Clinical Trials Register

Summary
EudraCT Number:	2011-002678-21
Sponsor's Protocol Code Number:	APO-Peg-03
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-11-24
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2011-002678-21

A.3

Full title of the trial

A PHASE III, RANDOMIZED, ACTIVE CONTROLLED, ASSESSORBLINDED
STUDY OF SAFETY AND EFFICACY OF PEGYLATED APOFILGRASTIM VERSUS US AND EU LICENSED NEULASTA® IN SUBJECTS WITH STAGE IIA, IIB OR IIIA BREAST CANCER RECEIVING TAC ANTICANCER CHEMOTHERAPY IN ADJUVANT SETTING

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

STUDY OF SAFETY AND EFFICACY OF PEGYLATED APOFILGRASTIM VERSUS US AND EU LICENSED NEULASTA® IN PATIENTS WITH BREAST CANCER

A.4.1

Sponsor's protocol code number

APO-Peg-03

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Apotex Inc
B.1.3.4	Country	Canada
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Apotex Inc
B.4.2	Country	Canada
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Accelsiors CRO and Consultancy Services
B.5.2	Functional name of contact point	Clinical Trials Info
B.5.3	Address:
B.5.3.1	Street Address	50 Miskolci Ut
B.5.3.2	Town/ city	Budapest
B.5.3.3	Post code	1147
B.5.3.4	Country	Hungary
B.5.4	Telephone number	+3612990091
B.5.5	Fax number	+3612990096
B.5.6	E-mail	clinicaltrials@accelsiors.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Pegylated Apo-Filgrastim
D.3.2	Product code	Pegylated Apo-Filgrastim
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PEGFILGRASTIM
D.3.9.1	CAS number	208265-92-3
D.3.9.2	Current sponsor code	Pegylated Apo-Filgrastim
D.3.9.3	Other descriptive name	Granulocyte Colony Stimulating Factors
D.3.9.4	EV Substance Code	SUB16451MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Neulasta
D.2.1.1.2	Name of the Marketing Authorisation holder	Amgen Europe BV
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PEGFILGRASTIM
D.3.9.1	CAS number	208265-92-3
D.3.9.4	EV Substance Code	SUB16451MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Neulasta
D.2.1.1.2	Name of the Marketing Authorisation holder	Amgen Inc.
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PEGFILGRASTIM
D.3.9.1	CAS number	208265-92-3
D.3.9.4	EV Substance Code	SUB16451MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Febrile neutropenia in breast cancer patients undergoing TAC chemotherapy

E.1.1.1

Medical condition in easily understood language

Low white blood cell counts in breast cancer patients undergoing chemotherapy

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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10016288
E.1.2	Term	Febrile neutropenia
E.1.2	System Organ Class	10005329 - Blood and lymphatic system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To demonstrate an equivalent efficacy of Pegylated Apo‐Filgrastim as
compared to each of the commercially available US and EU licensed
Neulasta® in patients suffering from early breast cancer and receiving TAC
(docetaxel, doxorubicin, cyclophosphamide) anticancer chemotherapy in
adjuvant setting.

E.2.2

Secondary objectives of the trial

• To assess the safety of Pegylated Apo‐Filgrastim as compared to that
of commercially available US and EU licensed Neulasta® when administered through 6 cycles of TAC anticancer chemotherapy
• To assess the potential antigenicity of Pegylated Apo‐Filgrastim during the chemotherapy and 30 weeks after the completion of chemotherapy

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Female, ≥18 of age, suitable and intended to undergo adjuvant TAC (docetaxel, doxorubicin, cyclophosphamide) chemotherapy.
2. Body weight within 40 and 120 kg
3. Subjects within 60 days of complete surgical resection of the primary breast tumor: either lumpectomy or mastectomy with sentinel lymph node biopsy or axillary dissection, with clear margins for both invasive and ductal carcinoma in situ (DCIS)
4. Stage IIA, IIB or IIIA breast cancer
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
6. Absolute neutrophil count (ANC) ≥1,5 x 109/L; platelet count ≥100 x 109/L
7. Adequate renal (serum creatinine <1,5 x upper limit of normal (ULN)) and hepatic function (bilirubin < ULN, transaminases and alkaline phosphatase (AP) <1,5 x ULN)
8. Normal cardiac function evidenced by a left ventricle ejection fraction (LVEF) ≥55%
9. No evidence of metastatic disease
10. Baseline bilateral mammography (or other scan to exclude cancer on the contralateral breast)
11. Subjects must not intend to conceive during or shortly after the study. They must be either post‐menopausal, surgically incapable of bearing children, or practicing an acceptable method of birth control (e.g., hormonal contraceptives, intrauterine device, or spermicide and barrier) and be willing to continue the same method of birth control during the entire course of the study
12. Females of child‐bearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test before the first dose of study medication
13. Willing and able to give written informed consent
14. Willing and able to undergo procedures required by this protocol.

E.4

Principal exclusion criteria

1. Bilateral breast cancer (concomitant or prior) except in situ lesion, either ductal or lobular, of the contralateral breast
2. History of severe hypersensitivity reaction to medications intended to use in this protocol
3. Prior chemotherapy (either adjuvant or neoadjuvant) for this breast cancer
4. History of myocardial infarction, heart failure, uncontrolled angina, severe uncontrolled arrhythmias, pericardial disease, or electrocardiographic evidence of acute ischemic changes
5. Immunotherapy, hormonal therapy (e.g. tamoxifen or aromatase inhibitors), Herceptin (trastuzumab) concurrently or within 30 days of screening
6. Concurrent radiation therapy
7. Investigational therapy concurrently or within 30 days of screening
8. Peripheral neuropathy >Grade 1
9. Major organ allograft or condition requiring chronic immunosuppression (i.e. kidney, liver, lung, heart, bone marrow transplant, or autoimmune diseases). Patients who received corneal transplants or cadaver skin or bone transplants are eligible.
10. Serious uncontrolled intercurrent medical or psychiatric illness, including serious viral (including clinically defined acquired immunodeficiency syndrome ‐ AIDS), bacterial or fungal infection; or history of uncontrolled seizures, or diabetes, or central nervous system disorders deemed by the Investigator to be clinically
significant, precluding informed consent
11. Active hepatitis B or hepatitis C with abnormal liver function tests (LFTs) or is known to be HIV positive
12. History of other malignancy within the last 5 years (except cured basal cell carcinoma of skin, carcinoma in situ of uterine cervix or DCIS)
13. Pregnancy or breastfeeding.

E.5 End points

E.5.1

Primary end point(s)

Duration of severe neutropenia (DSN) in cycle 1. Severe neutropenia is
defined as occurrence of ANC below 0,5 x 109/L.

E.5.1.1

Timepoint(s) of evaluation of this end point

D0,D1,D3,D5,D6,D8 and D10-15

E.5.2

Secondary end point(s)

Secondary efficacy endpoints:
• The frequency of grade 3 and 4 severe neutropenia (ANC below 1,0 x
109/L and 0,5 x 109/L, respectively)
• The depth of ANC nadir in cycles 1
• The time to the post nadir ANC recovery (ANC ≥2,0 X 109) in cycle 1
• The rates of Febrile Neutropenia (FN) by cycle and across the cycles.
The definition of FN used for the purpose of this protocol will be,
single temperature: ≥38,3°C measured orally or ≥38,0°C for over 1
hour; neutropenia: ANC <0,5 X 109/L or <1 X 109/L and a predicted
decline to ≤0,5 X 109/L over the next 48 hours.
• The ANC‐time profile in cycle 1 (The time from the beginning of
chemotherapy to the occurrence of the ANC nadir)
• The frequency and type of (culture‐confirmed) infections
• The incidence of i.v. antibiotic therapy and hospitalization
• The mobilization of CD34+ cells (in selected centers only)
• Incidence, severity and distribution of bone pain
• Percentage of scheduled chemotherapy dose that was delivered
• Proportion with chemotherapy doses reduced, omitted, or delayed
• Number of days of delay of chemotherapy
• Occurrence and/or resolution of chemotherapy‐induced mucositis
Safety endpoints
• Incidence of adverse events (all severe and serious) classified by
system organ class, preferred term, severity, and relationship to
study medication
• Injection site reactions
• Vital signs
• Presence of antibodies and abnormal clinical laboratory results.

E.5.2.1

Timepoint(s) of evaluation of this end point

Cycle1: D0,D1,D2,D3,D5,D6,D7,D9 and D8, D10-15
Cycle 2-6:D1,D2,D9±1, W20,W24,W36 and W48

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

Yes

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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

Belarus

Bosnia and Herzegovina

Bulgaria

Czech Republic

Egypt

Georgia

Hungary

Morocco

Poland

Romania

Russian Federation

Serbia

Slovakia

Tunisia

Turkey

Ukraine

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

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.2.1	Number of subjects for this age range:	545
F.1.3	Elderly (>=65 years)	Yes
F.1.3.1	Number of subjects for this age range:	55
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	No
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	100
F.4.2	For a multinational trial
F.4.2.1	In the EEA	225
F.4.2.2	In the whole clinical trial	600

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-01-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-01-02

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-05-30

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials