E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
chemotherapy-induced neutropenia in patients with stage II/III breast cancer receiving docetaxel, doxorubicin, and cyclophosphamide (TAC) anti-cancer chemotherapy |
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E.1.1.1 | Medical condition in easily understood language |
Having dangerously low white blood cells (Neutropenia) in patients as a result of taking chemotherapy drugs for breast cancer. This makes them susceptible to infections. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029354 |
E.1.2 | Term | Neutropenia |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006187 |
E.1.2 | Term | Breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 the study is to compare the efficacy of MYL-1401H versus Neulasta® for the prophylactic treatment of chemotherapy-induced neutropenia in patients with stage II/III breast cancer receiving TAC anti-cancer chemotherapy. |
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E.2.2 | Secondary objectives of the trial |
- To assess the safety of MYL-1401H and Neulasta® when administered through 6 cycles of TAC anti-cancer chemotherapy - To assess the potential immunogenicity of MYL-1401H and Neulasta® during chemotherapy and up to 24 weeks following the first administration |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed and dated written informed consent. 2. Patients aged ≥ 18 years. 3. Women of child-bearing potential must agree to use effective methods of birth control during the treatment period from the first dose of study drug until 6 months following the last dose of study drug. Acceptable methods of contraception include nonhormonal intrauterine device and barrier methods (male condom, female condom, diaphragm or cervical cap) with spermicide. Female patients who normally abstain from sexual activity may be recruited providing they remain abstinent during the study or if they become sexually active, they must agree to use effective methods of birth control as described above. 4. Male patients without a vasectomy must agree to use a condom and their female partners of child-bearing potential must agree to use another form of contraception (hormonal contraceptives, intrauterine device, diaphragm with spermicide, or cervical cap with spermicide) during the treatment period from the first dose of study drug until 6 months following the last dose of study drug. 5. Newly diagnosed, pathologically confirmed breast cancer. 6. Stage II or III breast cancer with adequate staging workup (NCCN guidelines; Version 1.201413) and adequate surgery if receiving adjuvant therapy. 7. Patients planned/eligible to receive neoadjuvant or adjuvant treatment with TAC for their breast cancer. 8. Cancer Chemotherapy and Radiotherapy naïve. 9. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 10. Absolute neutrophil count ≥ 1.5 × 10 (9)/L. 11. Platelet count ≥ 100 × 10 (9)/L. 12. Hemoglobin > 10 g/dL without blood transfusions or cytokine support during the 2 weeks previous to the hemoglobin level. 13. Adequate cardiac function (including left ventricular ejection fraction ≥ 50% as assessed by echocardiography) within 4 weeks prior to start of chemotherapy. 14. Adequate renal function, i.e., creatinine < 1.5 × upper limit of normal (ULN). |
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E.4 | Principal exclusion criteria |
1. Participation in a clinical trial in which they received an investigational drug within 28 days before randomization. 2. Previous exposure to filgrastim, pegfilgrastim, lenograstim, lipegfilgrastim, or other filgrastims on the market or in clinical development. 3. Received blood transfusions or erythroid growth factors within 2 weeks prior to first dose of chemotherapy. 4. Known hypersensitivity to any drugs or excipients that patients will be receiving during the study. 5. Known hypersensitivity to E. coli-derived products. 6. Known fructose intolerance (related with sorbitol excipient). 7. Underlying neuropathy of grade 2 or higher. 8. Active infectious disease or any other medical condition which might put the patient at significant risk to tolerate 6 courses of TAC chemotherapy (e.g., recent myocardial infarction). 9. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 × ULN, ALT and/or AST > 1.5 × ULN with alkaline phosphatase (ALP) > 2.5 × ULN; any bilirubin > ULN. Any alteration of liver function and/or ALP elevation, even within acceptance limits, should be investigated before randomization to exclude any stage IV disease. 10. Treatment with systemically active antibiotics within 5 days before first dose of chemotherapy. 11. Patients under treatment with lithium. 12. Chronic use of oral corticosteroids. 13. Splenomegaly of unknown origin by physical examination and/or computerized tomography scan or ultrasound and any condition which can cause splenomegaly, e.g., thalassemia, glandular fever, hemolytic anemias, and malaria. 14. Myeloproliferative or myelodysplastic disorders, sickle cell disorders, and 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. 15. Increase potential risk of Adult Respiratory Distress Syndrome. 16. Pregnant or nursing women. 17. Patients known to be seropositive for human immunodeficiency virus (HIV), or who have had an acquired immunodeficiency syndrome (AIDS) defining illness or a known immunodeficiency disorder. 18. A known active abuse of drugs or alcohol should preclude patient participation and evaluation in the study. 19. Any known psychiatric conditions. 20. Any disease or physical condition that may not allow for the adequate performance of study assessments, such as lack of access to patient’s domiciliary, and distance of patient’s domiciliary from clinic site. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is the DSN in Cycle 1, defined as days with ANC < 0.5 × 10 (9) /L. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Efficacy: • The frequency of the worst grade (grade 3 or 4) neutropenia by cycle and across all cycles • The depth of the ANC nadir in Cycle 1 • The time to the post-nadir ANC recovery in Cycle 1 • The ANC-time to nadir in Cycle 1 (i.e., time from the beginning of chemotherapy to the occurrence of the ANC nadir) • The rate of Febrile Neutropenia (FN) defined by the ESMO Clinical Practice Guidelines with a single oral temperature > 38.5°C or 2 consecutive readings of an oral temperature > 38.0°C for 2 hours, by cycle and across all cycles • Percentage of scheduled chemotherapy doses that were delivered • Proportion of chemotherapy doses reduced, omitted, or delayed related to neutropenia, FN, or documented infections • Number of days of delay of chemotherapy related to neutropenia, FN, or documented infections
Safety: • Incidence, nature, and severity of AEs including adverse drug reactions (ADRs) • Incidence, severity, and distribution of bone pain by BPI form (Short Form) in Cycle 1 and Cycle 2 only • Incidence, severity, and distribution of infections • Injection site tolerance • Incidence, titer, and neutralizing capacity of antibodies against MYL-1401H and Neulasta® |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
throughout Cycles 1-6 as documented above |
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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 | 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 | No |
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 | 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) | Yes |
E.8.2.2 | Placebo | No |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
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 |
Georgia |
Germany |
Hungary |
Poland |
Ukraine |
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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
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |