E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Anemia associated with Low- or Intermediate-1-Risk Myelodysplastic
Syndrome |
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E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028534 |
E.1.2 | Term | Myelodysplastic syndrome NOS |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10002272 |
E.1.2 | Term | Anemia |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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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 |
The primary objective is to assess the clinical efficacy of siltuximab,
demonstrated by a reduction in RBC transfusions to treat the anemia of
MDS. |
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E.2.2 | Secondary objectives of the trial |
• To demonstrate symptomatic improvement of subjects treated with siltuximab compared with the placebo group
• To compare the number of RBC units transfused to treat the anemia of MDS, and the proportion of subjects treated with siltuximab who do not require a RBC transfusion to treat the anemia of MDS, from Week 5 to Week 12, compared with the placebo group
• To assess the change in hemoglobin among MDS subjects treated with siltuximab compared with the placebo group
• To compare disease progression (proportion of bone marrow blasts and cytogenetic change) for subjects treated with siltuximab compared with the placebo group
• To assess the safety profile of siltuximab and RBC transfusions among subjects with Low- or Intermediate-1 (INT-1)-risk MDS
• To assess the pharmacodynamics, pharmacokinetics, and antibodies to siltuximab (immunogenicity) in MDS subjects
•See protocol for additional objectives |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Confirmed diagnosis of myelodysplastic syndrome (MDS), according to World Heath Organization or the French-American-British Cooperative Group pathologic classification, with an International Prognostic Scoring System score 0, 0.5, or 1.0, indicating Low- or INT-1-risk disease.
- Documented RBC transfusion of at least 2 units of RBC for the treatment of the anemia of MDS in the 8 weeks preceding the start of the Screening Period. - Adequate iron stores, demonstrated by either the presence of stainable iron in the bone marrow or a serum ferritin of > 100 ng/mL.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2.
- Symptomatic anemia (defined by a score > 0 on the Non-Chemotherapy Anemia Symptom Scale [NCA-SS]). |
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E.4 | Principal exclusion criteria |
- Had treatment with drugs or other agents targeting IL-6 or its receptor within 4 weeks of randomization.
- Any condition that, in the opinion of the investigator, would make participation not in the best interest (eg, compromise the well-being) of the patient or that could prevent, limit, or confound the protocol-specified assessments.
- Patients with Chronic Myelomonocytic Leukemia (CMML).
- Causes other than MDS contributing to anemia, such as Vitamin B12 or folate deficiency, bleeding, hemolysis, hemoglobinopathy, or chronic renal failure. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients achieving a reduction in RBC transfusions |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
8 week period from week 5 to week 12 |
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E.5.2 | Secondary end point(s) |
1. Hemoglobin Assessment
2. Bone Marrow Examination
3. Anemia Symptom Assessment |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. At Week 12
2. At Week 13 and every 24 weeks during treatment
3. Daily for 12 weeks, then monthly for remainder of treatment period |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Open; study will continue until death, unacceptable toxicity, withdraw consent, or clinical cutoff |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 4 |
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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
Netherlands |
Russian Federation |
Spain |
Sweden |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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Clinical cut-off is 24 weeks after the last patient has been randomized.
Study end is 36 weeks after the last patient has been randomized. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 4 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 4 |