E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of anaemic subjects with multiple myeloma and iron restricted erythropoiesis receiving chemotherapy. |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049467 |
E.1.2 | Term | Erythropoiesis abnormal |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluation of efficacy of FCM given without erythropoiesis stimulating agents (ESA) in the correction of haemoglobin (Hb) levels in subjects with multiple myeloma (MM), undergoing chemotherapy. |
|
E.2.2 | Secondary objectives of the trial |
Describe safety and tolerability of FCM.
Describe the effect of treatment with FCM on iron status variables in MM subjects.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects (male or female) aged ≥18, suffering from a newly diagnosed or progressed/relapsed MM and scheduled to receive anti myeloma treatment. Progression is defined according to “Uniform Response Criteria for Multiple Myeloma”, please refer to Appendix 1.
2. Subjects with progressed/relapsed MM should have had stable disease (during the last 6 months since prior treatment).
3. Life expectancy at least 6 months.
4. 8.5 g/dL ≤Hb ≤11 g/dL at time of randomisation.
5. Iron restricted erythropoiesis defined as: a) Stainable iron in bone marrow (BM) combined with at least one of the following: • Transferrin saturation (TSAT) ≤25% • percentage of hypochromic red cells (HYPO%) ≥5% • blood reticulocyte haemoglobin content (CHr) <30 pg
b) In case that evaluation of stainable iron in BM is not possible or available, subjects should have: • Ferritin >30 ng/mL (women) or >40 ng/mL (men) and - HYPO% ≥5% or CHr <30 pg combined with - TSAT ≤25%.
6. Females of child-bearing potential must have a negative urine pregnancy test at screening.
7. Before any study-specific procedure, the appropriate written informed consent must be obtained.
|
|
E.4 | Principal exclusion criteria |
1. Any anaemia treatment within 4 weeks prior to randomisation (including red blood cell transfusions, treatment with ESA or any oral/parenteral iron preparations).
2. Anthacycline containing chemotherapy regimens.
3. Subjects weighing <35 kg.
4. Folate deficiency (serum-folate <4.5 nmol/L) and/or Vitamin B12 deficiency (serum-cobalamin <145 pmol/L).
5. Ongoing haemolysis defined as serum-haptoglobin <0.2 g/L.
6. Known chronic renal failure, glomerular filtration rate <30 mL/min/m2.
7. Recent (within last 4 weeks) significant bleeding/surgery, defined as drop in Hb of ≥2 g/dL.
8. Ongoing or recent history (within 6 months) of venous thromboembolism.
9. Clinically relevant active inflammatory disease other than MM (according to the judgement of the Investigator).
10. Clinically relevant ongoing infectious disease including known human immunodeficiency virus.
11. Serum ferritin >800 ng/mL.
12. Ongoing significant neurological or psychiatric disorders including psychotic disorders or dementia.
13. Significant cardiovascular disease prior to study inclusion including myocardial infarction within 12 months prior to study inclusion, congestive heart failure New York Heart Association Grade III or IV, or poorly controlled hypertension according to the judgment of the Investigator.
14. Elevation of liver enzymes (aspartate aminotransferase, alanine aminotransferase) over 3 times above the normal range or known acute hepatic disorder.
15. Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(ies), or subject is receiving other investigational agent(s).
16. Subject of child-bearing potential is evidently pregnant (e.g., positive human chorionic gonadotropin test) or is breast feeding.
17. Subject is not using adequate contraceptive precautions. Adequate contraceptive precautions are defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intra-uterine devices, sexual abstinence or vasectomised partner. Non-childbearing potential includes being surgically sterilised at least 6 months prior to the study or post menopausal, defined as amenorrhea for at least 12 months.
18. Subject has known sensitivity to any of the products to be administered during dosing.
19. Subject will not be available for follow-up assessment.
20. Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint: • Mean change in Hb from baseline to Weeks 4, 6 and 8 (end of treatment) in the absence of any red cell transfusion or ESA treatment.
Secondary Endpoints: • The percentage of subjects with blood Hb response of at least 1 g/dL at any study week in the absence of any red cell transfusion or ESA treatment.
• The percentage of subjects with a Hb correction to at least 12 g/dL in the absence of any red cell transfusion or ESA treatment.
• The median time to Hb response defined as increase in Hb ≥1 g/dL in the absence of any red cell transfusion or ESA treatment.
• The proportion of subjects receiving red blood cell transfusions or subjects treated with ESA during the study period.
• Adverse events: type, nature, incidence and outcome.
• Time to transfusion/treatment with ESA.
• Change in iron variables from baseline to the Weeks 2, 4, 6, 8 (ferritin, TSAT, serum iron, endogenous erythropoetin, CHr, HYPO%).
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
standard care (the subjects will be treated according to the local institutional practice) |
|
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of the study will be when the LPLV takes place i.e. when last subject recruited completes Visit 6 (week 8). |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 1 |