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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01619046




Registration number
NCT01619046
Ethics application status
Date submitted
31/05/2012
Date registered
12/06/2012
Date last updated
2/07/2014

Titles & IDs
Public title
Safety, Efficacy and Pharmacokinetics of GreenGene™ F to Previously Treated Patients With Severe Hemophilia A
Scientific title
Determination of Safety, Efficacy and Pharmacokinetics of GreenGene™ F in Previously Treated Patients 12 Years of Age or Older Diagnosed With Severe Hemophilia A
Secondary ID [1] 0 0
GreenGeneF_P3
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hemophilia A 0 0
Condition category
Condition code
Blood 0 0 0 0
Clotting disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - GreenGene™ F and an approved recombinant Factor VIII product
Other interventions - GreenGene™ F
Other interventions - GreenGene™ F
Other interventions - GreenGene™ F

Active Comparator: PK substudy - A cohort of 13-18 subjects will be included in the pharmacokinetic (PK) evaluation of GreenGene™ F and an approved recombinant Factor VIII product (Refacto AF); a minimum of 13 of these subjects will be re-evaluated at study end (50 exposure day).

Experimental: Prophylaxis safety and efficacy substudy - Hemostatic efficacy of GreenGene™ F will be assessed by its effectiveness in controlling spontaneous or traumatic bleeding episodes and by the rate of breakthrough bleeding during prophylaxis over = 50 exposure days.

Experimental: On-demand safety and efficacy substudy - Hemostatic efficacy of GreenGene™ F will be assessed by its effectiveness in controlling spontaneous or traumatic bleeding episodes and by the rate of breakthrough bleeding in a minimum of 10 on demand treated subjects during 50 exposure days.

Experimental: Surgical substudy - Peri-operative hemostatic control of GreenGene™ F in surgery or invasive procedures will be assessed in at least 10 surgeries, some of them major, in at least five subjects


Other interventions: GreenGene™ F and an approved recombinant Factor VIII product
one 50 IU/kg, intra-venous infusion over 5 minutes, Infusion rate < 10 mL/min

Other interventions: GreenGene™ F
intra-venous infusion, 30 ± 5 IU/kg infusions 3 times per week with dose escalation to 45 ± 5 IU/kg if appropriate, for 50 exposure days

Other interventions: GreenGene™ F
intra-venous infusion,
On-demand safety and efficacy substudy:
minor bleed = 10-20 IU/kg moderate bleed = 15-30 IU/kg major bleed = 30-50 IU/kg

Other interventions: GreenGene™ F
intra venous infusion,
Surgical substudy:
Minor surgery including tooth extraction = Post in fusion FVIII level of 60-100% of normal. A single bolus infusion (30-50 IU/kg) beginning within one hour of the operation. Optional additional dosing every 12 to 24 hours as needed to control bleeding.
Major surgery = Pre- and post infusion FVIII level 80-120% of normal. Preoperative bolus infusion: 40-60 IU/kg. Verified 100% activity prior to surgery. Maintenance bolus infusion (40-60 IU/kg) repeat infusions every 8 to 24 hours, depending on the desired level.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of subject with development of inhibitors - Development of neutralizing antibodies (inhibitors) will be followed during the regular visits, average of 3 months.
Timepoint [1] 0 0
evert 3 months, up to 18 months
Secondary outcome [1] 0 0
Describe the PK profile of GreenGene™ F - AUC, AUMC, Half-life, Incremental recovery, Mean residence time (MRT), Clearance, Volume of distribution - steady state, Cmax, Tmax
Timepoint [1] 0 0
Pre-dose, 0~48hours post-dose

Eligibility
Key inclusion criteria
1. Male or female subjects age = 12 years at the time of informed consent

2. Body weight = 35 kg

3. Diagnosed with severe hemophilia A. All subjects must have severe hemophilia A with
baseline FVIII <1% activity; <0.01 IU/mL

4. Have = 150 previous exposure days to FVIII concentrates, as documented in the
subject's medical records

5. Subjects included in the on-demand treatment cohort must have a verifiable record of
at least three bleeding episodes per month on average in the last 6 months prior to
enrollment

6. Negative assays for FVIII inhibitor at inclusion (<0.6BU Nijmegen assay)

7. Negative assays for FVIII inhibitor in subject files (<0.6BU Nijmegen assay) No
history of positive inhibitor is allowed

8. Normal liver and kidney function.

9. Platelet count = 100,000 µL

10. Normal prothrombin time or International Normalized Ratio (INR) < 1.5

11. Subjects receiving therapy for human immunodeficiency virus (HIV) or hepatitis must be
on a stable treatment regimen

12. Subjects must be able to withhold FVIII infusions for approximately 72 h prior to each
FVIII activity and inhibitor assay (96 h if participating in the PK sub study)

13. Absolute CD4 lymphocyte cell count = 200 µL

14. Signed the written informed consent form or informed consent was obtained from the
subject's legal guardian

15. Females must not be lactating or pregnant at Screening or Baseline (as documented by a
negative beta-human chorionic gonadotropin [ß hCG] test with a minimum sensitivity of
25 IU/L or equivalent units of ß hCG). A separate baseline assessment is required if a
negative screening pregnancy test was obtained more than 72 hours before the first
dose of study drug

16. All females will be considered to be of childbearing potential unless they are
postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age
group and without other known or suspected cause) or have been sterilized surgically
(i.e. bilateral tubal ligation, total hysterectomy or bilateral oophorectomy, all with
surgery at least one month before dosing)

17. Willing and able to comply with all aspects of the protocol
Minimum age
12 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Presence at Screening of FVIII inhibitor = 0.6 BU as tested with the Nijmegen
modification of the Bethesda assay in either central or local laboratory

2. History of FVIII inhibitor of = 0.6 BU as measured using the Nijmegen modification of
the Bethesda assay

3. History of FVIII inhibitor = 1.0 BU if the subject has been tested routinely using the
original Bethesda assay, or history of periods with low recovery and no response to
Factor VIII treatment

4. Demonstrated an inability to respond to conventional doses of FVIII therapy

5. History of incremental recovery of Factor VIII <1.35% per IU/kg infused

6. Hematological disorders or blood coagulation diseases (e.g., idiopathic
thrombocytopenic purpura, von Willebrand disease, etc.) other than hemophilia A

7. Laboratory or clinical evidence of portal vein hypertension including,(but not limited
to, an INR > 1.4, the presence of splenomegaly and/or spider angiomata on physical
examination and/or a history of esophageal hemorrhage or documented esophageal varices

8. Uncontrolled hypertension (diastolic blood pressure >100 mm Hg)

9. Hemoglobin < 10 g.dL

10. HIV disease symptoms regardless of presence of HIV antibodies

11. Routine administration (or planned routine administration during the course of the
study), of immunosuppressive or immunomodulating drugs other than antiretroviral
therapy (e.g., steroids, beta-interferon)

12. Severe renal dysfunction (creatinine > 2x upper limit of normal [ULN], total bilirubin
> 2x the ULN)

13. Liver disease (alanine aminotransferase [ALT], aspartate aminotransferase [ AST] > 3x
the ULN)

14. History of diabetes or other metabolic disease

15. History of hypersensitivity or serious adverse reaction to recombinant or
plasma-derived FVIII concentrate

16. History of pretreatment prior to the administration of FVIII products (e.g., of
antihistamines)

17. Regular use of antifibrinolytics or medications affecting platelet function

18. Hypersensitivity to hamster-or mouse derived proteins

19. Blood transfusions within 30 days of enrollment into the study

20. Current participation in another investigational drug or device study, or participated
in a clinical study involving an investigational drug or device within 30 days of
enrollment into the study

21. Unable or unwilling to cooperate with study procedures

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Idaho
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Oregon
Country [10] 0 0
Canada
State/province [10] 0 0
Alberta
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
New Zealand
State/province [12] 0 0
Christchurch
Country [13] 0 0
Poland
State/province [13] 0 0
Warszawa
Country [14] 0 0
Poland
State/province [14] 0 0
Lodzi
Country [15] 0 0
Russian Federation
State/province [15] 0 0
Barnaul
Country [16] 0 0
Russian Federation
State/province [16] 0 0
Kirov
Country [17] 0 0
Russian Federation
State/province [17] 0 0
Moscow
Country [18] 0 0
Russian Federation
State/province [18] 0 0
Samara
Country [19] 0 0
Russian Federation
State/province [19] 0 0
Ufa
Country [20] 0 0
Ukraine
State/province [20] 0 0
Dnepropetrovsk
Country [21] 0 0
Ukraine
State/province [21] 0 0
Donetsk
Country [22] 0 0
Ukraine
State/province [22] 0 0
Kharkov
Country [23] 0 0
Ukraine
State/province [23] 0 0
Kyiv
Country [24] 0 0
Ukraine
State/province [24] 0 0
Lviv
Country [25] 0 0
Ukraine
State/province [25] 0 0
Zaporzhye
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Cornwall
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Hull
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Lancashire
Country [29] 0 0
United Kingdom
State/province [29] 0 0
London
Country [30] 0 0
United Kingdom
State/province [30] 0 0
North Hampshire
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Liverpool
Country [32] 0 0
United Kingdom
State/province [32] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Green Cross Corporation
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Atlantic Research Group
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to assess the safety, efficacy and pharmacokinetics of
GreenGene™ F in subjects with severe hemophilia A previously treated (> 150 exposure days)
with a Factor VIII concentrate and without presence or history of inhibitors to FVIII (Factor
VIII).
Trial website
https://clinicaltrials.gov/show/NCT01619046
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Paul LeoFrancis Giangrande, MD
Address 0 0
Oxford Haemophilic Centre and Thrombosis Unit, Churchill Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Kevin Wait
Address 0 0
Country 0 0
Phone 0 0
540-649-5490
Fax 0 0
Email 0 0
kwait@atlanticresearchgroup.com
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Not applicable