Clinical trial NCT01859637: Immunogenicity, Safety, and Efficacy of Zarzio®/Filgrastim HEXAL® in Patients With Severe Chronic Neutropenia
Official title: Twelve-month Study on the Immunogenicity, Safety, and Efficacy of Zarzio®/Filgrastim HEXAL® in Patients With Severe Chronic Neutropenia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Severe Chronic Neutropenia
Keywords: Filgrastim, immunogenicity, severe chronic neutropenia
Lead sponsor: Sandoz
Sponsor class: INDUSTRY
Collaborators: name: Sandoz GmbH
First posted: 2013-05-22
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Incidence of Anti- Recombinant Human Granulocyte Colony Stimulating Factor (rhG-CSF) Antibodies
timeFrame: screening, 3, 6, 9 and 12 months
Secondary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: 12 months
measure: Change in Absolute Neutrophile Count (ANC)
timeFrame: 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.
Other outcomes:
Locations:
city: Hannover
country: Germany
facility: Medizinischen Hochschule (MHH) Hannover
city: Stockholm
country: Sweden
facility: Karolinska Institut
Study officials:
affiliation: Sandoz Biopharmaceutical, Hexal AG, Germany
name: Roumen Nakov, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.