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

NCT ID: NCT01859637

Last Updated: 2016-03-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-31
• Study Completion Date: 2015-09-30

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.

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

Conditions

Severe Chronic Neutropenia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Filgrastim

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: BIOLOGICAL

Other Intervention Names

Zarzio®/Filgrastim HEXAL®; EP2006; rhG-CSF

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sandoz GmbH

INDUSTRY

Sponsor Role: collaborator

Sandoz

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roumen Nakov, MD, PhD

Role: STUDY_DIRECTOR

Sandoz Biopharmaceutical, Hexal AG, Germany

Locations

Medizinischen Hochschule (MHH) Hannover

Hanover, , Germany

Karolinska Institut

Stockholm, , Sweden

Countries

Germany; Sweden

References

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.

Reference Type: BACKGROUND

PMID: 12555210 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18043240 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17631177 (View on PubMed)

Other Identifiers

EP06-401

Identifier Type: -

Identifier Source: org_study_id