E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS) |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028533 |
E.1.2 | Term | Myelodysplastic syndrome |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and tolerability of AMG 531 in thrombocytopenic subjects with low or Intermediate-1 risk MDS. |
|
E.2.2 | Secondary objectives of the trial |
Part A:
To evaluate the platelet response of thrombocytopenic subjects with low or intermediate-1 risk MDS receiving AMG 531.
Part B:
Part B: To assess the pharmacodynamics (PD) and pharmacokinetics (PK) of three dosing schedules of AMG 531 administered via subcutaneous or intravenous administration in thrombocytopenic subjects with MDS. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Diagnosis of MDS using the World Health Organization classification Low or intermediate-1 risk MDS using the IPSS The mean of the two platelet counts taken within 1 week prior to dosing must be ≤50 x 109/L, with no individual count >55 x 109/L (5 patients enrolled at the MTD must be ≤20 x 109/L). Standrad of care platelet assessments taken prior to Informed Consent may be used as 1 of the 2 counts taken within 3 weeks prior to study day 1. Subjects must be 18 years of age at the time of obtaining informed consent Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Adequate Liver Function, as evidenced by a serum bilirubin ≤1.5 times the laboratory normal range (except for patients with a confirmed diagnosis of Gilbert’s Disease), ALT ≤ 3 times the laboratory normal range, and AST ≤ 3 times the laboratory normal range A serum creatinine concentration ≤ 2 mg/dl (≤176.8 mmol/L) Written Informed Consent
|
|
E.4 | Principal exclusion criteria |
Currently receiving any treatment for MDS other than transfusions and erythropoeitic growth factors. If granulocyte growth factors are currently being received, they cannot be used on or after study day 1. Clinically significant bleeding within 2 weeks prior to screening ( eg, GI bleeds, intracranial hemorrhage) . Prior malignancy ( other than controlled prostate cancer, in situ cervical cancer or basal cell cancer of the skin) unless treated with curative intent and without evidence of disease for = 3 years before screening. Prior history of bone marrow transplantation. Persistent peripheral blood monocytosis (> 3 months with an absolute monocyte count > 1,000/pL). Unstable angina, congestive heart failure [NYHA > class II], uncontrolled hypertension [diastolic > 100 mmHg], uncontrolled cardiac arrhythmia, or recent (within 1 year) myocardial infarction. Received Anti-Thymocyte Globuline (ATG) within 6 months of screening. Received hypomethylating agents, immunomodulating agents, histone deacetylase inhibitors, cyclosporine or mycophenolate within 6 weeks of screening. Received IL-11 (oprelvekin) within 4 weeks before screening. Concurrent use of granulocyte growth factors (i.e. G-CSF(Neupogen°, Granocyte°), pegfilgrastim (Neulasta°), GM-CSF (Leukine, Prokine, Sargramostim)). Have ever previously received rTPO, PEG-rHuMGDF, eltrombopag, or AMG 531. Less than 4 weeks since receipt of any therapeutic drug or device that is not FDA approved for any indication. Other investigational procedures are excluded. History of arterial thrombosis (eg, stroke or transient ischemic attack) in the past year. History of venous thrombosis that currently requires anti- coagulation therapy. Untreated B12 or folate deficiency. Subject is evidently pregnant (eg, positive HCG test) or is breast feeding. Subject is not using adequate contraceptive precautions. Subject has known hypersensitivity to any recombinant E coli- derived product. Subject previously has enrolled in this study. Subject will not be available for follow- up assessment. 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) |
The primary endpoint is the incidence and severity of all adverse events and evaluation of antibody status. The MTD of AMG 531 in thrombocytopenic subjects with low or intermediate-1 risk MDS will be identified based on safety data. The MTD is defined as the dose where < 34% of subjects experience a related grade 3-4 toxicity. The key secondary endpoint is the proportion of subjects achieving a complete or major platelet response (platelet response defined by a modified MDS International Working Group Classification).
|
|
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 | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | Yes |
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 | No |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
sequential cohort dose escalation study |
|
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 | No |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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 | Information not present in EudraCT |
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 |
|
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 15 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 15 |