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

NCT01859637 | Terminated Phase 4 Results

• 1 other identifier: EP06-401
• Study Type: interventional
• Target: 6
• Locations: 2 countries
• Sites: 2

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.

Conditions

Severe Chronic Neutropenia

Keywords

Filgrastim, immunogenicity, severe chronic neutropenia

Outcome Measures

Primary Outcomes (1)

• 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).

  screening, 3, 6, 9 and 12 months

Secondary Outcomes (2)

• Number of Participants With Adverse Events (AEs)

  12 months

• Change in Absolute Neutrophile Count (ANC)

  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.

Study Arms (1)

Zarzio®/Filgrastim HEXAL®

EXPERIMENTAL

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

Interventions

Filgrastim 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.

Also known as: Zarzio®/Filgrastim HEXAL®, EP2006, rhG-CSF

Zarzio®/Filgrastim HEXAL®

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Written informed consent of patient

You may not qualify if:

• 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

Sponsors & Collaborators

• Sandoz: lead
• Sandoz GmbH: collaborator

Study Sites (2)

Medizinischen Hochschule (MHH) Hannover

Hanover, Germany

Location

Karolinska Institut

Stockholm, Sweden

Location

Related Publications (3)

• 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.

  PMID: 12555210 BACKGROUND

• 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.

  PMID: 18043240 BACKGROUND

• 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.

  PMID: 17631177 BACKGROUND

MeSH Terms

Conditions

Neutropenia, severe chronic

Interventions

Filgrastim; pegfilgrastim; pegylated granulocyte colony-stimulating factor

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Limitations and Caveats

This was an Additional Pharmacovigilance Activity (MEA005). Based on interim study data, complemented with clinical data from continued global development \& extensive post-marketing experience MEA005 was considered fulfilled and the study terminated.

Results Point of Contact

• Title: Roumen Nakov
• Organization: Sandoz Biopharmaceutical, Hexal AG

roumen.nakov@sandoz.com

+49 8024 4764704

Study Officials

• Roumen Nakov, MD, PhD

  Sandoz Biopharmaceutical, Hexal AG, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2013
• First Posted: May 22, 2013
• Study Start: July 1, 2011
• Primary Completion: March 1, 2014
• Study Completion: September 1, 2015
• Last Updated: March 28, 2016
• Results First Posted: March 28, 2016

Record last verified: 2016-02

Data Sharing

• IPD Sharing: Will share

Locations

DE (1); SE (1)