E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chemotherapy induced Neutropenia |
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E.1.1.1 | Medical condition in easily understood language |
Decrease in some types of white blood cells |
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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 | 19.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10029355 |
E.1.2 | Term | Neutropenias |
E.1.2 | System Organ Class | 100000004851 |
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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 of this study is to assess the safety and tolerability of 5 μg/kg tbo-filgrastim in the pediatric population with solid tumors without bone marrow involvement. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to assess the pharmacokinetics using sparse
sampling strategy, pharmacodynamics, efficacy, and immunogenicity of tbo-filgrastim in this patient population. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients may be included in the study only if they meet all of the following criteria:
a. Male or female infants, children and adolescents aged 1 month to <16 years.
b. Patients with solid tumors without bone marrow involvement (ie, non-myeloid neoplasms), who are scheduled to receive myelosuppressive CTX.
c. Body weight ≥5 kg.
d. Written informed consent provided by parent(s)/legal representative(s)
e. Patients must have an initial diagnosis and histologic proof of their malignancy, recurrence of their disease, clear radiographic or biopsy evidence is required within 4 weeks prior to study entry.
f. All enrolled subjects should have signed consent for a CTX regimen that is known to be myelotoxic, with counts expected to drop below the ANC of 0.5 × 109/L for at least 3 days. These regimens would include at least 1 of the following:
Etoposide
doxorubicin
ifosfamide
cyclophosphamide
g. Patients must have an ANC >1 × 109/L and a platelet count >100 × 109/L at the start of CTX.
h. Normal cardiac, renal, and hepatic function.
i. All subjects must have a life expectancy of 12 weeks or more.
j. Performance Status: Lansky performance score >60 (age 1 to <16 years).
k. Adequate contraceptive use.
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E.4 | Principal exclusion criteria |
Patients will be excluded from participating in this study if they meet any of the following criteria:
a. Bone marrow involvement.
b. Active myelogenous leukemia or history of myelogenous leukemia.
c. Previous treatment with colony-stimulating factors (G-CSF, granulocyte-macrophage
colony-stimulating factor, Interleukin 11 [IL-11]) less than 6 weeks prior to study entry.
d. Known hypersensitivity to any component of this product.
e. History of congenital neutropenia or cyclic neutropenia.
f. Any illness or condition that in the opinion of the investigator may affect the safety of the patient or the evaluation of any study endpoint.
g. Pregnant or nursing female patients.
h. Do not agree to use adequate contraceptive.
i. Prior bone marrow or stem cell transplant, or prior radiation to ≥25% of bone marrow within the 4 weeks prior to the first tbo-filgrastim dose.
j. Ongoing active infection or history of infectious disease within 2 weeks prior to the screening visit.
k. Treatment with lithium at screening or planned during the study.
l. Participation in an interventional clinical study within 30 days or 5
half-lives of the investigational product before enrollment, whichever is
longer. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety Measures and Endpoints
The safety of tbo-filgrastim will be assessed by evaluating the following:
adverse event reports throughout the study clinical laboratory test results at screening and at the end-of-study visit vital signs measurements at screening, throughout the study treatment, and at the end-of-study visit
Electrocardiography (ECG) findings at screening, pre-dose, and 4 and 6 hours after the first tbo-filgrastim administration, and at the end-of-study visit
physical examination results at screening and at the end-of-study visit concomitant medication usage throughout the study local tolerability at the injection site at 1 hour (±30 min) after each study drug injection spleen sonography assessments at screening, on day 4 of tbo-filgrastim treatment, at the end-of-study visit, and if the patient reports left upper abdominal and/or shoulder tip pain.
ADA assessment prior to the first tbo-filgrastim dministration, at the end-of-study visit, and at 30 days and 3 months after the last tbo-filgrastim study drug treatment in the first cycle.
survival at 90 day follow-up.
Pharmacokinetic Measures and Endpoints
The pharmacokinetic measure for this study is serum concentration of tbo-filgrastim.
Blood samples for pharmacokinetics will be obtained on study day 1 within 1 hour prior to tbofilgrastim
administration (pre-dose) and at 2, 4, 6, 8, and 12 hours thereafter.
Pharmacodynamic Measures and Endpoints
Blood samples for ANC measurement will be obtained within 1 hour prior to tbo-filgrastim
administration on study day 1 and on days 5, 6, 7, 10, 12, and 15 (optional if day 15 coincides with CTX-day 21).
The pharmacodynamic measure for this study is ANC in blood (see Section 7.2.1).
Efficacy Measures and Endpoint
The efficacy measures for this study are axillary or external ear temperature and ANC in blood
(see Section 8.1).
The primary outcome variables and endpoints for this study are safety
evaluations. Statistical Considerations: The overall sample size of 50 is considered sufficient to allow exploratory analysis.
Data will be evaluated using statistical approaches for exploratory data analyses.
No powered primary endpoints |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety at end of study visit and immunogenicity at day 30 and 90 of the follow up period, survival at day 90 |
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E.5.2 | Secondary end point(s) |
The secondary objectives are to assess the pharmacokinetics using sparse sampling strategy, pharmacodynamics, efficacy, and immunogenicity of tbo-filgastrim |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
End of study (D21, following cycle 1). |
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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 | No |
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 | No |
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 | 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 | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 3 |
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 |
Bulgaria |
Croatia |
Hungary |
Poland |
Romania |
Russian Federation |
Serbia |
Ukraine |
United States |
|
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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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 | 4 |
E.8.9.1 | In the Member State concerned days | 15 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |