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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

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Severe Chronic Neutropenia
Intervention Biological: Filgrastim
Enrollment 6
Recruitment Details First patient in: 05-Jul-2011, last patient in: 12-Feb-2013. 2 sites (medical school and university hospital)
Pre-assignment Details  
Arm/Group Title Zarzio®/Filgrastim HEXAL® (EP2006)
Hide Arm/Group Description Open label single arm. All patients received Zarzio® subcutaneously dosed as per recommendations in Summary of Product Characteristics (SmPC).
Period Title: Overall Study
Started 6
Completed 6
Not Completed 0
Arm/Group Title Zarzio®/Filgrastim HEXAL®
Hide Arm/Group Description Open label single arm. All patients received Zarzio®/Filgrastim HEXAL® subcutaneously dosed as per recommendations in SmPC.
Overall Number of Baseline Participants 6
Hide Baseline Analysis Population Description
Intent-to treat (ITT): All patients with at least one dose EP2006. Safety population (SAF): ITT and at least one post-baseline safety assessment. Immunogenicity population: ITT and at least one available anti-rhG-CSF antibody assessment. No patient was excluded of any of the populations. Results presented for SAF.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 6 participants
45.0
(27 to 77)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants
Female
5
  83.3%
Male
1
  16.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants
Caucasian 5
Latin American 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants
Sweden 4
Germany 2
Severe Chronic Neutropenia (SCN) diagnosis  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants
Congenital neutropenia 1
Cyclic neutropenia 1
Idiopathic neutropenia 4
Granulocyte Colony Stimulating Factor (G-CSF) pretreatment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants
Yes 6
No 0
Height  
Median (Full Range)
Unit of measure:  Cm
Number Analyzed 6 participants
165.0
(159 to 174)
Weight  
Median (Full Range)
Unit of measure:  Kg
Number Analyzed 6 participants
67.0
(55 to 98)
1.Primary Outcome
Title Incidence of Anti- Recombinant Human Granulocyte Colony Stimulating Factor (rhG-CSF) Antibodies
Hide Description

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).

Time Frame screening, 3, 6, 9 and 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population (SAF): All patients with at least one dose Zarzio®/Filgrastim HEXAL® and at least one post-baseline safety assessment. All six patients were screened for anti-rhG-CSF antibodies at all six study visits, except for one missing assessment (no sample was taken for patient 0204 at Visit 03, which was an optional visit).
Arm/Group Title Zarzio®/Filgrastim HEXAL®
Hide Arm/Group Description:
All patients received open-label Zarzio®/Filgrastim HEXAL®
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: participants
Visit 1 - negative 6
Visit 3 - negative 5
Visit 4 - negative 6
Visit 5 - negative 6
Visit 6 - negative 6
Visit 7 - negative 6
2.Secondary Outcome
Title Number of Participants With Adverse Events (AEs)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population (SAF): all patients with at least one dose Zarzio®/Filgrastim HEXAL® and at least one post-baseline safety assessment
Arm/Group Title Zarzio®/Filgrastim HEXAL®
Hide Arm/Group Description:
All patients received open-label Zarzio®/Filgrastim HEXAL®
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: participants
6
3.Secondary Outcome
Title Change in Absolute Neutrophile Count (ANC)
Hide Description

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.

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.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population (SAF): all patients with at least one dose Zarzio®/Filgrastim HEXAL® and at least one post-baseline safety assessment
Arm/Group Title Zarzio®/Filgrastim HEXAL®
Hide Arm/Group Description:
All patients received open-label Zarzio®/Filgrastim HEXAL®
Overall Number of Participants Analyzed 6
Median (Full Range)
Unit of Measure: 10^9 cells/L
ANC Visit 1 Screening to Baseline (Visit 2)
-1.252
(-10.90 to 2.84)
ANC Visit 3 Week 6 to Baseline (Visit 2)
6.873
(-11.20 to 16.40)
ANC Visit 4 Month 3 to Baseline (Visit 2)
-0.198
(-11.00 to 25.50)
ANC Visit 5 Month 6 to Baseline (Visit 2)
-0.711
(-10.80 to 12.38)
ANC Visit 6 Month 9 to Baseline (Visit 2)
1.506
(-9.60 to 14.70)
ANC Visit 7 Month 12 to Baseline (Visit 2)
1.579
(-10.80 to 18.87)
Time Frame 12 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Open-label Zarzio®/Filgrastim HEXAL®
Hide Arm/Group Description All patients received open-label Zarzio®/Filgrastim HEXAL®
All-Cause Mortality
Open-label Zarzio®/Filgrastim HEXAL®
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Open-label Zarzio®/Filgrastim HEXAL®
Affected / at Risk (%) # Events
Total   1/6 (16.67%)    
Renal and urinary disorders   
Nephrolithiasis * 1 [1]  1/6 (16.67%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (17.0)
[1]
Patient (0101) experienced severe nephrolithiasis leading to hospitalization. No action was taken with respect to the study medication; Resolved completely 17 days after onset; Not suspected to be causally related to study medication
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Open-label Zarzio®/Filgrastim HEXAL®
Affected / at Risk (%) # Events
Total   6/6 (100.00%)    
Gastrointestinal disorders   
Abdominal pain * 1  1/6 (16.67%)  1
Diarrhoea * 1  1/6 (16.67%)  1
Mouth ulceration * 1  1/6 (16.67%)  2
Vomiting * 1  1/6 (16.67%)  1
General disorders   
Fatigue * 1  2/6 (33.33%)  2
Local swelling * 1  1/6 (16.67%)  1
Malaise * 1  1/6 (16.67%)  1
Infections and infestations   
Nasopharyngitis * 1  3/6 (50.00%)  5
Genital infection fugal * 1  1/6 (16.67%)  1
Gingivitis * 1  1/6 (16.67%)  1
Groin abscess * 1  1/6 (16.67%)  1
Herpes virus infection * 1  1/6 (16.67%)  1
Mucosal infection * 1  1/6 (16.67%)  2
Oral herpes * 1  1/6 (16.67%)  1
Pneumonia * 1  1/6 (16.67%)  1
Rash pustular * 1  1/6 (16.67%)  4
Sinusitis * 1  1/6 (16.67%)  1
Subcutaneous abscess * 1  1/6 (16.67%)  1
Tonsilitis * 1  1/6 (16.67%)  1
Upper respiratory tract infection * 1  1/6 (16.67%)  1
Investigations   
Neutrophil count decreased * 1  1/6 (16.67%)  1
Musculoskeletal and connective tissue disorders   
Arthralgia * 1  1/6 (16.67%)  1
Nervous system disorders   
Headache * 1  3/6 (50.00%)  3
Skin and subcutaneous tissue disorders   
Alopecia * 1  1/6 (16.67%)  1
Pruritus * 1  1/6 (16.67%)  1
Skin induration * 1  1/6 (16.67%)  1
Surgical and medical procedures   
Tooth extraction * 1  1/6 (16.67%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (17.0)
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.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Roumen Nakov
Organization: Sandoz Biopharmaceutical, Hexal AG
Phone: +49 8024 4764704
EMail: roumen.nakov@sandoz.com
Layout table for additonal information
Responsible Party: Sandoz
ClinicalTrials.gov Identifier: NCT01859637     History of Changes
Other Study ID Numbers: EP06-401
First Submitted: May 8, 2013
First Posted: May 22, 2013
Results First Submitted: January 20, 2016
Results First Posted: March 28, 2016
Last Update Posted: March 28, 2016