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)

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2016-001965-98-NL
• Date of registration: 26/01/2017
• Prospective Registration: No
• Primary sponsor: Prolong Pharmaceuticals, LLC
• Public title: 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)
• Scientific title: 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)
• Date of first enrolment: 10/01/2017
• Target sample size: 65
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001965-98
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: Dose-finding; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: yes; Other specify the comparator: pegfilgrastim (Neulasta R); Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Netherlands

Contacts

• Name: Paul MANLEY
• Affiliation: Prolong Pharmaceuticals, LLC

• Name: Paul MANLEY
• Affiliation: Prolong Pharmaceuticals, LLC

Key inclusion & exclusion criteria

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 65
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

chemotherapy-induced neutropenia (CIN)
MedDRA version: 20.0 Level: LLT Classification code 10076734 Term: Chemotherapy induced neutropenia System Organ Class: 100000004851

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: ANF-RHO
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Not assigned
CAS Number: Not assigned
Current Sponsor code: ANF-RHO
Other descriptive name: PP-103, PEGANGRASTIM
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Trade Name: Neulasta ®
Product Name: Neulasta
Pharmaceutical Form: Solution for injection
INN or Proposed INN: PEGFILGRASTIM
CAS Number: 208265-92-3
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Secondary Objective: • 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)

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

Main Objective: • 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).

Timepoint(s) of evaluation of this end point: 1 cycle = 21 days

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 68 days

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).

Secondary ID(s)

PGFN-001

Source(s) of Monetary Support

Prolong Pharmaceuticals, LLC

Ethics review

Status: Approved
Approval date:
Contact: