- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03559387
Randomized Phase 2, Dose-finding Efficacy, Safety Study of ANF-RHO™ Versus Neulasta® in Chemotherapy-Induced Neutropenia
A Randomized and Open-label Dose-finding, Ph. 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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Paris, France, 75475
- Hôpital Saint Louis - Center des Maladies du Sein
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Reims, France, 51100
- Institut de Cancérologie Jean Godinot
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Strasbourg, France, 67000
- Strasbourg Oncologie Liberale
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Tours, France, 37044
- CHU de Tours
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Rotterdam, Netherlands, 3008
- Erasmus Medical Center
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Rotterdam, Netherlands, 3038
- Ikazia Ziekenhuis
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Rotterdam, Netherlands, 3079
- Maasstad Ziekenhuis
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Schiedam, Netherlands, 3118
- Franciscus Gasthuis & Vlietland
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Adult female patients, 18 years of age or older
- Signed and dated written consent/assent by the patient or legally authorized representative
- Histologically confirmed non-metastatic breast cancer
- ECOG performance status ≤ 2
- Myelosuppressive chemotherapy naive
Scheduled to receive and anticipated to complete the following chemotherapy regimen
- FEC (fluorouracil/epirubicin (100) / cyclophosphamide) (3 cycles);
- Docetaxel (3 cycles) chemotherapy
- White blood cells (WBC) ≥ 3 × 10^9/L; Absolute neutrophil count (ANC) ≥ 2.0 × 10^9/L; platelet count ≥ 100 × 10^9/L; and hemoglobin ≥ 10 g/dL (6.2 mmol/L)
- Adequate cardiac function (e.g. LVEF > 50% as determined by standard care) and adequate hepatic function (e.g. liver transaminases < 2.5 x ULN)
- 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 implants, injectables, combined oral contraceptives and intrauterine devices (IUDs)). Periodic abstinence is not an acceptable contraceptive method during the study period.
Exclusion Criteria: A subject will not be enrolled if any they meet any of the following criteria:
- Known hypersensitivity to E.coli derived products or polyethylene glycol
- 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
- Evidence of myelodysplasia, aplastic anemia, myelofibrosis, rheumatoid arthritis, systemic lupus erythematosus, or sickle cell disease
- 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
- Previous exposure to filgrastim, perfilgrastim or lipegfilgrastim within 30 days before randomization
- Treatment with systemically active antibiotics within 72 hours before chemotherapy
- Chronic use of oral corticosteroids
- Participation in a pharmacological clinical trial within 30 days before randomization
- Clinical diagnosis of drug abuse or substance abuse within 30 days prior to screening
- Documented alcohol abuse within 30 days prior to screening
- Unwilling and/or not capable of ensuring compliance with the provisions of the study protocol
- 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
- Other serious medical condition that would prevent individual from receiving protocol treatment
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: ANF-RHO™
Subjects will receive the ANF-RHO™ dose with a volume equivalent to 10 µg/kg, 20 µg/kg and 30 µg/kg as a subcutaneous injection.
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Subjects randomized to the ANF-RHO™ treatment arm will receive the investigational product on Day 1(day of chemotherapy treatment) of each Chemotherapy cycle. ANF-RHO™ will be administered to the subjects as a subcutaneous injection. Subjects will receive the ANF-RHO™ dose with a volume equivalent to 10 µg/kg, 20 µg/kg and 30 µg/kg. ANF-RHO™ is provided as a single-use glass vial containing 1.0 ml of solution at a concentration of 5 mg/ml
Other Names:
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Active Comparator: Neulasta®
Neulasta® will be administered to the subjects at a dose of 6.0 mg in 0.6 ml as a subcutaneous injection.
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Subjects randomized to the Neulasta® treatment arm will receive the comparator drug on Day 2(day after chemotherapy treatment) of each Chemotherapy cycle. Neulasta® will be administered to the subjects at a standard dose of 6.0 mg in 0.6 ml as a subcutaneous injection. Neulasta® is also provided as a single-use pre-filled syringe.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Duration of neutropenia grade 1 or worse (absolute neutrophil count [ANC] ≤ 2.0 x 10^9/L) in the first cycle of chemotherapy (FE100C).
Time Frame: 21 days
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21 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Duration of neutropenia grade 1 or worse (absolute neutrophil count [ANC] ≤ 2.0 x 10^9/L) in the fourth cycle of chemotherapy (docetaxel).
Time Frame: 21 days
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21 days
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Duration of severe neutropenia (ANC < 0.5 x 10^9/L) during the first chemotherapy cycle (21-day cycle FE100C)
Time Frame: 21 days
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21 days
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Duration of severe neutropenia (ANC < 0.5 x 10^9/L) during the fourth chemotherapy cycle (21-day cycle docetaxel)
Time Frame: 21 days
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21 days
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Incidence of severe neutropenia (ANC < 0.5 x 10^9/L) during all chemotherapy cycles
Time Frame: ~ 128 ± 2 days
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~ 128 ± 2 days
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Incidence and duration of febrile neutropenia defined as peak temperature ≥38.5°C and ANC < 0.5 x 10^9/L, during all chemotherapy cycles
Time Frame: ~ 128 ± 2 days
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~ 128 ± 2 days
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Incidence and duration of febrile neutropenia defined as peak temperature ≥38.0°C for two readings over two hours and ANC < 0.5 x 10^9/L, during all chemotherapy cycles
Time Frame: ~ 128 ± 2 days
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~ 128 ± 2 days
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Incidence and duration of infection and infection-related events based on use of antibiotics during all chemotherapy cycles
Time Frame: ~ 128 ± 2 days
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~ 128 ± 2 days
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Incidence and duration of infection and infection-related events based on the need for hospitalization during all chemotherapy cycles
Time Frame: ~ 128 ± 2 days
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~ 128 ± 2 days
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Incidence and duration of moderate (ANC ≥ 50 x 10^9/L) leukocytosis during all chemotherapy cycles
Time Frame: ~ 128 ± 2 days
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~ 128 ± 2 days
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Incidence and duration of severe (ANC ≥ 100 x 10^9/L) leukocytosis during all chemotherapy cycles
Time Frame: ~ 128 ± 2 days
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~ 128 ± 2 days
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Clinically meaningful changes in vital signs during all chemotherapy cycles - Assessment of Blood pressure
Time Frame: ~ 128 ± 2 days
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Assessment of Blood pressure (systolic and diastolic) helps determine the safety of the medications under study - ANF-RHO and Neulasta
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~ 128 ± 2 days
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Clinically meaningful changes in vital signs during all chemotherapy cycles - Assessment of Heart rate
Time Frame: ~ 128 ± 2 days
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Assessment of Heart rate helps determine the safety of the medications under study - ANF-RHO and Neulasta
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~ 128 ± 2 days
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Clinically meaningful changes in vital signs during all chemotherapy cycles - Assessment of Respiratory rate
Time Frame: ~ 128 ± 2 days
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Assessment of Respiratory rate helps determine the safety of the medications under study - ANF-RHO and Neulasta
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~ 128 ± 2 days
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Clinically meaningful changes in vital signs during all chemotherapy cycles - Assessment of Body Temperature
Time Frame: ~ 128 ± 2 days
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Assessment of Respiratory rate helps determine the safety of the medications under study - ANF-RHO and Neulasta
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~ 128 ± 2 days
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Incidence of bone pain, determined by a numerical rating scale, as well as other reported adverse events
Time Frame: ~ 128 ± 2 days
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~ 128 ± 2 days
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Duration of bone pain, determined by a numerical rating scale, as well as other reported adverse events
Time Frame: ~ 128 ± 2 days
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~ 128 ± 2 days
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Severity of bone pain, determined by a numerical rating scale, as well as other reported adverse events
Time Frame: ~ 128 ± 2 days
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~ 128 ± 2 days
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Site of bone pain, determined by a numerical rating scale, as well as other reported adverse events
Time Frame: ~ 128 ± 2 days
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~ 128 ± 2 days
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Pharmacokinetic profile of ANF-RHO and Neulasta - Measurement of Maximum Plasma Concentration (Cmax)
Time Frame: ~ 128 ± 2 days
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Cmax is the maximum concentration of the drug (either ANF-RHO or Neulasta) that is achieved after administration of a dose
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~ 128 ± 2 days
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Pharmacokinetic profile of ANF-RHO and Neulasta - Measurement of Time taken to reach the maximum concentration (Tmax)
Time Frame: ~ 128 ± 2 days
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Tmax is the time taken to reach the maximum concentration (Cmax) after administration of a dose.
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~ 128 ± 2 days
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Pharmacokinetic profile of ANF-RHO and Neulasta - Measurement of half-life (T1/2)
Time Frame: ~ 128 ± 2 days
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T1/2 is the time taken for ANF-RHO and Neulasta to reach half the value of their initial concentrations.
T1/2 determination helps in understanding the duration for which ANF-RHO or Neulasta would be active upon administration.
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~ 128 ± 2 days
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Pharmacokinetic profile of ANF-RHO and Neulasta - Area Under the Curve (AUC[0-t])
Time Frame: ~ 128 ± 2 days
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AUC[0-t] is an important parameter for determining as to how much of the drug is available in the body after administration of a drug formulation, in this case ANF-RHO vs Neulasta.
Understanding the AUC for both these drug formulations will help us to determine the efficacy and safety profiles of these medicines.
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~ 128 ± 2 days
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Pharmacokinetic profile of ANF-RHO and Neulasta - Area Under the Curve (AUC[0-∞])
Time Frame: ~ 128 ± 2 days
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Similar to AUC[0-t] which is estimated till time 't', in AUC[0-∞], the estimation is done on the concentration of the drug to an infinite time.
Calculation of the AUC[0-∞], helps understand how much of the drug is available in the body at extremely low concentrations, beyond the limits of measurable concentrations.
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~ 128 ± 2 days
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Pharmacokinetic profile of ANF-RHO and Neulasta - Area Under the Curve (AUC[0-t]/AUC[0-∞])
Time Frame: ~ 128 ± 2 days
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The parameter AUC[0-t]/AUC[0-∞] is useful to calculate the fraction of the Total AUC that was added due to the extrapolated AUC (AUC[0-∞]).
It helps understand if the methods employed for determining the total AUC and drug's availability in the body are correct.
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~ 128 ± 2 days
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Incidence of anti-drug antibodies to ANF-RHO and Neulasta
Time Frame: ~ 128 ± 2 days
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~ 128 ± 2 days
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PGFN-001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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