E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 20.0 |
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.1.3 | 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 present trial is to assess the efficacy, safety, and tolerability of three doses of GX-G3 with the aim of selecting the optimal dose by comparing each of the doses with the reference product (Neulasta®). The major aim for including one group with delayed administration (250 μg/kg of GX-G3 on day 3 after R-CHOP dosing) is to evaluate the optimal point in time for dosing of the test product. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the present trial are to investigate the pharmacokinetics of GX-G3 and the safety of the immunogenicity of GX-G3. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
[1] Male or female patients ≥18 years of age (Republic of Korea: ≥19 years of age) [2] Patients with Non-Hodgkin’s Lymphoma confirmed by immunohistochemistry or flow cytometry: - stage III-IV follicular lymphoma (Ann Arbor staging1) OR - CD20 positive diffuse large B cell non-Hodgkin lymphoma* [3] Patients who fulfil the criteria for receiving R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) therapy for at least 2 cycles of 21 days each [4] Patients who are about to receive the first two cycles of R-CHOP therapy within a series of several cycles (previous exposure to R-CHOP is allowed but in another series of cycles more than 3 months before randomization in the present trial) [5] ECOG performance status 0, 1, or 2 [6] Life expectancy with treatment of at least 6 months [7] Patients willing and able (e.g. mental and physical condition) to participate in all aspects of the study, attending scheduled visits, and compliance with protocol requirements as evidenced by providing signed written informed consent *Stage III-IV |
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E.4 | Principal exclusion criteria |
[1] History of hypersensitivity or intolerance to the active substance or any of the excipients of the study medication (e.g. sorbitol, fructose, or to latex) or to any of the components of R-CHOP therapy [2] Known hypersensitivity to E coli-derived products (e.g., Filgrastim, HUMULIN® Insulin, L-Asparaginase, HUMATROPE® Growth Hormone, INTRON A®) [3] Burkitt's or B-lymphoblastic lymphoma [4] Non-Hodgkin’s Lymphoma with CNS involvement [5] Active infection requiring treatment with systemic (intravenous or oral) antiinfectives (antibiotic, antifungal, antiviral) at baseline [6] Exposure to R-CHOP therapy or pegfilgrastim within the last 3 months before randomization [7] Known lack of neutropenia in patients previously exposed to R-CHOP therapy [8] Positive serologic findings for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibodies [9] Any premalignant myeloid condition or any malignancy with myeloid characteristics (e.g., myelodysplastic syndromes, acute or chronic myelogenous leukaemia) [10] Prior malignancy within the last 5 years, with the exception of surgically cured basal cell carcinoma, squamous skin cell carcinoma, or in situ carcinoma of the cervix [11] Prior bone marrow or stem cell transplantation [12] Severe hepatic impairment: serum bilirubin above 51.3 μmol/l (3 mg/dl) or serum albumin below 28 g/l (2.8 g/dl) [13] Baseline neutrophil count <1.5 x 109/l or platelet count <100 x 109/l [14] Demyelinating form of Charcot-Marie-Tooth syndrome [15] Any of the following during the last month before randomization: pneumonia, pulmonary oedema, interstitial lung disease, lung infiltrations [16] Sickle cell trait or sickle cell disease [17] Major surgery within 2 weeks prior to randomization [18] Patient is currently enrolled in, or has completed less than 30 days before the screening examination of the present trial another clinical trial with an investigational drug [19] Previous enrolment in this study [20] Women of childbearing potential unable or unwilling to undergo pregnancy tests and practice adequate contraceptive measures*. Reliable methods for women are hormonal contraceptives**, surgical intervention (e.g. tubal ligation), intrauterine device (IUD) and sexual abstinence [21] Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope and possible consequences of the study [22] Alcohol/drug dependence or abuse (excluding tobacco abuse) [23] Unreliability or lack of cooperation. [24] Urinary outflow obstruction [25] Impaired cardiac function: myocardial insufficiency, recent (last 6 months) myocardial infarction, severe arrhythmias [26] Any other condition of the patient (e.g., serious or unstable medical or psychological condition, acute psychosis, severe and long-lasting febrile neutropenia) that in the opinion of the investigator may compromise evaluation of the study treatment or may jeopardize patient’s safety, compliance or adherence to protocol requirements [27] Pregnant or breast-feeding women [28] Any change in the dosage of R-CHOP treatment after the first cycle of the trial
*Highly effective contraceptive measures are to be used up to 36 days after administration of study medication in cycle 2. **Only the following hormonal contraceptives are allowed: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints in the present trial are time to recover from severe neutropenia (defined as ANC <0.5x10^9/l) to a target ≥0.5x10^9/l after each administration of R-CHOP chemotherapy in cycles 1 and 2. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After conclusion of the clinical part of the trial and database lock. |
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E.5.2 | Secondary end point(s) |
- time to recover from severe neutropenia (defined as ANC <0.5x10^9/l) to a target ≥0.5x10^9/l after each administration of R-CHOP chemotherapy in cycles 1 and 2 - total duration of severe neutropenia in chemotherapy induction cycles 1 and 2 - time to recover from severe neutropenia (defined as ANC <0.5x10^9/l) to a target ≥1x10^9/l and ≥2x10^9/l after each administration of R-CHOP chemotherapy in cycles 1 and 2 - incidence of febrile neutropenia - incidence of very severe neutropenia (defined as <0.1x10^9/l) - incidence of infections |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After conclusion of the clinical part of the trial and database lock. |
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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 | 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 | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | 5 |
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 | 9 |
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 |
Korea, Republic of |
Turkey |
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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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LVLS. Final examination will be performed up to 7 days after end of 2nd cycle. |
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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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |