Clinical Trial Results:
A phase 3b, randomized, controlled, multicentre study with oral ferric maltol (Feraccru) or intravenous iron (ferric carboxymaltose; FCM), for the treatment of iron deficiency anaemia in subjects with inflammatory bowel disease
Summary
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EudraCT number |
2015-002496-26 |
Trial protocol |
DE BE ES HU |
Global end of trial date |
02 Jan 2019
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Results information
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Results version number |
v1 |
This version publication date |
18 Apr 2020
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First version publication date |
18 Apr 2020
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Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
ST10-01-304
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02680756 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Shield TX (UK) Limited
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Sponsor organisation address |
Nothern Design Centre, Baltic Business Quarter, Gateshead Quays, United Kingdom, NE8 3DF
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Public contact |
Clinical Operations, Shield TX (UK) Ltd., 44 1915118511, jmitchell@shieldtx.com
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Scientific contact |
Clinical Operations, Shield TX (UK) Ltd., 44 1915118511, jmitchell@shieldtx.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
25 Jun 2019
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
02 Jan 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To compare the efficacy of ferric maltol and intravenous iron (FCM) in the treatment and maintenance of iron deficiency anaemia in subjects with IBD
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Protection of trial subjects |
Subjects were males or females aged ≥18 years with a confirmed diagnosis of IBD (endoscopic or biopsy). All patients were required to be in remission or to have a mild-to-moderate disease activity of IBD (as defined by a Simple Clinical Colitis Activity Index [SCCAI] >5 or a Crohn’s Disease Activity Index [CDAI] score <300 at screening). All subjects were required to have IDA, defined by a haemoglobin (Hb) concentration ≥8.0 g/dL and ≤11.0 g/dL for women OR a Hb ≥8.0 g/dL and ≤12.0 g/dL for
men, as well as ferritin levels <30 ng/mL or Ferritin <100 ng/mL with Transferrin saturation (TSAT)
<20% at screening. Female subjects of childbearing potential had to agree to use a reliable
method of contraception until they had completed the study and for at least 4 weeks following their final study visit. Safety assessments conducted throughout the study included adverse event monitoring, routine clinical safety laboratory testing, changes in CDAI and SCCAI. Subjective Quality of Life score was also assessed over the study duration using SF-36.
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Background therapy |
The following concomitant medications were allowed at baseline and during the study: • ESAs, but the subject had to have been on a stable dose for the preceding 3 months before randomisation • Vitamin B12 and folic acid supplements/replacement • Immunosuppressants, including variations to dosing at the discretion of the investigator, so long as there was no clinical evidence or suspicion of the immunosuppressant contributing to the subject’s anaemia or affecting erythropoiesis. Subjects with anaemia unrelated to iron deficiency or who had received depot iron preparations within 8 weeks of screening or blood transfusions within 12 weeks of screening were excluded. Other reasons for exclusion were: oral iron treatment within 4 weeks of randomization; treatment with immunosuppressants known to induce anemia; uncorrected folate or vitamin B12 deficiency; and pregnancy. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
21 Dec 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 39
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Country: Number of subjects enrolled |
Belgium: 1
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Country: Number of subjects enrolled |
France: 23
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Country: Number of subjects enrolled |
Germany: 69
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Country: Number of subjects enrolled |
Hungary: 53
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Country: Number of subjects enrolled |
United States: 65
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Worldwide total number of subjects |
250
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EEA total number of subjects |
185
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
228
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From 65 to 84 years |
22
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Screening assessments included demographics, medical history, concomitant medication, physical examination, vital signs, clinical laboratory tests (including liver function, iron markers and pregnancy test for women of childbearing potential), status of their disease using SSCAI or CDAI. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Period 1 (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Blinding implementation details |
N/A
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Ferric Maltol | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Ferric maltol 30mg BID | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Ferric maltol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
One capsule (30mg) taken bid, first thing in the morning at least 1 hour before food and concomitant medications, and last thing at night before bed at least 2 hours after food and concomitant medications. Capsules had to be taken on an empty stomach with water only with at least 8 hours between doses.
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Arm title
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IV Iron | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
IV iron, ferric carboxymaltose | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Ferric carboxymaltose
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Investigational medicinal product code |
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Other name |
FCM
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Subjects randomised to IV iron received FCM in accordance with the dosing instructions as per the local SmPC/PI. A copy of the relevant local SmPC/PI for FCM is available in the TMF. Initial dosing and the number of IV iron doses administered were calculated based on the subject’s starting Hb and weight. For ongoing treatment decisions, ferritin was measured at Visit 4 (Week 12) and Visits 5 and 6 (Week 24, and Week 36) for subjects prior to protocol amendment 7.0. Subjects continuing after Week 12 who were iron deficient (ferritin below 100 ng/mL) at any of Visits 4-6 received additional FCM doses according to the formula in the local SmPC/PI.
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Notes [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Week 54 was F/U visit and includes patients who did not complete the trial [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Week 54 was F/U visit and includes patients who did not complete the trial [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Week 54 was F/U visit and includes patients who did not complete the trialWeek 54 was F/U visit and includes patients who did not complete the trialWeek 54 was F/U visit and includes patients who did not complete the trial [4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Week 54 was F/U visit and includes patients who did not complete the trial [5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Week 54 was F/U visit and includes patients who did not complete the trial [6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Week 54 was F/U visit and includes patients who did not complete the trial [7] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Week 54 was F/U visit and includes patients who did not complete the trial |
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Baseline characteristics reporting groups
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Reporting group title |
Ferric Maltol
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Reporting group description |
Ferric maltol 30mg BID | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
IV Iron
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Reporting group description |
IV iron, ferric carboxymaltose | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
PP population
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The PP population consisted of those randomised subjects who did not have major protocol deviations during the first 12 weeks of the study.
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Subject analysis set title |
ITT population
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The intention-to-treat (ITT) population included all subjects who were randomised.
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End points reporting groups
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Reporting group title |
Ferric Maltol
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Reporting group description |
Ferric maltol 30mg BID | ||
Reporting group title |
IV Iron
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Reporting group description |
IV iron, ferric carboxymaltose | ||
Subject analysis set title |
PP population
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The PP population consisted of those randomised subjects who did not have major protocol deviations during the first 12 weeks of the study.
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Subject analysis set title |
ITT population
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The intention-to-treat (ITT) population included all subjects who were randomised.
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End point title |
Proportion of subjects achieving either a 2 g/dL increase in Hb or normalisation of Hb (>12 g/dL women, >13 g/dL men) at Week 12 - PP | ||||||||||||||||||||
End point description |
The primary efficacy endpoint was the proportion of subjects achieving either a 2 g/dL increase in Hb or normalisation of Hb (>12 g/dL women, >13 g/dL men) at Week 12 in PP population
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End point type |
Primary
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End point timeframe |
12 weeks (primary efficacy endpoint of study)
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Statistical analysis title |
Statistical testing Hb responder rate at 12 weeks | ||||||||||||||||||||
Comparison groups |
Ferric Maltol v IV Iron
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Number of subjects included in analysis |
179
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [1] | ||||||||||||||||||||
P-value |
= 0.017 | ||||||||||||||||||||
Method |
t-test, 2-sided | ||||||||||||||||||||
Confidence interval |
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Notes [1] - Risk difference (95% CI) in responder rate is -0.1, within the non-inferiority margin of 20% (-0.2), thus demonstrating that ferric maltol is non-inferior to IV iron. |
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End point title |
Proportion of subjects achieving either a 2 g/dL increase in Hb or normalisation of Hb (>12 g/dL women, >13 g/dL men) at Week 12 - ITT | ||||||||||||||||||||
End point description |
The primary efficacy endpoint was the proportion of subjects achieving either a 2 g/dL increase in Hb or normalisation of Hb (>12 g/dL women, >13 g/dL men) at Week 12 in ITT population
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End point type |
Primary
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End point timeframe |
12 weeks (primary efficacy endpoint of study)
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Statistical analysis title |
Statistical testing Hb responder rate at 12 weeks | ||||||||||||||||||||
Comparison groups |
Ferric Maltol v IV Iron
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Number of subjects included in analysis |
250
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [2] | ||||||||||||||||||||
P-value |
= 0.219 | ||||||||||||||||||||
Method |
t-test, 2-sided | ||||||||||||||||||||
Confidence interval |
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Notes [2] - The risk difference in the responder rates was -0.2 with a two-sided p-value of 0.219 (95% CI: -0.3, -0.1). The results for the ITT did not confirm those of the primary analysis in the PP. |
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End point title |
Change from Baseline in Haemoglobin Concentration Over the Treatment Period | ||||||||||||
End point description |
The key secondary efficacy endpoint was change from baseline in Hb concentration at Week 12.
The change from baseline in Hb concentration was analysed using an ANCOVA model adjusted for treatment group, baseline Hb, and IBD subgroup and was based on the PP using an OC approach.
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End point type |
Secondary
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End point timeframe |
12 weeks
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No statistical analyses for this end point |
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End point title |
Change in Hb concentration from baseline to Week 4 | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At week 4
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No statistical analyses for this end point |
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End point title |
Change in Hb concentration from baseline to Week 4 in subjects with baseline Hb <9.5 g/dL | ||||||||||||
End point description |
Change in Hb concentration from baseline to Week 4 in subjects with a baseline
Hb <9.5 g/dL
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End point type |
Secondary
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End point timeframe |
At week 4
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No statistical analyses for this end point |
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End point title |
Change in Hb concentration from baseline at Week 12 in subjects with baseline Hb <9.5 g/dL | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At 12 weeks
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No statistical analyses for this end point |
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End point title |
Proportion of subjects who experience a change from baseline (CFB) in Hb concentration ≥1.0 g/dL at Week 12 | |||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At week 12
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No statistical analyses for this end point |
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End point title |
Proportion of subjects with baseline Hb <9.5 g/dL that achieve an increase in Hb concentration of ≥1 g/dL at Week 12 | |||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At 12 weeks
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No statistical analyses for this end point |
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End point title |
Proportion of subjects who experience a CFB in Hb concentration ≥2.0 g/dL at Week 12 | |||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At week 12
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No statistical analyses for this end point |
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End point title |
Proportion of subjects with baseline Hb <9.5 g/dL that achieve an increase in Hb concentration of ≥2 g/dL at Week 12 | |||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At week 12
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No statistical analyses for this end point |
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End point title |
Proportion of subjects who experience a CFB in Hb concentration ≥1.0 g/dL at Week 4 | |||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At week 4
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No statistical analyses for this end point |
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End point title |
Proportion of subjects with baseline Hb <9.5 g/dL that achieve an increase in Hb concentration of ≥1 g/dL at Week 4 | |||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At week 4
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No statistical analyses for this end point |
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End point title |
Proportion of subjects who experience a CFB in Hb concentration ≥2.0 g/dL at Week 4 | |||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At week 4
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No statistical analyses for this end point |
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End point title |
Proportion of subjects with baseline Hb <9.5 g/dL that achieve an increase in Hb concentration of ≥2 g/dL at Week 4 | |||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At week 4
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No statistical analyses for this end point |
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End point title |
Proportion of subjects with Hb concentration within normal limits at Week 12 | |||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At week 12
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No statistical analyses for this end point |
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End point title |
Proportion of subjects with baseline Hb concentration <9.5 g/dL that is within normal limits at Week 12 | |||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At week 12
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No statistical analyses for this end point |
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End point title |
Proportion of subjects with Hb concentration within normal limits at Week 4 | |||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At week 4
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No statistical analyses for this end point |
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End point title |
Proportion of subjects with baseline Hb concentration <9.5 g/dL that is within normal limits at Week 4 | |||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At week 4
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No statistical analyses for this end point |
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End point title |
Change in ferritin concentration from baseline to Week 12 | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At week 12
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No statistical analyses for this end point |
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End point title |
Long term efficacy endpoints, Anaemic status | ||||||||||||||||||
End point description |
Number of subjects with non-anaemic status at week 24, week 36 and week 52 (or early termination)
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End point type |
Other pre-specified
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End point timeframe |
At week 24, week 36 and week 52
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No statistical analyses for this end point |
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End point title |
Long term efficacy endpoint, normal ferritin levels | ||||||||||||||||||
End point description |
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End point type |
Other pre-specified
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End point timeframe |
At week 24, week 36 and week 52 (or early termination)
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No statistical analyses for this end point |
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End point title |
Quality of life - Medical outcome study SF-36 | ||||||||||||||||||||||||||||||||||||
End point description |
Changes from baseline in physical component (PCS) and mental component (MCS) for SF-36 questionnaires. Data is from the last observation carried forward
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End point type |
Other pre-specified
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End point timeframe |
At week 12
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
The analysis of AEs focuses on TEAEs, which were defined as any AE that occurred on or
worsened after the first dose of IMP and up to 14 days after the last dose of IMP.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.1
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Reporting groups
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Reporting group title |
Ferric maltol - Safety data set
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Reporting group description |
Treatment Emergent Adverse Events (TEAEs) reported in the treatment arm with Ferric Maltol | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
IV Iron - Safety dataset
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Reporting group description |
Treatment Emergent Adverse Events (TEAEs) reported in the treatment arm with IV Ironl | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 2% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
12 Feb 2015 |
Global Amendment 1 (protocol version 3.0). MAJOR CHANGES: 1. Addition of secondary endpoints to give specific information on the efficacy in population with baseline Hb concentration < 9.5g/dL. 2. Update to Primary objective wording to include only subjects with IBD in whom other oral iron therapies have failed. 3. Changes to inclusion criteria, to include subjects with Hb >= 8.0 g/dL and Ferritin <30 ng/ml or Ferritin <100 ng/ml an to clarify the wording for female with childbearing potential. 4. Changes to exclusion criteria, to clarify the permitted use of some immunosuppressant; to exclude patient who received oral iron supplementation within 4 weeks, to broaden the IBD population by changing the SCCAI and CDAI score for exclusion; to clarify exclusion for allergy sufferers; to only exclude patients with serious adverse reactions with IV iron from the trial. 5. Changes to concomitant medications to clarify the permitted use of immunosuppressant. 6. Addition of advice regarding ptential ferric maltol drug interactions. 7. Changes to individual discontinuation criteria, to discontinue patients from the study in case of use of prohibited co-medications, blood transfusions, change in immunosuppressant route. 8. Changes to the non-inferiority margin to 20% and the power of the study to 90%. this increased the number of required subjects to 108 per arm (121 to allow for protocol deviations).
Various minor / administrative changes. |
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08 Jul 2016 |
Global Amendment 2 (protocol version 4.0). MAJOR CHANGES. 1. Addition of secondary endpoints related to Hb concentration at week 4. 2. Change to primary objective to clarify the population also includes patients for whom other oral iron therapies are not considered suitable. 3. Expansion of the study to US as well as in the EU.
Various minor / administrative changes to reflect the change of the name of the sponsor (from Iron therapeutics to Shield TX, legal entity remains the same) and include background to reflect the extension of the study to the US. |
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04 Jan 2017 |
Global Amendment 3 (protocol version 5.0). MAJOR CHANGES. 1 and 2. Change in primary objective and inclusion criteria to include OFP-naive patients, and not only following OFP failure or unsuitability. 3. Small widening of the iron deficiency anaemia definition from <11 or 12 g/dL to <= 11 or 12 g/dL. 4 and 16. Clarification of permitted changes in the immunosuppressnt co-medication. 5. Clarification to refer to ferric carboxymaltose as intravenous iron in the exclusion criteria to ensure consistency for all countries. 6. Vitamin B12 or folic acid deficiency definition as an exclusion criteria is to be determined by the central laboratory screening results only and no longer by the investigator. 7. the exclusion criteria regarding subject with severe renal impairment is mentioned as applicable to US sites only. 8. Change to the discontinuation criteria for TSAT to above 60%, as it happens in the study population and is not indicative of iron overload. 9 to 15. Change in the dosing requirement of ferric maltol to clarify timing of administration of concomitant medication and introducing a 8-hour gap between doses. This change is implemented at each visit for compliance check and as a dosing reminder for patients. 11. and 15. Patients will be given 3 bottles of study drug (instead of 4) at visit 2 (randomisation) that will cover the 12 weeks of treatment before the next visit, and 4 bottles at visit 5 (week 36) that will cover for the final 16 weeks of treatment. Patients will be reminded at each visit that the number of bottle they are given (3 or 4) are sufficient for the treatment until the next visit. 17. Secondary endpoints regarding increase of Hb concentration of 1g/dL and 2g/dL have been split into two separate endpoints.
Various minor / administrative changes, including an update to the number of sites in US and EU. |
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11 Jul 2017 |
Global Amendment 4 (protocol version 6.0). MAJOR CHANGES. 1, 2 and 6. Change in the exclusion criteria to allow dose change in immunosuppressant co-medication. This would reflect the current practice and also help to address low recruitment rates. 3. dosing information added in the previous amendment have been added to the section regarding interaction for consistency. 4. Changes in the discontinuation criteria to clarify the definition of transient rise or TSAT or ferritin and to allow immunosuppressent dose change as per amended exclusion criteria (see 1.). 5. Administration of IV iron at week 4 should only be done if clinically required.
Various minor / administrative changes to correct spelling. |
||
30 Apr 2018 |
Global amendment 5 (Protocol v7.0). MAJOR CHANGES. The study duration change from 52 weeks to 12 weeks (for new patients, existing patients will continue until their next scheduled visit) in an effort to improve recruitment rate. this change is reflected in various sections of the protocol: study design (5.4.3), dose selection (5.5), discontinuation criteria (7.4.6), IMP (8.1), clinical laboratory (10.2.12).
The schedule of assessment for visit 4 and after have been revised in line with the amended study duration (patient's next visit after visit 4 will be the end of treatment visit).
Various minor / administrative changes for consistency with protocol changes. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |