The primary objective of the study is to evaluate the safety of a high IV iron dosing regimen of iron iso-maltoside 1000 in subjects with IDA secondary to IBD. The secondary objectives of the study are: · To evaluate the efficacy of a high IV iron…
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Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of the study is the type and incidence of adverse drug
reactions (ADRs).
Secondary outcome
The secondary safety endpoints are:
1. Number of adverse events (AEs) of special interest (i.e. hypersensitivity
reactions or hypotension at pre-specified time points in relation to
administration of study drug)
2. Change in complete blood count, s-sodium, s-potassium, s-calcium,
s-phosphate, s-urea, s-creatinine, s-albumin, s-bilirubin, ASAT, and ALAT from
Baseline to Week 1, 4, 8 in Treatment Group A and B and to Week 9, 12, 16 in
Treatment Group B
3. Change in vital signs (pulse and blood pressure) from Baseline to Week 1, 4,
8 in Treatment Group A and B and to Week 9, 12, 16 in Treatment Group B
4. Change in electrocardiogram (ECG) from Baseline to Week 8 in Treatment Group
A and to Week 16 in Treatment Group B
5. Change in weight from Baseline to Week 8 in Treatment Group A and to Week 16
in Treatment Group B
6. Change in physical condition from Screening to Week 8 in Treatment Group A
and to Week 16 in Treatment Group B
The secondary efficacy endpoints are:
1. Number of subjects who obtain a target Hb (>= 13 g/dL in men and >= 12g/dL in
women) at Week 1, 4, 8 in Treatment Group A and B or at Week 9, 12, 16 in
Treatment Group B
2. Number of subjects who have an increase in Hb concentration >= 2.0 g/dL from
Baseline to Week 8 in Treatment Group A and B or to Week 16 in Treatment Group
B
3. Number of subjects who have an increase in Hb concentration >= 1.0 g/dL from
Baseline to Week 8 in Treatment Group A and B or to Week 16 in Treatment Group
B
4. Time to obtain an increase in Hb concentration >= 1.0 g/dL or >= 2.0 g/dL
5. Change in Hb concentration from Baseline to Week 1, 4, 8 in Treatment Group
A and B and to Week 9, 12, 16 in Treatment Group B
6. Change in concentrations of s-iron, s-ferritin, transferrin, TfS,
reticulocytes, reticulocyte haemo-globin content (CHr), and soluble transferrin
receptor (sTfR) from Baseline to Week 1, 4, 8 in Treatment Group A and B and to
Week 9, 12, 16 in Treatment Group B
7. Change in QoL score (Short-form Health Survey 12 Version 2 (SF-12 V2) and
Multidimensional Fatigue Inventory 20 (MFI-20) questionnaires) from Baseline to
week 8 in Treatment Group A and B and to Week 16 in Treatment Group B
8. Change in subject related absence from work (Work Productivity and Activity
Impairment (WPAI) questionnaire) from Baseline to week 8 in Treatment Group A
and B and to Week 16 in Treat-ment Group B
9. Subject related travel time utilization and Willingness To Pay (WTP
questionnaire) survey at Week 8
10. Health care related time utilization for treatment administration at
Baseline in Treatment Group A and B
Exploratory endpoints:
1. Change in inflammatory parameters (C-reactive Protein (CRP), Interleukin-6
(IL-6), Tumour Ne-crosis Factor a (TNF-a), and Hepcidin) from Baseline to Week
1, 4, 8 in Treatment Group A and B and to Week 9, 12, 16 in Treatment Group B
2. Change in faecal calprotectin from Baseline to Week 4 and 8 in Treatment
Group A and B and to Week 16 in Treatment Group B
3. Change in FGF23 from Baseline to Week 1, 4, 8 in Treatment Group A and B and
to Week 9, 12, 16 in Treatment Group B
Background summary
Anaemia in IBD is one of the most common systemic complications of IBD. Anaemia
is often not treated correctly despite its impact on Quality of Life (QoL), and
in Scandinavia approximately 20 % of the sub-jects with IBD are anaemic.
The predominant types of anaemia identified in the context of IBD are Iron
Deficiency Anaemia (IDA) and anaemia of chronic disease (ACD). Often the two
conditions are overlapping which can lead to diffi-culties in distinguishing
them. Iron deficiency is caused by chronic blood loss, malnutrition, and
inflam-mation. Therapy for IDA includes treatment of its underlying cause and
restoration of normal Hb concen-trations and iron stores. However, many anaemic
IBD subjects may not tolerate oral iron, and enteral iron absorption is
severely impaired in patients with active disease due to inflammation (with
hepcidin blockage of enterocyte iron absorption) signifying that oral iron will
have no effect. In an international guideline on diagnosis and management of
anaemia and iron deficiency in IBD it was argued that, alt-hough some patients
may respond to oral iron, intravenous (IV) iron appears to be more effective
and better tolerated than oral iron supplements.
The full iron replacement dose necessary in IBD often exceeds 1,000 mg, and if
the full iron replacement dose could be administered in a single visit it would
offer optimal convenience and improved pharmaco-economics for the patient and
the society. Hence a study with a product allowing high single dosing is
warranted.
Study objective
The primary objective of the study is to evaluate the safety of a high IV iron
dosing regimen of iron iso-maltoside 1000 in subjects with IDA secondary to
IBD.
The secondary objectives of the study are:
· To evaluate the efficacy of a high IV iron dosing regimen of iron
isomaltoside 1000
· To evaluate QoL and pharmacoeconomic parameters of a high IV iron dosing
regimen of iron isomaltoside 1000
In addition, the effect of iron isomaltoside 1000 on disease activity and
Fibroblast Growth Factor 23 (FGF23) will be evaluated. However, these analyses
will be purely exploratory.
Study design
The study is a prospective, non-controlled, open-label multi-centre pilot
safety study of iron isomaltoside 1000 (Monofer®) administered to subjects with
anaemia and Inflammatory Bowel Disease (IBD). Based upon haemoglobin (Hb)
level, the subjects are divided into two treatment groups, A and B. Depending
on the body weight, subjects in Treatment Group A will receive a total dose of
1,500 mg or 2,000 mg IV iron isomaltoside 1000 where 1,500 mg is administered
as a single infusion and 2,000 mg is divided into two administrations, whereas
subjects in Treatment Group B will receive a total dose of 2,500 mg or 3,000 mg
IV iron isomaltoside 1000 divided into two administrations.
Intervention
Depending on the body weight, subjects in Treatment Group A will receive a
total dose of 1,500 mg or 2,000 mg IV iron isomaltoside 1000 where 1,500 mg is
administered as a single infusion and 2,000 mg is divided into two
administrations, whereas subjects in Treatment Group B will receive a total
dose of 2,500 mg or 3,000 mg IV iron isomaltoside 1000 divided into two
administrations.
Study burden and risks
As with all parenteral administrations risks and adverse reactions can occur.
Parenteral adminstration of iron preparations can cause acute, severe
anaphylactoid reactions, althought they are rare . From the 600 doses
administered in earlier studies with Monofer® , no serious
anaphylactioid/anphylactic events have been reported. Administration will
immedeately be stopped in case of signs of anaphylactoid reactions and study
staff will have acces to treat this if this occurs.
Other less severe manifestations of hypersensitivity can occur, although also
uncommon. These include urticaria, raskes, itching, nausea and shivering. As a
special precaution, your blood pressure and pulse will be measured and
monitored during and after the administration of the study medication.
Delayed reactions may also occur. They are characterized by arthralgia, myalgia
and sometimes fever. The onset varies form several hours up to 4 days after
administration. Symptoms usually last 2-4 days and settle spontaneously or
following the use of simple analgetics. In addition, exacerbation of joint pain
in rheumatoid arthritis can occur and local reactions may cause pain and
inflammation at or near the injection site and a local phlebetic reaction.
(Risks for) side effects from the use of Monofer® may vary in amount and
severity per user and are desbribed below:
Uncommon side effects: blurred vision, numbness, dyspnoea, nausea, emesis,
abdominal pain, flushing, pruritis, rash, hot flashes, fever, dysphonia, and
cramps
Rare side effects: arrhythmia, tachycardia, loss of consciousness, seizure,
dizziness, restlessness, tremor, fatigue, altered mental status, chest pain,
hypotension, angioedema, sweating (around the eyes), diarrhea
Very rare side effects are palpitations, haemolysis, headache, paresthesia,
transient deafness and hypertension.
Blood sampling could be inconvenient, including pain, burning feeling at
injection site and risk of infection and hemorrhage.
No diary will be kept in this study, The patient will be asked to complete 5
different questionnaires. Three of these questionnaires will be completed each
2 or 3 times.
Rorvangsvej 30
Holbaek DK-4300
DK
Rorvangsvej 30
Holbaek DK-4300
DK
Listed location countries
Age
Inclusion criteria
1. Subjects with age >= 18 years;2. Subjects diagnosed with IBD either in remission or active ;3. Hb < 12 g/dL for women and Hb < 13 g/dL for men;4. Subjects with a CRP above upper limit of normality must have a ferritin below 100 µg/L, whereas subjects with a CRP below or equal to upper limit of normality must have a ferritin below 30 µg/L ;5. Willingness to participate after signing informed consent
Exclusion criteria
1. Patient judged by the physician to be in need of surgery due to Crohn's disease or ulcerative colitis within the next 2 months;2. Anaemia predominantly caused by factors other than IDA ;3. Iron overload or disturbance in utilisation of iron (e.g. haemochromatosis and haemosiderosis);4. Known hypersensitivity to any excipients of iron isomaltoside 1000;5. History of multiple allergies;6. Decompensated liver cirrhosis or active viral hepatitis (defined as Alanine Aminotransferase (ALAT) > 3 times upper limit of normal);7. Acute and/or chronic infections ;8. Body weight < 50 kg;9. Rheumatoid arthritis with symptoms or signs of active joint inflammation ;10. Pregnancy and nursing. In order to avoid pregnancy, women have to be postmenopausal, surgically sterile, or use one of the following contraceptives during the whole study period and 5 days after the study has ended (i.e. 5 times plasma biological half-life of the investigational medicinal product): intrauterine devices and hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release);11. Blood transfusion within the previous 12 weeks;12. Subjects with a history of asthma, allergic eczema, or other atopic allergy ;13. Planned elective surgery during the study;14. Untreated Vitamin B12 or folate deficiency, defined as values below the lower reference range;15. Participation in any other clinical study within 3 months prior to Screening;16. IV iron treatment within 8 weeks prior to Screening ;17. Oral iron treatment within 1 week prior to Screening;18. ESA treatment within 8 weeks prior to Screening ;19. Any other medical condition that, in the opinion of Investigator, may cause the subject to be unsuitable for the completion of the study or place the subject at potential risk from being in the study
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-003121-94-NL |
| ClinicalTrials.gov | NCT01599702 |
| CCMO | NL45165.078.13 |