Condition category
Haematological Disorders
Date applied
23/01/2009
Date assigned
03/02/2009
Last edited
03/02/2009
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Ms Martina Jansen

ORCID ID

Contact details

Oberlaaerstrasse 235
Vienna
1100
Austria
+43 (0)1 61032 1208
martina.jansen@octapharma.com

Additional identifiers

EudraCT number

2008-006172-29

ClinicalTrials.gov number

Protocol/serial number

GENA-09

Study information

Scientific title

Acronym

Study hypothesis

Comparison of pharmacokinetics of human-cl rhFVIII and Kogenate®/Helexate® in severe haemophilia A patients, followed by a 6-month open prophylactic treatment period to investigate the efficacy.

Ethics approval

Ministry of Health and Social Affairs of the Russian Federation, Federal Supervision Service for Public Health and Social Affairs gave approval on the 16th January 2009 (ref: no. 6)

Study design

Prospective randomised cross-over open-label trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Severe haemophilia A

Intervention

In the cross-over PK phase (part I), the PK properties of human-cl rhFVIII and Kogenate®/Helexate® will be studied: each one single treatment with 50 IU rFVIII/kg body weight (BW) will be given intravenously als a bolus injection. Subjects who completed part I will then be followed up for a period of 6 months and at least 50 EDs (part II). During this phase, prophylactic and on-demand treatments with human-cl rhFVIII are documented. The subjects get 30 IU rFVIII/kg BW every other day as a prophylactic treatment. Bleedings are treated in addition. Dose and duration of these treatments depend on the severity and the site of the bleeding. All treatments are intravenous injections.

Intervention type

Drug

Phase

Phase II

Drug names

Human-cl rhFVIII, Kogenate®/Helexate®

Primary outcome measures

To compare the area under curve (AUC) of human-cl rhFVIII and Kogenate®/Helexate® for FVIII:C using both the chromogenic (CHR) and the one-stage (OS) assays and the actual potency of human-cl rhFVIII and Kogenate®/Helexate®.

Secondary outcome measures

1. Pharmacokinetic (PK) parameters:
1.1. In vivo half-life (T1/2), Cmax, Tmax, MRT, Vd, and CL, calculated for FVIII:C using both the CHR and the OS assays and the actual potency of human-cl rhFVIII and Kogenate®/Helexate®
1.2. In-vivo recovery calculated from the FVIII levels before and peak level obtained in the 0.25, 0.5, 0.75, or 1 hour post-infusion samples
2. Efficacy in prophylactic treatment:
2.1. Overall efficacy assessment after a total of 50 EDs and at the end of the study
2.2. The frequency of bleeds under prophylactic treatment
2.3. Study drug consumption data (FVIII IU/kg per month, per year) per subject and in total
2.4. Efficacy assessment of each IMP injection and an overall efficacy assessment at the end of each BE
2.5. Surgical prophylaxis: the overall efficacy assessment after the end of the surgical prophylactic treatment phase by the surgeon and haematologist
2.6. Average and maximum expected estimated blood loss compared to the actual estimated blood loss
3. Safety: clinical tolerability assessed by:
3.1. Monitoring vital signs: blood pressure, heart rate, respiratory rate and body temperature will be assessed at pre-defined time-points
3.2. Laboratory parameters: the following routine safety laboratory parameters will be tested at pre-defined time-points:
3.2.1. Haematological parameters: red blood cell count, white blood cell count, haemoglobin, haematocrit, and platelet count
3.2.2. Clinical chemistry: total bilirubin, alanine aminotransferase, aspartate transaminase, blood urea nitrogen, serum creatinine, lactate dehydrogenase (LDH)
3.2.3. Serum electrolytes: sodium, potassium, bicarbonate, calcium
3.2.4. Urine analysis: urine dipstick chemical analysis (leucocyturia, haematuria, proteinuria, glucose, ketones, bilirubin, nitrites – if positive including microscopic examination)
3.3. Monitoring adverse events (AEs): at each study visit, all adverse events are documented by the Investigator.
3.4. Inhibitors against FVIII and anti-rhFVIII antibodies determined at pre-determined time points and in cases where an inhibitor development is suspected
3.5. Immunogenicity: inhibitor activity will be determined by the modified Bethesda assay (Nijmegen modification) at study entry, then immediately before the first human-cl rhFVIII administration, after 1 ED, after 10 to 15 EDs and the 3-months and 6-months visit. At the same time-point the anti-rhFVIII antibodies will be measured.

Overall trial start date

01/03/2009

Overall trial end date

01/12/2009

Reason abandoned

Eligibility

Participant inclusion criteria

1. Must have severe haemophilia A (FVIII:C less than 1%; historical value as documented in subject records)
2. Aged greater than 18 and less than 65 years, male
3. Body weight 45 kg to 110 kg
4. Previously treated with FVIII concentrate, at least 150 exposure days (EDs)
5. Immunocompetent (CD4+ count greater than 200/µL)
6. Negative for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) or respective viral load less than 200 particles/µL
7. Freely given written informed consent

Participant type

Patient

Age group

Adult

Gender

Male

Target number of participants

20

Participant exclusion criteria

1. Other coagulation disorder than haemophilia A
2. Present or past FVIII inhibitor activity (greater than 0.6 BU)
3. Severe liver or kidney disease (alanine aminotransferase [ALAT] and aspartate aminotransferase [ASAT] levels greater than 5 times of upper limit of normal, creatinine greater than 120 µmol/L)
4. Receiving or scheduled to receive immuno-modulating drugs (other than anti-retroviral chemotherapy) such as alpha-interferon, prednisone (equivalent to greater than 10 mg/day), or similar drugs
5. Participation in another clinical study currently or during the past month

Recruitment start date

01/03/2009

Recruitment end date

01/12/2009

Locations

Countries of recruitment

Russian Federation

Trial participating centre

Oberlaaerstrasse 235
Vienna
1100
Austria

Sponsor information

Organisation

Octapharma AG (Switzerland)

Sponsor details

Seidenstrasse 2
Lachen
CH-8853
Switzerland
+41 (0)55 4512121
sigurd.knaub@octapharma.ch

Sponsor type

Industry

Website

http://www.octapharma.com

Funders

Funder type

Industry

Funder name

Octapharma AG (Switzerland)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes