E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
CD20 positive B-cell non-Hodgkin lymphoma |
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E.1.1.1 | Medical condition in easily understood language |
CD20 positive B-cell non-Hodgkin lymphoma |
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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 | HLGT |
E.1.2 | Classification code | 10025320 |
E.1.2 | Term | Lymphomas non-Hodgkin's B-cell |
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 evaluate the efficacy of ABP 798 compared with rituximab |
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E.2.2 | Secondary objectives of the trial |
To assess the pharmacokinetics (PK), pharmacodynamics, safety, tolerability, and immunogenicity of ABP 798 compared with rituximab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Males and females 18 years of age and older
Histological confirmed (by lymph node or extranodal region biopsy), Grade 1, 2, 3a follicular B-cell NHL expressing CD20 within 12 months before randomization
Stage 2, 3, or 4 (per Cotswold’s Modification of Ann Arbor Staging System) with measurable disease (per International Working Group) • subjects must have a baseline scan (computed tomography [CT]) of the neck (if palpable lymph node > 1.0 cm), chest, abdomen, and pelvis to assess disease burden within 6 weeks before randomization • subjects must have had a baseline bone marrow biopsy within 12 months before randomization. Previously confirmed positive bone marrow involvement does not need to be repeated for purposes of screening.
Low tumor burden based on the Groupe d'Etudes des Lymphomes Folliculaires (GELF) criteria -largest nodal or extranodal mass ≤ 7 cm -no more than 3 nodal sites with diameter > 3 cm -no splenomegaly > 16 cm by CT scan and no symptomatic splenomegaly -no significant pleural or peritoneal serous effusions by CT -lactate dehydrogenase ≤ upper limit of normal (ULN) -no B symptoms (night sweats, fever [temperature > 38°C], weight loss > 10% in the previous 6 months) 5. Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1.
Blood counts: • absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1,500/μL) • lymphocytes < 1.5 x the ULN • platelets ≥ 100 x 109/L (100,000/μL) • hemoglobin ≥ 10.0 g/dL
Adequate hepatic function as defined by: • aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2 × ULN
Adequate renal function as defined by creatinine < 1.5 x ULN or estimated creatinine clearance ≥ 50 mL/min calculated by the Cockcroft-Gault method
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E.4 | Principal exclusion criteria |
Diffuse large cell component and/or Grade 3b follicular NHL
History or known presence of central nervous system metastases
Malignancy other than NHL within 5 years (except treated in-situ cervical cancer, or squamous or basal cell carcinoma of the skin)
Any of the following in the 6 months before randomization: • clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure [New York Heart Association ≥ Class III], serious uncontrolled cardiac arrhythmia); peripheral vascular disease, cerebrovascular accident, or transient ischemic attack in the previous 6 months
Medically uncontrolled hypertension or systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg
Known active or history of active tuberculosis (TB)
Positive for hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C virus antibody at screening
Known to be human immunodeficiency virus positive
Recent infection requiring a course of systemic anti-infective agents that was completed ≤ 7 days before randomization (with the exception of uncomplicated urinary tract infection)
Other investigational procedures that can impact the study data, results, or patient safety while participating in this study are excluded; participation in observational studies is allowed.
Subject is currently enrolled in or has not yet completed at least 30 days or 5 half-lives (whichever is longer) since ending other investigational device or drug study(s), including vaccines, or subject is receiving other investigational agent(s)
Previous use of either commercially available or investigational chemotherapy, biological, or immunological therapy for NHL (including rituximab or biosimilar rituximab, or other anti-CD20 treatments)
Systemic corticosteroid use within 3 months before randomization (inhaled are allowable)
Live vaccines within 28 days prior to the first dose of IP
History of neurologic symptoms suggestive of central nervous system demyelinating disease
Woman of childbearing potential who is pregnant or is breastfeeding
Woman of childbearing potential who does not consent to use highly effective methods of birth control (eg, true abstinence, sterilization, birth control pills, Depo Provera injections, or contraceptive implants) during treatment and for an additional 12 months after the last administration of the protocol specified-treatment
Man with a partner of childbearing potential who does not consent to use highly effective methods of birth control (eg, true abstinence, vasectomy, or a condom in combination with hormonal birth control or barrier methods used by the woman) during treatment and for an additional 12 months after the last administration of the protocol specified treatment
Subject has known sensitivity to any of the products to be administered during the study, including mammalian cell derived drug products
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoint: (risk difference [RD] of overall response rate [ORR] by week 28 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Clinical disease assessment & PK sampling: v1 (D1), v2 (w2), v3 (w3), v4 (w4), v5 (w12), v6 (w20), end of study (w28)
CT Scan: screening, v5 (w12), end of study (w28)
Bone marrow biopsy: screening, end of study (w28)
Serum chemistry & Hematology: screening, v1 (D1), v2 (w2), v3 (w3), v4 (w4), v5 (w12), v6 (w20), end of study (w28)
Pharmacodynamic (CD19) and IgG and IgM: v1 (D1), v2 (w2), v3 (w3), v4 (w4), end of study (w28)
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E.5.2 | Secondary end point(s) |
Secondary Efficacy Criteria: Risk difference (RD) of ORR at week 12
Pharmacokinetic and Pharmacodynamic Criteria: • Serum concentrations at predose and immediately after the end of infusion at week 12. • Percent of subjects with complete depletion of CD19 cell count, from baseline to study day 8, and total IgG and IgM antibody levels
Safety Criteria: • Treatment-emergent adverse events (AEs) and serious AEs (SAEs) and events of interest (EOIs) • Clinically significant changes in laboratory values and vital signs • Incidence of anti-drug antibodies • On study progression-free survival (PFS) • On study overall survival (OS)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Clinical disease assessment & PK sampling: v1 (D1), v2 (w2), v3 (w3), v4 (w4), v5 (w12), v6 (w20), end of study (w28)
CT Scan: screening, v5 (w12), end of study (w28)
Bone marrow biopsy: screening, end of study (w28)
Serum chemistry & Hematology: screening, v1 (D1), v2 (w2), v3 (w3), v4 (w4), v5 (w12), v6 (w20), end of study (w28)
Pharmacodynamic (CD19) and IgG and IgM: v1 (D1), v2 (w2), v3 (w3), v4 (w4), end of study (w28)
Antidrug antibodies: v1 (D1), v5 (w12), v6 (w20), end of study (w28)
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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 | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity; Tolerance |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 | 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 78 |
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 |
Australia |
Bulgaria |
Canada |
Colombia |
Czech Republic |
France |
Georgia |
Germany |
Greece |
India |
Israel |
Italy |
Japan |
Korea, Republic of |
Mexico |
Poland |
Romania |
Russian Federation |
Spain |
Ukraine |
United States |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |