Phase III Study Comparing the Efficacy and Safety of LA-EP2006 and Neulasta®

Study Overview
=================
Brief Summary
-----------------
The study will assess the efficacy of LA-EP2006 compared to Neulasta® with respect to the mean duration of severe neutropenia during treatment with myelosuppressive chemotherapy in breast cancer patients.

Detailed Description
-----------------
This randomized, double-blind trial compared the proposed biosimilar LA-EP2006 with the reference Neulasta® in women (≥18 years) receiving chemotherapy for breast cancer. Therefore patients were randomized to receive LA-EP2006 (n = 159) or the reference product (n = 157) for ≤6 cycles of (neo)-adjuvant TAC (docetaxel 75mg/m^2, doxorubicin 50 mg/m^2, and cyclophosphamide 500mg/m^2) chemotherapy. The primary end point was the duration of severe neutropenia (DSN) during Cycle 1 (defined as number of consecutive days with absolute neutrophil count <0.5 × 10^9/l). The equivalence was confirmed if 95% CIs were within a ±1 day margin. LA-EP2006 was equivalent to the reference product in DSN (difference: 0.07 days; 95% CI [-0.12, 0.26]). Further, LA-EP2006 and the reference Neulasta® showed no clinically meaningful differences regarding efficacy and safety.

Official Title
-----------------
A Randomized, Double-blind, Parallel-group, Multi-center Phase 3 Comparative Study Investigating Efficacy and Safety of LA-EP2006 and Neulasta® in Breast Cancer Patients Treated With Myelosuppressive Chemotherapy

Conditions
-----------------
Neutropenic Complications, Breast Neoplasms, Chemotherapy-induced Neutropenia, Chemotherapeutic Toxicity

Intervention / Treatment
-----------------
* Drug: LA-EP2006
* Drug: Neulasta®


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: histologically proven breast cancer eligible for six cycles of neoadjuvant or adjuvant chemotherapy Exclusion Criteria: concurrent or prior chemotherapy for breast cancer concurrent or prior anti-cancer treatment for breast cancer such as endocrine therapy, immunotherapy, monoclonal antibodies, and/or biological therapy concurrent prophylactic antibiotics previous therapy with any G-CSF (granulocyte-colony stimulating factor) product Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Neulasta®<br>During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. | Drug: Neulasta®<br>* Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.<br>* Other names: pegfilgrastim;|
| Experimental: LA-EP2006<br>During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. | Drug: LA-EP2006<br>* Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.<br>* Other names: pegfilgrastim;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Duration of Severe Neutropenia (DSN) During Cycle 1 of Chemotherapy | Mean duration of severe neutropenia, defined as number of consecutive days with ANC <0.5 × 10^9 cells/L (grade 4 neutropenia). | 21 days (Cycle 1 of chemotherapy treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Febrile Neutropenia (FN) | FN was defined as an oral temperature ≥ 38.3°C while having an absolute neutrophil count (ANC) < 0.5 × 10^9 cells/L. Serious treatment-emergent adverse events (TEAEs) were reconciled with the fever and ANC results recorded in the patient diary and CRF and therefore only the serious TEAEs of FN (febrile neutropenia, neutropenic sepsis) were taken into account. | across all cycles (18 weeks) | 
| Number of Patients With at Least One Episode of Fever by Cycle and Across All Cycles | Fever was defined as an oral temperature ≥ 38.3°C. Fever episodes were characterized by maximum oral temperature and the number of patients who had fever at least once. | across al cycles (18 weeks) | 
| Depth of ANC Nadir in Cycle 1 | The depth of ANC nadir was defined as the patient's lowest ANC (10^9 cells/L) in Cycle 1. Only the evaluable patients with a depth of ANC in Cycle 1 are given. | Cycle 1 (3 weeks) | 
| Number of Patients With ANC Nadir Per Day in Cycle 1 | Numbers of patients with ANC nadir based per day during Cycle 1 are given. | Cycle 1 (3 weeks) | 
| Time to ANC Recovery in Days in Cycle 1 | Time to absolute neutrophil count (ANC) recovery in Cycle 1 was defined as the time in days from ANC nadir until the patient's ANC had increased to ≥ 2 × 10^9 cells/L. Only the evaluable patients with a depth of ANC in Cycle 1 and a later increase of ANC ≥ 2 × 10^9 cells/L are given. | across Cycle 1 (3 weeks) | 
| Frequency of Infections by Cycle and Across All Cycles | The number of patients with infections was recorded for each cycle and across all cycles. Infections were identified by the AE documentation page selecting all events coded with System Organ Class Infections and Infestations. | across all cycles (18 weeks) | 
| Mortality Due to Infection | Number of patients with death due to infections | Study course (41 weeks) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
biosimilars, Pegfilgrastim,, G-CSF,, neutropenia,, breast cancer,, myelosuppressive chemotherapy,, supportive care, granulocyte-colony-stimulating factor