Clinical Trials Register

Summary
EudraCT Number:	2016-001965-98
Sponsor's Protocol Code Number:	PGFN-001
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2017-01-26
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

Netherlands - Competent Authority

A.2

EudraCT number

2016-001965-98

A.3

Full title of the trial

A randomized and open-label dose-finding, phase 2, efficacy, safety, and pharmacokinetic study of once-per-cycle prophylactic injections of ANF-RHO™ versus pegfilgrastim (Neulasta®) in non-metastatic breast cancer patients at high risk of chemotherapy-induced neutropenia (CIN)

A.3.1

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

A.4.1

Sponsor's protocol code number

PGFN-001

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	Prolong Pharmaceuticals, LLC
B.1.3.4	Country	United States
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	Prolong Pharmaceuticals, LLC
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Prolong Pharmaceuticals, LLC
B.5.2	Functional name of contact point	Paul MANLEY
B.5.3	Address:
B.5.3.1	Street Address	300 Corporate Court, Suite B
B.5.3.2	Town/ city	South Plainfield, New Jersey
B.5.3.3	Post code	07080
B.5.3.4	Country	United States
B.5.4	Telephone number	1908444-4660
B.5.5	Fax number	1908444-4661
B.5.6	E-mail	pmanley@prolongmail.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	ANF-RHO
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	Not assigned
D.3.9.1	CAS number	Not assigned
D.3.9.2	Current sponsor code	ANF-RHO
D.3.9.3	Other descriptive name	PP-103, PEGANGRASTIM
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	5
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	No
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 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	Neulasta
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	No
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

chemotherapy-induced neutropenia (CIN)

E.1.1.1

Medical condition in easily understood language

Reduction of white blood cells number after chemotherapy

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10076734
E.1.2	Term	Chemotherapy induced neutropenia
E.1.2	System Organ Class	100000004851

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 assess the Absolute Neutrophil Count [ANC = PMN (polynorphonuclear leukocytes) +Bands] grade decline (neutropenia as
assessed by CTCAE v5.0) observed after escalating doses of ANF-RHO and to assess the incidence (in Part B) and incidence and duration (in Part C) of neutropenia grade 3 (ANC < 1.0×109/L - ≥ 0.5×109/L) and grade 4 (ANC < 0.5×109/L) in the first chemotherapy docetaxel cycle (21-day cycle).

E.2.2

Secondary objectives of the trial

• Assess efficacy of escalating doses of ANF-RHO (Part B) and v Neulasta (Part C) on the:
- incidence & duration of neutropenia ≥ G1 in the first chemo cycle (21d
with Docetaxel).
- incidence & duration of G3 and G4 neutropenia during all Docetaxel
chemo cycles.
- incidence and duration of febrile neutropenia in breast cancer pts
undergoing 3 cycles of high-risk myelosuppressive chemo with Docetaxel.
• Evaluate PK of escalating doses of ANF-RHO in breast cancer pts undergoing 3 cycles of high-risk myelosuppressive chemo with Docetaxel (Parts B & C)
• Evaluate immunogenicity of escalating doses of ANF-RHO in breast cancer pts undergoing 3 cycles of high-risk myelosuppressive chemo with Docetaxel (Parts B & C)
• Evaluate safety of subcutaneous injections of ANF-RHO in breast cancer pts undergoing 3 cycles of high-risk myelosuppressive chemo with Docetaxel, including incidence & severity of bone pain, leukocytosis and febrile neutropenia (Part B) compared to Neulasta (Part C)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Adult female patients, 18 years of age or older
2. Signed and dated written consent/assent by the patient or legally
authorized representative
3. Histologically confirmed non-metastatic breast cancer
4. ECOG performance status ≤ 2
5. Must have received FE100C (fluorouracil/epirubicin
(100)/cyclophosphamide) (3 cycles) prior to study entry
6. Scheduled to receive and anticipated to complete the following chemotherapy regimen after FE100C: 3 Docetaxel chemotherapy cycles
7. White blood cell (WBC) ≥ 3 × 109/L; ANC ≥ 2.0 × 109/L; platelet
count ≥ 100 × 109/L; and hemoglobin ≥ 10 g/dL (6.2 mmol/L)
8. Adequate cardiac function and adequate hepatic function (e.g., liver
transaminases < 2.5 x ULN)
9. Women of childbearing potential with a negative serum pregnancy
test and using a highly effective method of birth control (i.e., one that
results in a less than 1% per year failure rate when used consistently
and correctly, such as intrauterine devices (IUDs)). Periodic abstinence
is not an acceptable contraceptive method during the study period.

E.4

Principal exclusion criteria

Subjects will not be enrolled if they meet any of the following criteria:
1. Known hypersensitivity to E.coli derived products or polyethylene glycol
2. No other malignancy except carcinoma in situ and basal-cell and
squamous cell carcinoma of the skin, unless the other malignancy was
treated ≥5 years ago with curative intent
3. Evidence of myelodysplasia, aplastic anemia, myelofibrosis,
rheumatoid arthritis, systemic lupus erythematosus, or sickle cell disease
4. Clinical diagnosis or history of chronic infection such as hepatitis B
virus(HBV), hepatitis C Virus (HCV) or Human immunodeficiency
virus(HIV) or history of tuberculosis
5. Subjects experiencing Febrile Neutropenia during any of the three
chemotherapy cycles with FE100C
6. Treatment with systemically active antibiotics within 72 hours before chemotherapy
7. Chronic use of oral corticosteroids
8. Participation in a clinical pharmacological trial within 30 days before
randomization
9. Clinical diagnosis of drug abuse or substance abuse within 30 days
prior to screening
10. Documented alcohol abuse within 30 days prior to screening.
11. Unwilling and/or not capable of ensuring compliance with the
provisions of the study protocol
12. Pregnant or breastfeeding women where pregnancy is defined as the
state of a female after conception and until the termination of gestation,
confirmed by a positive serum HCG laboratory test
13. Other serious medical condition that would prevent individual from
receiving protocol treatment

E.5 End points

E.5.1

Primary end point(s)

•Incidence (in Part B) and incidence and duration (in Part C) of neutropenia grade 3 (ANC < 1.0×109/L - ≥ 0.5×109/L) or grade 4 (ANC
< 0.5×109/L) in the first cycle of Docetaxel chemotherapy, following 3
standard care cycles of FE100C, with escalating doses of ANF-RHO

E.5.1.1

Timepoint(s) of evaluation of this end point

1 cycle = 21 days

E.5.2

Secondary end point(s)

• Incidence and duration of neutropenia grade 1 or worse (ANC ≤ 2.0×109/L) in the first cycle of chemotherapy (Docetaxel) with escalating doses of ANF-RHO (Part B) and recommended ANF-RHO dose versus Neulasta (Part C)
• Incidence and duration of Grade 3 (ANC < 1.0×109/L - ≥ 0.5×109/L) and grade 4 neutropenia (ANC < 0.5×109/L) during all Docetaxel chemotherapy cycles (21-day cycle Docetaxel) with escalating doses of ANF-RHO (Part B) and recommended ANF-RHO dose versus Neulasta
(Part C)
• Incidence and duration of febrile neutropenia defined as peak temperature ≥ 38.5°C (or ≥ 38.0°C for two readings over two hours) and ANC < 0.5×109/L, during all Docetaxel chemotherapy cycles (Parts B and C)**
• Incidence and duration of infection and infection-related events (e.g.,
antibiotic use, need for hospitalization, etc.) during all Docetaxel chemotherapy cycles (Parts B and C)**
• Incidence and duration of moderate (ANC ≥ 50×109/L) and severe
(ANC ≥ 100×109/L) leukocytosis during all chemotherapy cycles**
• Clinically meaningful changes in vital signs during all Docetaxel
chemotherapy cycles (Parts B and C)**
• Incidence, duration, severity and site of bone pain, determined by a
numerical rating scale, as well as other reported adverse events (Parts B
and C)**
• Pharmacokinetic profile of ANF-RHO and Neulasta (Parts B and C)**
• Incidence of anti drug antibodies (ADA) to ANF-RHO and Neulasta
(Parts B and C)**
**These secondary objectives were also assessed in Part A (cohort
completed; ANF-RHO 10 μg/kg vs Neulasta). Part A had 6 chemotherapy
cycles (3 cycles of FE100C and 3 cycles of Docetaxel).

E.5.2.1

Timepoint(s) of evaluation of this end point

68 days

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Dose-finding

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

Yes

E.8.2.3.1

Comparator description

pegfilgrastim (Neulasta R)

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

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

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

LVLS

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None.

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

2016-12-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-01-10

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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