate based on their demographics, medical/surgical history, physical examination, concomitant medications, vital signs, clinical laboratory tests (including pregnancy test for females of child-bearing potential) and current IBD disease status (based on SCCAI clinical score). FAS - Safety
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	64 participants	64 participants	128 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	62 96.9%	63 98.4%	125 97.7%
	>=65 years	2 3.1%	1 1.6%	3 2.3%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	64 participants	64 participants	128 participants
		40.1 (13.52)	38.5 (12.3)	39.2 (12.9)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	64 participants	64 participants	128 participants
	Female	40 62.5%	43 67.2%	83 64.8%
	Male	24 37.5%	21 32.8%	45 35.2%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	64 participants	64 participants	128 participants
United Kingdom		15	10	25
Hungary		11	15	26
Germany		35	32	67
Austria		4	6	10
Duration of ulcerative colitis (years) [1]; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	64 participants	64 participants	128 participants
		9.0 (8.28)	10.99 (11.43)	9.99 (9.8)
		[1] Measure Description: Duration of ulcerative colitis (years); for participants with UC
Time since last IBD flare-up (months) [1]; Mean (Standard Deviation); Unit of measure: Months
	Number Analyzed	64 participants	64 participants	128 participants
		24.8 (59.16)	21.51 (38.46)	23.2 (48.4)
		[1] Measure Description: Time since last IBD flare-up (months) recorded at baseline
Time since last OFP dose (months) [1]; Mean (Standard Deviation); Unit of measure: Months
	Number Analyzed	64 participants	64 participants	128 participants
		36.17 (40.1)	33.34 (44.04)	34.76 (41.7)
		[1] Measure Description: Time since last prior oral ferrous product (OFP) dose (months)
Haemoglobin concentration at baseline [1]; Mean (Standard Deviation); Unit of measure: g/dL
	Number Analyzed	64 participants	64 participants	128 participants
		11 (1.03)	11.1 (0.85)	11.05 (0.93)
		[1] Measure Description: Haemoglobin concentration at baseline of the 12 week double-blind phase
Serum Ferritin concentration at baseline [1]; Mean (Standard Deviation); Unit of measure: μg/L
	Number Analyzed	64 participants	64 participants	128 participants
		8.6 (6.8)	8.2 (6.5)	8.4 (6.6)
		[1] Measure Description: Serum Ferritin concentration at baseline of the 12 week double-blind phase
TSAT% at baseline [1]; Mean (Standard Deviation); Unit of measure: Percentage
	Number Analyzed	64 participants	64 participants	128 participants
		10.6 (11.7)	9.5 (7.5)	10.05 (9.6)
		[1] Measure Description: TSAT% (transferrin saturation %) at baseline of the 12 week double-blind phase
Irritable Bowel Disease Questionnaire (IBDQ) score at baseline [1]; Mean (Standard Deviation); Unit of measure: Score on a scale
	Number Analyzed	64 participants	64 participants	128 participants
		175.0 (30.92)	171.0 (33.56)	173.02 (32.23)
		[1] Measure Description: Irritable Bowel Disease Questionnaire (IBDQ) score at baseline (randomisation) of the 12 week 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.
Simple Clinical Colitis Activity Index (SCCAI) score at baseline [1]; Mean (Full Range); Unit of measure: Score on a scale
	Number Analyzed	64 participants	64 participants	128 participants
		1.8; (0 to 3)	1.4; (0 to 3)	1.6; (0 to 3)
		[1] Measure Description: Simple Clinical Colitis Activity Index (SCCAI) score at baseline (randomisation) of the 12-week double-blind phase (in participants 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

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS)

Arm/Group Title	ST10	Placebo
Arm/Group Description:	ST10: 30 mg Ferric Maltol capsules taken orally twice a day during 12-week double-blind phase. For study participants in the UK, DE and HU only, the 12-week double-blind phase was followed by a 52-week open-label ST10 extension treatment phase.	Matching Placebo capsules taken orally twice a day during 12-week double-blind phase. For study participants in the UK, DE and HU only, the 12-week double-blind phase was followed by a 52-week open-label ST10 extension treatment phase.
Overall Number of Participants Analyzed	58	53
Mean (Standard Deviation); Unit of Measure: g/dL
	2.26 (1.184)	0.01 (0.764)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ST10, Placebo
	Comments	ANCOVA for primary endpoint, Change in Hb concentration from Baseline to Week 12 in double-blind phase, FAS
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.18
	Confidence Interval	(1-Sided) 97.5%; 1.81
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.19
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Proportion of Subjects That Achieved ≥1 g/dL Change From Baseline in Hb Concentration at Week 12 (Full Analysis Set, FAS)
Description	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
Time Frame	Subjects that achieved ≥1 g/dL change from baseline in Hb concentration at Week 12 - double-blind phase

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS)

Arm/Group Title	ST10	Placebo
Arm/Group Description:	ST10: 30 mg Ferric Maltol capsules taken orally twice a day during 12-week double-blind phase. For study participants in the UK, DE and HU only, the 12-week double-blind phase was followed by a 52-week open-label ST10 extension treatment phase.	Matching Placebo capsules taken orally twice a day during 12-week double-blind phase. For study participants in the UK, DE and HU only, the 12-week double-blind phase was followed by a 52-week open-label ST10 extension treatment phase.
Overall Number of Participants Analyzed	64	64
Measure Type: Count of Participants; Unit of Measure: Participants
Yes	50 78.1%	7 10.9%
No	14 21.9%	57 89.1%

3. Secondary Outcome

Title	Proportion of Subjects That Achieved ≥2 g/dL Change From Baseline in Hb Concentration at Week 12 (Full Analysis Set, FAS)
Description	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
Time Frame	Baseline to Week 12 - double-blind phase

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	ST10	Placebo
Arm/Group Description:	ST10: 30 mg Ferric Maltol capsules taken orally twice a day during 12-week double-blind phase.	Matching Placebo capsules taken orally twice a day during 12-week double-blind phase.
Overall Number of Participants Analyzed	64	64
Measure Type: Count of Participants; Unit of Measure: Participants
Yes	36 56.3%	0 0.0%
No	28 43.8%	64 100.0%

4. Secondary Outcome

Title	Proportion of Subjects That Achieved Hb Concentration Within Normal Range at Week 12 (Full Analysis Set, FAS)
Description	Logistic regression analysis of proportion of subjects that achieved Hb concentration within normal range at Week 12 - end of double-blind phase
Time Frame	Baseline to Week 12 - double-blind phase

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	ST10	Placebo
Arm/Group Description:	ST10: 30 mg Ferric Maltol capsules taken orally twice a day during 12-week double-blind phase.	Matching Placebo capsules taken orally twice a day during 12-week double-blind phase.
Overall Number of Participants Analyzed	64	64
Measure Type: Count of Participants; Unit of Measure: Participants
Yes	42 65.6%	8 12.5%
No	22 34.4%	56 87.5%

5. Secondary Outcome

Title	Change in Hb Concentration From Baseline to Week 4 (Full Analysis Set, FAS)
Description	ANCOVA analysis of the change in Hb concentration from Baseline to Week 4 of the double-blind phase - Full Analysis Set, multiple imputation
Time Frame	Baseline to Week 4 - double-blind phase

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	ST10	Placebo
Arm/Group Description:	ST10: 30 mg Ferric Maltol capsules taken orally twice a day during 12-week double-blind phase.	Matching Placebo capsules taken orally twice a day during 12-week double-blind phase.
Overall Number of Participants Analyzed	59	61
Mean (Standard Deviation); Unit of Measure: g/dL
	1.08 (0.676)	0 (0.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ST10, Placebo
	Comments	ANCOVA analysis of the change in Hb concentration from Baseline to Week 4 of the double-blind phase - Full Analysis Set, multiple imputation
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.04
	Confidence Interval	(1-Sided) 97.5%; 0.82
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Change in Hb Concentration From Baseline to Week 8 (Full Analysis Set, FAS)
Description	ANCOVA analysis of Change in Hb concentration from Baseline to Week 8 of double-blind phase - FAS, multiple imputation
Time Frame	Baseline to Week 8 - double-blind phase

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	ST10	Placebo
Arm/Group Description:	ST10: 30 mg Ferric Maltol capsules taken orally twice a day during 12-week double-blind phase.	Matching Placebo capsules taken orally twice a day during 12-week double-blind phase.
Overall Number of Participants Analyzed	59	56
Mean (Standard Deviation); Unit of Measure: g/dL
	1.79 (1.037)	0.04 (0.722)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ST10, Placebo
	Comments	ANCOVA analysis of Change in Hb concentration from Baseline to Week 8 of double-blind phase - FAS, multiple imputation
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.73
	Confidence Interval	(1-Sided) 97.5%; 1.43
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Change in Haemoglobin Concentration From Baseline to Week 16 (Full Analysis Set, FAS)
Description	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.
Time Frame	Baseline to Week 16 - open-label phase

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	ST10 - Open-label Continuation From Active Arm in Double-blind	Placebo Switch to Open-label Extension ST10 Treatment
Arm/Group Description:	Open-label extension of ST10 active treatment arm from double-blind phase	Open-label extension ST10 treatment arm for placebo subjects completing double-blind phase
Overall Number of Participants Analyzed	46	45
Mean (Standard Deviation); Unit of Measure: g/dL
	2.34 (1.281)	1.04 (1.023)

8. Secondary Outcome

Title	Change in Haemoglobin Concentration From Baseline to Week 20 (Full Analysis Set, FAS)
Description	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
Time Frame	Baseline to Week 20 - open-label phase

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	ST10 - Open-label Continuation From Active Arm in Double-blind	Placebo Switch to Open-label Extension ST10 Treatment
Arm/Group Description:	Open-label extension of ST10 active treatment arm from double-blind phase	Open-label extension ST10 treatment arm for placebo subjects completing double-blind phase
Overall Number of Participants Analyzed	43	43
Mean (Standard Deviation); Unit of Measure: g/dL
	2.45 (1.213)	1.46 (1.056)

9. Secondary Outcome

Title	Change in Haemoglobin Concentration From Baseline to Week 24 (Full Analysis Set, FAS)
Description	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
Time Frame	Baseline to Week 24 - open-label phase

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	ST10 - Open-label Continuation From Active Arm in Double-blind	Placebo Switch to Open-label Extension ST10 Treatment
Arm/Group Description:	Open-label extension of ST10 active treatment arm from double-blind phase	Open-label extension ST10 treatment arm for placebo subjects completing double-blind phase
Overall Number of Participants Analyzed	43	41
Mean (Standard Deviation); Unit of Measure: g/dL
	2.68 (1.127)	1.87 (1.195)

10. Secondary Outcome

Title	Change in Haemoglobin Concentration From Baseline to Week 36 (Full Analysis Set, FAS)
Description	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
Time Frame	Baseline to Week 36 - open-label phase

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	ST10 - Open-label Continuation From Active Arm in Double-blind	Placebo Switch to Open-label Extension ST10 Treatment
Arm/Group Description:	Open-label extension of ST10 active treatment arm from double-blind phase	Open-label extension ST10 treatment arm for placebo subjects completing double-blind phase
Overall Number of Participants Analyzed	41	36
Mean (Standard Deviation); Unit of Measure: g/dL
	2.85 (1.227)	2.17 (1.048)

11. Secondary Outcome

Title	Change in Haemoglobin Concentration From Baseline to Week 48 (Full Analysis Set, FAS)
Description	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
Time Frame	Baseline to Week 48 - open-label phase

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	ST10 - Open-label Continuation From Active Arm in Double-blind	Placebo Switch to Open-label Extension ST10 Treatment
Arm/Group Description:	Open-label extension of ST10 active treatment arm from double-blind phase	Open-label extension ST10 treatment arm for placebo subjects completing double-blind phase
Overall Number of Participants Analyzed	40	37
Mean (Standard Deviation); Unit of Measure: g/dL
	3.09 (1.339)	2.0 (1.191)

12. Secondary Outcome

Title	Change in Haemoglobin Concentration From Baseline to Week 64 (Full Analysis Set, FAS)
Description	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
Time Frame	Baseline to Week 64 - open-label phase

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	ST10 - Open-label Continuation From Active Arm in Double-blind	Placebo Switch to Open-label Extension ST10 Treatment
Arm/Group Description:	Open-label extension of ST10 active treatment arm from double-blind phase	Open-label extension ST10 treatment arm for placebo subjects completing double-blind phase
Overall Number of Participants Analyzed	35	36
Mean (Standard Deviation); Unit of Measure: g/dL
	3.07 (1.457)	2.19 (1.605)

13. Secondary Outcome

Title	Change in Haemoglobin Concentration From Baseline to Week 64 EOS (Full Analysis Set, FAS)
Description	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
Time Frame	Baseline to Week 64 EOS - open-label phase

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	ST10 - Open-label Continuation From Active Arm in Double-blind	Placebo Switch to Open-label Extension ST10 Treatment
Arm/Group Description:	Open-label extension of ST10 active treatment arm from double-blind phase	Open-label extension ST10 treatment arm for placebo subjects completing double-blind phase
Overall Number of Participants Analyzed	10	17
Mean (Standard Deviation); Unit of Measure: g/dL
	1.32 (1.713)	0.52 (1.417)

14. Secondary Outcome

Title	Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 16 (Full Analysis Set, FAS)
Description	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
Time Frame	Baseline to Week 16 - open-label phase

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	ST10 - Open-label Continuation From Active Arm in Double-blind	Placebo Switch to Open-label Extension ST10 Treatment
Arm/Group Description:	Open-label extension of ST10 active treatment arm from double-blind phase	Open-label extension ST10 treatment arm for placebo subjects completing double-blind phase
Overall Number of Participants Analyzed	46	45
Measure Type: Count of Participants; Unit of Measure: Participants
Yes	36 78.3%	17 37.8%
No	10 21.7%	28 62.2%

15. Secondary Outcome

Title	Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 36 (Full Analysis Set, FAS)
Description	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
Time Frame	Baseline to Week 36 - open-label phase

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	ST10 - Open-label Continuation From Active Arm in Double-blind	Placebo Switch to Open-label Extension ST10 Treatment
Arm/Group Description:	Open-label extension of ST10 active treatment arm from double-blind phase	Open-label extension ST10 treatment arm for placebo subjects completing double-blind phase
Overall Number of Participants Analyzed	41	36
Measure Type: Count of Participants; Unit of Measure: Participants
Yes	35 85.4%	29 80.6%
No	6 14.6%	7 19.4%

16. Secondary Outcome

Title	Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 64 (Full Analysis Set, FAS)
Description	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
Time Frame	Baseline to Week 64 - open-label phase

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	ST10 - Open-label Continuation From Active Arm in Double-blind	Placebo Switch to Open-label Extension ST10 Treatment
Arm/Group Description:	Open-label extension of ST10 active treatment arm from double-blind phase	Open-label extension ST10 treatment arm for placebo subjects completing double-blind phase
Overall Number of Participants Analyzed	36	36
Measure Type: Count of Participants; Unit of Measure: Participants
Yes	31 86.1%	30 83.3%
No	5 13.9%	6 16.7%

17. Other Pre-specified Outcome

Title	Change in Haemoglobin Concentration From Baseline to Week 12 (Per Protocol Analysis Set, PPAS)
Description	ANCOVA sensitivity analysis of the Primary efficacy endpoint analysis on the PPAS - Change in Haemoglobin Concentration from Baseline to Week 12
Time Frame	Baseline to Week 12 - double-blind phase

Outcome Measure Data

Analysis Population Description

Per-Protocol Analysis Set - sensitivity analysis of primary endpoint

Arm/Group Title	ST10	Placebo
Arm/Group Description:	ST10: 30 mg Ferric Maltol capsules taken orally twice a day during 12-week double-blind phase.	Matching Placebo capsules taken orally twice a day during 12-week double-blind phase.
Overall Number of Participants Analyzed	55	57
Least Squares Mean (Standard Error); Unit of Measure: g/dL
	2.23 (0.13)	0.05 (0.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ST10, Placebo
	Comments	ANCOVA sensitivity analysis of the Primary efficacy endpoint analysis on the PPAS
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.18
	Confidence Interval	(1-Sided) 97.5%; 1.87
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.17
	Estimation Comments	[Not Specified]

18. Other Pre-specified Outcome

Title	Change in Haemoglobin Concentration From Baseline to Week 12 (Full Analysis Set [FAS] LOCF)
Description	ANCOVA sensitivity analysis of the Primary efficacy endpoint analysis on the FAS LOCF - Change in Haemoglobin Concentration from Baseline to Week 12
Time Frame	Baseline to Week 12 - double-blind phase

Outcome Measure Data

Analysis Population Description

FAS LOCF - sensitivity analysis of primary endpoint

Arm/Group Title	ST10	Placebo
Arm/Group Description:	ST10: 30 mg Ferric Maltol capsules taken orally twice a day during 12-week double-blind phase.	Matching Placebo capsules taken orally twice a day during 12-week double-blind phase.
Overall Number of Participants Analyzed	64	64
Least Squares Mean (Standard Error); Unit of Measure: g/dL
	2.11 (0.12)	-0.03 (0.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ST10, Placebo
	Comments	ANCOVA sensitivity analysis of the Primary efficacy endpoint analysis on the FAS LOCF - Change in Haemoglobin Concentration from Baseline to Week 12
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.15
	Confidence Interval	(1-Sided) 97.5%; 1.82
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.16
	Estimation Comments	[Not Specified]

19. Other Pre-specified Outcome

Title	Change in Serum Ferritin Concentration From Baseline to Week 12 (Full Analysis Set, FAS)
Description	Change in serum Ferritin concentration from Baseline to Week 12 (Full Analysis Set), after 12-week double-blind phase
Time Frame	Baseline to Week 12 - double-blind phase

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	ST10	Placebo
Arm/Group Description:	ST10: 30 mg Ferric Maltol capsules taken orally twice a day during 12-week double-blind phase.	Matching Placebo capsules taken orally twice a day during 12-week double-blind phase.
Overall Number of Participants Analyzed	59	53
Mean (Standard Deviation); Unit of Measure: μg/dL
	17.3 (28.3)	1.2 (7.85)

20. Other Pre-specified Outcome

Title	Change in Serum Ferritin Concentration From Baseline to Week 64 (Full Analysis Set, FAS)
Description	Change in serum Ferritin concentration from Baseline to Week 64 (FAS), after 12-week double-blind phase and 52 weeks open-label ST10 treatment
Time Frame	Baseline to Week 64 - open-label phase

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	ST10 - Open-label Continuation From Active Arm in Double-blind	Placebo Switch to Open-label Extension ST10 Treatment
Arm/Group Description:	Open-label extension of ST10 active treatment arm from double-blind phase	Open-label extension ST10 treatment arm for placebo subjects completing double-blind phase
Overall Number of Participants Analyzed	36	36
Mean (Standard Deviation); Unit of Measure: μg/dL
	60.4 (93.35)	36.6 (46.8)

21. Other Pre-specified Outcome

Title	Change in Serum TSAT% From Baseline to Week 12 (Full Analysis Set, FAS)
Description	Change in serum TSAT% from Baseline to Week 12 (FAS), after 12-week double-blind phase
Time Frame	Baseline to Week 12 - double-blind phase

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	ST10	Placebo
Arm/Group Description:	ST10: 30 mg Ferric Maltol capsules taken orally twice a day during 12-week double-blind phase.	Matching Placebo capsules taken orally twice a day during 12-week double-blind phase.
Overall Number of Participants Analyzed	59	52
Mean (Standard Deviation); Unit of Measure: % serum TSAT
	18.0 (20.17)	-0.4 (7.82)

22. Other Pre-specified Outcome

Title	Change in Serum TSAT% From Baseline to Week 64 (Full Analysis Set, FAS)
Description	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
Time Frame	Baseline to Week 64 - open-label phase

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	ST10 - Open-label Continuation From Active Arm in Double-blind	Placebo Switch to Open-label Extension ST10 Treatment
Arm/Group Description:	Open-label extension of ST10 active treatment arm from double-blind phase	Open-label extension ST10 treatment arm for placebo subjects completing double-blind phase
Overall Number of Participants Analyzed	36	36
Mean (Standard Deviation); Unit of Measure: % serum TSAT
	18.8 (12.46)	17.7 (16.2)

23. Other Pre-specified Outcome

Title	Irritable Bowel Disease Questionnaire (IBDQ) Score at Week 12 (Full Analysis Set, FAS)
Description	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.
Time Frame	Week 12 - double-blind phase

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	ST10	Placebo
Arm/Group Description:	ST10: 30 mg Ferric Maltol capsules taken orally twice a day during 12-week double-blind phase.	Matching Placebo capsules taken orally twice a day during 12-week double-blind phase.
Overall Number of Participants Analyzed	60	60
Mean (Standard Deviation); Unit of Measure: score on a scale
	178.3 (32.36)	176.3 (31.5)

24. Other Pre-specified Outcome

Title	Irritable Bowel Disease Questionnaire (IBDQ) Score at Week 64 (Full Analysis Set, FAS)
Description	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.
Time Frame	Week 64 - open-label phase

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	ST10 - Open-label Continuation From Active Arm in Double-blind	Placebo Switch to Open-label Extension ST10 Treatment
Arm/Group Description:	Open-label extension of ST10 active treatment arm from double-blind phase	Open-label extension ST10 treatment arm for placebo subjects completing double-blind phase
Overall Number of Participants Analyzed	37	36
Mean (Standard Deviation); Unit of Measure: score on a scale
	180.7 (30.14)	177.2 (36.97)

25. Other Pre-specified Outcome

Title	Change From Baseline in Simple Clinical Colitis Activity Index (SCCAI) Score at Week 12 (Full Analysis Set, FAS)
Description	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
Time Frame	Baseline to Week 12 - double-blind phase

Outcome Measure Data

Analysis Population Description

FAS - participants with UC only

Arm/Group Title	ST10	Placebo
Arm/Group Description:	ST10: 30 mg Ferric Maltol capsules taken orally twice a day during 12-week double-blind phase.	Matching Placebo capsules taken orally twice a day during 12-week double-blind phase.
Overall Number of Participants Analyzed	28	29
Median (Full Range); Unit of Measure: score on a scale
	0; (-2 to 5)	0; (-1 to 5)

26. Other Pre-specified Outcome

Title	Change From Baseline in Simple Clinical Colitis Activity Index (SCCAI) Score at Week 64 (Full Analysis Set)
Description	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
Time Frame	Baseline to Week 64 - open-label phase

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	ST10 - Open-label Continuation From Active Arm in Double-blind	Placebo Switch to Open-label Extension ST10 Treatment
Arm/Group Description:	Open-label extension of ST10 active treatment arm from double-blind phase	Open-label extension ST10 treatment arm for placebo subjects completing double-blind phase
Overall Number of Participants Analyzed	19	19
Median (Full Range); Unit of Measure: score on a scale
	0; (-3 to 2)	0; (-2 to 5)

Adverse Events

Time Frame	Adverse events (AEs) were solicited after informed consent and until 4 weeks after the last dose of study drug (at study completion or early termination).
Adverse Event Reporting Description	Subjects were expected to volunteer information about AEs they experienced. The Investigator/designee also questioned the subject at each visit about AEs and recorded these as well as all other AEs apparent. AEs/SAEs were monitored until they were resolved or determined to be due to a subject's on-going condition or inter-current illness.
Arm/Group Title	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
Arm/Group Description	Adverse events reported in the double-blind phase active treatment arm with ST10 (Ferric Maltol). ST10 30 mg capsules taken orally twice a day during a 12-week double-blind phase. For study participants in the UK, DE and HU only, the 12-week double-blind phase was followed by a 52-week open-label ST10 extension treatment phase.		Adverse events reported in the double-blind phase placebo treatment arm. Matching placebo capsules for ST10 taken orally twice a day during a 12-week double-blind phase. For study participants in the UK, DE and HU only, the 12-week double-blind phase was followed by a 52-week open-label ST10 extension treatment phase.		Adverse events reported in the open-label extension phase for continuation of active treatment with ST10 (Ferric Maltol) from the double-blind phase active treatment arm.		Adverse events reported in the open-label extension phase from those subjects continuing treatment from the double-blind placebo arm; subjects commenced ST10 open-label treatment after completion of the double-blind phase at the Week 12 visit.
All-Cause Mortality
	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
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/64 (0.00%)		0/64 (0.00%)		0/50 (0.00%)		0/47 (0.00%)
Serious Adverse Events
	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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/64 (1.56%)		2/64 (3.13%)		8/50 (16.00%)		2/47 (4.26%)
Cardiac disorders
Angina pectoris † 1	0/64 (0.00%)	0	0/64 (0.00%)	0	0/50 (0.00%)	0	1/47 (2.13%)	1
Gastrointestinal disorders
Abdominal Pain † 1	1/64 (1.56%)	1	0/64 (0.00%)	0	2/50 (4.00%)	2	0/47 (0.00%)	0
Diarrhoea † 1	1/64 (1.56%)	1	0/64 (0.00%)	0	0/50 (0.00%)	0	0/47 (0.00%)	0
Crohn's disease † 1	1/64 (1.56%)	1	1/64 (1.56%)	1	0/50 (0.00%)	0	0/47 (0.00%)	0
Rectal abscess † 1	0/64 (0.00%)	0	1/64 (1.56%)	1	0/50 (0.00%)	0	0/47 (0.00%)	0
Colitis ulcerative † 1	0/64 (0.00%)	0	0/64 (0.00%)	0	1/50 (2.00%)	1	0/47 (0.00%)	0
Rectal haemorrhage † 1	0/64 (0.00%)	0	0/64 (0.00%)	0	1/50 (2.00%)	1	0/47 (0.00%)	0
General disorders
Hernia † 1	0/64 (0.00%)	0	0/64 (0.00%)	0	1/50 (2.00%)	1	0/47 (0.00%)	0
Infections and infestations
Herpes zoster † 1	0/64 (0.00%)	0	0/64 (0.00%)	0	1/50 (2.00%)	1	0/47 (0.00%)	0
Peritonitis † 1	0/64 (0.00%)	0	0/64 (0.00%)	0	1/50 (2.00%)	1	0/47 (0.00%)	0
Pneumonia † 1	0/64 (0.00%)	0	0/64 (0.00%)	0	0/50 (0.00%)	0	1/47 (2.13%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism † 1	0/64 (0.00%)	0	0/64 (0.00%)	0	0/50 (0.00%)	0	1/47 (2.13%)	1
Surgical and medical procedures
Cholesteatoma removal † 1	0/64 (0.00%)	0	0/64 (0.00%)	0	1/50 (2.00%)	1	0/47 (0.00%)	0
1 Term from vocabulary, MedDRA (16.0); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	3%
	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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/64 (60.94%)		46/64 (71.88%)		40/50 (80.00%)		35/47 (74.47%)
Gastrointestinal disorders
Rectal haemorrhage † 1	3/64 (4.69%)	3	1/64 (1.56%)	1	0/50 (0.00%)	0	1/47 (2.13%)	1
Abdominal discomfort † 1	3/64 (4.69%)	3	0/64 (0.00%)	0	1/50 (2.00%)	1	0/47 (0.00%)	0
Abdominal distension † 1	2/64 (3.13%)	2	0/64 (0.00%)	0	0/50 (0.00%)	0	2/47 (4.26%)	2
Abdominal pain † 1	7/64 (10.94%)	8	5/64 (7.81%)	6	2/50 (4.00%)	2	7/47 (14.89%)	8
Abdominal pain upper † 1	1/64 (1.56%)	1	3/64 (4.69%)	3	1/50 (2.00%)	1	4/47 (8.51%)	4
Abdominal pain lower † 1	0/64 (0.00%)	0	0/64 (0.00%)	0	0/50 (0.00%)	0	2/47 (4.26%)	2
Constipation † 1	5/64 (7.81%)	5	1/64 (1.56%)	1	2/50 (4.00%)	2	1/47 (2.13%)	1
Colitis ulcerative † 1	0/64 (0.00%)	0	0/64 (0.00%)	0	4/50 (8.00%)	4	6/47 (12.77%)	7
Crohn's disease † 1	0/64 (0.00%)	0	4/64 (6.25%)	4	2/50 (4.00%)	2	5/47 (10.64%)	6
Diarrhoea † 1	5/64 (7.81%)	6	4/64 (6.25%)	5	4/50 (8.00%)	4	6/47 (12.77%)	6
Flatulence † 1	4/64 (6.25%)	4	0/64 (0.00%)	0	3/50 (6.00%)	3	3/47 (6.38%)	3
Gastrooesophageal reflux disease † 1	2/64 (3.13%)	2	0/64 (0.00%)	0	1/50 (2.00%)	1	1/47 (2.13%)	1
Haematochezia † 1	1/64 (1.56%)	1	1/64 (1.56%)	1	1/50 (2.00%)	1	2/47 (4.26%)	2
Nausea † 1	0/64 (0.00%)	0	1/64 (1.56%)	1	2/50 (4.00%)	2	3/47 (6.38%)	3
Vomiting † 1	1/64 (1.56%)	1	2/64 (3.13%)	2	1/50 (2.00%)	1	2/47 (4.26%)	2
Sinusitis † 1	0/64 (0.00%)	0	1/64 (1.56%)	1	2/50 (4.00%)	2	1/47 (2.13%)	1
General disorders
Fatigue † 1	2/64 (3.13%)	2	3/64 (4.69%)	3	0/50 (0.00%)	0	0/47 (0.00%)	0
Pyrexia † 1	1/64 (1.56%)	1	2/64 (3.13%)	2	1/50 (2.00%)	1	1/47 (2.13%)	1
Immune system disorders
Seasonal allergy † 1	0/64 (0.00%)	0	2/64 (3.13%)	2	2/50 (4.00%)	2	2/47 (4.26%)	2
Infections and infestations
Gastroenteritis † 1	0/64 (0.00%)	0	1/64 (1.56%)	1	2/50 (4.00%)	2	0/47 (0.00%)	0
Influenza † 1	2/64 (3.13%)	2	0/64 (0.00%)	0	2/50 (4.00%)	2	0/47 (0.00%)	0
Nasopharyngitis † 1	4/64 (6.25%)	4	8/64 (12.50%)	8	12/50 (24.00%)	14	8/47 (17.02%)	8
Upper respiratory tract infection † 1	1/64 (1.56%)	1	2/64 (3.13%)	2	0/50 (0.00%)	0	0/47 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	3/64 (4.69%)	3	0/64 (0.00%)	0	4/50 (8.00%)	4	3/47 (6.38%)	3
Back pain † 1	0/64 (0.00%)	0	0/64 (0.00%)	0	1/50 (2.00%)	1	3/47 (6.38%)	3
Musculoskeletal stiffness † 1	0/64 (0.00%)	0	0/64 (0.00%)	0	2/50 (4.00%)	2	0/47 (0.00%)	0
Nervous system disorders
Headache † 1	2/64 (3.13%)	2	4/64 (6.25%)	4	1/50 (2.00%)	1	2/47 (4.26%)	3
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain † 1	0/64 (0.00%)	0	3/64 (4.69%)	3	0/50 (0.00%)	0	2/47 (4.26%)	2
Cough † 1	0/64 (0.00%)	0	0/64 (0.00%)	0	3/50 (6.00%)	3	0/47 (0.00%)	0
Skin and subcutaneous tissue disorders
Pruritus † 1	0/64 (0.00%)	0	2/64 (3.13%)	2	0/50 (0.00%)	0	0/47 (0.00%)	0
Rash † 1	0/64 (0.00%)	0	1/64 (1.56%)	1	1/50 (2.00%)	1	2/47 (4.26%)	2
1 Term from vocabulary, MedDRA (16.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Jackie Mitchell MA DPhil
• Organization: Shield Therapeutics
• Phone: +44 (0) 191 511 8515
• EMail: jmitchell@shieldtx.com

Publications of Results:

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.

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.

• Responsible Party: Shield Therapeutics
• ClinicalTrials.gov Identifier: NCT01340872
• Other Study ID Numbers: ST10-01-301; 2010-023588-16 ( EudraCT Number )
• First Submitted: April 19, 2011
• First Posted: April 25, 2011
• Results First Submitted: June 9, 2017
• Results First Posted: August 3, 2018
• Last Update Posted: October 30, 2020