E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
CD20 positive Diffuse Large B cell Lymphoma (DLBCL) patients diagnosed according to WHO classification of lymphomas, eligible for rituximab treatment according to MabThera SmPC with life expectance at least 6 months |
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E.1.1.1 | Medical condition in easily understood language |
Diffuse Large B-cell Lymphoma (DLBCL) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
Primary objective of the study is to demonstrate biosimilarity between MabionCD20 (MABION SA) and the reference product: MabThera (rituximab by Hoffman-La Roche) in patients with CD20-positive diffuse large B-cell lymphoma, based on evaluation of primary endpoints. |
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E.2.2 | Secondary objectives of the trial |
To demonstrate biosimilarity between MabionCD20 (MABION SA) and the reference product MabThera (rituximab by Hoffman-La Roche) in patients with CD20-positive diffuse large B-cell lymphoma based on comparative analysis of the pharmacodynamic parameters, pharmacokinetic parameters, efficacy endpoints, comparative safety and immunogenicity. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients with histological confirmed CD20 positive diffuse large B cell lymphoma (DLBCL);
Patients that had been diagnosed according to the WHO classification;
Performance status ≤ 2 on the ECOG/WHO scale, performance status of 3 will be accepted if impairment is caused by DLBCL complications and improvement is expected once therapy is initiated;
Patients eligible for rituximab treatment according to MabThera indications;
Life expectance at least 6 months;
Laboratory values within normal range unless abnormalities are related to lymphoma.
A negative serum and urine pregnancy test prior to treatment.
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E.4 | Principal exclusion criteria |
Life expectance less than 6 months;
Any chemotherapy, radiotherapy, immunotherapy, biologic, investigational or hormonal therapy for treatment of lymphoma within 28 days prior to treatment;
Rituximab, other anti-CD20 mAb drug treatment, treatment with any cell depleting therapies (e.g., anti-CD4, anti-CD5, anti-CD3, anti-CD19, anti CD11a, anti-CD22, BLys/BAFF) within 1,5 years prior to screening
History of other invasive malignancy within 5 years except for localized/in situ carcinomas such as non-melanoma skin cancer or cervical carcinoma in situ;
Primary or secondary immunodeficiency;
Evidence of significant uncontrolled concomitant disease such as, but not limited to, nervous system, renal, hepatic, endocrine, or gastrointestinal disorders within 5 years prior to screening which, in the Investigator's opinion, would preclude subject participation;
Active infections: known active bacterial, viral, fungal, mycobacterial, other infection (including tuberculosis, sepsis, opportunistic infections) but excluding fungal infections of nail beds;
III or IV class of the New York Heart Association (NYHA) Classification;
Pregnancy and lactation (positive serum pregnancy test for women of child bearing age);
Recent vaccination (< 4 weeks prior treatment);
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E.5 End points |
E.5.1 | Primary end point(s) |
Area under the plasma concentration-time curve from time zero to final time point (AUC 0-t) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
measured after the first administration (Week 1) until the second administration at Week 4 and measured at steady state after the fifth administration (Week 13) until Week 26 |
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E.5.2 | Secondary end point(s) |
Area under the plasma concentration-time curve from time zero to final time point,
Pharmacodynamic endpoint (B-cel concentration in blood),
efficacy and safety of Investigational Medicinal Product
immunogenicity |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Drug concentration (AUC) measured after the first administration (Week 1) until Week 26, before 8 administration and after 5 and 8 administration
Pharmacodynamic endpoints measured from the first administration until week 26
Efficacy and safety endpoints measured at week 26
Immunogenicity endpoint measured at week 26 |
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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 | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
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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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 |
Bosnia and Herzegovina |
Croatia |
Georgia |
Moldova, Republic of |
Poland |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
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 | 15 |