Trial Outcomes & Findings for Immunogenicity, Safety, and Efficacy of Zarzio®/Filgrastim HEXAL® in Patients With Severe Chronic Neutropenia (NCT NCT01859637)

NCT ID: NCT01859637

Last Updated: 2016-03-28

Results Overview

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).

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

6 participants

Primary outcome timeframe

screening, 3, 6, 9 and 12 months

Results posted on

2016-03-28

Participant Flow

First patient in: 05-Jul-2011, last patient in: 12-Feb-2013. 2 sites (medical school and university hospital)

Participant milestones

Participant milestones
Measure
Zarzio®/Filgrastim HEXAL® (EP2006)
Open label single arm. All patients received Zarzio® subcutaneously dosed as per recommendations in Summary of Product Characteristics (SmPC).
Overall Study
STARTED
6
Overall Study
COMPLETED
6
Overall Study
NOT COMPLETED
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Zarzio®/Filgrastim HEXAL®
n=6 Participants
Open label single arm. All patients received Zarzio®/Filgrastim HEXAL® subcutaneously dosed as per recommendations in SmPC.
Age, Continuous
45.0 years
n=5 Participants
Sex: Female, Male
Female
5 Participants
n=5 Participants
Sex: Female, Male
Male
1 Participants
n=5 Participants
Race/Ethnicity, Customized
Caucasian
5 participants
n=5 Participants
Race/Ethnicity, Customized
Latin American
1 participants
n=5 Participants
Region of Enrollment
Sweden
4 participants
n=5 Participants
Region of Enrollment
Germany
2 participants
n=5 Participants
Severe Chronic Neutropenia (SCN) diagnosis
Congenital neutropenia
1 participants
n=5 Participants
Severe Chronic Neutropenia (SCN) diagnosis
Cyclic neutropenia
1 participants
n=5 Participants
Severe Chronic Neutropenia (SCN) diagnosis
Idiopathic neutropenia
4 participants
n=5 Participants
Granulocyte Colony Stimulating Factor (G-CSF) pretreatment
Yes
6 participants
n=5 Participants
Granulocyte Colony Stimulating Factor (G-CSF) pretreatment
No
0 participants
n=5 Participants
Height
165.0 cm
n=5 Participants
Weight
67.0 kg
n=5 Participants

PRIMARY outcome

Timeframe: screening, 3, 6, 9 and 12 months

Population: 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).

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).

Outcome measures

Outcome measures
Measure
Zarzio®/Filgrastim HEXAL®
n=6 Participants
All patients received open-label Zarzio®/Filgrastim HEXAL®
Incidence of Anti- Recombinant Human Granulocyte Colony Stimulating Factor (rhG-CSF) Antibodies
Visit 1 - negative
6 participants
Incidence of Anti- Recombinant Human Granulocyte Colony Stimulating Factor (rhG-CSF) Antibodies
Visit 3 - negative
5 participants
Incidence of Anti- Recombinant Human Granulocyte Colony Stimulating Factor (rhG-CSF) Antibodies
Visit 4 - negative
6 participants
Incidence of Anti- Recombinant Human Granulocyte Colony Stimulating Factor (rhG-CSF) Antibodies
Visit 5 - negative
6 participants
Incidence of Anti- Recombinant Human Granulocyte Colony Stimulating Factor (rhG-CSF) Antibodies
Visit 6 - negative
6 participants
Incidence of Anti- Recombinant Human Granulocyte Colony Stimulating Factor (rhG-CSF) Antibodies
Visit 7 - negative
6 participants

SECONDARY outcome

Timeframe: 12 months

Population: Safety population (SAF): all patients with at least one dose Zarzio®/Filgrastim HEXAL® and at least one post-baseline safety assessment

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

Outcome measures

Outcome measures
Measure
Zarzio®/Filgrastim HEXAL®
n=6 Participants
All patients received open-label Zarzio®/Filgrastim HEXAL®
Number of Participants With Adverse Events (AEs)
6 participants

SECONDARY outcome

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.

Population: Safety population (SAF): all patients with at least one dose Zarzio®/Filgrastim HEXAL® and at least one post-baseline safety assessment

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.

Outcome measures

Outcome measures
Measure
Zarzio®/Filgrastim HEXAL®
n=6 Participants
All patients received open-label Zarzio®/Filgrastim HEXAL®
Change in Absolute Neutrophile Count (ANC)
ANC Visit 6 Month 9 to Baseline (Visit 2)
1.506 10^9 cells/L
Interval -9.6 to 14.7
Change in Absolute Neutrophile Count (ANC)
ANC Visit 1 Screening to Baseline (Visit 2)
-1.252 10^9 cells/L
Interval -10.9 to 2.84
Change in Absolute Neutrophile Count (ANC)
ANC Visit 3 Week 6 to Baseline (Visit 2)
6.873 10^9 cells/L
Interval -11.2 to 16.4
Change in Absolute Neutrophile Count (ANC)
ANC Visit 4 Month 3 to Baseline (Visit 2)
-0.198 10^9 cells/L
Interval -11.0 to 25.5
Change in Absolute Neutrophile Count (ANC)
ANC Visit 5 Month 6 to Baseline (Visit 2)
-0.711 10^9 cells/L
Interval -10.8 to 12.38
Change in Absolute Neutrophile Count (ANC)
ANC Visit 7 Month 12 to Baseline (Visit 2)
1.579 10^9 cells/L
Interval -10.8 to 18.87

Adverse Events

Open-label Zarzio®/Filgrastim HEXAL®

Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Open-label Zarzio®/Filgrastim HEXAL®
n=6 participants at risk
All patients received open-label Zarzio®/Filgrastim HEXAL®
Renal and urinary disorders
Nephrolithiasis
16.7%
1/6 • Number of events 1 • 12 months

Other adverse events

Other adverse events
Measure
Open-label Zarzio®/Filgrastim HEXAL®
n=6 participants at risk
All patients received open-label Zarzio®/Filgrastim HEXAL®
Infections and infestations
Nasopharyngitis
50.0%
3/6 • Number of events 5 • 12 months
Infections and infestations
Genital infection fugal
16.7%
1/6 • Number of events 1 • 12 months
Infections and infestations
Gingivitis
16.7%
1/6 • Number of events 1 • 12 months
Infections and infestations
Groin abscess
16.7%
1/6 • Number of events 1 • 12 months
Infections and infestations
Herpes virus infection
16.7%
1/6 • Number of events 1 • 12 months
Infections and infestations
Mucosal infection
16.7%
1/6 • Number of events 2 • 12 months
Infections and infestations
Oral herpes
16.7%
1/6 • Number of events 1 • 12 months
Infections and infestations
Pneumonia
16.7%
1/6 • Number of events 1 • 12 months
Infections and infestations
Rash pustular
16.7%
1/6 • Number of events 4 • 12 months
Infections and infestations
Sinusitis
16.7%
1/6 • Number of events 1 • 12 months
Infections and infestations
Subcutaneous abscess
16.7%
1/6 • Number of events 1 • 12 months
Infections and infestations
Tonsilitis
16.7%
1/6 • Number of events 1 • 12 months
Infections and infestations
Upper respiratory tract infection
16.7%
1/6 • Number of events 1 • 12 months
General disorders
Fatigue
33.3%
2/6 • Number of events 2 • 12 months
General disorders
Local swelling
16.7%
1/6 • Number of events 1 • 12 months
General disorders
Malaise
16.7%
1/6 • Number of events 1 • 12 months
Nervous system disorders
Headache
50.0%
3/6 • Number of events 3 • 12 months
Skin and subcutaneous tissue disorders
Alopecia
16.7%
1/6 • Number of events 1 • 12 months
Skin and subcutaneous tissue disorders
Pruritus
16.7%
1/6 • Number of events 1 • 12 months
Skin and subcutaneous tissue disorders
Skin induration
16.7%
1/6 • Number of events 1 • 12 months
Gastrointestinal disorders
Abdominal pain
16.7%
1/6 • Number of events 1 • 12 months
Gastrointestinal disorders
Diarrhoea
16.7%
1/6 • Number of events 1 • 12 months
Gastrointestinal disorders
Mouth ulceration
16.7%
1/6 • Number of events 2 • 12 months
Gastrointestinal disorders
Vomiting
16.7%
1/6 • Number of events 1 • 12 months
Investigations
Neutrophil count decreased
16.7%
1/6 • Number of events 1 • 12 months
Musculoskeletal and connective tissue disorders
Arthralgia
16.7%
1/6 • Number of events 1 • 12 months
Surgical and medical procedures
Tooth extraction
16.7%
1/6 • Number of events 1 • 12 months

Additional Information

Roumen Nakov

Sandoz Biopharmaceutical, Hexal AG

Phone: +49 8024 4764704

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: GT60