Phase III Study Comparing the Efficacy and Safety of LA-E... | NCT01516736

NCT01516736

Status Module

Sponsor/Collaborators Module

Name	Class
Sandoz GmbH	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
LA-EP2006	Experimental	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application.	Drug: LA-EP2006
Neulasta®	Active Comparator	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application.	Drug: Neulasta®

Interventions

Name	Type	Description	Arm Group Labels	Other Names
LA-EP2006	Drug	Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle LA-EP2006 is injected s.c. post chemotherapy application.

Outcomes Module

Primary Outcomes

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/l (grade 4 neutropenia).	21 days (Cycle 1 of chemotherapy treatment)

Secondary Outcomes

Measure	Description	Time Frame
Incidence of Febrile Neutropenia (FN)	FN was defined as 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.

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Sandoz Biopharmaceutical Clinical Development	Sandoz Biopharmaceuticals	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Sandoz Investigational Site		Hot Springs	Arkansas	71913	United States
Sandoz Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
27091420	Background	Blackwell K, Donskih R, Jones CM, Nixon A, Vidal MJ, Nakov R, Singh P, Schaffar G, Gascon P, Harbeck N. A Comparison of Proposed Biosimilar LA-EP2006 and Reference Pegfilgrastim for the Prevention of Neutropenia in Patients With Early-Stage Breast Cancer Receiving Myelosuppressive Adjuvant or Neoadjuvant Chemotherapy: Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2), a Phase III, Randomized, Double-Blind Trial. Oncologist. 2016 Jul;21(7):789-94. doi: 10.1634/theoncologist.2016-0011. Epub 2016 Apr 18.
28637287

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	LA-EP2006	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle LA-EP2006 is injected s.c. post chemotherapy application.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Patient demographics (FAS set)

Arm/Group Information

ID	Title	Description
BG000	LA-EP2006	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle LA-EP2006 is injected s.c. post chemotherapy application.
BG001	Neulasta®	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: 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.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

FAS

- ParticipantsOG000151
- ParticipantsOG001149

Title	Measurements
	OG0001.36± 1.133

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The primary objective of the study was to compare LA-EP2006 and Neulasta in terms of the DSN in Cycle 1. It was to be shown in a hierarchical way: that LA-EP2006 is equivalent (margin: ±1 day) to Neulasta® with respect to DSN duration in Cycle 1 and, if this was successfully established, that LA-EP2006 is non-inferior (margin: -0.6 days) to Neulasta® with respect to DSN duration in Cycle 1.	ANCOVA	The primary endpoints was analyzed with analysis of covariance (ANCOVA).	0.05		Mean Difference (Net)	-0.16			2-Sided	95	-0.40	0.08					Equivalence

Secondary

Incidence of Febrile Neutropenia (FN)

FN was defined as 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.

FAS set = full analysis set

Posted

Count of Participants

Participants

across all cycles (18 weeks)

ID	Title	Description
OG000	LA-EP2006	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle LA-EP2006 is injected s.c. post chemotherapy application.
OG001	Neulasta®	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: 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.

Units	Counts

Secondary

Number of Patients With at Least One Episode of Fever by Cycle and Across All Cycles

Fever was defined as an oral body temperature of ≥ 38.3°C. Fever episodes were described by maximum oral temperature and the number of patients who had fever at least once.

Patients with more than 1 event during the study (overall) are counted only once. FAS set = full analysis set

Posted

Count of Participants

Participants

across al cycles (18 weeks)

ID	Title	Description
OG000	LA-EP2006	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle LA-EP2006 is injected s.c. post chemotherapy application.
OG001	Neulasta®	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: 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.

Units	Counts
Participants

Secondary

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.

FAS set = full analysis set

Posted

Mean

Standard Deviation

10^9 cells/L

Cycle 1 (3 weeks)

ID	Title	Description
OG000	LA-EP2006	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle LA-EP2006 is injected s.c. post chemotherapy application.
OG001	Neulasta®	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: 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.

Units	Counts
Participants	OG000

Secondary

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.

FAS set = full analysis set

Posted

Count of Participants

Participants

Cycle 1 (3 weeks)

ID	Title	Description
OG000	LA-EP2006	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle LA-EP2006 is injected s.c. post chemotherapy application.
OG001	Neulasta®	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: 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.

Units	Counts
Participants	OG000

Secondary

Time to ANC Recovery in Days in Cycle 1

Time to absolute neutrophil count (ANC) recovery was defined as the time in days from ANC nadir until the patient's ANC had increased to ≥ 2 × 10^9 cells/L after the nadir in Cycle 1.

FAS set = full analysis set

Posted

Mean

Standard Deviation

days

across Cycle 1 (3 weeks)

ID	Title	Description
OG000	LA-EP2006	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle LA-EP2006 is injected s.c. post chemotherapy application.
OG001	Neulasta®	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: 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.

Units	Counts
Participants

Secondary

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".

Patients with more than 1 event during the study (overall) are counted only once. FAS set = full analysis set

Posted

Count of Participants

Participants

across all cycles (18 weeks)

ID	Title	Description
OG000	LA-EP2006	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle LA-EP2006 is injected s.c. post chemotherapy application.
OG001	Neulasta®	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: 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.

Units	Counts

Secondary

Mortality Due to Infection

Number of patients with death due to infections

FAS set = full analysis set

Posted

Count of Participants

Participants

Study course (19 weeks)

ID	Title	Description
OG000	LA-EP2006	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle LA-EP2006 is injected s.c. post chemotherapy application.
OG001	Neulasta®	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: 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.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	LA-EP2006	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle LA-EP2006 is injected s.c. post chemotherapy application.	3	155	29	155	147	155
EG001	Neulasta®	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: 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.	2	153	32	153	144	153

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	Systematic Assessment	EG00016 affected155 at risk EG00119 affected153 at risk
Neutropenia	Blood and lymphatic system disorders	Systematic Assessment	EG0004 affected155 at risk EG0016 affected153 at risk
Thrombocytopenia	Blood and lymphatic system disorders	Systematic Assessment	EG0001 affected155 at risk EG0011 affected153 at risk
Anemia	Blood and lymphatic system disorders	Systematic Assessment	EG0001 affected155 at risk EG0010 affected153 at risk
Abdominal pain	Gastrointestinal disorders	Systematic Assessment	EG0003 affected155 at risk EG0015 affected153 at risk
Diarrhea	Gastrointestinal disorders	Systematic Assessment	EG0002 affected155 at risk EG0015 affected153 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0002 affected155 at risk EG0014 affected153 at risk
Abdominal discomfort	Gastrointestinal disorders	Systematic Assessment	EG0001 affected155 at risk EG0010 affected153 at risk
Constipation	Gastrointestinal disorders	Systematic Assessment	EG0000 affected155 at risk EG0011 affected153 at risk
Gastric ulcer hemorrhage	Gastrointestinal disorders	Systematic Assessment	EG0001 affected155 at risk EG0010 affected153 at risk
Gastritis	Gastrointestinal disorders	Systematic Assessment	EG0001 affected155 at risk EG0010 affected153 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0000 affected155 at risk EG0011 affected153 at risk
Peptic ulcer	Gastrointestinal disorders	Systematic Assessment	EG0000 affected155 at risk EG0011 affected153 at risk
Proctalgia	Gastrointestinal disorders	Systematic Assessment	EG0000 affected155 at risk EG0011 affected153 at risk
Stomatitis	Gastrointestinal disorders	Systematic Assessment	EG0000 affected155 at risk EG0011 affected153 at risk
Gastroenteritis	Infections and infestations	Systematic Assessment	EG0000 affected155 at risk EG0012 affected153 at risk
Bronchitis	Infections and infestations	Systematic Assessment	EG0000 affected155 at risk EG0011 affected153 at risk
Clostridium difficile infection	Infections and infestations	Systematic Assessment	EG0001 affected155 at risk EG0010 affected153 at risk
Mastitis	Infections and infestations	Systematic Assessment	EG0000 affected155 at risk EG0011 affected153 at risk
Neutropenic sepsis	Infections and infestations	Systematic Assessment	EG0000 affected155 at risk EG0011 affected153 at risk
Staphylococcal infection	Infections and infestations	Systematic Assessment	EG0000 affected155 at risk EG0011 affected153 at risk
Upper respiratory tract infection	Infections and infestations	Systematic Assessment	EG0000 affected155 at risk EG0011 affected153 at risk
Asthenia	General disorders	Systematic Assessment	EG0000 affected155 at risk EG0013 affected153 at risk
Pyrexia	General disorders	Systematic Assessment	EG0001 affected155 at risk EG0012 affected153 at risk
Non-cardiac chest pain	General disorders	Systematic Assessment	EG0000 affected155 at risk EG0011 affected153 at risk
Atrial fibrillation	Cardiac disorders	Systematic Assessment	EG0000 affected155 at risk EG0011 affected153 at risk
Cardiac arrest	Cardiac disorders	Systematic Assessment	EG0001 affected155 at risk EG0010 affected153 at risk
Cardio-respiratory arrest	Cardiac disorders	Systematic Assessment	EG0001 affected155 at risk EG0010 affected153 at risk
Pericardial hemorrhage	Cardiac disorders	Systematic Assessment	EG0001 affected155 at risk EG0010 affected153 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 affected155 at risk EG0010 affected153 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected155 at risk EG0011 affected153 at risk
Organizing pneumonia	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected155 at risk EG0011 affected153 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected155 at risk EG0011 affected153 at risk
Dehydration	Metabolism and nutrition disorders	Systematic Assessment	EG0002 affected155 at risk EG0010 affected153 at risk
Decreased appetite	Metabolism and nutrition disorders	Systematic Assessment	EG0001 affected155 at risk EG0010 affected153 at risk
Convulsion	Nervous system disorders	Systematic Assessment	EG0001 affected155 at risk EG0010 affected153 at risk
Dizziness	Nervous system disorders	Systematic Assessment	EG0001 affected155 at risk EG0010 affected153 at risk
Lethargy	Nervous system disorders	Systematic Assessment	EG0001 affected155 at risk EG0010 affected153 at risk
Neuropathy peripheral	Nervous system disorders	Systematic Assessment	EG0001 affected155 at risk EG0010 affected153 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected155 at risk EG0012 affected153 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 affected155 at risk EG0011 affected153 at risk
Lung neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0001 affected155 at risk EG0010 affected153 at risk
Hypotension	Vascular disorders	Systematic Assessment	EG0000 affected155 at risk EG0011 affected153 at risk
Shock hemorrhagic	Vascular disorders	Systematic Assessment	EG0001 affected155 at risk EG0010 affected153 at risk
Eye irritation	Eye disorders	Systematic Assessment	EG0000 affected155 at risk EG0011 affected153 at risk
Hepatic hemorrhage	Hepatobiliary disorders	Systematic Assessment	EG0001 affected155 at risk EG0010 affected153 at risk
Hepatic necrosis	Hepatobiliary disorders	Systematic Assessment	EG0001 affected155 at risk EG0010 affected153 at risk
Neutrophil count decreased	Investigations	Systematic Assessment	EG0001 affected155 at risk EG0010 affected153 at risk
Platelet count decreased	Investigations	Systematic Assessment	EG0001 affected155 at risk EG0010 affected153 at risk
White blood cell count decreased	Investigations	Systematic Assessment	EG0001 affected155 at risk EG0010 affected153 at risk
Completed suicide	Psychiatric disorders	Systematic Assessment	EG0000 affected155 at risk EG0011 affected153 at risk
Renal failure	Renal and urinary disorders	Systematic Assessment	EG0001 affected155 at risk EG0010 affected153 at risk
Renal hemorrhage	Renal and urinary disorders	Systematic Assessment	EG0001 affected155 at risk EG0010 affected153 at risk
Uterine hemorrhage	Reproductive system and breast disorders	Systematic Assessment	EG0000 affected155 at risk EG0011 affected153 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Gastrointestinal disorders	Gastrointestinal disorders	Systematic Assessment	EG000111 affected155 at risk EG001100 affected153 at risk
General disorders and administration site conditions	General disorders	Systematic Assessment	EG00093 affected155 at risk EG00190 affected153 at risk
Blood and lymphatic system disorders	Blood and lymphatic system disorders	Systematic Assessment	EG00077 affected155 at risk EG00172 affected153 at risk
Skin and subcutaneous tissue disorders	Skin and subcutaneous tissue disorders	Systematic Assessment	EG00079 affected155 at risk EG00171 affected153 at risk
Musculoskeletal and connective tissue disorders	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG00045 affected155 at risk EG00140 affected153 at risk
Nervous system disorders	Nervous system disorders	Systematic Assessment	EG00032 affected155 at risk EG00125 affected153 at risk
Infections and infestations	Infections and infestations	Systematic Assessment	EG00024 affected155 at risk EG00127 affected153 at risk
Respiratory, thoracic and mediastinal disorders	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG00021 affected155 at risk EG00118 affected153 at risk
Metabolism and nutrition disorders	Metabolism and nutrition disorders	Systematic Assessment	EG00014 affected155 at risk EG00121 affected153 at risk
Investigations	Investigations	Systematic Assessment	EG00017 affected155 at risk EG00114 affected153 at risk
Vascular disorders	Vascular disorders	Systematic Assessment	EG00014 affected155 at risk EG0018 affected153 at risk
Reproductive system and breast disorders	Reproductive system and breast disorders	Systematic Assessment	EG00010 affected155 at risk EG0015 affected153 at risk
Eye disorders	Eye disorders	Systematic Assessment	EG0008 affected155 at risk EG0016 affected153 at risk
Injury, poisoning and procedural complications	Injury, poisoning and procedural complications	Systematic Assessment	EG0004 affected155 at risk EG0015 affected153 at risk
Renal and urinary disorders	Renal and urinary disorders	Systematic Assessment	EG0001 affected155 at risk EG0015 affected153 at risk

ID	Term
D001943	Breast Neoplasms
D009503	Neutropenia

Ancestor Terms

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D000380	Agranulocytosis
D007970	Leukopenia
D000095542	Cytopenia
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D007960	Leukocyte Disorders

ID	Term
C455861	pegfilgrastim

ParticipantsBG002308

The testing procedure was set up in a hierarchical structure, where first equivalence between LA-EP2006 and Neulasta® was assessed (margin ±1 day) and only if this was successfully established, non-inferiority between the two products was tested using a tighter margin of -0.6 days.