• Change of exclusion criterion 20 from ‘Pregnant or nursing women. In order to avoid pregnancy, women of childbearing potential have to use adequate contraception (e.g. intrauterine devices, hormonal contraceptives, or double barrier method) during the whole trial period and 7 days after the last dosing’ to ‘Pregnant or nursing women. In order to avoid pregnancy, women of childbearing potential have to use highly efficient contraception (e.g. intrauterine devices, hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release)) during the whole trial period and 7 days after the last dosing. A sterile sole partner or sexual abstinence is also considered acceptable provided it reflects the usual and preferred lifestyle of the participant’ due to a requirement from the Competent Authority in Denmark.

• Deletion of the exclusion criterion ‘Active malignant disease, disease-free for less than 5 years’ since exclusion of oncology patients was a mistake. • Deletion of the stratification based on type of underlying disease, as this was originally included in the protocol by mistake. • Correction of the volume of ferric carboxymaltose single-use vials from 15 mL to 20 mL in order to align with the available vial size. • Clarification that dilution of iron isomaltoside and ferric carboxymaltose was to a total volume of 100 mL instead of in 100 mL 0.9 % sodium chloride. • Clarification that the Ferinject® SmPC was the only reference document for choice of dose, investigational product administration, and SUSAR definition for ferric carboxymaltose. • Specification of TCT members (change from ‘QC/Regulatory’ to ‘Quality Assurance’, ‘Quality Control’, and ‘Regulatory’) in order to reflect the current TCT members.

• Change of trial design from open-label to double-blind in order to increase the scientific value of the trial. • Change of inclusion criteria 3 and 4 from ‘Hb < 10 g/dL’ and ‘Body weight > 70 kg’ to ‘Hb < 13 g/dL’ and ‘Body weight ≥ 50 kg’ in order to be able to include subjects with a need of a cumulative dose of 1500 mg iron and obtain information on the safety and efficacy of iron isomaltoside in this group of subjects. • Addition of exclusion criterion 2 ‘Hb ≥ 10 g/dL and body weight < 70 kg’ in order to ensure an iron need of minimum 1500 mg. • Change of dosing regimen from 1000 mg at baseline and at day 35 to 1000 mg at baseline and 500 or 1000 mg at day 35, i.e. the cumulative dose was changed from 2000 mg to 1500 or 2000 mg, in order to be able to include subjects with a need of a cumulative dose of 1500 mg iron. • Specification that the cumulative dose of 1500 or 2000 mg was dependent on the subject's screening Hb and body weight. • Change of infusion time for ferric carboxymaltose from at least 15 minutes to approximately 20 minutes. • Deletion of the exclusion criterion ‘History of a psychological illness or seizures’ since no contraindications or warnings related to psychological illness or seizures are included in the SmPC. • Deletion of the visit at week 13, thereby having week 10 as the last visit, in order to ease the burden on the subjects. • Addition of ESAs, radiotherapy, and chemotherapy to the list of prohibited medication and non-drug therapies in order to ensure alignment with the exclusion criteria. • Deletion of the measurement of pyridinoline in urine, since this was an exploratory endpoint with a limited value, which showed to be quite challenging to both site and subjects due to very specific requirements of the urine sample. • Clarification that alkaline phosphatase was measured in serum rather than in plasma.

• The following was added as a note to exclusion criterion 2 for clarification: ‘To ensure an iron need of minimum 1500 mg; subjects with a Hb ≥ 10 g/dL must have a body weight ≥ 70 kg. Subjects with a body weight of ≥ 50 kg to < 70 kg are eligible only if Hb is below 10 mg/dL.’ • In addition to the urine pregnancy test at baseline in all women of childbearing potential, a serum pregnancy test was added at screening and baseline for all women of childbearing potential enrolled in UK due to a requirement from the Competent Authority in UK.

• Deletion of the exclusion criterion ‘Vitamin D deficiency’ and deletion of vitamin D from the eligibility laboratory assessments, since it is not standard clinical practice to measure vitamin D prior to IV iron treatment. • Addition of details related to the blinding and randomisation procedures.

• Clarification that exploratory safety endpoints were to be analysed using the safety analysis set, while exploratory efficacy endpoints were to be analysed using the ITT analysis set. • Clarification that for the statistical analyses of change from baseline in Hb, s-ferritin, and TSAT, subjects without post-baseline assessments were to have change from baseline = 0 imputed at the first post-baseline visit. • Change of exclusion criterion 7 from ‘Treatment with erythropoietin or ESAs, red blood cell transfusion, radiotherapy, and/or chemotherapy within the last 30 days prior to screening’ to ‘Treatment with erythropoietin or ESAs, red blood cell transfusion, radiotherapy, and/or chemotherapy (except immune modulating therapy for standard IBD treatment) within the last 30 days prior to screening’ for clarification. • The following clarifications were made to the list of prohibited medication: ‘Any iron supplementation other than investigational drug (nutritional supplementation including iron is allowed unless it is assumed as treatment of the subject's anaemia)’ changed to ‘Any iron supplementation other than investigational drug (multivitamins including iron is allowed unless it is assumed as treatment of the subject's anaemia)’ and ‘Chemotherapy’ changed to ‘Chemotherapy (except immune modulating therapy for standard IBD treatment)’. • Inclusion of baseline body weight and baseline Hb as additional covariates in the sensitivity analysis of the primary endpoint. • Change of safety reference document for iron isomaltoside from the Monofer® Investigator's Brochure to the Monofer® SmPC since treatment with iron isomaltoside in this trial was within the label and the same SmPC is approved in all the participating countries.

• Omission of iFGF23 from the eligibility laboratory assessments at screening as iFGF23 was not part of any inclusion or exclusion criteria or stratification. • Deletion of the secondary safety objective ‘To compare the effects of iron isomaltoside and ferric carboxymaltose treatment in subjects with IDA due to IBD on proportion of subjects with hypophosphatemia at the last visit’ since this objective is already covered in the primary objective. • In the primary endpoint, the definition of hypophosphatemia was further detailed and the unit used for the time period was changed from days to weeks. • In the secondary safety endpoints, ‘s phosphate < 1.0 mg/dL’ was changed to ‘s phosphate ≤ 1.0 mg/dL’ in order to align with previous trials with iron isomaltoside. • Change of the endpoint ‘Incidence of s-phosphate < 1.0 mg/dL at any time from baseline to day 35’ to ‘Incidence of s-phosphate ≤ 1.0 mg/dL at any time from baseline to week 5 and at any time from baseline to week 10’ in order to align with previous trials with iron isomaltoside. • Addition of the secondary safety endpoints, ‘Incidence of hypophosphatemia at day 1 and weeks 1, 2, 5, 6, 7, and 10’ and ‘Incidence of s phosphate ≤ 1.0 mg/dL at day 1 and weeks 1, 2, 5, 6, 7, and 10’, including description of statistical analyses of these endpoints, in order to align with previous trials with iron isomaltoside. • Clarification that the secondary safety endpoint on fractional phosphate urinary excretion was derived as change from baseline to day 1 and weeks 1, 2, 5, 6, 7, and 10. • Change and expansion of the statistical analysis of AEs from ‘Number of subjects who experience an ADR including SUSARs will be compared between treatment groups’ to ‘The incidence of TEAEs, SAEs, ADRs including SUSARs as well as SARs will be compared between treatment groups’ in order to align with previous trials with iron isomaltoside.