E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neutropenia and febrile neutropenia in patients being treated with cytotoxic chemotherapy for malignancy. |
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E.1.1.1 | Medical condition in easily understood language |
Neutropenia is a blood disorder in which the number of neutrophils (type of white blood cell) in the bloodstream is reduced. Neutropenia is often caused by drugs used to treat cancer. |
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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 | 14.1 |
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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10016288 |
E.1.2 | Term | Febrile neutropenia |
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 |
To assess and compare the efficacy of RGB-02 versus Neulasta® in breast cancer patients receiving AT (docetaxel-doxorubicine) chemotherapy in adjuvant or neoadjuvant setting. |
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E.2.2 | Secondary objectives of the trial |
To evaluate safety and immunogenicity of RGB-02 compared to Neulasta® and collect long term safety and immunogenicity data for RGB-02 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Females ≥ 18 and ≤ 65 years of age.
2. Patients with invasive breast cancer (Stage IIB and III) appropriate for treatment with doxorubicin and docetaxel combination therapy in the neoadjuvant or adjuvant treatment setting.
3. ECOG performance status 0 or 1.
4. Chemotherapy naïve.
5. Adequate bone marrow function assessed during Screening, as indicated by:
a. ANC ≥ 1.5 x10^9/L,
b. Platelet count ≥ 100 x10^9/L, and
c. Hemoglobin > 8 g/dL.
6. Adequate renal and hepatic function assessed during Screening, as indicated by:
a. Estimated creatinine clearance ≥ 50 mL/min calculated by the Cockcroft-Gault method,
b. Bilirubin, aspartate transaminase, alanine transaminase < 1.5 x upper limit of normal (ULN), and
c. Alkaline phosphatase < 2.5 x ULN.
7. Female patients with childbearing potential must have a negative urine pregnancy test within 3 days prior to the first dose of chemotherapy (Day 1 of Cycle 1) and must agree to use 2 reliable methods of contraception throughout the treatment period and for 3 months after discontinuation of treatment. The 2 methods of reliable contraception must include 1 highly effective method (intrauterine device, hormonal pills, injections or implants, tubal ligation, partner’s vasectomy), and 1 additional effective (barrier) method (diaphragm, cervical cap, male condom). True abstinence is acceptable when this is in line with the patient’s preferred and usual lifestyle. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
8. Written informed consent given before any study-related assessment is performed.
9. Patient is able and willing to co-operate with the requirements of the study.
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E.4 | Principal exclusion criteria |
1. Pregnant or breast-feeding women.
2. Co-existing active infection, or received systemic anti-infectives within 4 weeks prior to the first dose of chemotherapy (Day 1 of Cycle 1).
3. Significant cardiovascular disease defined as any history of documented or current congestive heart failure, current high-risk uncontrolled arrhythmias, current uncontrolled angina pectoris, current clinically significant valvular disease, current evidence of transmural infarction on ECG, or any other significant cardiovascular disease which in the Investigator’s judgment contraindicates the planned therapy (especially doxorubicin).
4. Any malignancy other than the current breast cancer within the last 5 years prior to randomization, with the exception of cervical carcinoma in situ, non-melanoma skin cancer, or superficial bladder tumors (Ta, Tis, or T1) that have been successfully and curatively treated with no evidence of recurrent or residual disease.
5. Radiation therapy within 4 weeks prior to randomization into this study.
6. Concurrent anti-cancer therapy, including endocrine therapy, immunotherapy and monoclonal antibody therapy, and any concurrent treatment with bisphosphonates.
7. Prior bone marrow or stem cell transplantation.
8. Sickle cell disease.
9. Other investigational drug administration within 4 weeks prior to the first dose of chemotherapy (Day 1 of Cycle 1).
10. Previous exposure to filgrastim, lenograstim, or pegfilgrastim.
11. Known allergy to any of the study drugs, including chemotherapy agents.
12. Contraindication for use of corticosteroids.
13. Systemic corticosteroid therapy within 2 weeks prior to randomization into this study. The use of topical or inhaled corticosteroids within 2 weeks prior to randomization may be allowed at the discretion of the Investigator.
14. Any co-existing medical condition that in the Investigator’s judgment will substantially increase the risk associated with the patient’s participation in the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Duration of severe neutropenia (ANC < 0.5 x10^9/L) in Cycle 1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The length of severe neutropenia in Cycle 1 (given in days) will be determined via daily ANC assessments at the end of Cycle 1. |
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E.5.2 | Secondary end point(s) |
1. Duration of severe neutropenia (ANC < 0.5 x10^9/L) in Cycles 2, 3 and 4
2. Incidence of severe neutropenia in Cycle 1
3. Incidence of severe neutropenia in Cycle 2
4. Observed incidence of febrile neutropenia in Cycles 1 and 2
5. Overall incidence of febrile neutropenia in Cycles 1 and 2
6. Time to ANC recovery (reaching ANC ≥ 2 x10^9/L) in Cycles 1 and 2
7. Depth of ANC nadir in Cycles 1 and 2 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Length of severe neutropenia in Cycles 2-4 (days) will be determined via daily ANC assessments at end of Cycle 2-4.
2. Proportion of patients developing severe neutropenia will be determined via daily ANC assessments in Cycle 1.
3. Proportion of patients developing severe neutropenia will be determined via daily ANC assessments in Cycle 2-4.
4. and 5. Incidence of febrile neutropenia will be evaluated in Cycle 1-2.
6. Time to ANC recovery is the no. of days from the time of the first ANC value <0.5 10^9/L until the time of first ANC value after this, where the ANC value is ≥2.0 x 10^9/L.This will be evaluated in Cycle 1-2.
7. Depth of nadir defined as the change from baseline ANC value (value at Day-1,Cycle 1) to the lowest value in the cycle and evaluated for Cycle 1-2. |
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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 | 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 | 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 | 31 |
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 |
Russian Federation |
Serbia |
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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The date of the last protocol-specified visit/assessment for the last patient in the study or the date the study is closed by the Sponsor, whichever occurs first. |
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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 | 6 |
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 |