Assess the Efficacy and Safety of Personalized Prophylaxis Human-cl rhFVIII in Patients With Severe Haemophilia A

Study Overview
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Brief Summary
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The rationale of this study is to further fine-tune and individualize prophylactic treatment of patients with severe Haemophilia A with the goal of keeping the trough FVIII level above 1% between doses. Because trough FVIII levels are likely to be important predictors of the efficacy of prophylaxis, the focus of this study is on pharmacokinetic (PK) data.

Official Title
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Prospective, Open-label, Multi-centre Phase 3b Study to Assess the Efficacy and Safety of Personalized Prophylaxis With Human-cl rhFVIII in Previously Treated Adult Patients With Severe Haemophilia A

Conditions
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Severe Haemophilia A

Intervention / Treatment
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* Biological: Human cl rhFVIII


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe Haemophilia A (FVIII:C < 1%) Male patients >= 18 years of age Previous treatment with a FVIII concentrate for at least 150 EDs Good documentation regarding dosing and bleeding frequency in the 6 months preceding study start Immunocompetence (CD4+ count > 200/uL) Exclusion Criteria: Any coagulation disorder other than Haemophilia A Present of past FVIII inhibitor activity Severe liver or kidney disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Human-cl rhFVIII<br> | Biological: Human cl rhFVIII<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Total Bleeding Rate of Individually Tailored Prophylaxis | Total annualized bleeding rate (ABR) of individually tailored prophylaxis (GENA-21b) compared to historical bleeding rate in patients having received on-demand treatment (GENA-01) with Human-cl rhFVIII | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Spontaneous Bleeding Rate of Individually Tailored Prophylaxis | Spontaneous annualized bleeding rate (ABR) of individually tailored prophylaxis (GENA-21b) compared to historical bleeding rate in patients having received on-demand treatment (GENA-01) with Human-cl rhFVIII | 6 months | 
| Annualized Total Bleeding Rate in Patients With 2x/Week (or Less) Prophylaxis | Total annualized bleeding rate (ABR) in patients with 2x/week (or less) prophylaxis (GENA-21b) compared to historical bleeding rate in patients having received on-demand treatment (GENA-01) with Human-cl rhFVIII | 6 months | 
| Median Prophylactic Dosing Interval | Median over median actual dosing intervals between two prophylactic treatments per patient. The median time (hours) between two prophylactic doses of Human-cl rhFVIII in the prophylactic treatment Phase II per patient | 6 months | 
| Mean Prophylactic Dosing Interval | Mean over mean actual dosing intervals between two prophylactic treatments per patient. The mean time (hours) between two prophylactic doses of Human-cl rhFVIII in the prophylactic treatment Phase II per patient | 6 months | 
| AUC Divided by the Dose (AUCnorm) of Human-cl rhFVIII | AUCnorm of Human-cl rhFVIII measured using the one-stage (OS) assay | Before injection (within 1 h before injection) and up to 72 h (± 2 h) after the end of injection | 
| In-vivo Recovery (IVR) of Human-cl rhFVIII | IVR of Human-cl rhFVIII measured using the one-stage (OS) assay and will be determined from the FVIII level before the infusion and the peak level after the infusion of Human-cl rhFVIII | Before injection (within 1 h before injection) and up to 72 h (± 2 h) after the end of injection | 
| Half Life (t1/2) of Human-cl rhFVIII | T1/2 of Human-cl rhFVIII measured using the one-stage (OS) assay | Before injection (within 1 h before injection) and up to 72 h (± 2 h) after the end of injection | 
| Mean Residence Time (MRT) of Human-cl rhFVIII | MRT of Human-cl rhFVIII measured using the one-stage (OS) assay | Before injection (within 1 h before injection) and up to 72 h (± 2 h) after the end of injection | 
| Clearance (CL) of Human-cl rhFVIII | CL of Human-cl rhFVIII measured using the one-stage (OS) assay | Before injection (within 1 h before injection) and up to 72 h (± 2 h) after the end of injection | 
| Volume of Distribution at Steady State (Vss) of Human-cl rhFVIII | Vss of Human-cl rhFVIII measured using the one-stage (OS) assay | Before injection (within 1 h before injection) and up to 72 h (± 2 h) after the end of injection | 
| Usage of Human-cl rhFVIII (FVIII IU/kg BW Per Week Per Patient) | Average weekly consumption of Human-cl rhFVIII reported as IU/kg BW per week per patient was determined during individualized prophylactic treatment | 6 months | 
| Number of Patients With Adverse Events (AEs) | AEs were documented at each (scheduled or unscheduled) study visit. Severity and seriousness of all AEs were documented by the investigator according to pre-defined criteria | At each study visit over the study duration (7-9 months) |