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Immunogenicity, Safety, and Efficacy of Zarzio®/Filgrastim HEXAL® in Patients With Severe Chronic Neutropenia

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ClinicalTrials.gov Identifier: NCT01859637
Recruitment Status : Terminated (Additional pharmacovigilance activity was considered as fulfilled by the EMA.)
First Posted : May 22, 2013
Results First Posted : March 28, 2016
Last Update Posted : March 28, 2016
Sponsor:
Collaborator:
Sandoz GmbH
Information provided by (Responsible Party):
Sandoz

Brief Summary:
Purpose of the study is to investigate the safety, immunogenicity and the efficacy of Zarzio®/Filgrastim HEXAL® under chronic administration for 12 months in patients diagnosed with severe chronic neutropenia.

Condition or disease Intervention/treatment Phase
Severe Chronic Neutropenia Biological: Filgrastim Phase 4

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


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Twelve-month Study on the Immunogenicity, Safety, and Efficacy of Zarzio®/Filgrastim HEXAL® in Patients With Severe Chronic Neutropenia
Study Start Date : July 2011
Actual Primary Completion Date : March 2014
Actual Study Completion Date : September 2015


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).
Biological: Filgrastim
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:
  • Zarzio®/Filgrastim HEXAL®
  • EP2006
  • rhG-CSF




Primary Outcome Measures :
  1. 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).



Secondary Outcome Measures :
  1. 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

  2. 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.




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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. 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
  2. Patients ≥ 18 years of age at the day of inclusion
  3. Written informed consent of patient

Exclusion criteria:.

  1. Chemotherapy-induced neutropenia
  2. Neutropenia in combination with confirmed diagnosis of autoimmune disease, e.g. rheumatoid arthritis, Felty`s syndrome, or systemic lupus erythematosus
  3. Myelodysplastic syndrome or leukemia
  4. 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
  5. Sickle cell disease
  6. History of malignancy of any organ system, treated or untreated, with the exception of localized basal cell carcinoma of the skin
  7. 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.
  8. Known or suspected hypersensitivity to rhG-CSF products
  9. Known or suspected hypersensitivity to any of the excipients of Sandoz' filgrastim product
  10. Positive result of anti-rhG-CSF antibody assessment at screening
  11. Absolute and relative contraindications as specified in the SmPC of Sandoz' filgrastim
  12. Drug abuse, substance abuse, or alcohol abuse
  13. 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
  14. Patients unwilling and/or who are not capable of ensuring compliance with the provisions of the study protocol
  15. 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
  16. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01859637


Locations
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Germany
Medizinischen Hochschule (MHH) Hannover
Hannover, Germany
Sweden
Karolinska Institut
Stockholm, Sweden
Sponsors and Collaborators
Sandoz
Sandoz GmbH
Investigators
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Study Director: Roumen Nakov, MD, PhD Sandoz Biopharmaceutical, Hexal AG, Germany

Publications:
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Responsible Party: Sandoz
ClinicalTrials.gov Identifier: NCT01859637     History of Changes
Other Study ID Numbers: EP06-401
First Posted: May 22, 2013    Key Record Dates
Results First Posted: March 28, 2016
Last Update Posted: March 28, 2016
Last Verified: February 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Since there are only six patients enrolled, all the patient data is already provided in the registry.
Keywords provided by Sandoz:
Filgrastim, immunogenicity, severe chronic neutropenia
Additional relevant MeSH terms:
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Neutropenia
Agranulocytosis
Leukopenia
Leukocyte Disorders
Hematologic Diseases
Lenograstim
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs