Clinical Trials Register

Summary
EudraCT Number:	2010-019001-42
Sponsor's Protocol Code Number:	NEUGR-003
National Competent Authority:	Bulgarian Drug Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-04-13
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

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A. Protocol Information

A.1

Member State Concerned

Bulgarian Drug Agency

A.2

EudraCT number

2010-019001-42

A.3

Full title of the trial

A Randomized, Double-Blind, Active Comparator, Non-Inferiority Study of Subcutaneously Administered Neugranin (Recombinant Human Albumin-Human Granulocyte Colony Stimulating Factor) or Pegfilgrastim in Subjects with Breast Cancer Receiving Myelosuppressive Chemotherapy (Doxorubicin/Docetaxel)

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

NEUGR-003

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Teva Pharmaceutical Works Private Limited Company
B.1.3.4	Country	Hungary
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	Neugranin
D.3.2	Product code	CG-10639
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	neugranin
D.3.9.1	CAS number	941579-28-8
D.3.9.2	Current sponsor code	CG-10639, albugranin
D.3.9.3	Other descriptive name	human serum albumin/human granulocyte-colony stimulating factor
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	50
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Yes
D.3.11.13.1	Other medicinal product type	recombinant fusion protein composed of human serum albumin and human G-CSF
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 B.V.
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.3.1	Product name	NA
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	NA
D.3.9.3	Other descriptive name	NA
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Yes
D.3.11.13.1	Other medicinal product type	covalent conjugate of recombinant human G-CSF (r-metHuG-CSF) with a single 20 kd polyethylene glycol (PEG) molecule

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

breast cancer patients receiving myelosupressive chemotherapy (doxorubicin/docetaxel)

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.1
E.1.2	Level	LLT
E.1.2	Classification code	10006187
E.1.2	Term	Breast cancer

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 evaluate the efficacy of Neugranin compared to pegfilgrastim in subjects
receiving doxorubicin and docetaxel as evidenced by the duration of severe
neutropenia (DSN) in Cycle 1

E.2.2

Secondary objectives of the trial

- To determine the incidence of febrile neutropenia and documented infections
by cycle and across all cycles
- To assess the incidence of severe neutropenia by cycle and across all cycles
- To assess the duration of severe neutropenia in Cycles 2-4.
- To assess the time to ANC recovery (ANC >/= 1.5 x 10 9/L) in Cycles 1-4

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients with histologically or cytologically confirmed breast cancer scheduled
to receive doxorubicin 60 mg/m2 and docetaxel 75 mg/m2
2. 18 years of age or older
3. Adequate hematologic function: ANC >/= 1.5 x 10 9/L; Platelets >/= 100 x10 9/L
4. Adequate hepatic and renal function:Serum creatinine < 2.0 mg/dL; Total bilirubin within normal limits; Serum transaminases - SGOT and SGPT < 1.5 x upper
limit normal; Alkaline phosphatase < 2.5 x upper limit normal
5. ECOG performance status 0 - 2
6. Eligible to receive doxorubicin based on a left ventricular ejection fraction
(LVEF) >/= lower limit of normal for the local institution
7. Have the ability to understand the requirements of the study, provide written
informed consent (including consent for the use and disclosure of researchrelated
health information), and comply with the study protocol procedures

E.4

Principal exclusion criteria

1. More than 1 prior chemotherapy regimen (including adjuvant therapy if given
within the last 12 months prior to study chemotherapy)
2. Prior lifetime cumulative anthracycline dose exceeding 240 mg/m2 doxorubicin
or the equivalent dose of another anthracycline or anthracenedione
3. Prior chemotherapy/immunotherapy within 30 days prior to study
chemotherapy (within 6 weeks of study chemotherapy for nitrosoureas (BCNU,
CCNU) or mitomycin-C)
4. Concomitant trastuzumab (Herceptin)
5. Received any investigational agent within 30 days prior to study chemotherapy
6. Myocardial infarction within 6 months prior to study chemotherapy,
uncontrolled angina, severe uncontrolled ventricular arrhythmias, or ECG
abnormalities that may interfere with the accurate assessment of the QT
interval, including intraventricular conduction delays (QRS >120 msec) and
complete bundle branch blocks
7. Prior surgery within 2 weeks of study chemotherapy
8. Prior radiation therapy within 4 weeks of study chemotherapy (except spot
irradiation for bone metastases)
9. Prior high-dose chemotherapy with hematopoietic stem cell transplant
10. Prior use of G-CSF, GM-CSF or erythropoietin within 4 weeks of study
chemotherapy
11. Received systemic antibiotics within 72 hours of study chemotherapy
12. History of myeloid malignancy or myelodysplasia
13. Known brain metastases unless adequately treated (surgery or radiotherapy), no
evidence of progression with a minimum of 3 weeks observation and
neurologically stable off anticonvulsants and steroids.
14. Known sickle cell disease
15. Diagnosis of ARDS
16. Known history of allergies to yeast-derived products
17. Known hypersensitivity to E. coli-derived proteins‚ pegfilgrastim‚ filgrastim, or
any other component of pegfilgrastim
18. History of severe hypersensitivity reactions to docetaxel or other drugs
formulated with polysorbate 80 such as etoposide and vitamin E
19. Hypersensitivity to doxorubicin, any of its excipients, or other anthracyclines or
anthracenediones
20. Pregnant female or nursing mother. All non-sterile or non-postmenopausal
females must have a negative serum pregnancy test at screening and must
practice a medically accepted method of contraception over the course of the
study and for 30 days after the last dose of study drug (acceptable methods of
birth control in this study are: surgical sterilization, intrauterine devices, oral
contraceptive, contraceptive patch, long-acting injectable contraceptive,
partner’s vasectomy, a double-protection method (condom or diaphragm with
spermicide). Hormonal contraception must be accompanied by an additional
barrier method of birth control (condom).
21. Males who do not agree to use effective contraception throughout the study and
for a period of 30 days after the last dose of study drug
22. Known HIV positive or active hepatitis (Patients with unknown status will not
be tested)

E.5 End points

E.5.1

Primary end point(s)

Primary Outcome Measure(s):
Duration of severe neutropenia (severe neutropenia defined as an ANC <
0.5 x 109/L) in Cycle 1.

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

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

E.8.1.4

Double blind

Yes

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.8.3

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

Information not present in EudraCT

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

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

last patient last follow-up visit

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.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
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	50
F.4.2	For a multinational trial
F.4.2.1	In the EEA	90
F.4.2.2	In the whole clinical trial	300

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

2010-06-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-07-08

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-02-23

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