Nanogen Pegfilgrastim (Pegcyte) PK/PD Clinical Study in Breast Cancer Patients

A Randomized, Double-blind, Parallel Study Comparing Pharmacokinetic (PK) and Pharmacodynamic (PD) Parameters of Pegcyte (Nanogen) and Reference Product Neulastim (Roche) for Chemotherapy-induced Neutropenia in Breast-cancer Patients

Breast cancer patients scheduled to receive myelosuppressive chemotherapy (AC regimen) will be enrolled in this study. Eligible patients receive single SC injection of pegcyte or neulastim 24 hours after administration of chemotherapy (Doxorubicin and Cyclophosphamide) in the first cycle (14 days each cycle). Blood samples are collected to determine the serum concentration of investigational drugs at specific time points in the first cycle. Absolute neutrophil count, CD34+ count, Cmax (maximum serum concentration), AUC0-t (area under the curve of the plasma concentration time) and Tmax (time required to reach Cmax) will be calculated from the serum concentration profile

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Pegfilgrastim

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Vietnam
  • Hanoi, Vietnam
    • Vietnam National Cancer Institute (Hospital K)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female patients aged between 18 - 65 years.
• Patients with histological confirmed primary invasive breast cancer; stage I, II or III.
• Patients had no prior chemotherapy treatments.
• Patients scheduled to undergo myelosuppressive Doxorubicin and Cyclophosphamide chemotherapy for 04 cycles, and Paclitaxel chemotherapy for the next 04 cycles; patients were available for 14 days of each cycle for the first 03 chemotherapy cycles.
• Patients with baseline ANC ≥ 1.5 x 109/L, PLT ≥ 100 x 109/L, HgB ≥ 9 g/dL, WBC ≥ 3,000/mL and albumin ≥ 3.0 g/dL.
• Performance status as per ECOG (Eastern Cooperative Oncology Group) score 0, 1 or 2.
• Willing to give written and signed informed consent

Exclusion Criteria:

• Patients with prior exposure of G-CSF or GM-CSF or its pegylated products in clinical development less than 6 months prior to randomization.
• Myelotoxic concomitant treatment such as chloramphenicol, methotrexate, immunomodulating agents, interferons during 10 days before randomization.
• Received systemic antibiotic treatment within 72 hours of chemotherapy.
• Chronic use of corticosteroids, prior bone marrow or stem cell transplant.
• Patients who had an immediate/ concurrent exposure to radiotherapy or surgery (within 4 weeks).
• Severe medical disease: cardiovascular, hepatic, renal, pulmonary…
• Known cases of hematological disease (sickle cell anemia, AML…)
• History of HIV positive, active hepatitis.
• Pregnant and lactating women or patients planning to become pregnant.
• Known allergic reactions to study medications.
• Positive to anti-pegfilgrastim antibody test.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pegcyte (Nanogen pegfilgrastim); pegcyte 6 mg in the first cycle	Drug: Pegfilgrastim; PK,PD and safety assessment
Active Comparator: Neulastim (Roche pegfilgrastim); Neulastim 6 mg in the first cycle	Drug: Pegfilgrastim; PK,PD and safety assessment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve from time 0 to the last time point (AUC0-t) for serum Pegfilgrastim (PEG-GCSF)	(AUC0-t)	day 2 (0h, 3h, 6h, 12±4h), day 3 (24h), day 4 (48h), day 5 (72h), day 7 (120h), day 8 (144h), day 9 (168h), day 11 (216h), and day 14 (288h) of the first cycle

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apparent clearance (CL) for serum Pegfilgrastim		day 2 (0h, 3h, 6h, 12±4h), day 3 (24h), day 4 (48h), day 5 (72h), day 7 (120h), day 8 (144h), day 9 (168h), day 11 (216h), and day 14 (288h) of the first cycle
Maximum concentration (Cmax) for serum Pegfilgrastim		day 2 (0h, 3h, 6h, 12±4h), day 3 (24h), day 4 (48h), day 5 (72h), day 7 (120h), day 8 (144h), day 9 (168h), day 11 (216h), and day 14 (288h) of the first cycle
Half-life (T½) for serum Pegfilgrastim (PEG-GCSF)		day 2 (0h, 3h, 6h, 12±4h), day 3 (24h), day 4 (48h), day 5 (72h), day 7 (120h), day 8 (144h), day 9 (168h), day 11 (216h), and day 14 (288h) of the first cycle
Area under the serum concentration-time curve (AUC0-inf) of Pegfilgrastim		day 2 (0h, 3h, 6h, 12±4h), day 3 (24h), day 4 (48h), day 5 (72h), day 7 (120h), day 8 (144h), day 9 (168h), day 11 (216h), and day 14 (288h) of the first cycle
Time to maximum concentration (Tmax) for serum Pegfilgrastim		day 2 (0h, 3h, 6h, 12±4h), day 3 (24h), day 4 (48h), day 5 (72h), day 7 (120h), day 8 (144h), day 9 (168h), day 11 (216h), and day 14 (288h) of the first cycle
Terminal elimination rate constant (λz) for serum Pegfilgrastim		day 2 (0h, 3h, 6h, 12±4h), day 3 (24h), day 4 (48h), day 5 (72h), day 7 (120h), day 8 (144h), day 9 (168h), day 11 (216h), and day 14 (288h) of the first cycle
Maximum change in CD34+ count		day 2 (0h), day 5 (72h), day 7 (120h), and day 8 (144h) of the first cycle.
Area under the curve above baseline of ANC [ANC_AUC(0-tlast)]		day 2 (0h, 3h, 6h, 12±4h), day 3 (24h), day 4 (48h), day 5 (72h), day 7 (120h), day 8 (144h), day 9 (168h), day 11 (216h), and day 14 (288h) of the first cycle
Time of maximum change from baseline for ANC in days (ANC_Tmax)		day 2 (0h, 3h, 6h, 12±4h), day 3 (24h), day 4 (48h), day 5 (72h), day 7 (120h), day 8 (144h), day 9 (168h), day 11 (216h), and day 14 (288h) of the first cycle
Maximum change from baseline in absolute neutrophil count from time 0 to the last time point ANC AUC0-t		day 2 (0h, 3h, 6h, 12±4h), day 3 (24h), day 4 (48h), day 5 (72h), day 7 (120h), day 8 (144h), day 9 (168h), day 11 (216h), and day 14 (288h) of the first cycle
Maximum change from baseline in absolute neutrophil count (ANC); ANC_Cmax		day 2 (0h, 3h, 6h, 12±4h), day 3 (24h), day 4 (48h), day 5 (72h), day 7 (120h), day 8 (144h), day 9 (168h), day 11 (216h), and day 14 (288h) of the first cycle
Incidence of adverse events	Including changes in vitals and laboratory investigations	cycle 1 from day 2 to day 14

Collaborators and Investigators

• Sponsor: Nanogen Pharmaceutical Biotechnology Joint Stock Company

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2016
• Primary Completion (Actual): October 9, 2017
• Study Completion (Actual): November 6, 2017

Study Registration Dates

• First Submitted: December 12, 2017
• First Submitted That Met QC Criteria: December 15, 2017
• First Posted (Actual): December 18, 2017

Study Record Updates

• Last Update Posted (Actual): December 19, 2017
• Last Update Submitted That Met QC Criteria: December 17, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: NNG04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No