Hemophilia APhase 2NCT00989196
Clinical Study to Investigate the Pharmacokinetics, Efficacy, Safety and Immunogenicity of a Recombinant FVIII in Patients With Severe Hemophilia A
A Phase 2 study testing Human-cl rhFVIII and Kogenate FS in people with Hemophilia A, run by Octapharma at 9 sites in 3 countries.
Trial summary
This is a clinical study to investigate the pharmacokinetics, efficacy, safety and immunogenicity of human-cl rhFVIII, a newly developed human cell-line derived recombinant FVIII concentrate in previously treated patients with severe Hemophilia A. Read more about this study
- Who is it for?
- Ages 12 to 65 years, men only
- Conditions the study is for
- Hemophilia A
- What is being tested?
- Human-cl rhFVIII and Kogenate FS
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 9 sitesin 3 countries
- Study dates
- May 2010to Sep 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 65 years
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Severe hemophilia A (FVIII:C <= 1%)
- Male subjects between 12 and 65 years of age
- Body weight 25 kg to 110 kg
- Previously treated with FVIII concentrate for at least 150 EDs
Who cannot join
- Other coagulation disorder than hemophilia A
- Present or past FVIII inhibitor activity
Trial locations and contacts
9 sites in 3 countries.
9 sites in 3 countries
United States6 sites
RUSH University Medical Center
Chicago, Illinois, 60612
University of Colorado
Denver, Colorado, 80045
UCLA Orthodpedic Hospital
Los Angeles, California, 90007
University of Medicine and Dentistry
New Brunswick, New Jersey, 08903
University of California, Davis
Sacramento, California, 95817
Georgetown University
Washington D.C., District of Columbia, 20057
Germany2 sites
Vivantes Klinikum
Berlin
Medizinische Hochschule
Hanover, Lower Saxony
About this study
Official title: Clinical Study to Investigate the Pharmacokinetics, Efficacy, Safety and Immunogenicity of Human-cl rhFVIII, a Newly Developed Human Cell-line Derived Recombinant FVIII Concentrate in Previously Treated Patients With Severe Hemophilia A
This is a clinical study to investigate the pharmacokinetics, efficacy, safety and immunogenicity of human-cl rhFVIII, a newly developed human cell-line derived recombinant FVIII concentrate in previously treated patients with severe Hemophilia A.
- Conditions
- Hemophilia A
- Being tested
- Human-cl rhFVIII, Kogenate FS
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Human-cl rhFVIIIBiological
50 IU/kg for PK dose
Kogenate FSBiological
50 IU/kg for PK dose
| Study group | Role | What they receive |
|---|---|---|
| Human-cl rhFVIII | Experimental | Not described Receives: Biological: Human-cl rhFVIII |
| Kogenate FS | Active comparator | Not described Receives: Biological: Kogenate FS |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Area Under the Concentration Curve for Human-cl rhFVIII Compared to Kogenate FS
After the infusion of 50IU/kg bw of Human-cl rhFVIII and Kogenate FS respectively, FVIII activity levels were measured at various time points before and after the infusion. FVIII level results derived from the chromogenic FVIII assay were used to calculate the mean of the area under the curve normalized to the dose administered.
Measured: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion.
Secondary outcomes (8)
Invivo Half-life (T1/2) for Human-cl rhFVIII Compared to Kogenate FS
After the infusion of 50IU/kg bw of Human-cl rhFVIII and Kogenate FS respectively, FVIII activity levels were measured at various time points before and after the infusion. FVIII level results derived from the chromogenic FVIII assay were used to calculate the mean of the area under the curve normalized to the dose administered.
Measured: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion.
Maximum Plasma Concentration (Cmax) for Human-cl rhFVIII Compared to Kogenate FS
After the infusion of 50IU/kg bw of Human-cl rhFVIII and Kogenate FS respectively, FVIII activity levels were measured at various time points before and after the infusion. FVIII level results derived from the chromogenic FVIII assay were used to calculate the mean of the area under the curve normalized to the dose administered.
Measured: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion.
Time to Reach Maximum Plasma Concentration (Tmax) for Human-cl rhFVIII Compared to Kogenate FS
After the infusion of 50IU/kg bw of Human-cl rhFVIII and Kogenate FS respectively, FVIII activity levels were measured at various time points before and after the infusion. FVIII level results derived from the chromogenic FVIII assay were used to calculate the mean of the area under the curve normalized to the dose administered.
Measured: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion.
Mean Residence Time (MRT) for Human-cl rhFVIII Compared to Kogenate FS
After the infusion of 50IU/kg bw of Human-cl rhFVIII and Kogenate FS respectively, FVIII activity levels were measured at various time points before and after the infusion. FVIII level results derived from the chromogenic FVIII assay were used to calculate the mean of the area under the curve normalized to the dose administered.
Measured: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion.
Volume of Distribution at Steady State (Vss) for Human-cl rhFVIII Compared to Kogenate FS
After the infusion of 50IU/kg bw of Human-cl rhFVIII and Kogenate FS respectively, FVIII activity levels were measured at various time points before and after the infusion. FVIII level results derived from the chromogenic FVIII assay were used to calculate the mean of the area under the curve normalized to the dose administered.
Measured: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion.
Clearance (CL) for Human-cl rhFVIII Compared to Kogenate FS
After the infusion of 50IU/kg bw of Human-cl rhFVIII and Kogenate FS respectively, FVIII activity levels were measured at various time points before and after the infusion. FVIII level results derived from the chromogenic FVIII assay were used to calculate the mean of the area under the curve normalized to the dose administered.
Measured: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion.
Efficacy of On-demand Treatment of Bleeding Episodes
After each infusion of IMP and at the end of a BE, the following efficacy assessment is made by the subject (together with the Investigator in case of on-site treatment):
Excellent: Abrupt pain relief and/or unequivocal improvement in objective signs of bleeding within approximately 8 hours after a single infusion.
Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 - 12 hours after an infusion requiring up to 2 infusions for complete resolution.
Moderate: Probable or slight beneficial effect within approximately 12 hours after the first infusion requiring more than two infusions for complete resolution.
None: No improvement within 12 hours, or worsening of symptoms, requiring more than 2 infusions for complete resolution.
The assessment was made at the end of a BE in case more than one infusion was needed.
Measured: From 1st treatment after PK cycle 2 until study end.
Immunogenicity (Number of Patients That Developed an Inhibitor During the Course of the Study)
Inhibitor activity was determined by the modified Bethesda assay (Nijmegen modification) at study entry, then immediately before both PK cycles, in the 48 hour sample of both PK cycles, after 10 to 15 EDs with human-cl rhFVIII, at the 3-month visit (± 2 weeks), then every 3 months (± 2 weeks) until study completion, and after >50 EDs (except for some patients who may finish the study before they achieve 50 EDs), with human-cl rhFVIII (i.e. at the study completion visit).
Measured: study entry, then immediately before both PK cycles, in the 48 hour sample of both PK cycles, after 10 to 15 EDs with human-cl rhFVIII, at the 3-month visit (± 2 weeks), then every 3 months (± 2 weeks) until study completion, and after >50 EDs (except for
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2009 (estimated)
- Study startMay 2010
- Primary completionOct 2011
- Study completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hemophilia AStudies of the same condition, open and under way.
- More trials run by OctapharmaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Octapharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sigurd Knaub, PhD, Study director, Octapharma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00989196
- Sponsor's protocol ID
- GENA-01
- Status last verified
- Sep 2019
- First submitted
- 30 Sep 2009
- Last updated
- 8 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study to Investigate the Pharmacokinetics, Efficacy, Safety and Immunogenicity of Human-cl rhFVIII, a Newly Developed Human Cell-line Derived Recombinant FVIII Concentrate in Previously Treated Patients With Severe Hemophilia A
- ClinicalTrials.gov ID
- NCT00989196
- Acronym / sponsor ID
- GENA-01
- Conditions
- Hemophilia A
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- OctapharmaIndustry (pharma, biotech, devices)
- Study start
- May 2010
- Primary completion
- Oct 2011 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 2 Oct 2009 (estimated)
- Results
- Posted 17 Jan 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a clinical study to investigate the pharmacokinetics, efficacy, safety and immunogenicity of human-cl rhFVIII, a newly developed human cell-line derived recombinant FVIII concentrate in previously treated patients with severe Hemophilia A.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Human-cl rhFVIII | Experimental | Biological: Human-cl rhFVIII |
| Kogenate FS | Active comparator | Biological: Kogenate FS |
Who may qualify
- Ages
- 12 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Severe hemophilia A (FVIII:C <= 1%)
- Male subjects between 12 and 65 years of age
- Body weight 25 kg to 110 kg
- Previously treated with FVIII concentrate for at least 150 EDs
Key exclusion criteria (2 listed)
- Other coagulation disorder than hemophilia A
- Present or past FVIII inhibitor activity
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Human-cl rhFVIII50 IU/kg for PK dose | Biological | Human-cl rhFVIII |
| Kogenate FS50 IU/kg for PK dose | Biological | Kogenate FS |
Primary outcome
The Area Under the Concentration Curve for Human-cl rhFVIII Compared to Kogenate FS
Time frame: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion.
After the infusion of 50IU/kg bw of Human-cl rhFVIII and Kogenate FS respectively, FVIII activity levels were measured at various time points before and after the infusion. FVIII level results derived from the chromogenic FVIII assay were used to calculate the mean of the area under the curve normalized to the dose administered.
8 secondary outcomes
Invivo Half-life (T1/2) for Human-cl rhFVIII Compared to Kogenate FS
Time frame: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion.
Maximum Plasma Concentration (Cmax) for Human-cl rhFVIII Compared to Kogenate FS
Time frame: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion.
Time to Reach Maximum Plasma Concentration (Tmax) for Human-cl rhFVIII Compared to Kogenate FS
Time frame: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion.
Mean Residence Time (MRT) for Human-cl rhFVIII Compared to Kogenate FS
Time frame: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion.
Volume of Distribution at Steady State (Vss) for Human-cl rhFVIII Compared to Kogenate FS
Time frame: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion.
Clearance (CL) for Human-cl rhFVIII Compared to Kogenate FS
Time frame: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion.
Efficacy of On-demand Treatment of Bleeding Episodes
Time frame: From 1st treatment after PK cycle 2 until study end.
Immunogenicity (Number of Patients That Developed an Inhibitor During the Course of the Study)
Time frame: study entry, then immediately before both PK cycles, in the 48 hour sample of both PK cycles, after 10 to 15 EDs with human-cl rhFVIII, at the 3-month visit (± 2 weeks), then every 3 months (± 2 weeks) until study completion, and after >50 EDs (except for
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sigurd Knaub, PhD study director
Octapharma
9 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Human-cl rhFVIII and Kogenate FS in people with Hemophilia A, run by Octapharma at 9 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Germany, Bulgaria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Area Under the Concentration Curve for Human-cl rhFVIII Compared to Kogenate FS (time frame: At baseline (prior to infusion), 0.25, 0.5, 0.75, 1, 3, 6, 9, 12, 24, 30 and 48 hours after the end of the infusion.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2019.