- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01859637
Immunogenicity, Safety, and Efficacy of Zarzio®/Filgrastim HEXAL® in Patients With Severe Chronic Neutropenia
Twelve-month Study on the Immunogenicity, Safety, and Efficacy of Zarzio®/Filgrastim HEXAL® in Patients With Severe Chronic Neutropenia
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This was a prospective, open-label, non-comparative study. Eligible patients with Severe Chronic Neutropenia received Zarzio® for 12 months. Study visits were scheduled for screening, start of treatment with Zarzio®/Filgrastim HEXAL®, 6 weeks after start of treatment and at months 3, 6, 9 and 12.
Immunogenicity assessment: Patients were screened for anti-recombinant human granulocyte colony stimulating factor (rhG-CSF) antibodies at screening (Visit 01) and at every study visit with the exception of Visit 02 (start of treatment). The evaluation of the immune response to rhG-CSF administration was made by a three-step procedure comprising a validated binding antibody screening and confirmatory radioimmunoprecipitation assay (RIP). Samples positive for binding antibodies in the confirmatory RIP assay were evaluated for neutralizing antibodies using a validated cell-based neutralization antibody assay (NAB).
Efficacy: Complete blood counts with differential white blood cell counts were performed and absolute neutrophil count (ANC) were calculated at every study visit. For each time point the neutrophil counts are summarized by the SAF set using descriptive statistics for the ANC as well as for the changes from baseline.
Safety: Adverse events are listed for the safety population set (SAF) (term, date of AE onset, date of AE resolved, AE duration, severity grade, relationship to study drug, action taken, SAE). Additionally, the following variables were also listed: Serum human chorionic gonadotropin (hCG) pregnancy test, Physical examination, vital signs (pulse, blood pressure), weight (kg), height (cm), Laboratory (hematology, clinical chemistry, urinalysis) values
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion criteria:
- Patients with established congenital, cyclic or idiopathic severe chronic neutropenia having an indication for treatment with Sandoz' filgrastim according to the SmPC of the product
- Patients ≥ 18 years of age at the day of inclusion
- Written informed consent of patient
Exclusion criteria:.
- Chemotherapy-induced neutropenia
- Neutropenia in combination with confirmed diagnosis of autoimmune disease, e.g. rheumatoid arthritis, Felty's syndrome, or systemic lupus erythematosus
- Myelodysplastic syndrome or leukemia
- Thrombocytopenia (platelets < 50.000/mm3) or anemia (hemoglobin < 8 g/dl) with the exception of patients with Shwachman-Diamond syndrome, glycogen storage disease 1b, or Barth's syndrome
- Sickle cell disease
- History of malignancy of any organ system, treated or untreated, with the exception of localized basal cell carcinoma of the skin
- For patients with congenital severe chronic neutropenia only: Any cytogenetic aberrations in bone marrow aspirates with results not older than six months suspicious for malignant transformation.
- Known or suspected hypersensitivity to rhG-CSF products
- Known or suspected hypersensitivity to any of the excipients of Sandoz' filgrastim product
- Positive result of anti-rhG-CSF antibody assessment at screening
- Absolute and relative contraindications as specified in the SmPC of Sandoz' filgrastim
- Drug abuse, substance abuse, or alcohol abuse
- Use of any other investigational drug at the time of enrollment, or within 30 days or 5 half-lives prior to enrollment, whichever is longer
- Patients unwilling and/or who are 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
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, UNLESS they are 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 (e.g. calendar, ovulation, symptothermal, post-ovulation methods) is not acceptable.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Zarzio®/Filgrastim HEXAL®
Zarzio®/Filgrastim HEXAL® was administered according to Summary of Product Characteristics (SmPC).
It was provided as solution for injection in prefilled syringes with two strengths at 300 μg/0.5 ml (30 MU) and 480 μg/0.5 ml (48 MU).
|
Zarzio®/Filgrastim HEXAL® solution for injection was provided in prefilled syringes with two strengths at 300 μg/0.5 ml (30 MU) and 480 μg/0.5 ml (48 MU).
Dosage and duration for each patient is as per the recommendations in the SmPC.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Anti- Recombinant Human Granulocyte Colony Stimulating Factor (rhG-CSF) Antibodies
Time Frame: screening, 3, 6, 9 and 12 months
|
Incidence of anti-rhG-CSF antibodies was monitored. Patients were screened for anti-rhG-CSF antibodies at screening and at each study except visit 02 (start of treatment = baseline). Evaluation of immune response to rhG-CSF administration was made by a three-step procedure comprising a validated binding antibody screening and confirmatory radioimmunoprecipitation assay (RIP) and a validated cell-based neutralization antibody assay (NAB). |
screening, 3, 6, 9 and 12 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Adverse Events (AEs)
Time Frame: 12 months
|
Patients experiencing AEs by system organ class and preferred term (PT) and number of events.
Patients with more than one AE coded to the same PT were counted once per PT
|
12 months
|
Change in Absolute Neutrophile Count (ANC)
Time Frame: Participants were followed for a duration of 12 months and ANC was assessed at baseline, week 6, Month 3, Month 6, Month 9 and Month 12.
|
To evaluate the efficacy of Zarzio®/Filgrastim HEXAL® in patients with SCN in terms of changes in absolute neutrophile count (ANC). Change from each visit to baseline in ANC for all patients is calculated. |
Participants were followed for a duration of 12 months and ANC was assessed at baseline, week 6, Month 3, Month 6, Month 9 and Month 12.
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Roumen Nakov, MD, PhD, Sandoz Biopharmaceutical, Hexal AG, Germany
Publications and helpful links
General Publications
- Dale DC, Cottle TE, Fier CJ, Bolyard AA, Bonilla MA, Boxer LA, Cham B, Freedman MH, Kannourakis G, Kinsey SE, Davis R, Scarlata D, Schwinzer B, Zeidler C, Welte K. Severe chronic neutropenia: treatment and follow-up of patients in the Severe Chronic Neutropenia International Registry. Am J Hematol. 2003 Feb;72(2):82-93. doi: 10.1002/ajh.10255.
- Palmblad J, Papadaki HA. Chronic idiopathic neutropenias and severe congenital neutropenia. Curr Opin Hematol. 2008 Jan;15(1):8-14. doi: 10.1097/MOH.0b013e3282f172d3.
- Zeidler C, Welte K. Hematopoietic growth factors for the treatment of inherited cytopenias. Semin Hematol. 2007 Jul;44(3):133-7. doi: 10.1053/j.seminhematol.2007.04.003.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- EP06-401
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
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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