Clinical Trial Results:
Intravenous Ferric Carboxymaltose for improvement of metabolic parameters and vascular function in T2DM patients with iron deficiency
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Summary
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EudraCT number |
2011-005224-18 |
Trial protocol |
DE |
Global end of trial date |
16 May 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
09 Jun 2022
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First version publication date |
09 Jun 2022
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Other versions |
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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 |
CLEVER-2011
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01513369 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
GWT-TUD GmbH
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Sponsor organisation address |
Freiberger Str. 33, Dresden, Germany, 01067
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Public contact |
Medical Consulting, GWT-TUD GmbH, 0049 35125933100, medical.consulting@g-wt.de
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Scientific contact |
Medical Consulting, GWT-TUD GmbH, 0049 35125933100, medical.consulting@g-wt.de
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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 |
27 Nov 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 Oct 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
16 May 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 |
reduction in HBA1c-levels between baseline and after 12 weeks of treatment with FCM vs. placebo
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Protection of trial subjects |
The conduct of this study was in compliance with the Good Clinical Practice Guidelines and under the guiding principles detailed in the Declaration of Helsinki. The study was also carried out in keeping with applicable local law(s) and regulation(s). Participants were monitored for the occurrence of treatment-emergent adverse events and overall health status.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
13 Aug 2012
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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 |
Germany: 130
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Worldwide total number of subjects |
130
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EEA total number of subjects |
130
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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) |
0
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From 65 to 84 years |
130
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85 years and over |
0
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Recruitment
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Recruitment details |
From Aug 2012 through Oct 2016, a total of 162 patients were screened at 7 study sites in Germany. Of them, 12 did not meet the eligibilty criteria. In total, 162 patients were screened at 7 study sites in Germany. Of them, 150 met the inclusion criteria and were randomized to receive either IMP Ferinject® (76 pat.) or matching placebo (74 pat.). | |||||||||
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Pre-assignment
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Screening details |
The PPS comprised all subjects who were treated according to the protocol, had no other major protocol violations, and reached the defined study endpoint. This set was used for all final statistical analysis and included 130 subjects in total, 64 of the FCM group and 66 of the placebo group. | |||||||||
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Period 1
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Period 1 title |
overall period
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Single blind | |||||||||
Roles blinded |
Subject | |||||||||
Blinding implementation details |
The patient was blinded by using a black sheath which was wrapped around the infusion bottle. In addition, a black infusion set was used which conceals the colour of the infused solution to the patient.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Experimental Arm | |||||||||
Arm description |
- | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
ferric carboxymaltose (FCM)
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Investigational medicinal product code |
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Other name |
Ferinject®
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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 |
duration of 12 weeks, intravenous via drip infusion
Week 1b (Baseline): 1000mg (exception: with Hb ≥ 14 g/dL and ≤ 15 g/dL only 500mg)
Week 5 (Visit 2a): weight < 70kg & Hb < 10 g/dL: 500mg; weight < 70kg & Hb ≥ 10 g/dL: no dose; weight ≥ 70 kg & Hb < 10 g/dL: 1000mg; weight ≥ 70 kg & Hb ≥ 10 g/dL: 500mg; Any weight & Hb ≥ 14 g/dL and ≤ 15 g/dL: No dose
Week 5+ <=5d (Visit 2b): No dose (exception: Any weight & Hb ≥ 14 g/dL and ≤ 15 g/dL: 500mg, if still iron deficient)
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Arm title
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Placebo Arm | |||||||||
Arm description |
- | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Sodium chloride
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Investigational medicinal product code |
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Other name |
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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 |
duration of 12 weeks, intravenous via drip infusion
Week 1b (Baseline): 1000mg (exception: with Hb ≥ 14 g/dL and ≤ 15 g/dL only 500mg)
Week 5 (Visit 2a): weight < 70kg & Hb < 10 g/dL: 500mg; weight < 70kg & Hb ≥ 10 g/dL: no dose; weight ≥ 70 kg & Hb < 10 g/dL: 1000mg; weight ≥ 70 kg & Hb ≥ 10 g/dL: 500mg; Any weight & Hb ≥ 14 g/dL and ≤ 15 g/dL: No dose
Week 5+ <=5d (Visit 2b): No dose (exception: Any weight & Hb ≥ 14 g/dL and ≤ 15 g/dL: 500mg, if still iron deficient)
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Baseline characteristics reporting groups
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Reporting group title |
overall period
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Reporting group description |
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End points reporting groups
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Reporting group title |
Experimental Arm
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Reporting group description |
- | ||
Reporting group title |
Placebo Arm
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Reporting group description |
- | ||
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End point title |
Change in HbA1c levels | ||||||||||||
End point description |
The primary endpoint of this study was the change in HbA1c levels between baseline and after 12 weeks of treatment with FCM or placebo.
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End point type |
Primary
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End point timeframe |
between baseline and after 12 weeks
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Statistical analysis title |
Main analysis set | ||||||||||||
Statistical analysis description |
Includes all subjects of the FAS who are without major protocol violations and have data of HbA1c values at V3 .
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Comparison groups |
Experimental Arm v Placebo Arm
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Number of subjects included in analysis |
130
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.001 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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Adverse events information [1]
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Timeframe for reporting adverse events |
13 weeks
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Assessment type |
Systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||
Dictionary version |
22.0
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| Frequency threshold for reporting non-serious adverse events: 0% | |||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: A total of 150 adverse events (AEs) were recorded in 87 patients. 94 AEs in 48 patients treated with FCM and 56 AEs in 39 patients treated with placebo. 19 out of the 94 AEs (20.2%) reported in experimental group were assessed as likely or possibly related to the IMP, incl. increase in liver enzymes (4), fever (3), nausea (2), increase in ferritin (2), and vertigo, tiredness, headache, worsening of nephropathy, increased CRP, unpleasant aftertaste, Herpes, and elevated erythropoiesis (each 1). |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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12 Jul 2013 |
Version 2.4 dated 13.06.2013: multi-site setting (6 new study sites), change of in-/exclusion criteria |
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06 Feb 2014 |
Version 2.5 dated 22.11.2013: changes of in-/exclusion criteria [anemia is not an inclusion criterion anymore IDA → ID, serum ferritin < 100 ng/ml or TSAT < 20%, extension of contraindications due
to known hypersensitivity reaction (Rote Hand Brief), definition of HbA1c stability, implementation of interim analysis] |
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15 May 2015 |
Version 2.6 dated 17.03.2015: changes of inclusion criteria [serum ferritin < 150 ng/mL or TSAT < 25% if Hb < 14 g/dL; serum ferritin < 100 ng/mL or TSAT < 20% if Hb ≥ 14 g/dL and ≤ 15g/dL], changes of exclusion criteria [Hb > 15 g/dL, CRP > 15 mg/L] |
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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 | |||
