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

Primary Purpose

Severe Chronic Neutropenia

Status

Terminated

Phase

Phase 4

Locations

International

Study Type

Interventional

Intervention

Filgrastim

About this trial

This is an interventional treatment trial for Severe Chronic Neutropenia focused on measuring Filgrastim, immunogenicity, severe chronic neutropenia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Medizinischen Hochschule (MHH) Hannover
Karolinska Institut

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Zarzio®/Filgrastim HEXAL®

Arm Description

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).

Outcomes

Primary Outcome Measures

Incidence of Anti- Recombinant Human Granulocyte Colony Stimulating Factor (rhG-CSF) Antibodies

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

Number of Participants With Adverse Events (AEs)

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

Change in Absolute Neutrophile Count (ANC)

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.

Full Information

NCT ID

NCT01859637

First Posted

May 8, 2013

Last Updated

February 24, 2016

Sponsor

Sandoz

Collaborators

Sandoz GmbH

1. Study Identification

Unique Protocol Identification Number

NCT01859637

Brief Title

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

2. Study Status

Record Verification Date

February 2016

Overall Recruitment Status

Terminated

Why Stopped

Additional pharmacovigilance activity was considered as fulfilled by the EMA.

Study Start Date

July 2011 (undefined)

Primary Completion Date

March 2014 (Actual)

Study Completion Date

September 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sandoz

Collaborators

Sandoz GmbH

4. Oversight

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Severe Chronic Neutropenia

Keywords

Filgrastim, immunogenicity, severe chronic neutropenia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Zarzio®/Filgrastim HEXAL®

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Filgrastim

Other Intervention Name(s)

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

Intervention Description

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.

Primary Outcome Measure Information:

Title

Incidence of Anti- Recombinant Human Granulocyte Colony Stimulating Factor (rhG-CSF) Antibodies

Description

Time Frame

screening, 3, 6, 9 and 12 months

Secondary Outcome Measure Information:

Title

Number of Participants With Adverse Events (AEs)

Description

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

Time Frame

12 months

Title

Change in Absolute Neutrophile Count (ANC)

Description

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.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Roumen Nakov, MD, PhD

Organizational Affiliation

Sandoz Biopharmaceutical, Hexal AG, Germany

Official's Role

Study Director

Facility Information:

Facility Name

Medizinischen Hochschule (MHH) Hannover

City

Hannover

Country

Germany

Facility Name

Karolinska Institut

City

Stockholm

Country

Sweden

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Since there are only six patients enrolled, all the patient data is already provided in the registry.

Citations:

PubMed Identifier

12555210

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.

Results Reference

background

PubMed Identifier

18043240

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.

Results Reference

background

PubMed Identifier

17631177

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.

Results Reference

background

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

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